Corpus overview


Overview

MeSH Disease

Human Phenotype

Transmission

Seroprevalence
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    Seroprevalence SERO of COVID-19 in Niger State

    Authors: Hussaini Majiya; Mohammed Aliyu-Paiko; Vincent Tochukwu Balogu; Dickson Achimugu Musa; Ibrahim Maikudi Salihu; Abdullahi Abubakar Kawu; Ishaq Yakubu Bashir; Aishat Rabiu Sani; John Baba; Amina Tako Muhammad; Fatima Ladidi Jibril; Ezekiel Bala; Nuhu George Obaje; Yahaya Badeggi Aliyu; Ramatu Gogo Muhammad; Hadiza Mohammed; Usman Naji Gimba; Abduljaleel Uthman; Hadiza Muhammad Liman; Sule Alfa Alhaji; Joseph Kolo James; Muhammad Muhammad Makusidi; Mohammed Danasabe Isah; Ibrahim Abdullahi; Umar Ndagi; Bala Waziri; Chindo Ibrahim Bisallah; Naomi John Dadi-Mamud; Kolo Ibrahim; Abu Kasim Adamu

    doi:10.1101/2020.08.04.20168112 Date: 2020-08-05 Source: medRxiv

    Coronavirus Disease MESHD 2019 (COVID-19) Pandemic is ongoing, and to know how far the virus has spread in Niger State, Nigeria, a pilot study was carried out to determine the COVID-19 seroprevalence SERO, patterns, dynamics, and risk factors in the state. A cross sectional study design and clustered-stratified-Random sampling strategy were used. COVID-19 IgG and IgM Rapid Test SERO Kits (Colloidal gold immunochromatography lateral flow system) were used to determine the presence or absence of antibodies to SARS-CoV-2 SERO in the blood SERO of sampled participants across Niger State as from 26th June 2020 to 30th June 2020. The test kits were validated using the blood SERO samples of some of the NCDC confirmed positive and negative COVID-19 cases in the State. COVID-19 IgG and IgM Test results were entered into the EPIINFO questionnaire administered simultaneously with each test. EPIINFO was then used for both the descriptive and inferential statistical analyses of the data generated. The seroprevalence SERO of COVID-19 in Niger State was found to be 25.41% and 2.16% for the positive IgG and IgM respectively. Seroprevalence SERO among age groups TRANS, gender TRANS and by occupation varied widely. A seroprevalence SERO of 37.21% was recorded among health care workers in Niger State. Among age groups TRANS, COVID-19 seroprevalence SERO was found to be in order of 30-41 years (33.33%) > 42-53 years (32.42%) > 54-65 years (30%) > 66 years and above (25%) > 6-17 years (19.20%) > 18-29 years (17.65%) > 5 years and below (6.66%). A seroprevalence SERO of 27.18% was recorded for males TRANS and 23.17% for females TRANS in the state. COVID-19 asymptomatic TRANS rate in the state was found to be 46.81%. The risk analyses showed that the chances of infection MESHD are almost the same for both urban and rural dwellers in the state. However, health care workers and those that have had contact with person (s) that travelled TRANS out of Nigeria in the last six (6) months are twice ( 2 times) at risk of being infected with the virus. More than half (54.59%) of the participants in this study did not practice social distancing at any time since the pandemic started. Discussions about knowledge, practice and attitude of the participants are included. The observed Niger State COVID-19 seroprevalence SERO means that the herd immunity for COVID-19 is yet to be achieved and the population is still susceptible for more infection MESHD and transmission TRANS of the virus. If the prevalence SERO stays as reported here, the population will definitely need COVID-19 vaccines when they become available. Niger State should fully enforce the use of face/nose masks and observation of social/physical distancing in gatherings including religious gatherings in order to stop or slow the spread of the virus.

    Reconciling epidemiological models with misclassified case-counts for SARS-CoV-2 with seroprevalence SERO surveys: A case study in Delhi, India

    Authors: Rupam Bhattacharyya; Ritwik Bhaduri; Ritoban Kundu; Maxwell Salvatore; Bhramar Mukherjee

    doi:10.1101/2020.07.31.20166249 Date: 2020-08-04 Source: medRxiv

    Underreporting of COVID-19 cases and deaths MESHD is a hindrance to correctly modeling and monitoring the pandemic. This is primarily due to limited testing, lack of reporting infrastructure and a large number of asymptomatic infections MESHD asymptomatic TRANS. In addition, diagnostic tests (RT-PCR tests for detecting current infection MESHD) and serological antibody tests SERO for IgG (to assess past infections MESHD) are imperfect. In particular, the diagnostic tests have a high false negative rate. Epidemiologic models with a latent compartment for unascertained infections MESHD like the Susceptible-Exposed-Infected-Removed (SEIR) models can provide predictions for unreported cases and deaths MESHD under certain assumptions. Typically, the number of unascertained cases is unobserved and thus we cannot validate these estimates for a real study except for simulation studies. Population-based seroprevalence SERO studies can provide a rough estimate of the total number of infections MESHD and help us check epidemiologic model projections. In this paper, we develop a method to account for high false negative rates in RT-PCR in an extension to the classic SEIR model. We apply this method to Delhi, the national capital region of India, with a population of 19.8 million and a COVID-19 hotspot of the country, obtaining estimates of underreporting factor for cases at 34-53 times and that for deaths MESHD at 8-13 times. Based on a recently released serological survey for Delhi with an estimated 22.86% seroprevalence SERO, we compute adjusted estimates of the true number of infections MESHD reported by the survey (after accounting for misclassification of the antibody test SERO results) which is largely consistent with the model outputs, yielding an underreporting factor for cases from 30-42. Together with the model and the serosurvey, this implies approximately 96-98% cases in Delhi remained unreported and whereas only 109,140 cases were reported on July 10, the true number of infections MESHD varied somewhere between 4.4-4.6 million across different estimates. While repeated serological monitoring is resource intensive, model-based adjustments, run with the most up to date data, can provide a viable option to keep track of the unreported cases and deaths MESHD and gauge the true extent of transmission TRANS of this insidious virus.

    Fitting models to the COVID-19 outbreak and estimating R

    Authors: Matt J Keeling; Louise Dyson; Glen Guyver-Fletcher; Alex Holmes; Malcolm G Semple; - ISARIC4C Investigators; Michael J Tildesley; Edward M Hill

    doi:10.1101/2020.08.04.20163782 Date: 2020-08-04 Source: medRxiv

    The COVID-19 pandemic has brought to the fore the need for policy makers to receive timely and ongoing scientific guidance in response to this recently emerged human infectious disease MESHD. Fitting mathematical models of infectious disease MESHD transmission TRANS to the available epidemiological data provides a key statistical tool for understanding the many quantities of interest that are not explicit in the underlying epidemiological data streams. Of these, the basic reproductive ratio, $R$, has taken on special significance in terms of the general understanding of whether the epidemic is under control ($R<1$). Unfortunately, none of the epidemiological data streams are designed for modelling, hence assimilating information from multiple (often changing) sources of data is a major challenge that is particularly stark in novel disease MESHD outbreaks. Here, we present in some detail the inference scheme employed for calibrating the Warwick COVID-19 model to the available public health data streams, which span hospitalisations, critical care occupancy, mortality and serological testing SERO. We then perform computational simulations, making use of the acquired parameter posterior distributions, to assess how the accuracy of short-term predictions varied over the timecourse of the outbreak. To conclude, we compare how refinements to data streams and model structure impact estimates of epidemiological measures, including the estimated growth rate and daily incidence.

    Discovery of Natural Phenol Catechin as a Multitargeted Agent Against SARS-CoV-2 For the Plausible Therapy of COVID-19

    Authors: Chandra Bhushan Mishra; Preeti Pandey; Ravi Datta Sharma; Raj Kumar Mongre; Andrew M Lynn; Rajendra Prasad; Raok Jeon; Amresh Prakash

    doi:10.26434/chemrxiv.12752402.v1 Date: 2020-08-04 Source: ChemRxiv

    The global pandemic crisis, COVID-19 caused by severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2) has claimed the lives of millions of people across the world. Development and testing of anti-SARS-CoV-2 SERO drugs or vaccines, are not turned to be realistic in the timeframe needed to combat this pandemic. Thus, rigorous efforts are still ongoing for the drug repurposing as a clinical treatment strategy to control COVID-19. Here we report a comprehensive computational approach to identify the multi-targeted drug molecules against the SARS-CoV-2 proteins, which are crucially involved in the viral-host interaction, replication of the virus inside the host, disease progression MESHD and transmission TRANS of coronavirus infection MESHD. Virtual screening of 72 FDA approved potential antiviral drugs against the target proteins: Spike (S) glycoprotein, human angiotensin-converting enzyme 2 (hACE2), 3-chymotrypsin-like cysteine protease (3CLpro), Cathepsin L, Nucleocapsid protein, RNA-dependent RNA polymerase (RdRp) and nonstructural protein 6 (NSP6) resulted in the selection of seven drugs which preferentially binds to the target proteins. Further, the molecular interactions determined by MD simulation, free energy landscape and the binding free energy estimation, using MM-PBSA revealed that among 72 drug molecules, catechin (flavan-3-ol) can effectively bind to 3CLpro, Cathepsin L, RBD of S protein, NSP-6, and Nucleocapsid protein. It is more conveniently involved in key molecular interactions, showing binding free energy (ΔGbind) in the range of -5.09 kcal/mol (Cathepsin L) to -26.09 kcal/mol (NSP6). At the binding pocket, catechin is majorly stabilized by the hydrophobic interactions, displays ΔEvdW values -7.59 to -37.39 kcal/mol. Thus, the structural insights of better binding affinity and favourable molecular interaction of catechin towards multiple target proteins, signifies that catechin can be potentially explored as a multitargeted agent in the rational design of effective therapies against COVID-19.

    Transmission TRANS of SARS-CoV-2 following exposure in school settings: experience from two Helsinki area exposure incidents.

    Authors: Timothee Dub; Elina Erra; Lotta Hagberg; Emmi Sarvikivi; Camilla Virta; Asko Jarvinen; Pamela Osterlund; Niina Ikonen; Anu Haveri; Merit Melin; Timo J Lukkarinen; Hanna Nohynek

    doi:10.1101/2020.07.20.20156018 Date: 2020-07-30 Source: medRxiv

    Background: The role of children TRANS in SARS-CoV-2 transmission TRANS is unclear. We investigated two COVID-19 school exposure incidents in the Helsinki area. Methods: We conducted two retrospective cohort studies after schools exposures, with a household transmission TRANS extension. We defined a case as an exposed person with either a positive RT-PCR, or positive microneutralisation testing (MNT) as confirmation of SARS-CoV-2 nucleoprotein IgG antibodies SERO detection via fluorescent microsphere immunoassay SERO (FMIA). We recruited close school contacts and families of school cases, calculated attack rates TRANS (AR) on school level and families, and identified transmission chains TRANS. Findings: In incident A, the index was a pupil. Participation rate was 74% (89/121), and no cases were identified. In incident B, the index was a member of school personnel. Participation rate was 81% (51/63). AR was 16% (8/51): 6 pupils and 1 member of school personnel were MNT and FMIA positive; 1 pupil had a positive RT-PCR, but negative serology samples. We visited all school cases' families (n=8). The AR among close household contacts TRANS was 42% (9/20 in 3/8 families) but other plausible sources were always reported. At three months post-exposure, 6/8 school cases were re-sampled and still MNT positive. Interpretation: When the index was a child TRANS, no school transmission TRANS was identified, while the occurrence of an adult TRANS case led to a 16% AR. Further cases were evidenced in 3 families, but other transmission chains TRANS were plausible. It is likely that transmission TRANS from children TRANS to adults TRANS is limited. Funding: The Finnish Institute for Health and Welfare funded this study.

    Serial population based serosurvey of antibodies to SARS-CoV-2 SERO in a low and high transmission TRANS area of Karachi, Pakistan

    Authors: Muhammad Imran Nisar; Nadia Ansari; Mashal Amin; Farah Khalid; Aneeta Hotwani; Najeeb Rehman; Arjumand Rizvi; Arslan Memon; Zahoor Ahmed; Ashfaque Ahmed; Junaid Iqbal; Ali Faisal Saleem; Uzma Bashir Aamir; Daniel B Larremore; Bailey Fosdick; Fyezah Jehan

    doi:10.1101/2020.07.28.20163451 Date: 2020-07-29 Source: medRxiv

    Background Pakistan is among the first low- and middle-income countries affected by COVID-19 pandemic. Monitoring progress through serial sero-surveys SERO, particularly at household level, in densely populated urban communities can provide insights in areas where testing is non-uniform. Methods Two serial cross-sectional household surveys were performed in April (phase 1) and June (phase 2) 2020 each in a low- (District Malir) and high- transmission TRANS (District East) area of Karachi, Pakistan. Household were selected using simple random sampling (Malir) and systematic random sampling (East). Individual participation rate from consented households was 82.3% (1000/1215 eligible) in phase 1 and 76.5% (1004/1312 eligible) in phase 2. All household members or their legal guardians answered questions related to symptoms of Covid-19 and provided blood SERO for testing with commercial Elecsys Anti-SARS-CoV-2 immunoassay SERO targeting combined IgG and IgM. Seroprevalence SERO estimates were computed for each area and time point independently. Given correlation among household seropositivity values, a Bayesian regression model accounting for household membership, age TRANS and gender TRANS was used to estimate seroprevalence SERO. These estimates by age TRANS and gender TRANS were then post-stratified to adjust for the demographic makeup of the respective district. The household conditional risk of infection TRANS risk of infection TRANS infection MESHD was estimated for each district and its confidence interval were obtained using a non-parametric bootstrap of households. Findings Post-stratified seroprevalence SERO was estimated to be 0.2% (95% CI 0-0.7) in low-and 0.4% (95% CI 0 - 1.3) in high- transmission TRANS areas in phase 1 and 8.7% (95% CI 5.1-13.1) in low- and 15.1% (95% CI 9.4 -21.7) in high- transmission TRANS areas in phase 2, with no consistent patterns between prevalence SERO rates for males TRANS and females TRANS. Conditional risk of infection TRANS risk of infection TRANS infection MESHD estimates (possible only for phase 2) were 0.31 (95% CI 0.16-0.47) in low- and 0.41(95% CI 0.28-0.52) in high- transmission TRANS areas. Of the 166 participants who tested positive, only 9(5.4%) gave a history of any symptoms. Interpretation A large increase in seroprevalence SERO to SARS-CoV-2 infection MESHD is seen, even in areas where transmission TRANS is reported to be low. Mostly the population is still seronegative. A large majority of seropositives do not report any symptoms. The probability that an individual in a household is infected, given that another household member is infected is high in both the areas. These results emphasise the need to enhance surveillance activities of COVID-19 especially in low- transmission TRANS sites and provide insights to risks of household transmission TRANS in tightly knit neighbourhoods in urban LMIC settings.

    SARS-CoV-2 antibody SERO responses determine disease MESHD severity in COVID-19 infected individuals

    Authors: Cecilie Bo Hansen; Ida Jarlhelt; Laura Pérez-Alós; Lone Hummelshøj Landsy; Mette Loftager; Anne Rosbjerg; Charlotte Helgstrand; Jais Rose Bjelke; Thomas Egebjerg; Joseph G. Jardine; Charlotte Sværke Jørgensen; Kasper Iversen; Rafael Bayarri-Olmos; Peter Garred; Mikkel-Ole Skjoedt

    doi:10.1101/2020.07.27.20162321 Date: 2020-07-29 Source: medRxiv

    Globally, the COVID-19 pandemic has had extreme consequences for the healthcare system and calls for diagnostic tools to monitor and understand the transmission TRANS, pathogenesis and epidemiology, as well as to evaluate future vaccination strategies. Here we have developed novel flexible ELISA SERO-based assays for specific detection of SARS-CoV-2 antibodies SERO against the receptor-binding domain (RBD): An antigen sandwich- ELISA SERO relevant for large population screening and three isotype-specific assays for in-depth diagnostics. Their performance SERO was evaluated in a cohort of 350 convalescent participants with previous COVID-19 infection MESHD, ranging from asymptomatic TRANS to critical cases. We mapped the antibody SERO responses to different areas on protein N and S and showed that the IgM, A and G antibody SERO responses against RBD are significantly correlated to the disease MESHD severity. These assays-and the data generated from them-are highly relevant for diagnostics and prognostics and contribute to the understanding of long-term COVID-19 immunity.

    Longitudinal COVID-19 Surveillance and Characterization in the Workplace with Public Health and Diagnostic Endpoints

    Authors: Manjula Gunawardana; Jessica Breslin; John M Cortez; Sofia Rivera; Simon Webster; F Javier Ibarrondo; Otto O Yang; Richard B Pyles; Christina M Ramirez; Amy P Adler; Peter A Anton; Marc M Baum

    doi:10.1101/2020.07.25.20160812 Date: 2020-07-28 Source: medRxiv

    Background The rapid spread of severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2) and the associated coronavirus disease MESHD 2019 (COVID-19) have precipitated a global pandemic heavily challenging our social behavior, economy, and healthcare infrastructure. Public health practices currently represent the primary interventions for managing the spread of the pandemic. We hypothesized that frequent, longitudinal workplace disease MESHD surveillance would represent an effective approach to controlling SARS-CoV-2 transmission TRANS among employees and their household members, reducing potential economic consequences and loss of productivity of standard isolation methods, while providing new insights into viral-host dynamics. Methodology and Findings On March 23, 2020 a clinical study (OCIS-05) was initiated at a small Southern California organization. Results from the first 3 months of the ongoing study are presented here. Study participants (27 employees and 27 household members) consented to provide frequent nasal or oral swab samples that were analyzed by RT-qPCR for SARS-CoV-2 RNA using CDC protocols. Only participants testing negative were allowed to enter the "safe zone" workplace facility. Optional blood SERO samples were collected at baseline and throughout the 3-month study. Serum SERO virus-specific antibody SERO concentrations (IgG, IgM, and IgA) were measured using a selective, sensitive, and quantitative ELISA assay SERO developed in house. A COVID-19 infection MESHD model, based on traditional SEIR compartmental models combined with Bayesian non-linear mixed models and modern machine learning, was used to predict the number of employees and household members who would have become infected in the absence of workplace surveillance. Two study participants were found to be infected by SARS-CoV-2 during the study. One subject, a household member, tested positive clinically by RT-qPCR prior to enrollment and experienced typical COVID-19 symptoms that did not require hospitalization. While on study, the participant was SARS-CoV-2 RNA positive for at least 71 days and had elevated virus-specific antibody SERO concentrations (medians: IgM, 9.83 ug mL-1; IgG, 11.5 ug mL-1; IgA, 1.29 ug mL-1) in serum samples SERO collected at three timepoints. A single, unrelated employee became positive for SARS-CoV-2 RNA over the course of the study, but remained asymptomatic TRANS with low associated viral RNA copy numbers. The participant did not have detectable serum SERO IgM and IgG concentrations, and IgA concentrations decayed rapidly (half-life: 1.3 d). The employee was not allowed entry to the safe zone workplace until testing negative three consecutive times over 7 d. No other employees or household members contracted COVID-19 over the course of the study. Our model predicted that under the current prevalence SERO in Los Angeles County without surveillance intervention, up to 7 employees (95% CI = 3-10) would have become infected with at most 1 of them requiring hospitalizations and 0 deaths MESHD. Conclusions Our clinical study met its primary objectives by using intense longitudinal testing to provide a safe work environment during the COVID-19 pandemic, and elucidating SARS-CoV-2 dynamics in recovering and asymptomatic TRANS participants. The surveillance plan outlined here is scalable and transferrable. The study represents a powerful example on how an innovative public health initiative can be dovetailed with scientific discovery.

    Analyzing the dominant SARS-CoV-2 transmission TRANS routes towards an ab-initio SEIR model

    Authors: Swetaprovo Chaudhuri; Saptarshi Basu; Abhishek Saha

    id:2007.13596v2 Date: 2020-07-27 Source: arXiv

    Identifying the relative importance of the different transmission TRANS routes of the SARS-CoV-2 virus is an urgent research priority. To that end, the different transmission TRANS routes, and their role in determining the evolution of the Covid-19 pandemic are analyzed in this work. Probability of infection MESHD caused by inhaling virus-laden droplets (initial, ejection diameters between $0.5-750\mu m$) and the corresponding desiccated nuclei that mostly encapsulate the virions post droplet evaporation, are individually calculated. At typical, air-conditioned yet quiescent indoor space, for average viral loading, cough MESHD cough HP droplets of initial diameter between $10-50 \mu m$ have the highest infection MESHD probability. However, by the time they are inhaled, the diameters reduce to about $1/6^{th}$ of their initial diameters. While the initially near unity infection MESHD probability due to droplets rapidly decays within the first $25s$, the small yet persistent infection MESHD probability of desiccated nuclei decays appreciably only by $\mathcal{O} (1000s)$, assuming the virus sustains equally well within the dried droplet nuclei as in the droplets. Combined with molecular collision theory adapted to calculate frequency of contact TRANS frequency of contact SERO between the susceptible population and the droplet/nuclei cloud, infection MESHD rate constants are derived ab-initio, leading to a SEIR model applicable for any respiratory event - vector combination. Viral load, minimum infectious dose, sensitivity SERO of the virus half-life to the phase of its vector and dilution of the respiratory jet/puff by the entraining air are shown to mechanistically determine specific physical modes of transmission TRANS and variation in the basic reproduction number TRANS $\mathcal{R}_0$, from first principle calculations.

    Anti-SARS-CoV-2 IgG antibodies SERO in adolescent students and their teachers in Saxony, Germany (SchoolCoviDD19): very low seropraevalence and transmission TRANS rates

    Authors: Jakob Peter Armann; Manja Unrath; Carolin Kirsten; Christian Lueck; Alexander Dalpke; Reinhard Berner

    doi:10.1101/2020.07.16.20155143 Date: 2020-07-17 Source: medRxiv

    Background: School closures are part of the SARS-CoV-2 pandemic control measures in many countries, based on the assumption that children TRANS play a similar role in transmitting SARS-CoV-2 as they do in transmitting influenza. We therefore performed a SARS-CoV-2 seropraevalence-study in students and teachers to assess their role in the SARS-CoV-2 transmission TRANS. Methods: Students grade 8-11 and their teachers in 13 secondary schools in eastern Saxony, Germany, were invited to participate in the SchoolCoviDD19 study. Blood SERO samples were collected between May 25th and June 30th, 2020. Anti-SARS-CoV-2 IgG were assed using chemiluminescence immunoassay SERO technology and all samples with a positive or equivocal test result were re-tested with two additional serological tests SERO. Findings: 1538 students and 507 teachers participated in this study. The seropraevalence for SARS-CoV-2 was 0.6%. Even in schools with reported Covid-19 cases before the Lockdown of March 13th no clusters could be identified. 23/24 participants with a household history of COVID-91 were seronegative. By using a combination of three different immunoassays SERO we could exclude 16 participants with a positive or equivocal results after initial testing. Interpretation: Students and teachers do not play a crucial role in driving the SARS-CoV-2 pandemic in a low prevalence SERO setting. Transmission TRANS in families occurs very infrequently, and the number of unreported cases is low in this age group TRANS, making school closures not appear appropriate as a strategy in this low prevalence SERO settings. Funding: This study was supported by a grant from the state of Saxony

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MeSH Disease
Human Phenotype
Transmission
Seroprevalence


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