title: Population age structure only partially explains the large number of COVID-19 deaths at the oldest ages

text: To date any attention paid to the age shape of COVID-19 deaths has been mostly in relation to attempts to understand the differences in case fatality rates between countries. The aim of this paper is to explore differences in age distribution of deaths from COVID-19 among European countries which have old age structures. We do this by way of a cross-country comparison and put forward some reasons for potential differences.


title: Clinical course and risk factors for mortality of COVID-19 patients with pre-existing cirrhosis: A multicenter cohort study

text: Background: Patients with pre-existing cirrhosis are considered at increased risk of severe coronavirus disease 2019 (COVID-19) but the clinical course in these patients has not yet been reported. This study aimed to provide a detailed report of the clinical characteristics and outcomes among COVID-19 patients with pre-existing cirrhosis. Methods: In this retrospective, multicenter cohort study, we consecutively included all adult inpatients with laboratory-confirmed COVID-19 and pre-existing cirrhosis that had been discharged or had died by 24 March 2020 from 16 designated hospitals in China. Demographic, clinical, laboratory and radiographic findings on admission, treatment, complications during hospitalization and clinical outcomes were collected and compared between survivors and non-survivors. Findings: Twenty-one patients were included in this study, of whom 16 were cured and 5 died in hospital. Seventeen patients had compensated cirrhosis and hepatitis B virus infection was the most common etiology. Lymphocyte and platelet counts were lower, and direct bilirubin levels were higher in patients who died than those who survived (p= 0.040, 0.032, and 0.006, respectively). Acute respiratory distress syndrome and secondary infection were both the most frequently observed complications. Only one patient developed acute on chronic liver failure. Of the 5 non-survivors, all patients developed acute respiratory distress syndrome and 2 patients progressed to multiple organ dysfunction syndrome. Interpretation: Lower lymphocyte and platelet counts, and higher direct bilirubin level might represent poor prognostic indicators in SARS-CoV-2-infected patients with pre-existing cirrhosis.


title: Social and travel lockdown impact considering coronavirus disease (Covid-19) on air quality in megacities of india: Present benefits, future challenges and way forward

text: The coronavirus disease (COVID-19) created enormous pressure across the globe due to an increasing number of COVID-19 infected cases. All the governments’ primary focus is to save humanity from this pandemic problem, and they have lockdown almost the entire nation to stop the spread of infection. This lockdown resulted in a considerable impact on the global as well as a local economy that will take a long time to perform with business as usual scenario. However, improvement in the air quality of the cities across the globe has emerged as a key benefit of this lockdown. Therefore, this study aims to assess the overall impact of social and travel lockdown in five megacities of India; Delhi, Mumbai, Chennai, Kolkata, and Bangalore. The study evaluated the spatiotemporal variations in five criteria pollutants over two time periods, i.e., March–April 2019 and March–April 2020 and 10 th–20 thMarch 2020 (before lockdown) and 25 thMarch to 6 thApril 2020 (during lockdown). The results highlighted a statistically significant decline in all the pollutants in all the megacities except for ozone. It was observed that the concentration of PM 2.5, PM 10, NO 2and CO declined by ~41% (66–39 µg m –3), ~52% (153–73 µg m –3), ~51% (39–19 µg m –3) and ~28% (0.9–0.65 mg m –3) during the lockdown phase in comparison to the before lockdown in Delhi, respectively. Similar decline in pollutant concentration was observed in other megacities as well. Further, the study conducted an expert survey to identify the possible challenges India might face after lockdown is over. All the experts said that reviving the economy will be a big challenge for the government, and it may result in some tradeoff while managing the air quality in the near future due to scarcity of funds, etc.


docid: rgqvdzna

title: Low SARS-CoV-2 sero-prevalence based on anonymized residual sero-survey before and after first wave measures in British Columbia, Canada, March-May 2020

text: Background: The province of British Columbia (BC) has been recognized for successful SARS-CoV-2 control, with surveillance data showing amongst the lowest case and death rates in Canada. We estimate sero-prevalence for two periods flanking the start (March) and end (May) of first-wave mitigation measures in BC. Methods: Serial cross-sectional sampling was conducted using anonymized residual sera obtained from an outpatient laboratory network, including children and adults in the Greater Vancouver Area (population ~3 million) where community attack rates were expected to be highest. Screening used two chemiluminescent immuno-assays for spike (S1) and nucleocapsid antibodies. Samples sero-positive on either screening assay were assessed by a third assay targeting the S1 receptor binding domain plus a neutralization assay. Age-standardized sero-prevalence estimates were based on dual-assay positivity. The May sero-prevalence estimate was extrapolated to the source population to assess surveillance under-ascertainment, quantified as the ratio of estimated infections versus reported cases. Results: Serum collection dates spanned March 5-13 and May 15-27, 2020. In March, two of 869 specimens were dual-assay positive, with age-standardized sero-prevalence of 0.28% (95%CI=0.03-0.95). Neither specimen had detectable neutralizing antibodies. In May, four of 885 specimens were dual-assay positive, with age-standardized sero-prevalence of 0.55% (95%CI=0.15-1.37%). All four specimens had detectable neutralizing antibodies. We estimate ~8 times more infections than reported cases. Conclusions: Less than 1% of British Columbians had been infected with SARS-CoV-2 when first-wave mitigation measures were relaxed in May 2020. Our findings indicate successful suppression of community transmission in BC, but also substantial residual susceptibility. Further sero-survey snapshots are planned as the pandemic unfolds.


title: Key points of serious adverse event and protection of patients in ophthalmic clinical trials during novel coronavirus pneumonia outbreak/ 新型冠状病毒肺炎防控期间眼科临床试验流程管理及受试者随访防护要点

text: The prevention and control of novel coronavirus pneumonia is the most priority recently, and various measures during the prevention and control period will have varying degrees of impact on the implement of clinical trials.However, various examinations in ophthalmological clinical trials need close contact between operators and patients, which put us at risk of cross-infection.This paper indicated some suggestions based on the criteria of clinical trials under major public health emergencies, the management of clinical trials during epidemic period, including the follow-up of subjects, the treatment of epidemic serious adverse event (SAE) and the management requirements of co-sponsors, as well as the requirements and management principles for environment, subjects, examiners and inspection equipment in the process of ophthalmic clinical trials.It may be helpful to the ophthalmic clinical trial researchers and subjects during the period of novel coronavirus infection.


title: Mathematical framework to model Covid-19 daily deaths

text: The novel coronavirus (2019-nCoV) pandemic has caused widespread socio-economic disruption and, as of 04/07/2020, resulted in more than 72,614 confirmed deaths worldwide. Robust prediction of the trajectory of the death incidence curve is helpful for policy decisions during this ongoing crisis. We propose a non-parametric model to fit the number of daily deaths in a region, which hypothesizes that the death incidence curve will have a convex shape in the beginning, a concave shape near the peak, and a convex shape in the final stage of the death incidence curve after the peak. Using this, we performed robust short-term predictions on phases in five countries worldwide and five US states. Our analysis shows while the five states are all at peaks or past their peaks, US as a country is possibly not at peak yet. Our model can be easily fitted on daily death data from any region.


docid: ahxnhutv

title: Kidney impairment is associated with in-hospital death of COVID-19 patients

text: Background: Information on kidney impairment in patients with coronavirus disease 2019 (COVID-19) is limited. This study aims to assess the prevalence and impact of abnormal urine analysis and kidney dysfunction in hospitalized COVID-19 patients in Wuhan. Method: We conducted a consecutive cohort study of COVID-19 patients admitted in a tertiary teaching hospital with 3 branches following a major outbreak in Wuhan in 2020. Hematuria, proteinuria, serum creatinine concentration and other clinical parameters were extracted from the electronic hospitalization databases and laboratory databases. Incidence rate for acute kidney injury (AKI) was examined during the study period. Association between kidney impairment and in-hospital death was analyzed. Results: We included 710 consecutive COVID19 patients, 89 (12.3%) of whom died in hospital. The median age of the patients was 63 years (inter quartile range, 51-71), including 374 men and 336 women. On admission, 44% of patients have proteinuria hematuria and 26.9% have hematuria, and the prevalence of elevated serum creatinine and blood urea nitrogen were 15.5% and 14.1% respectively. During the study period, AKI occurred in 3.2% patients. Kaplan-Meier analysis demonstrated that patients with kidney impairment have higher risk for in-hospital death. Cox proportional hazard regression confirmed that elevated serum creatinine, elevated urea nitrogen, AKI, proteinuria and hematuria was an independent risk factor for in-hospital death after adjusting for age, sex, disease severity, leukocyte count and lymphocyte count. Conclusion: The prevalence of kidney impairment (hematuria, proteinuria and kidney dysfunction) in hospitalized COVID-19 patients was high. After adjustment for confounders, kidney impairment indicators were associated with higher risk of in-hospital death. Clinicians should increase their awareness of kidney impairment in hospitalized COVID-19 patients.


title: "No test is better than a bad test": Impact of diagnostic uncertainty in mass testing on the spread of Covid-19

text: Background: The cessation of lock-down measures will require an effective testing strategy. Much focus at the beginning of the UK's Covid-19 epidemic was directed to deficiencies in the national testing capacity. The quantity of tests may seem an important focus, but other characteristics are likely more germane. False positive tests are more probable than positive tests when the overall population has a low prevalence of the disease, even with highly accurate tests. Methods: We modify an SIR model to include quarantines states and test performance using publicly accessible estimates for the current situation. Three scenarios for cessation of lock-down measures are explored: (1) immediate end of lock-down measures, (2) continued lock-down with antibody testing based immunity passports, and (3) incremental relaxation of lock-down measures with active viral testing. Sensitivity, specifcity, prevalence and test capacity are modified for both active viral and antibody testing to determine their population level effect on the continuing epidemic. Findings: Diagnostic uncertainty can have a large effect on the epidemic dynamics of Covid-19 within the UK. The dynamics of the epidemic are more sensitive to test performance and targeting than test capacity. The quantity of tests is not a substitute for an effective strategy. Poorly targeted testing has the propensity to exacerbate the peak in infections. Interpretation: The assessment that 'no test is better than a bad test' is broadly supported by the present analysis. Antibody testing is unlikely to be a solution to the lock-down, regardless of test quality or capacity. A well designed active viral testing strategy combined with incremental relaxation of the lock-down measures is shown to be a potential strategy to restore some social activity whilst continuing to keep infections low.


title: Factors associated with hospitalization and critical illness among 4,103 patients with COVID-19 disease in New York City

text: Background: Little is known about factors associated with hospitalization and critical illness in Covid-19 positive patients. Methods: We conducted a cross-sectional analysis of all patients with laboratory-confirmed Covid-19 treated at a single academic health system in New York City between March 1, 2020 and April 2, 2020, with follow up through April 7, 2020. Primary outcomes were hospitalization and critical illness (intensive care, mechanical ventilation, hospice and/or death). We conducted multivariable logistic regression to identify risk factors for adverse outcomes, and maximum information gain decision tree classifications to identify key splitters. Results: Among 4,103 Covid-19 patients, 1,999 (48.7%) were hospitalized, of whom 981/1,999 (49.1%) have been discharged home, and 292/1,999 (14.6%) have died or were discharged to hospice. Of 445 patients requiring mechanical ventilation, 162/445 (36.4%) have died. Strongest hospitalization risks were age [≥]75 years (OR 66.8, 95% CI, 44.7-102.6), age 65-74 (OR 10.9, 95% CI, 8.35-14.34), BMI>40 (OR 6.2, 95% CI, 4.2-9.3), and heart failure (OR 4.3 95% CI, 1.9-11.2). Strongest critical illness risks were admission oxygen saturation <88% (OR 6.99, 95% CI 4.5-11.0), d-dimer>2500 (OR 6.9, 95% CI, 3.2-15.2), ferritin >2500 (OR 6.9, 95% CI, 3.2-15.2), and C-reactive protein (CRP) >200 (OR 5.78, 95% CI, 2.6-13.8). In the decision tree for admission, the most important features were age >65 and obesity; for critical illness, the most important was SpO2<88, followed by procalcitonin >0.5, troponin <0.1 (protective), age >64 and CRP>200. Conclusions: Age and comorbidities are powerful predictors of hospitalization; however, admission oxygen impairment and markers of inflammation are most strongly associated with critical illness.


title: Development and Evaluation of A CRISPR-based Diagnostic For 2019-novel Coronavirus

text: Background: The recent outbreak of infections by the 2019 novel coronavirus (2019-nCoV), the third zoonotic CoV has raised great public health concern. The demand for rapid and accurate diagnosis of this novel pathogen brought significant clinical and technological challenges. Currently, metagenomic next-generation sequencing (mNGS) and reverse-transcription PCR (RT-PCR) are the most widely used molecular diagnostics. Methods: 2019-nCoV infections were confirmed in 52 specimens by mNGS. Genomic information was analyzed and used for the design and development of an isothermal, CRISPR-based diagnostic for this novel virus. The diagnostic performance of CRISPR-nCoV was assessed and compared across three technology platforms (mNGS, RT-PCR and CRISPR). Results: 2019-nCoVs sequenced in our study were conserved with the Wuhan strain, and shared certain genetic similarity with SARS-CoV. A high degree of variation in the level of viral RNA was observed in clinical specimens. CRISPR-nCoV demonstrated a near single-copy sensitivity and great clinical sensitivity with a shorter turn-around time than RT-PCR. Conclusion: CRISPR-nCoV presents as a promising diagnostic option for the emerging pathogen.


title: Phylogenetic clustering of the Indian SARS-CoV-2 genomes reveals the presence of distinct clades of viral haplotypes among states

text: The first Indian cases of COVID-19 caused by SARS-Cov-2 were reported in February 29, 2020 with a history of travel from Wuhan, China and so far above 4500 deaths have been attributed to this pandemic. The objectives of this study were to characterize Indian SARS-CoV-2 genome-wide nucleotide variations, trace ancestries using phylogenetic networks and correlate state-wise distribution of viral haplotypes with differences in mortality rates. A total of 305 whole genome sequences from 19 Indian states were downloaded from GISAID. Sequences were aligned using the ancestral Wuhan-Hu genome sequence (NC_045512.2). A total of 633 variants resulting in 388 amino acid substitutions were identified. Allele frequency spectrum, and nucleotide diversity (π) values revealed the presence of higher proportions of low frequency variants and negative Tajima’s D values across ORFs indicated the presence of population expansion. Network analysis highlighted the presence of two major clusters of viral haplotypes, namely, clade G with the S:D614G, RdRp: P323L variants and a variant of clade L [Lv] having the RdRp:A97V variant. Clade G genomes were found to be evolving more rapidly into multiple sub-clusters including clade GH and GR and were also found in higher proportions in three states with highest mortality rates namely, Gujarat, Madhya Pradesh and West Bengal.


title: Genomic surveillance of SARS-CoV-2 reveals community transmission of a major lineage during the early pandemic phase in Brazil

text: Despite all efforts to control the COVID-19 spread, the SARS-CoV-2 reached South America within three months after its first detection in China, and Brazil became one of the hotspots of COVID-19 in the world. Several SARS-CoV-2 lineages have been identified and some local clusters have been described in this early pandemic phase in Western countries. Here we investigated the genetic diversity of SARS-CoV-2 during the early phase (late February to late April) of the epidemic in Brazil. Phylogenetic analyses revealed multiple introductions of SARS-CoV-2 in Brazil and the community transmission of a major B.1.1 lineage defined by two amino acid substitutions in the Nucleocapsid and ORF6. This SARS-CoV-2 Brazilian lineage was probably established during February 2020 and rapidly spread through the country, reaching different Brazilian regions by the middle of March 2020. Our study also supports occasional exportations of this Brazilian B.1.1 lineage to neighboring South American countries and to more distant countries before the implementation of international air travels restrictions in Brazil.


title: Effect of statins on SARS-CoV-2 infection

text: The retrospective analysis of clinical data of patients suffering from COVID-19 has indicated that statin therapy, used to lower plasma cholesterol levels, is associated with a better clinical outcome. We therefore investigated the effect of statins on SARS-CoV-2 infection and found that selective statins reduced SARS-CoV-2 cell entry and inhibited high and low pathogenic coronavirus infection in human cells. A retrospective study on hospitalized patients with COVID-19 implies that reduced high density lipoprotein levels, which are typically counteracted by statin therapy, are associated with aggravated disease outcome. These results suggest that statin therapy poses no additional risk to individuals exposed to SARS-CoV-2 and that some statins may have a mild beneficial effect on COVID-19 outcome.


Names and numbers: How COVID-19 impacted on de-humanization of ICU patients


title: Unproven herbal remedy against COVID-19 could fuel drug-resistant malaria, scientists warn

text: An herbal tonic developed in Madagascar and touted as a cure for COVID-19 could fuel drug-resistant malaria in Africa, scientists warn Several African countries have said they are placing orders for the brew, whose efficacy has yet to be shown Branded Covid-Organics, the therapy was developed by the Malagasy Institute of Applied Research (IMRA) Its chief ingredient is reported to be sweet wormwood (Artemisia annua), a plant of Asian origin that gave rise to the antimalarial drug artemisinin At its launch last month, Malagasy President Andry Rajoelina claimed the tonic had passed scientific scrutiny and cured two patients of COVID-19 The island nation has 151 confirmed coronavirus cases and no deaths


title: Olfactory transmucosal SARS-CoV-2 invasion as port of Central Nervous System entry in COVID-19 patients

text: The newly identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19, a pandemic respiratory disease presenting with fever, cough, and often pneumonia. Moreover, thromboembolic events throughout the body including the central nervous system (CNS) have been described. Given first indication for viral RNA presence in the brain and cerebrospinal fluid and in light of neurological symptoms in a large majority of COVID-19 patients, SARS-CoV-2-penetrance of the CNS is likely. By precisely investigating and anatomically mapping oro- and pharyngeal regions and brains of 32 patients dying from COVID-19, we not only describe CNS infarction due to cerebral thromboembolism, but also demonstrate SARS-CoV-2 neurotropism. SARS-CoV-2 enters the nervous system via trespassing the neuro-mucosal interface in the olfactory mucosa by exploiting the close vicinity of olfactory mucosal and nervous tissue including delicate olfactory and sensitive nerve endings. Subsequently, SARS-CoV-2 follows defined neuroanatomical structures, penetrating defined neuroanatomical areas, including the primary respiratory and cardiovascular control center in the medulla oblongata.


title: Blood single cell immune profiling reveals the interferon-MAPK pathway mediated adaptive immune response for COVID-19

text: The coronavirus disease 2019 (COVID-19) outbreak is an ongoing global health emergence, but the pathogenesis remains unclear. We revealed blood cell immune response profiles using 5' mRNA, TCR and BCR V(D)J transcriptome analysis with single-cell resolution. Data from 134,620 PBMCs and 83,387 TCR and 12,601 BCR clones was obtained, and 56 blood cell subtypes and 23 new cell marker genes were identified from 16 participants. The number of specific subtypes of immune cells changed significantly when compared patients with controls. Activation of the interferon-MAPK pathway is the major defense mechanism, but MAPK transcription signaling is inhibited in cured patients. TCR and BCR V(D)J recombination is highly diverse in generating different antibodies against SARS-CoV-2. Therefore, the interferon-MAPK pathway and TCR- and BCR-produced antibodies play important roles in the COVID-19 immune response. Immune deficiency or immune over-response may result in the condition of patients with COVID-19 becoming critical or severe.


Internatioanl News Letter - April 2020


docid: agwhkfcb

title: Negative impact of the COVID-19 pandemic on sleep quantitative parameters, quality, and circadian alignment: Implications for psychological well-being and emotional regulation

text: Background The COVID-19 pandemic has spread worldwide, affecting millions of people and exposing them to home quarantine, isolation, and social distancing. While recent reports showed increased distress and depressive/anxiety state related to COVID-19 crisis, we investigated how home quarantine affected sleep parameters in healthy individuals. Methods 160 healthy individuals who were in home quarantine in April 2020 for at least one month participated in this study. Participants rated and compared their quantitative sleep parameters (time to go to bed, sleep duration, getting-up time) and sleep quality factors, pre-and during home quarantine due to the COVID-19 pandemic. Furthermore, participants chronotype was determined to see if sleep parameters are differentially affected in different chronotypes. Results The time to fall asleep and get-up in the morning were significantly delayed in all participants, indicating a significant circadian misalignment. Sleep quality was reported to be significantly poorer in all participants and chronotypes, and included more daily disturbances (more sleep disturbances, higher daily dysfunctions due to low quality of sleep) and less perceived sleep quality (lower subjective sleep quality, longer time taken to fall asleep at night, more use of sleep medication for improving sleep quality) during home quarantine. Conclusions Home quarantine due to COVID-19 pandemic has a detrimental impact on sleep quality. Online interventions including self-help sleep programs, stress management, relaxation practices, stimulus control, sleep hygiene, and mindfulness training are available interventions in the current situation.


docid: zhvwwvte

title: Environmental sampling for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during a coronavirus disease (COVID-19) outbreak aboard a commercial cruise ship

text: Background A COVID-19 outbreak occurred in a cruise ship with 3711 passengers and crew in 2020. This study is to test the hypothesis that environmental surfaces played important roles in transmission for SARS-CoV-2 during this outbreak. Methods We sampled environmental surfaces including air from common areas in the cruise ship and cabins in which confirmed COVID-19 cases and non-cases had stayed after they left the cabins. We tested the samples for SARS-CoV-2 by rt-PCR and conducted viral isolation. Findings Of 601 samples tested, SARS-CoV-2 RNA was detected from 58 samples (10%) from case-cabins from which they left 1-17 days before sampling, but not from non-case-cabins. Except for one sample from an air hood in a corridor, SARS-CoV-2 RNA was not detected from samples in common areas. SARS-CoV-2 RNA was not detected from all 14 air samples. RNA was most often detected on the floor around toilet in the bathroom (39%, 13/33, cycle quantification (Cq): 26.21-37.62) and bed pillow (34%, 11/32, Cq: 34.61-38.99). There was no difference in the detection proportion between cabins for symptomatic (15%, 28/189, Cq: 29.79-38.86) and asymptomatic cases (21%, 28/131, Cq: 26.21-38.99). No SARS-CoV-2 virus was isolated from any of the samples. Interpretation The environment around the COVID-19 cases was extensively contaminated from SARS-CoV-2 during COVID-19 outbreak in the cruise ship. Transmission risk of SARS-CoV-2 from symptomatic and asymptomatic patients seems to be similar and the environmental surface could involve viral transmission through direct contact.


SARS-CoV-2 infection in neonate: What do we know so far?


title: Learning as We Go: An Examination of the Statistical Accuracy of COVID19 Daily Death Count Predictions

text: A recent model developed at the Institute for Health Metrics and Evaluation (IHME) provides forecasts for ventilator use and hospital beds required for the care of COVID19 patients on a state-by-state basis throughout the United States over the period March 2020 through August 2020 (See the related website https://covid19.healthdata.org/projections for interactive data visualizations). In addition, the manuscript and associated website provide projections of deaths per day and total deaths throughout this period for the entire US, as well as for the District of Columbia. This research has received extensive attention in social media, as well as in the mass media. Moreover, this work has influenced policy makers at the highest levels of the United States government, having been mentioned at White House Press conferences, including March 31, 2020. In this paper, we evaluate the predictive validity of model forecasts for COVID19 outcomes as data become sequentially available, using the IHME prediction of daily deaths. We have found that the predictions for daily number of deaths provided by the IHME model have been highly inaccurate. The model has been found to perform poorly even when attempting to predict the number of next day deaths. In particular, the true number of next day deaths has been outside the IHME prediction intervals as much as 70% of the time.


title: Comparative risk science for the coronavirus pandemic

text: Judgment, decision making, and risk researchers have learned a great deal over the years about how people prepare for and react to global risks. In recent years, risk scholars have increasingly focused their energies on climate change, and as pandemic coronavirus has swept the globe many of these scholars are comparing the coronavirus pandemic with climate change to inform risk management. Risk communication research and the best practices developed from it are predicated on findings from the 1970’s to the present showing that there are structural similarities in how people think about widely divergent risks. Consequently, these lessons from risk communication of climate change (and from the canon of best practices) apply to the coronavirus pandemic. In the empirical comparison of student perceptions reported here, we replicate these structural similarity findings, but also find that moral concerns in particular deserve attention as a potentially distinct dimension of risk perception, on which different risks may also differ, as pandemic risks appear to evoke less moral concern than climate change. The need for communications to be timely, honest, credible, empathetic, and informative for useful individual actions is fundamental and essential for communicating effectively about the coronavirus epidemic. Some countries have heeded risk sciences, and are coping more successfully with pandemic coronavirus. Others have failed to implement these old lessons, which our data suggest still apply. While these failures may reinforce cynicism about political and public enthusiasm for accepting science, comparisons between the coronavirus pandemic and climate change may also foster greater aspirations for collective action.


title: Chemoprophylaxis of COVID-19 with hydroxychloroquine: Astudy of health care workers attitude, adherence to regimeand side effects

text: Background: There are apprehensions amongst healthcare worker (HCWs) about COVID-19. The HCWs have been given hydroxychloroquine (HCQ) chemoprophylaxis for seven weeks as per Government of India guidelines. Objectives: To assess the apprehensions amongst HCWs about COVID-19 and to document accessibility, adherence and side effects related to HCQ prophylaxis in HCWs. Methods: A longitudinal follow up study was conducted in a tertiary care hospital. HCQ was given in the dose of 400 mg twice on day one, and then 400 mg weekly for seven weeks. 391 HCWs were interviewed using semi-structured questionnaire. Results: 62.2% HCWs expressed perceived danger posted by COVID-19 infection. Doctors (54%) showed least acceptance and paramedics (88%) showed highest acceptance to chemoprophylaxis. 17.5% participants developed at least one of the side effects to HCQ. Females and nursing profession were significantly associated with adverse effects. Common side effects were gastro-intestinal symptoms, headache and abnormal mood change. Most of these were mild, not requiring any intervention. Gender, professions and perceived threat of COVID-19 were significantly associated with acceptance and adherence to HCQ prophylaxis. Conclusion: Two thirds of HCWs had perceived danger due to COVID-19. Three fourth of the HCWs accepted chemoprophylaxis and four out of five who accepted had complete adherence to prophylaxis schedule. One out of five had developed at least one of side effects; however, most of these were mild not requiring any intervention.


title: Immune Status of COVID-19 Patients with Reference to SARS and MERS

text: During this global pandemic of COVID-19 infection, it became well known that morbidity and mortality is especially high at the extreme of life especially in certain racial or ethnic groups like Americans and Africans This is presumed due to low immunity associated with other comorbid conditions like diabetes, hypertension, cardiovascular disease, obesity and metabolic syndrome But the information available on the immune status of COVID-19 patients is limited Attempts must be made to enhance our understanding of the immune status of COVID-19 patients by revisiting our knowledge on the immune mechanisms of already known coronaviruses such as SARS-CoV and MERS-CoV Early elevation of the serum levels of pro-inflammatory cytokines observed in SARS and MERS infection suggests a possible same type of cytokine storm-mediated lung damage in COVID-19 patients too Dysregulation of interferon-1 response and downstream cascade in initial innate immune response at virus entry point has been related to lethal pneumonia in COVID-19 patients Adaptive response of increased CD8+ levels in COVID-19 patients seems to be useful in mild cases where it causes deteriorating effects in progressed severe disease patients resulting in destruction of type 2 pneumocytes hence inability to regenerate the alveolar epithelium A phenomenon called cytokine storm activates violent immunological reactions in the lung tissue resulting in ARDS followed by multiple organ system damages in COVID-19 patients Several immune evading mechanisms are thought to be employed by severe respiratory syndrome virus-2 (SARS-CoV-2) that might have resulted in its extremely increased contagiousness probably related with its frequent RNA mutations Failure to develop adequate virus limiting immune reactions by some cured patients warrant monitoring of all recovered patients This rapid mini review is aimed to enhance our knowledge of the immune status of COVID-19 infected patients with reference to SARS-CoV and MERS-CoV


title: Unequal impact of structural health determinants and comorbidity on COVID-19 severity and lethality in older Mexican adults: Looking beyond chronological aging

text: BACKGROUND: COVID-19 has had a disproportionate impact on older adults. The population of Mexico is younger, yet the impact of COVID-19 on older adults is comparable to countries with older population structures. Here, we aim to identify health and structural determinants that increase susceptibility to COVID-19 in older Mexican adults beyond chronological aging. METHODS: We analyzed confirmed COVID-19 cases in older adults using data from the General Directorate of Epidemiology of Mexican Ministry of Health. We modeled risk factors for increased COVID-19 severity and mortality, using mixed models to incorporate multilevel data concerning healthcare access and marginalization. We also evaluated structural factors and comorbidity profiles compared to chronological age for improving COVID-19 mortality risk prediction. RESULTS: We analyzed 7,029 confirmed SARS-CoV-2 cases in adults aged [≥]60 years. Male sex, smoking, diabetes, and obesity were associated with pneumonia, hospitalization and ICU admission in older adults, CKD and COPD were associated with hospitalization. High social lag indexes and access to private care were predictors of COVID-19 severity and mortality. Age was not a predictor of COVID-19 severity in individuals without comorbidities and structural factors and comorbidities were better predictors of COVID-19 lethality and severity compared to chronological age. COVID-19 baseline lethality hazards were heterogeneously distributed across Mexican municipalities, particularly when comparing urban and rural areas. CONCLUSIONS: Structural factors and comorbidity explain excess risk for COVID-19 severity and mortality over chronological age in older Mexican adults. Clinical decision-making related to COVID-19 should focus away from chronological aging onto more a comprehensive geriatric care approach.


title: Factors influencing the epidemiological characteristics of pandemic COVID 19: A TISM approach

text: The COVID 19 is a pandemic having an epidemic nature influencing the human health and economy in a global level. The major limitation to overcome the issue is the lack of potential vaccines or effective medicines to treat or control the disease. Considering the shortness of time to act, the purpose of the paper was to identify and categorise the climatic, socio-biological factors that influence the global super-spread of the epidemic using a theory building approach, ‘Total Interpretive Structural Modelling’ (TISM). MICMAC analysis of the identified factors, based on their interdependence categorized the triggering factors, air temperature, humidity, age, airflow and ventilation, responsible for the increased mortality rate of COVID 19 compared to SARS and MERS. So the model explains why the temperate countries of similar climatic zones and aged people are more vulnerable. It also predicts the susceptibility of countries based on their geographic locations and upcoming climatic conditions which were found to be influential in sustaining longevity and aerosol spread of the virus. Since many of these factors remain unaltered or out of human control, the linkage factors identified in this paper; change in host behaviour and number of contacts can be given priorities in order to overcome the situation. Furthermore, this is the first attempt made to understand epidemiological characteristics of COVID 19 using TISM approach.


title: Structural basis of RNA recognition by the SARS-CoV-2 nucleocapsid phosphoprotein

text: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the Coronavirus disease 2019 (COVID-19) which is currently negatively affecting the population and disrupting the global economy. SARS-CoV-2 belongs to the +RNA virus family that utilize single-stranded positive-sense RNA molecules as genomes. SARS-CoV-2, like other coronaviruses, has an unusually large genome for a +RNA virus that encodes four structural proteins – the matrix (M), small envelope (E), spike (S) and nucleocapsid phosphoprotein (N) - and sixteen nonstructural proteins (nsp1-16) that together ensure replication of the virus in the host cell. The nucleocapsid phosphoprotein N is essential for linking the viral genome to the viral membrane. Its N-terminal RNA binding domain (N-NTD) captures the RNA genome while the C-terminal domain anchors the ribonucleoprotein complex to the viral membrane via its interaction with the M protein. Here, we characterized the structure of the N-NTD and its interaction with RNA using NMR spectroscopy. We observed a positively charged canyon on the surface of the N-NTD lined with arginine residues suggesting a putative RNA binding site. Next, we performed an NMR titration experiment using an RNA duplex. The observed changes in positions of signals in the N-NTD NMR spectra allowed us to construct a model of the N-NTD in complex with RNA.


title: Evolution and impact of COVID-19 outbreaks in care homes: population analysis in 189 care homes in one geographic region

text: Background: COVID-19 has had large impact on care-home residents internationally. This study systematically examines care-home outbreaks of COVID-19 in a large Scottish health board. Methods: Analysis of testing, cases and deaths using linked care-home, testing and mortality data for 189 care-homes with 5843 beds in a large Scottish Health Board up to 15/06/20. Findings: 70 (37.0%) of care-homes experienced a COVID-19 outbreak, 66 of which were in care-homes for older people where care-home size was strongly associated with outbreaks (OR per 20-bed increase 3.50, 95%CI 2.06 to 5.94). There were 852 confirmed cases and 419 COVID-related deaths, 401 (95.7%) of which occurred in care-homes with an outbreak, 16 (3.8%) in hospital, and two in the 119 care-homes without a known outbreak. For non-COVID related deaths, there were 73 excess deaths in care-homes with an outbreak, but no excess deaths in care-homes without an outbreak, and 24 fewer deaths than expected of care-home residents in hospital. A quarter of COVID-19 related cases and deaths occurred in five (2.6%) care-homes, and half in 13 (6.9%) care-homes. Interpretation: The large impact on excess deaths appears to be primarily a direct effect of COVID-19, with cases and deaths are concentrated in a minority of care homes. A key implication is that there is a large pool of susceptible residents if community COVID-19 incidence increases again. Shielding residents from potential sources of infection and rapid action into minimise outbreak size where infection is introduced will be critical in any wave 2. Funding: Not externally funded.


docid: qlfutcgh

title: COVID-19 and North Africa


title: Environmental contamination of the SARS-CoV-2 in healthcare premises: An urgent call for protection for healthcare workers

text: Importance A large number of healthcare workers (HCWs) were infected by SARS-CoV-2 during the ongoing outbreak of COVID-19 in Wuhan, China. Hospitals are significant epicenters for the human-to-human transmission of the SARS-CoV-2 for HCWs, patients, and visitors. No data has been reported on the details of hospital environmental contamination status in the epicenter of Wuhan. Objective To investigate the extent to which SARS-CoV-2 contaminates healthcare settings, including to identify function zones of the hospital with the highest contamination levels and to identify the most contaminated objects, and personal protection equipment (PPE) in Wuhan, China. Design A field investigation was conducted to collect the surface swabs in various environments in the hospital and a laboratory experiment was conducted to examine the presence of the SARS-CoV-2 RNA. Setting Six hundred twenty-six surface samples were collected within the Zhongnan Medical Center in Wuhan, China in the mist of the COVID-19 outbreak between February 7 - February 27, 2020. Participants Dacron swabs were aseptically collected from the surfaces of 13 hospital function zones, five major objects, and three major personal protection equipment (PPE). The SARS-CoV-2 RNAs were detected by reverse transcription-PCR (RT-PCR). Main Outcomes and Measures SARS-CoV-2 RNAs Results The most contaminated zones were the intensive care unit specialized for taking care of novel coronavirus pneumonia (NCP) (31.9%), Obstetric Isolation Ward specialized for pregnant women with NCP (28.1%), and Isolation Ward for NCP (19.6%). We classified the 13 zones into four contamination levels. The most contaminated objects are self-service printers (20.0%), desktop/keyboard (16.8%), and doorknob (16.0%). Both hand sanitizer dispensers (20.3%) and gloves (15.4%) were most contaminated PPE. Conclusions and Relevance Many surfaces were contaminated with SARS-CoV-2 across the hospital in various patient care areas, commonly used objects, medical equipment, and PPE. The 13 hospital function zones were classified into four contamination levels. These findings emphasize the urgent need to ensure adequate environmental cleaning, strengthen infection prevention training, and improve infection prevention precautions among HCWs during the outbreak of COVID-19. The findings may have important implications for modifying and developing urgently needed policy to better protect healthcare workers during this ongoing pandemic of SARS-CoV-2.


title: TMPRSS2, a SARS-CoV-2 internalization protease is downregulated in head and neck cancer patients

text: Objectives Two of the main target tissues of SARS-coronavirus 2 are the oral cavity pharynx-larynx epithelium, the main virus entry site, and the lung epithelium. The virus enters host cells through binding of the Spike protein to ACE2 receptor and subsequent S priming by the TMPRSS2 protease. Herein we aim to assess differences in both ACE2 and TMPRSS2 expression in normal tissues from oral cavity-pharynx-larynx and lung tissues as well as neoplastic tissues from the same histological areas. The information provided in this study may contribute to better understanding of SARS-coronavirus 2 ability to interact with different biological systems and contributes to cumulative knowledge on potential mechanisms to inhibit its diffusion. Materials and Methods The study has been conducted using The Cancer Genome Atlas (TCGA) and the Regina Elena Institute (IRE) databases and validated by experimental model in HNSCC and Lung cancer cells. Data from one COVID19 positive patient who was operated on for HNSCC was also included. We have analyzed 478 tumor samples and 44 normal samples from TCGA HNSCC cohort for whom both miRNA and mRNA sequencing was available. The dataset included 391 HPV- and 85 HPV+ cases, with 331 P53 mutated and 147 P53 wild type cases respectively. 352 out of 478 samples were male and 126 female. In IRE cohort we analyzed 66 tumor samples with matched normal sample for miRNA profiling and 23 tumor\normal matched samples for mRNA profiling. 45 out of 66 tumors from IRE cohort were male and 21 female, 38 were P53 mutated and 27 wild type. Most patients (63 of 66) in IRE cohort were HPV negative. Normalized TCGA HNSCC gene expression and miRNA expression data were obtained from Broad Institute TCGA Genome Data Analysis Center (http://gdac.broadinstitute.org/). mRNA expression data from IRE cohort used in this study has been deposited to NCBI’s Gene Expression Omnibus and is accessible through GEO series accession number GSE107591. In order to inference about potential molecular modulation of TMPRSS2, we also included miRNAs expression for the 66 IRE cohort matched tumor and normal samples from Agilent platform. DNA methylation data for TCGA tumors were obtained from Wanderer (http://maplab.imppc.org/wanderer/). We used miRWalk and miRNet web tools for miRNA-target interaction prediction and pathway enrichment analysis. The correlation and regression analyses as well as the miRNA and gene modulation and the survival analysis were conducted using Matlab R2019. Results TMPRSS2 expression in HNSCC was significantly reduced compared to the normal tissues and had a prognostic value in HNSCC patients. Reduction of TMPRSS2 expression was more evident in women than in men, in TP53 mutated versus wild TP53 tumors as well as in HPV negative patients compared to HPV positive counterparts. Functionally, we assessed the multivariate effect on TMPRSS2 in a single regression model. We observed that all variables had an independent effect on TMPRSS2 in HNSCC patients with HPV negative, TP53 mutated status and with elevated TP53-dependent Myc-target genes associated with low TMPRSS2 expression. Investigation of the molecular modulation of TMPRSS2 in both HNSCC and lung cancers revealed that expression of microRNAs targeting TMPRSS2 anti-correlated in both TCGA and IRE HNSCC datasets, while there was not evidence of TMPRSS2 promoter methylation in both tumor cohorts. Interestingly, the anti-correlation between microRNAs and TMPRSS2 expression was corroborated by testing this association in a SARS-CoV-2 positive HNSCC patient. Conclusions Collectively, these findings suggest that tumoral tissues, herein exemplified by HNSCC and lung cancers might be more resistant to SARS-CoV-2 infection due to reduced expression of TMPRSS2. The protective mechanism might occur, at least partially, through the aberrant activation of TMPRSS2 targeting microRNAs; thereby providing strong evidence on the role of non-coding RNA molecule in host viral infection. These observations may help to better assess the frailty of SARS-CoV-2 positive cancer patients.


title: Spatial and temporal regularization to estimate COVID-19 Reproduction Number R(t): Promoting piecewise smoothness via convex optimization

text: Among the different indicators that quantify the spread of an epidemic, such as the on-going COVID-19, stands first the reproduction number which measures how many people can be contaminated by an infected person. In order to permit the mon- itoring of the evolution of this number, a new estimation procedure is proposed here, assuming a well-accepted model for current incidence data, based on past observa- tions. The novelty of the proposed approach is twofold: 1) the estimation of the repro- duction number is achieved by convex optimization within a proximal-based inverse problem formulation, with constraints aimed at promoting piecewise smoothness; 2) the approach is developed in a multivariate setting, allowing for the simultaneous handling of multiple time series attached to different geographical regions, together with a spatial (graph-based) regularization of their evolutions in time. The effectiveness of the approach is first supported by simulations, and two main applications to real COVID-19 data are then discussed. The first one refers to the comparative evolution of the reproduction number for a number of countries, while the second one focuses on French counties and their joint analysis, leading to dynamic maps revealing the temporal co-evolution of their reproduction numbers.


title: Dispersion of a new coronavirus SARS-CoV-2 by airlines in 2020: Temporal estimates of the outbreak in Mexico.

text: On January 23, 2020, China imposed a quarantine on the city of Wuhan to contain the SARS-CoV-2 outbreak. Regardless of this measure the new infection has spread to several countries around the world. Here, we developed a method to study the dissemination of this infection by the airline routes and we give estimations of the time of arrival of the outbreaks to the different cities. In this work we show an analysis of the dispersion of this infection to other cities by airlines based on the classic model the Kermack and McKendrick complemented with diffusion on a graph composed of nodes which represent the cities and edges which represent the airline routes. We do several numerical simulations to estimate the date of arrival to different cities starting the infection at Wuhan, China and to show the robustness of the estimation respect to changes in the epidemiological parameters and to changes on the graph. We use Mexico City as an example. In this case, our estimate of the arrival time is between March 20 and March 30, 2020. This analysis is limited to the analysis of dispersion by airlines, so this estimate should be taken as an overestimate since the infection can arrive by other means. This model estimates the arrival of the infectious outbreak to Mexico between March 20 and March 30. This estimation gives a time period to implement and strengthen preventive measures aimed at the general population, as well as to strengthen hospital infrastructure and training of human resources in health.


title: The FDA- approved gold drug Auranofin inhibits novel coronavirus (SARS-COV-2) replication and attenuates inflammation in human cells

text: SARS-COV-2 has recently emerged as a new public health threat. Herein, we report that the FDA-approved gold drug, auranofin, inhibits SARS-COV-2 replication in human cells at low micro molar concentration. Treatment of cells with auranofin resulted in a 95% reduction in the viral RNA at 48 hours after infection. Auranofin treatment dramatically reduced the expression of SARS-COV-2-induced cytokines in human cells. These data indicate that auranofin could be a useful drug to limit SARS-CoV-2 infection and associated lung injury due to its anti-viral, anti-inflammatory and anti-ROS properties. Auranofin has a well-known toxicity profile and is considered safe for human use.


title: Rapid development of an inactivated vaccine for SARS-CoV-2

text: The COVID-19 pandemic caused by SARS-CoV-2 has brought about an unprecedented crisis, taking a heavy toll on human health, lives as well as the global economy. There are no SARS-CoV-2-specific treatments or vaccines available due to the novelty of this virus. Hence, rapid development of effective vaccines against SARS-CoV-2 is urgently needed. Here we developed a pilot-scale production of a purified inactivated SARS-CoV-2 virus vaccine candidate (PiCoVacc), which induced SARS-CoV-2-specific neutralizing antibodies in mice, rats and non-human primates. These antibodies potently neutralized 10 representative SARS-CoV-2 strains, indicative of a possible broader neutralizing ability against SARS-CoV-2 strains circulating worldwide. Immunization with two different doses (3μg or 6 μg per dose) provided partial or complete protection in macaques against SARS-CoV-2 challenge, respectively, without any antibody-dependent enhancement of infection. Systematic evaluation of PiCoVacc via monitoring clinical signs, hematological and biochemical index, and histophathological analysis in macaques suggests that it is safe. These data support the rapid clinical development of SARS-CoV-2 vaccines for humans. One Sentence Summary A purified inactivated SARS-CoV-2 virus vaccine candidate (PiCoVacc) confers complete protection in non-human primates against SARS-CoV-2 strains circulating worldwide by eliciting potent humoral responses devoid of immunopathology


Covid-19: It's too soon to lift lockdown


title: Working from Home: How We Managed Our Team Remotely with Technology

text: During the early stages of the COVID-19 pandemic, the College’s library and the office of institutional research & training (OIRT), along with all departments of our college, shifted to working from home (WFH) overnight. This column shares examples from the literature regarding experiences and lessons learned from both the corporate world and academic libraries’ experiences managing teams remotely with technology. Finally, we share how the College’s academic library and OIRT transitioned to working from home during the COVID-19 pandemic with the variety of online tools we already used, but further enhanced during this experience, to communicate and collaborate effectively with our team members.


title: Associations between COVID-19 infection, tobacco smoking and nicotine use, common respiratory conditions and inhaled corticosteroids: a prospective QResearch-Case Mix Programme data linkage study January-May 2020

text: Introduction Epidemiological and laboratory research seems to suggest that smoking and perhaps nicotine alone could reduce the severity of COVID-19. Likewise, there is some evidence that inhaled corticosteroids could also reduce its severity, opening the possibility that nicotine and inhaled steroids could be used as treatments. Methods In this prospective cohort study, we will link English general practice records from the QResearch database to Public Health England's database of SARS-CoV-2 positive tests, Hospital Episode Statistics, admission to intensive care units, and death from COVID-19 to identify our outcomes: hospitalisation, ICU admission, and death due to COVID. Using Cox regression, we will perform sequential adjustment for potential confounders identified by separate directed acyclic graphs to: 1. Assess the association between smoking and COVID-19 disease severity, and how that changes on adjustment for smoking-related comorbidity. 2. More closely characterise the association between smoking and severe COVID-19 disease by assessing whether the association is modified by age (as a proxy of length of smoking), gender, ethnic group, and whether people have asthma or COPD. 3. Assess for evidence of a dose-response relation between smoking intensity and disease severity, which would help create a case for causality. 4. Examine the association between former smokers who are using NRT or are vaping and disease severity. 5. Examine whether pre-existing respiratory disease is associated with severe COVID-19 infection. 6. Assess whether the association between chronic obstructive pulmonary disease (COPD) and asthma and COVID-19 disease severity is modified by age, gender, ethnicity, and smoking status. 7. Assess whether the use of inhaled corticosteroids is associated with severity of COVID-19 disease. 8. To assess whether the association between use of inhaled corticosteroids and severity of COVID-19 disease is modified by the number of other airways medications used (as a proxy for severity of condition) and whether people have asthma or COPD. Conclusions This representative population sample will, to our knowledge, present the first comprehensive examination of the association between smoking, nicotine use without smoking, respiratory disease, and severity of COVID-19. We will undertake several sensitivity analyses to examine the potential for bias in these associations.


title: Interest in COVID-19 vaccine trials participation among young adults in China: Willingness, reasons for hesitancy, and demographic and psychosocial determinants

text: Background: With the demand for rapid COVID-19 vaccine development and evaluation, this paper aimed to describe the prevalence and correlates of willingness to participate in COVID-19 vaccine trials among university students in China. Methods: A cross-sectional survey with 1,912 Chinese university students was conducted during March and April 2020. Bivariate and multivariate analyses were performed to identify variables associated with willingness to participate. Results: The majority of participants (64.01%) indicated willingness to participate in COVID-19 vaccine trials. Hesitancy over signing informed consent documents, concerns over time necessary for participating in a medical study, and perceived COVID-19 societal stigma were identified as deterrents, whereas lower socioeconomic status, female gender, perception of likely COVID-19 infection during the pandemic, and COVID-19 prosocial behaviors were facilitative factors. Further, public health mistrust and hesitancy over signing informed consent documents had a significant interactive effect on vaccine trial willingness. Conclusions: High standards of ethical and scientific practice are needed in COVID-19 vaccine research, including providing potential participants full and accurate information and ensuring participation free of coercion, socioeconomic inequality, and stigma. Attending to the needs of marginalized groups and addressing psychosocial factors including stigma and public health mistrust may also be important to COVID-19 vaccine development and future uptake.


title: Estimating cases of COVID-19 from Daily Death Data in Italy

text: COVID-19 is an emerging infectious disease which has been declared a pan- demic by the World Health Organisation. Due to limited testing capacity for this new virus, variable symptomatology the majority of infected showing non-specific mild or no symptoms it is likely current prevalence data is an underestimate. Methods: We present an estimate of the number of cases of COVID-19 com- pared to the number of confirmed case in Italy based on the daily reported deaths and information about the incubation period, time from symptom on- set to death and reported case fatality rate. Results: Our model predicts that on the 31st of January 2020 when the first 3 infected cases had been identified by Italian authorise there were already nearly 30 cases in Italy, and by the 24th of February 2020 only 0.5% cases had been detected and confirmed by Italian authorities. While official statistics had 132 confirmed case we believe a more accurate estimate would be closer to 26000. With a case-doubling period of about 2.5 days.


title: Estimates of the ongoing need for social distancing and control measures post-"lockdown" from trajectories of COVID-19 cases and mortality.

text: By 21st April 2020 COVID_19 had caused more than 2m cases across more than 200 countries. The majority of countries with significant outbreaks introduced social distancing or "lockdown" measures to reduce viral transmission. The key question now in many countries is when, how, and to what extent these measures can be lifted. By fitting regression models to publically available data on daily numbers of newly-confirmed cases and mortality, trajectories, doubling times and reproduction number (R0) were estimated both before and under the control measures. These data ran up to 21st April 2020, and covered 67 countries that had provided sufficient data for modelling. The estimates of R0, before lockdown, based on these data were broadly consistent with those previously published at between 2.0 and 3.7 in the countries with the largest number of cases available for analysis (USA, Italy, Spain, France and UK). There was little evidence to suggest that the restrictions had reduced R far below 1 in many places, with Spain having the most rapid reductions - R0 0.71 (95%CI 0.65-0.78) based on cases and 0.81 (95%CI 0.77-0.85) based on mortality. Intermittent lockdown has been proposed as a means of controlling the outbreak while allowing periods of increase freedom and economic activity. These data suggest that few countries could have even one week per month unrestricted without seeing resurgence of the epidemic. Similarly, restoring 20% of the activity that has been prevented by the lockdowns looks difficult to reconcile with preventing the resurgence of the disease in most countries.


title: Acute cardiac injury in patients with COVID-19

text: Introduction: Cardiac complications of COVID-19 are potentially life-threatening. The occurrence of myocardial injury in the context of COVID-19 is multifactorial and has generated increasing interest. Methods: A systematic review with meta-analysis of the literature was performed. MEDLINE and EMBASE were searched. Two independente reviewers evaluated the selected manuscripts for the outcome myocardial injury, defined by troponin elevation above the 99th percentile. Study heterogeneity and risk of bias were evaluated. Results: Eight studies, with a total of 1229 patients, were included. The frequency of myocardial injury was 16% (95% CI: 9% - 27%). The heterogeneity among studies was high (93%). Conclusions: Myocardial injury may occur in patients with COVID-19, with a frequency of 16% among current studies. Continuous research is needed to update these findings, as the pandemic evolves, and to define the implications of myocardial injury in the context of this infection.


title: Longitudinal peripheral blood transcriptional analysis of COVID-19 patients captures disease progression and reveals potential biomarkers

text: COVID-19, caused by SARS-CoV-2, is an acute self-resolving disease in most of the patients, but some patients can develop a severe illness or even death. To characterize the host responses and identify potential biomarkers during disease progression, we performed a longitudinal transcriptome analysis for peripheral blood mononuclear cells (PBMCs) collected from 4 COVID-19 patients at 4 different time points from symptom onset to recovery. We found that PBMCs at different COVID-19 disease stages exhibited unique transcriptome characteristics. SARS-CoV-2 infection dysregulated innate immunity especially type I interferon response as well as the disturbed release of inflammatory cytokines and lipid mediators, and an aberrant increase of low-density neutrophils may cause tissue damage. Activation of cell death, exhaustion and migratory pathways may lead to the reduction of lymphocytes and dysfunction of adaptive immunity. COVID-19 induced hypoxia may exacerbate disorders in blood coagulation. Based on our analysis, we proposed a set of potential biomarkers for monitoring disease progression and predicting the risk of severity.


title: Clinical characteristics of patients hospitalized with COVID-19 in Spain: results from the SEMI-COVID-19 Network.

text: Background. Spain has been one of the countries most affected by the COVID-19 pandemic. Objective. To create a registry of patients with COVID-19 hospitalized in Spain in order to improve our knowledge of the clinical, diagnostic, therapeutic, and prognostic aspects of this disease. Methods. A multicentre retrospective cohort study, including consecutive patients hospitalized with confirmed COVID-19 throughout Spain. Epidemiological and clinical data, additional tests at admission and at seven days, treatments administered, and progress at 30 days of hospitalization were collected from electronic medical records. Results. Up to April 30th 2020, 6,424 patients from 109 hospitals were included. Their median age was 69.1 years (range: 18-102 years) and 56.9% were male. Prevalences of hypertension, dyslipidemia, and diabetes mellitus were 50.2%, 39.7%, and 18.7%, respectively. The most frequent symptoms were fever (86.2%) and cough (76.5%). High values of ferritin (72.4%), lactate dehydrogenase (70.2%), and D-dimer (61.5%), as well as lymphopenia (52.6%), were frequent. The most used antiviral drugs were hydroxychloroquine (85.7%) and lopinavir/ritonavir (62.4%). 31.5% developed respiratory distress. Overall mortality rate was 21.1%, with a marked increase with age (50-59 years: 4.2%, 60-69 years: 9.1%, 70-79 years: 21.4%, 80-89 years: 42.5%, [≥] 90 years: 51.1%). Conclusions. The SEMI-COVID-19 Network provides data on the clinical characteristics of patients with COVID-19 hospitalized in Spain. Patients with COVID-19 hospitalized in Spain are mostly severe cases, as one in three patients developed respiratory distress and one in five patients died. These findings confirm a close relationship between advanced age and mortality.


title: Role of 1’-Ribose Cyano Substitution for Remdesivir to Effectively Inhibit both Nucleotide Addition and Proofreading in SARS-CoV-2 Viral RNA Replication

text: COVID-19 has recently caused a global health crisis and an effective interventional therapy is urgently needed. SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) provides a promising but challenging drug target due to its intrinsic proofreading exoribonuclease (ExoN) function. Nucleoside triphosphate (NTP) analogues added to the growing RNA chain should supposedly terminate viral RNA replication, but ExoN can cleave the incorporated compounds and counteract their efficacy. Remdesivir targeting SARS-CoV-2 RdRp exerts high drug efficacy in vitro and in vivo. However, its underlying inhibitory mechanisms remain elusive. Here, we performed all-atom molecular dynamics (MD) simulations with an accumulated simulation time of 12.6 microseconds to elucidate the molecular mechanisms underlying the inhibitory effects of remdesivir in nucleotide addition (RdRp complex: nsp12-nsp7-nsp8) and proofreading (ExoN complex: nsp14-nsp10). We found that the 1’-cyano group of remdesivir possesses the dual role of inhibiting both nucleotide addition and proofreading. For nucleotide addition, we showed that incorporation of one remdesivir is not sufficient to terminate RNA synthesis. Instead, the presence of the polar 1’-cyano group of remdesivir at an upstream site causes instability via its electrostatic interactions with a salt bridge formed by Asp865 and Lys593, rendering translocation unfavourable. This may eventually lead to a delayed chain termination of RNA extension by three nucleotides. For proofreading, remdesivir can inhibit cleavage via the steric clash between the 1’-cyano group and Asn104. To further examine the role of 1’-cyano group in remdesivir’s inhibitory effects, we studied three additional NTP analogues with other types of modifications: favipiravir, vidarabine, and fludarabine. Our simulations suggest that all three of them are prone to ExoN cleavage. Our computational findings were further supported by an in vitro assay in Vero E6 cells using live SARS-CoV-2. The dose-response curves suggest that among tested NTP analogues, only remdesivir exerts significant inhibitory effects on viral replication. Our work provides plausible mechanisms at molecular level on how remdesivir inhibits viral RNA replication, and our findings may guide rational design for new treatments of COVID-19 targeting viral replication.


Commercially available endoscopy facemasks to prevent aerosolizing spread of droplets during COVID-19 outbreak


title: Facial Pressure Ulcers in a COVID-19 50-year-old Female Intubated Patient

text: In case of severe acute respiratory distress syndrome (ARDS), as in coronavirus disease 2019 (COVID-19) affected patients, the invasive ventilation in prone position can improve the prognosis, albeit with an increased risk of facial pressure ulcers. In this report, we will relate a case of facial pressure ulcers in a SARS-CoV-2 positive 50 year-old woman with the aim to describe the high-complexity management of COVID 19 in which healthcare professionals across the world are still involved.


Tackling COVID-19 is a crucible for privacy


title: COVID Faster R-CNN: A Novel Framework to Diagnose Novel Coronavirus Disease (COVID-19) in X-Ray Images

text: COVID-19 or novel coronavirus disease, which has already been declared as a worldwide pandemic, at first had an outbreak in a small town of China, named Wuhan. More than two hundred countries around the world have already been affected by this severe virus as it spreads by human interaction. Moreover, the symptoms of novel coronavirus are quite similar to the general flu. Screening of infected patients is considered as a critical step in the fight against COVID-19. Therefore, it is highly relevant to recognize positive cases as early as possible to avoid further spreading of this epidemic. However, there are several methods to detect COVID-19 positive patients, which are typically performed based on respiratory samples and among them one of the critical approach which is treated as radiology imaging or X-Ray imaging. Recent findings from X-Ray imaging techniques suggest that such images contain relevant information about the SARS-CoV-2 virus. In this article, we have introduced a Deep Neural Network (DNN) based Faster Regions with Convolutional Neural Networks (Faster R-CNN) framework to detect COVID-19 patients from chest X-Ray images using available open-source dataset. Our proposed approach provides a classification accuracy of 97.36%, 97.65% of sensitivity, and a precision of 99.28%. Therefore, we believe this proposed method might be of assistance for health professionals to validate their initial assessment towards COVID-19 patients.


docid: ezrztuwf

title: Reply: Cardiovascular Magnetic Resonance in COVID-19-Related Myocarditis


title: The story of COVID-19: A comparative analysis

text: A review on COVID-19 COVID-19 induces a distinct host transcriptome


title: Psychological resources against the traumatic experience of COVID-19

text: Psychological resources, such as defense mechanism and mindfulness practice, can mediate the individual reaction to traumatic experiences as the ongoing COVID-19 pandemic outbreak. A novel self-reported measure based on the DMRS (DMRS-SR-30), has been developed with the aim of assessing potential adaptive defensive strategies against the traumatic experience of COVID-19. Preliminary validation of the DMRS-SR-30 showed good internal consistency in both overall defensive functioning and subscales. Combining adaptive defense mechanisms and mindfulness practice could prevent psychological distress due to the effect of COVID-19 losses and quarantining.


title: Structural basis for the inhibition of SARS-CoV-2 main protease by antineoplastic drug Carmofur

text: The antineoplastic drug Carmofur was shown to inhibit SARS-CoV-2 main protease (Mpro). Here the X-ray crystal structure of Mpro in complex with Carmofur reveals that the carbonyl reactive group of Carmofur is covalently bound to catalytic Cys145, whereas its fatty acid tail occupies the hydrophobic S2 subsite. Carmofur inhibits viral replication in cells (EC50 = 24.30 μM) and it is a promising lead compound to develop new antiviral treatment for COVID-19.


title: SARS-CoV-2 transmission chains from genetic data: a Danish case study

text: Background The COVID-19 pandemic caused by the SARS-CoV-2 virus started in China in December 2019 and has since spread globally. Information about the spread of the virus in a country can inform the gradual reopening of a country and help to avoid a second wave of infections. Denmark is currently opening up after a lockdown in mid-March. Methods We perform a phylogenetic analysis of 742 publicly available Danish SARS-CoV-2 genome sequences and put them into context using sequences from other countries. Result Our findings are consistent with several introductions of the virus to Denmark from independent sources. We identify several chains of mutations that occurred in Denmark and in at least one case find evidence that the virus spread from Denmark to other countries. A number of the mutations found in Denmark are non-synonymous, and in general there is a considerable variety of strains. The proportions of the most common haplotypes is stable after lockdown. Conclusion Our work shows how genetic data can be used to identify routes of introduction of a virus into a region and provide alternative means for verifying existing assumptions. For example, our analysis supports the hypothesis that the virus was brought to Denmark by skiers returning from Ischgl. On the other hand, we identify transmission chains suggesting that Denmark was part of a network of countries among which the virus was being transmitted; thus challenging the common narrative that Denmark only got infected from abroad. Our analysis does not indicate that the major haplotypes appearing in Denmark have a different degree of virality. Our methods can be applied to other countries, regions or even highly localised outbreaks. When used in real-time, we believe they can serve to identify transmission events and supplement traditional methods such as contact tracing.


title: Connecting in COVID 19: Neurology tele-follow-up experience

text: Introduction: The lockdown due to COVID-19 pandemic led to temporary closure of routine hospital services. This prompted the initiation of teleconsult follow-up in our department. The study outlines the experience of tele-follow-up at a tertiary care teaching hospital in India, and the perspective of neurologists about this novel approach. Methods: The tele-follow-up was started from 26th March 2020. Data of follow up appointments was provided by the medical record section. The faculty and senior residents conducted the tele-follow-up. Communication was made via voice calls. The data for initial ten days was analyzed to find the utility and experience of the new service. Results: In the initial ten working days, data of 968 patients was provided for tele-follow-up. A successful communication was made in 50.3% patients (contact with patients: 27.7% and family members 22.6%). The phone numbers which were not contactable/invalid/not available constituted 36.8% of the data. A total of 35 faculty and residents conducted the tele-follow-up. The utility of tele-follow-up was perceived as good by 71.4% of neurologists. Majority of neurologists (71.4%) observed that [≥]90% of patients were continuing medications. Patients outside the city constituted 50-75% of the list. The survey revealed that all neurologists felt the need to continue tele-follow-up for far off stable patients post lock down and resumption of regular outpatient services. Conclusion: The survey established the feasibility and utility of teleconsult for follow up of patients with neurological diseases who were attending the regular outpatient services before the lock down.


title: A deductive approach to modeling the spread of COVID-19

text: Severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), previously known as 2019-nCoV, is responsible for the atypical pneumonia pandemic designated as Coronavirus Disease 2019 (COVID-19). The confirmed number of cases continues to grow exponentially reaching 492,000 people in 175 countries as of March 25, 2020. 22,169 people (~4.5%) infected with SARS-COV-2 virus have died. We have developed an exponential regression model using the COVID-19 case data (Jan 22 - Mar 22, 2020). Our primary model uses designated Phase 1 countries, who exceed 2500 cases on Mar 22. The model is then applied to Phase 2 countries: those that escaped the initial Phase 1 global expansion of COVID-19. With the exception of stabilizing countries (South Korea, Japan, and Iran) all Phase 1 countries are growing exponentially, as per I2500(t)=120.4 × e0.238t, with a rate, r = 0.238 ± 0.068. Excluding China, the BRICS developing nations and Australia are in Phase 2. Case data from Phase 2 countries are following the model derived from Phase 1 countries. In the absence of measures employed to flatten the curve including social distancing, quarantine, and healthcare expansion, our model projects over 274,000 cases and 12,300 deaths in the US by Mar 31. India can expect 123,000 cases by April 16. By flattening the curve to the growth rate of stabilizing countries (r = 0.044 ± 0.062), the US would prevent 8,500 deaths by Mar 31, and India would prevent 5,500 deaths by April 16.


title: Remdesivir data offer hope, with caveats

text: Gilead Sciences’ experimental antiviral remdesivir helped people with COVID-19 recover faster, according to limited data released on April 29 from a trial led by the US National Institute of Allergy and Infectious Diseases The Food and Drug Administration is expected in the coming days to take the unprecedented step of issuing an emergency use authorization, which will make the drug more readily available for stockpiling The study by NIAID, which is part of the National Institutes of Health, is considered to be the highest quality among the myriad Phase III trials testing remdesivir’s effectiveness against COVID-19, the disease caused by the novel coronavirus Unlike most other trials, it includes a placebo arm, a part of a trial’s design that scientists rely on for a clear signal of a treatment’s worth The trial enrolled 1,063 people, 20% of whom received the standard of care rather than remdesivir The primary end point View: PDF ;Full Text HTML


title: Characteristics and Outcomes of Hospitalized Young Adults with Mild to Moderate Covid-19 at a University Hospital in India

text: Background: Stormy course has been reported among hospitalized adults with covid-19 in high- and middle-income countries. To assess clinical outcomes in consecutively hospitalized patients with mild covid-19 in India we performed a study. Methods: We developed a case registry of successive patients admitted with suspected covid-19 infection to our hospital (n=501). Covid-19 was diagnosed using reverse transcriptase polymerase chain reaction (RT-PCR). Demographic, clinical, investigations details and outcomes were recorded. Descriptive statistics are presented. Results: Covid-19 was diagnosed in 234 (46.7%) and data compared with 267 (53.3%) negative controls. Mean age of covid-9 patients was 35.1+16.6y, 59.4% were <40y and 64% men. Symptoms were in less than 10% and comorbidities were in 4-8%. History of BCG vaccination was in 49% cases vs 10% controls. Cases compared to controls had significantly greater white cell (6.96+1.89 vs 6.12+1.69x109 cells/L) and lower lymphocyte count (1.98+0.79 vs 2.32+0.91x109 cells/L). No radiological and electrocardiographic abnormality was observed. All these were isolated or quarantined in the hospital and observed. Covid-19 patients received hydroxychloroquine and azithromycin according to prevalent guidelines. One patient needed oxygen support while hospital course was uncomplicated in the rest. All were discharged alive. Conversion to virus negative status was in 10.2+6.4 days and was significantly lower in age >40y (9.1+5.2) compared to 40-59y (11.3+6.1) and >60y (16.4+13.3) (p=0.001). Conclusions: This hospital-based registry shows that mildly symptomatic or asymptomatic young covid-19 patients have excellent prognosis.


title: Nucleotide Analogues as Inhibitors of SARS-CoV Polymerase

text: SARS-CoV-2, a member of the coronavirus family, has caused a global public health emergency.1 Based on our analysis of hepatitis C virus and coronavirus replication, and the molecular structures and activities of viral inhibitors, we previously reasoned that the FDA-approved heptatitis C drug EPCLUSA (Sofosbuvir/Velpatasvir) should inhibit coronaviruses, including SARS-CoV-2.2 Here, using model polymerase extension experiments, we demonstrate that the activated triphosphate form of Sofosbuvir is incorporated by low-fidelity polymerases and SARS-CoV RNA-dependent RNA polymerase (RdRp), and blocks further incorporation by these polymerases; the activated triphosphate form of Sofosbuvir is not incorporated by a host-like high-fidelity DNA polymerase. Using the same molecular insight, we selected two other anti-viral agents, Alovudine and AZT (an FDA approved HIV/AIDS drug) for evaluation as inhibitors of SARS-CoV RdRp. We demonstrate the ability of two HIV reverse transcriptase inhibitors, 3’-fluoro-3’-deoxythymidine triphosphate and 3’-azido-3’-deoxythymidine triphosphate (the active triphosphate forms of Alovudine and AZT), to be incorporated by SARS-CoV RdRp where they also terminate further polymerase extension. Given the 98% amino acid similarity of the SARS-CoV and SARS-CoV-2 RdRps, we expect these nucleotide analogues would also inhibit the SARS-CoV-2 polymerase. These results offer guidance to further modify these nucleotide analogues to generate more potent broad-spectrum anti-coronavirus agents.


title: Clinical Characteristics of Patients with Severe Pneumonia Caused by the 2019 Novel Coronavirus in Wuhan, China

text: Abstract Background: A new virus broke out in Wuhan, Hubei, China, and was later named 2019 novel coronavirus (2019-nCoV). The clinical characteristics of severe pneumonia caused by 2019-nCoV are still not clear. Objectives: The aim of this study was to explore the clinical characteristics and risk factors of the severe pneumonia caused by the 2019-nCoV in Wuhan, China. Method: The study included patients hospitalized at the central hospital of Wuhan who had been diagnosed with a pneumonia caused by the novel coronavirus. Clinical features, chronic co-morbidities, demographic data, laboratory examinations, and chest computed tomography (CT) scans were reviewed through electronic medical records. SPSS was used for data analysis to explore the clinical characteristics and risk factors of the patients with the severe pneumonia. Results: A total of 110 patients diagnosed with 2019 novel coronavirus pneumonia were included in the study, including 38 with severe pneumonia and 72 with non-severe pneumonia. Statistical analysis showed that advanced age, an increase of D-dimer, and a decrease of lymphocytes were characteristics of the patients with severe pneumonia. Moreover, in the early stage of the disease, chest CT scans of patients with the severe pneumonia showed the illness can progress rapidly. Conclusions: Advanced age, lymphocyte decline, and D-dimer elevation are important characteristics of patients with severe pneumonia. Clinicians should focus on these characteristics to identify high-risk patients at an early stage.


Enhancing the psychological benefits of audiologic care during the COVID-19 pandemic


docid: jbhomwbx

title: Stochastic Modelling and Estimation of Covid-19 Population Dynamics

text: The aim of the paper is to describe a model of the development of the COVID-19 contamination of the population of a country or a region For this purpose a special branching process with two types of individuals is considered This model intends to use only the observed daily statistics to estimate the main parameter of the contamination and to give a prediction of the mean value of the non-observed population of the contaminated individuals This is a serious advantage in comparison with other more complicated models where the observed official statistics are not sufficient In this way the specific development of the COVID-19 epidemics is considered for different countries


title: Prevalence of Hospital PCR Confirmed Covid-19 Cases in Patients with Chronic Inflammatory and Autoimmune Rheumatic Diseases

text: ABSTRACT Background. The susceptibility of patients with rheumatic diseases, and the risks or benefits of immunosuppressive therapies for COVID-19 are unknown. Methods. We performed a retrospective study with patients under follow-up in rheumatology departments from seven hospitals in Spain. We matched updated databases of rheumatology patients with SARS-CoV-2 positive PCR tests performed in the hospital to the same reference populations. Incidences of PCR+ confirmed COVID-19 were compared among groups. Results. Patients with chronic inflammatory diseases had 1.32-fold higher prevalence of hospital PCR+ COVID-19 than the reference population (0.76% vs 0.58%). Systemic autoimmune or immune mediated diseases (AI/IMID) patients showed a significant increase, whereas inflammatory arthritis (IA) or systemic lupus erythematosus (SLE) patients did not. COVID-19 cases in some but not all diagnostic groups had older ages than cases in the reference population. IA patients on targeted-synthetic or biological disease-modifying antirheumatic drugs (ts/bDMARD), but not those on conventional-synthetic (csDMARD), had a greater prevalence despite a similar age distribution. Conclusion. Patients with AI/IMID show a variable risk of hospital diagnosed COVID-19. Interplay of aging, therapies, and disease specific factors seem to contribute. These data provide a basis to improve preventive recommendations to rheumatic patients and to analyze the specific factors involved in COVID-19 susceptibility.


title: A Covid-19 case mortality rate without time delay systematics

text: Concerning the two approaches to the Covid-19 case mortality rate published in the literature, namely computing the ratio of (a) the daily number of deaths to a time delayed daily number of confirmed infections; and (b) the cumulative number of deaths to confirmed infections up to a certain time, both numbers having been acquired in the middle of an outbreak, it is shown that each suffers from systematic error of a different source. We further show that in the absence of detailed knowledge of the time delay distribution of (a), the true case mortality rate is obtained by pursuing method (b) at the end of the outbreak when the fate of every case has decisively been rendered. The approach is then employed to calculate the mean case mortality rate of 13 regions of China where every case has already been resolved. This leads to a mean rate of 0.527 +/- 0.001 %.


title: Adolescents' health literacy, health protective measures, and health-related quality of life during the Covid-19 pandemic

text: Purpose: First, to describe adolescents' health information sources and knowledge, health literacy (HL), health protective measures, and health-related quality of life (HRQoL) during the initial phase of the Covid-19 pandemic in Norway. Second, to investigate the association between HL and the knowledge and behavior relevant for preventing spread of the virus. Third, to explore variables associated with HRQoL in a pandemic environment. Methods: This cross-sectional study includes survey data from 2,205 Norwegian adolescents 16-19 years of age. The participants reported on their health information sources, HL, handwashing knowledge and behavior, number of social interactions, and HRQoL. Associations between study variables and specified outcomes were explored using multiple linear and logistic regression analyses. Results: Television (TV) and family were indicated to be the main sources for pandemic-related health information. Handwashing, physical distancing, and limiting the number of social contacts were the most frequently reported measures. HL and handwashing knowledge and HL and handwashing behavior were significantly associated. For each unit increase on the HL scale, the participants were 5% more likely to socialize less with friends in comparison to normal. The mean HRQoL was very poor compared to European norms. Being quarantined or isolated and having confirmed or suspected Covid-19 were significantly negatively associated with HRQoL, but seeing less friends than normal was not associated. HL was significantly positively associated with HRQoL, albeit of minor clinical importance. Conclusion: Adolescents follow the health authorities' guidelines and appear highly literate. However, high fidelity requires great sacrifice because the required measures seem to collide with certain aspects that are important for the adolescents' HRQoL.


title: Clinical and CT characteristics which indicate timely radiological reexamination in patients with COVID-19: A retrospective study in Beijing, China

text: OBJECTIVE: Chest CT is useful in assessing the disease course of coronavirus disease-19 (COVID-19). This study aims to identify the characteristics of patients in whom imaging progression occurred while clinical symptoms were relieved and to guide radiological reexamination. METHODS: This retrospective study included 73 patients with reverse transcription-polymerase chain reaction (RT-PCR) confirmed severe acute respiratory syndrome-2 (SARS-CoV-2) infection. All patients received CT reexaminations within 24 h after symptomatic remission. We divided patients into two groups according to the matching degree between clinical and imaging outcomes. RESULTS: 21 patients displayed imaging progression while symptoms relieved. Patients with imaging progression were prone to be advanced in age [years: 60 (46–65) v 47 (37–60.75), P = 0.030]; lymphopenia (66.7% v 40.4%, P = 0.042) and low level of C-reactive protein [mg/L: 5.7 (1.9–20.2) v 18.9 (6.7–38.9), P = 0.038]. An age over 50 was an independent risk factor for imaging progression (OR = 3.41, 95%CI 1.14–10.20, P = 0.028). In CT images, they were inclined to present lesions with clear border (94.7% v 64.7%, P = 0.012), pure peripheral distribution (89.5% v 39.2%, P < 0.001), without bilateral lungs involved (57.9% v 29.4%, P = 0.028) especially with left lung involved only (42.1% v 17.6%, P = 0.034). CONCLUSION: In order to improve the therapeutic effect, the interval before radiological follow-up should be shortened appropriately especially in patients over the age of 50. It is essential to proceed to CT reexamination before symptomatic remission.


title: Deep Learning-Based Recognizing COVID-19 and other Common Infectious Diseases of the Lung by Chest CT Scan Images

text: Purpose: COVID-19 has become global threaten. CT acts as an important method of diagnosis. However, human-based interpretation of CT imaging is time consuming. More than that, substantial inter-observer-variation cannot be ignored. We aim at developing a diagnostic tool for artificial intelligence (AI)-based classification of CT images for recognizing COVID-19 and other common infectious diseases of the lung. Experimental Design: In this study, images were retrospectively collected and prospectively analyzed using machine learning. CT scan images of the lung that show or do not show COVID-19 were used to train and validate a classification framework based on convolutional neural network. Five conditions including COVID-19 pneumonia, non-COVID-19 viral pneumonia, bacterial pneumonia, pulmonary tuberculosis, and normal lung were evaluated. Training and validation set of images were collected from Wuhan Jin Yin-Tan Hospital whereas test set of images were collected from Zhongshan Hospital Xiamen University and the fifth Hospital of Wuhan. Results: Accuracy, sensitivity, and specificity of the AI framework were reported. For test dataset, accuracies for recognizing normal lung, COVID-19 pneumonia, non-COVID-19 viral pneumonia, bacterial pneumonia, and pulmonary tuberculosis were 99.4%, 98.8%, 98.5%, 98.3%, and 98.6%, respectively. For the test dataset, accuracy, sensitivity, specificity, PPV, and NPV of recognizing COVID-19 were 98.8%, 98.2%, 98.9%, 94.5%, and 99.7%, respectively. Conclusions: The performance of the proposed AI framework has excellent performance of recognizing COVID-19 and other common infectious diseases of the lung, which also has balanced sensitivity and specificity.


title: Shared Antigen-specific CD8+ T cell Responses Against the SARS-COV-2 Spike Protein in HLA A*02:01 COVID-19 Participants

text: We report here on antigens from the SARS-CoV-2 virus spike protein, that when presented by Class I MHC, can lead to cytotoxic CD8+ T cell anti-viral responses in COVID-19 patients. We present a method in which the SARS-CoV-2 spike protein is converted into a library of peptide antigen-Major Histocompatibility Complexes (pMHCs) as single chain trimers that contain the peptide antigen, the MHC HLA allele, and the {beta}-2 microglobulin sub-unit. That library is used to detect the evolution of virus-specific T cell populations from two COVID-19 patients, at two time points over the course of infection. Both patients exhibit similar virus-specific T cell populations, but very different time-trajectories of those populations. These results can be used to track those virus-specific T cell populations over the course of an infection, thus providing deep insight into the variations in immune system trajectories observed in different COVID-19 patients.


title: Virus-Specific Antibody, in the Absence of T Cells, Mediates Demyelination in Mice Infected with a Neurotropic Coronavirus

text: Mice infected with mouse hepatitis virus strain JHM develop an inflammatory demyelinating disease in the central nervous system with many similarities to human multiple sclerosis. The mouse disease is primarily immune-mediated because demyelination is not detected in JHM-infected mice lacking T or B cells but does occur after transfer of JHM-specific T cells. Although less is known about the ability of antibodies to mediate demyelination, the presence of oligoclonally expanded B cells and high concentrations of antibodies (against self or infectious agents) in the central nervous system of many multiple sclerosis patients suggests that antibodies may also contribute to myelin destruction. Here, we show that anti-JHM antibodies, in the absence of T or B cells, caused demyelination in JHM-infected mice. Anti-JHM antibody was detected adjacent to areas of demyelination, consistent with a direct interaction between antibody and infected cells. Demyelination was reduced by 85 to 90% in infected RAG1−/− mice lacking normal expression of activating Fc receptors (FcRγ−/−) and by ∼76% when complement was depleted by treatment with cobra venom factor. These data demonstrate that JHM-specific antibodies are sufficient to cause demyelination and that myelin destruction in the presence of anti-virus antibodies results from a combination of complement- and Fc receptor-dependent mechanisms.


title: How to manage the post pandemic opening? A Pontryagin Maximum Principle approach

text: The COVID-19 pandemic has completely disrupted the operation of our societies. Its elusive transmission process, characterized by an unusually long incubation period, as well as a high contagion capacity, has forced many countries to take quarantine and social isolation measures that conspire against the performance of national economies. This situation confronts decision makers in different countries with the alternative of reopening the economies, thus facing the unpredictable cost of a rebound of the infection. This work tries to offer an initial theoretical framework to handle this alternative.


title: Repurposing of drugs for Covid-19: a systematic review and meta-analysis

text: Objective: The aim of this systematic review is to evaluate the data currently available regarding the repurposing of different drugs for Covid-19 treatment. Participants with suspected or diagnosed Covid-19 will be included. The interventions being considered are drugs being repurposed, and comparators will include standard of care treatment or placebo. Methods: We searched Ovid-MEDLINE, EMBASE, Cochrane library, clinical trial registration site in the UK(NIHR), Europe (clinicaltrialsregister.eu), US (ClinicalTrials.gov) and internationally (isrctn.com), and reviewed the reference lists of articles for eligible articles published up to April 22, 2020. All studies in English that evaluated the efficacy of the listed drugs were included. Cochrane RoB 2.0 and ROBINS-I tool were used to assess study quality. This systematic review adheres to the PRISMA guidelines. The protocol is available at PROSPERO (CRD42020180915). Results: From 708 identified studies or clinical trials, 16 studies and 16 case reports met our eligibility criteria. Of these, 6 were randomized controlled trials (763 patients), 7 cohort studies (321 patients) and 3 case series (191 patients). Chloroquine (CQ) had a 100% discharge rate compared to 50% with lopinavir-ritonavir at day 14, however a trial has recommended against a high dosage due to cardiotoxic events. Hydroxychloroquine (HCQ) has shown no significant improvement in negative seroconversion rate which is also seen in our meta-analysis (p=0.68). Adverse events with HCQ have a significant difference compared to the control group (p=0.001). Lopinavir-ritonavir has shown no improvement in time to clinical improvement which is seen in our meta-analyses (p=0.1). Remdesivir has shown no significant improvement in time to clinical improvement but this trial had insufficient power. Discussion: Due to the paucity in evidence, it is difficult to establish the efficacy of these drugs in the treatment of Covid-19 as currently there is no significant clinical effectiveness of the repurposed drugs. Further large clinical trials are required to achieve more reliable findings. A risk-benefit analysis is required on an individual basis to weigh out the potential improvement in clinical outcome and viral load reduction compared to the risks of the adverse events. (1-16)


From our homes to yours


title: Informative Ranking of Stand Out Collections of Symptoms: A New Data-Driven Approach to Identify the Strong Warning Signs of COVID 19

text: We develop here a data-driven approach for disease recognition based on given symptoms, to be efficient tool for anomaly detection. In a clinical setting and when presented with a patient with a combination of traits, a doctor may wonder if a certain combination of symptoms may be especially predictive, such as the question, "Are fevers more informative in women than men?" The answer to this question is, yes. We develop here a methodology to enumerate such questions, to learn what are the stronger warning signs when attempting to diagnose a disease, called Conditional Predictive Informativity, (CPI), whose ranking we call CPIR. This simple to use process allows us to identify particularly informative combinations of symptoms and traits that may help medical field analysis in general, and possibly to become a new data-driven advised approach for individual medical diagnosis, as well as for broader public policy discussion. In particular we have been motivated to develop this tool in the current environment of the pressing world crisis due to the COVID 19 pandemic. We apply the methods here to data collected from national, provincial, and municipal health reports, as well as additional information from online, and then curated to an online publically available Github repository.