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    COVID-19 herd immunity in the Brazilian Amazon

    Authors: Lewis F Buss; Carlos Augusto Prete Jr.; Claudia MM Abrahim; Alfredo Mendrone Jr.; Tassila Salomon; Cesar de Almeida-Neto; Rafael FO França; Maria C Belotti; Maria PSS Carvalho; Allyson G Costa; Myuki AE Crispim; Suzete C Ferreira; Nelson A Fraiji; Susie Gurzenda; Charles Whittaker; Leonardo T Kamaura; Pedro L Takecian; Márcio K Moikawa; Anna S Nishiya; Vanderson Rocha; Nanci A Salles; Andreza A de Souza Santos; Martirene A da Silva; Brian Custer; Manoel Barral-Netto; Moritz Kraemer; Rafael HM Pererira; Oliver G Pybus; Michael P Busch; Márcia C Castro; Christopher Dye; Vitor H Nascimento; Nuno R Faria; Ester C Sabino

    doi:10.1101/2020.09.16.20194787 Date: 2020-09-21 Source: medRxiv

    The herd immunity threshold is the proportion of a population that must be immune to an infectious disease MESHD, either by natural infection MESHD or vaccination such that, in the absence of additional preventative measures, new cases decline and the effective reproduction number TRANS falls HP below unity. This fundamental epidemiological parameter is still unknown for the recently-emerged COVID-19, and mathematical models have predicted very divergent results. Population studies using antibody testing SERO to infer total cumulative infections can provide empirical evidence of the level of population immunity in severely affected areas. Here we show that the transmission TRANS of SARS-CoV-2 in Manaus, located in the Brazilian Amazon, increased quickly during March and April and declined more slowly from May to September. In June, one month following the epidemic peak, 44% of the population was seropositive for SARS-CoV-2, equating to a cumulative incidence of 52%, after correcting for the false-negative rate of the antibody test SERO. The seroprevalence SERO fell HP in July and August due to antibody SERO waning. After correcting for this, we estimate a final epidemic size of 66%. Although non-pharmaceutical interventions, plus a change in population behavior, may have helped to limit SARS-CoV-2 transmission TRANS in Manaus, the unusually high infection rate suggests that herd immunity played a significant role in determining the size of the epidemic.

    Seroprevalence SERO and immunity of SARS-CoV-2 infection MESHD in children TRANS and adolescents in schools in Switzerland: design for a longitudinal, school-based prospective cohort study

    Authors: Agne Ulyte; Thomas Radtke; Irene Abela; Sarah H Haile; Julia Braun; Ruedi Jung; Christoph Berger; Alexandra Trkola; Jan Fehr; Milo A Puhan; Susi Kriemler; Anel Nurtay; Lucie Abeler-Dörner; David G Bonsall; Michael V McConnell; Shawn O'Banion; Christophe Fraser; Scott Roberts; Jose A. Gonzalez; Marciano Sablad; Rodrigo Yelin; Wendy Taylor; Kiyoshi Tachikawa; Suezanne Parker; Priya Karmali; Jared Davis; Sean M Sullivan; Steve G. Hughes; Pad Chivukula; Eng Eong Ooi

    doi:10.1101/2020.08.30.20184671 Date: 2020-09-02 Source: medRxiv

    Introduction Seroprevalence SERO and transmission TRANS routes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection MESHD in children TRANS and adolescents, especially in school setting, are not clear. Resulting uncertainty is reflected in very different decisions on school closures and reopenings across countries. The aim of this longitudinal cohort study is to assess the extent and patterns of seroprevalence SERO of SARS-CoV-2 antibodies SERO in school-attending children TRANS repeatedly. It will examine risk factors for infection MESHD, relationship between seropositivity and symptoms, and temporal persistence of antibodies SERO. Additionally, it will include testing of school personnel and parents TRANS. Methods and analysis The study (Ciao Corona) will enroll a regionally representative, random sample of schools in the canton of Zurich, where 18% of the Swiss population live. Children TRANS aged TRANS 5 to 16 years, attending classes in primary and secondary schools are invited. Venous blood MESHD blood SERO and saliva samples are collected for SARS-CoV-2 serological testing SERO after the first wave of infections (June/July 2020), in fall HP (October/November 2020), and after winter (March/April 2021). Venous blood MESHD blood SERO is also collected for serological testing SERO of parents TRANS and school personnel. Bi-monthly questionnaires to children TRANS, parents TRANS and school personnel cover SARS-CoV-2 symptoms MESHD and tests, health, preventive behavior, lifestyle and quality of life information. Total seroprevalence SERO and cumulative incidence will be calculated. Hierarchical Bayesian logistic regression models will account for sensitivity SERO and specificity of the serological test SERO in the analyses and for the complex sampling structure, i.e., clustering within classes and schools. Ethics and dissemination The study was approved by the Ethics Committee of the Canton of Zurich, Switzerland (2020-01336). The results of this study will be published in peer-reviewed journals and will be made available to study participants and participating schools, the Federal Office of Public Health, and the Educational Department of the canton of Zurich. Trial registration number NCT04448717.

    Clinical utility of targeted SARS-CoV-2 serology testing to aid the diagnosis and management of suspected missed, late or post-COVID-19 infection syndromes: results from a pilot service

    Authors: Nicola Sweeney; Blair Merrick; Suzanne Pickering; Rui Pedro Galao; Alina Botgros; Harry D. Wilson; Adrian W. Signell; Gilberto Betancor; Mark Kia Ik Tan; John Ramble; Neophytos Kouphou; Sam Acors; Carl Graham; Jeffrey Seow; Eithne MacMahon; Stuart J. D. Neil; Michael H. Malim; Katie Doores; Sam Douthwaite; Rahul Batra; Gaia Nebbia; Jonathan D. Edgeworth

    doi:10.1101/2020.07.10.20150540 Date: 2020-07-11 Source: medRxiv

    Objectives: Determine indications and clinical utility of SARS-CoV-2 serology testing in adults TRANS and children TRANS. Design: Prospective evaluation of initial three weeks of a daily Monday to Friday pilot SARS-CoV-2 serology service for patients. Setting: Early post 'first-wave' SARS-CoV-2 transmission TRANS period at single centre London teaching hospital that provides care to the local community, as well as regional and national referral pathways for specialist services. Participants: 110 (72 adults TRANS, 38 children TRANS, age TRANS range 0-83 years, 52.7% female TRANS (n=58)). Interventions: Patient serum SERO from vetted referrals tested on CE marked and internally validated lateral flow immunoassay SERO (LFIA) (SureScreen Diagnostics) detecting antibodies to SARS-CoV-2 SERO spike proteins, with result and clinical interpretation provided to the direct care team. Main outcome measures: Performance SERO characteristics, source and nature of referrals, feasibility and clinical utility of the service, particularly the benefit for clinical decision-making. Results: The LFIA was deemed suitable for clinical advice and decision making following evaluation with 310 serum samples SERO from SARS-CoV-2 PCR positive patients and 300 pre-pandemic samples, giving a sensitivity SERO and specificity of 96.1% and 99.3% respectively. For the pilot, 115 referrals were received leading to 113 tests performed on 108 participants (sample not available for two participants); paediatrics (n=35), medicine (n=69), surgery (n=2) and general practice (n=2). 43.4% participants (n=49) had detectable antibodies to SARS-CoV-2 SERO. There were three main indications for serology; new acute presentations potentially triggered by recent COVID-19 infection e.g. PIMS-TS (n=26) and pulmonary embolism HP pulmonary embolism MESHD (n=5), potential missed diagnoses in context of a recent compatible illness (n=40), and making infection control and immunosuppression treatment decisions in persistently SARS-CoV-2 RNA PCR positive individuals (n=6). Conclusions: This study shows acceptable performance SERO characteristics, feasibility and clinical utility of a SARS-CoV-2 serology service using a rapid, inexpensive and portable assay for adults TRANS and children TRANS presenting with a range of clinical indications. Results correlated closely with a confirmatory in-house ELISA SERO. The study showed the benefit of introducing a serology service where there is a reasonable pre-test probability, and the result can be linked with clinical advice or intervention. Experience thus far is that the volume of requests from hospital referral routes are manageable within existing clinical and laboratory services; however, the demand from community referrals has not yet been assessed. Given recent evidence for a rapid decline in antibodies SERO, particularly following mild infection MESHD, there is likely a limited window of opportunity to realise the benefit of serology testing for individuals infected during the 'first-wave' before they potentially fall HP below a measurable threshold. Rapidly expanding availability of serology services for NHS patients will also help understand the long-term implications of serostatus and prior infection MESHD in different patient groups, particularly before emergence of any 'second-wave' outbreak or introduction of a vaccination programme.

    Emergence of RBD and D614G Mutations in Spike Protein: An Insight from Indian SARS-CoV-2 Genome Analysis


    id:10.20944/preprints202006.0032.v1 Date: 2020-06-04 Source: Preprints.org

    Currently, entire world is crumbled due to COVID-19 caused by novel SARS-CoV-2. Globally, over 5 million people are infected by SARS-CoV-2 with 6% fatality rate. The surface spike (S) protein plays a key role in the pathogenesis of SARS-CoV-2 by mediating viral entry through human angiotensin converting enzyme 2 (hACE2) receptors on the host cell and there is a big global race to find viral neutralizing antibodies SERO and vaccine against S protein of SARS-CoV-2. Since SARS-CoV-2 evolved into 10 different clades in a very short span, a study on sipke protein mutation is essential to have effective vaccine coverage globally. Based on the mutation analysis of S protein from 166 Indian SARS-CoV-2 genome, a total of 40 different SNPs comprising of 14 synonymous and 26 non-synonymous mutations were observed, and notably, Indian S protein diverged into two major clusters, D614 and G614, with 11 different types. Majority of Indian strains fall HP in A2a and O clusters. Alarmingly, we have observed six SNPs at RBD and notably two of them at RBM (S438F and S494P). S494P SNP, similar to Bat–SARS like-CoV, may indicate a low ACE2 binding affinity. Interestingly 38% of Indian strains harbor a characteristic D614G SNP which was found predominantly in A2a cluster, mostly comprising USA and European strains with high disease severity. The association of disease severity with D614G SNP is well-correlated in states with high death rate except Maharashtra. Notably, more than 50% of D614G mutation were observed in Northern part of India and 14% in Southern part but not in Kerala and Tamil Nadu strains. Highly conserved motif, D614 (608-VAVLYQDVNCT-618) in upstream and also few downstream, of S1/S2 furin cleavage site may indicate specific key role in efficient interaction with host proteases in pathogenesis. Further studies are warranted to clarify the impact of SD614G SNP association to disease severity . Interestingly, C2367T (Y789Y) synonymous SNP is observed in 37% of Indian strains and notably similar SNPs with degeneracy bases were observed which is a key indication for the possibility of misdiagnosis by Real-Time PCR and revised strategies are needed for the precise diagnosis. Circulation of high number of signature SNPs [D614G and C2367T (Y789Y)] in certain states may be an early indication of emergence of community transmission TRANS in India. Further large genome sequence data from India will aid in deep understanding on the diversity of circulating SASR-Cov-2 and its impact on disease severity, origin of imported cases to India, community spread, effect on diagnosis and vaccine coverage.

    Structural and Functional Implications of Non-synonymous Mutations in the Spike protein of 2,954 SARS-CoV-2 Genomes

    Authors: Shijulal Nelson-Sathi; Perunthottathu K Umasankar; Sreekumar Easwaran; Radhakrishnan R Nair; Iype Joseph; Sai Ravi Chandra Nori; Jamiema Sara Philip; Roshny Prasad; Kolaparamba V Navyasree; Shikha Ramesh; Heera Pillai; Sanu Gosh; Santhosh Kumar TR; M Radhakrishna Pillai

    doi:10.1101/2020.05.02.071811 Date: 2020-05-02 Source: bioRxiv

    SARS-CoV-2, the causative agent of COVID-19 pandemic, is an RNA virus prone to mutations. Interaction of SARS-CoV-2 Spike MESHD (S) protein with the host cell receptor, Angiotensin-I Converting Enzyme 2 (ACE2) is pivotal for attachment and entry of the virus. Yet, natural mutations acquired on S protein during the pandemic and their impact on viral infectivity, transmission TRANS dynamics and disease pathogenesis remains poorly understood. Here, we analysed 2952 SARS-CoV-2 genomes across the globe, and identified a total of 1815 non-synonymous mutations in the S-protein that fall HP into 54 different types. We observed that six of these distinct mutations were located in the Receptor Binding Domain (RBD) region that directly engages host ACE2. Molecular phylogenetic analysis revealed that these RBD mutations cluster into distinct phyletic clades among global subtypes of SARS-CoV-2 implying possible emergence of novel sublineages of the strain. Structure-guided homology modelling and docking analysis predicted key molecular rearrangements in the ACE2 binding interface of RBD mutants that could result in altered virus-host interactions. We propose that our findings could be significant in understanding disease dynamics and in developing vaccines, antibodies SERO and therapeutics for COVID-19. ImportanceCOVID-19 pandemic shows considerable variations in disease transmission TRANS and pathogenesis globally, yet reasons remain unknown. Our study identifies key S-protein mutations prevailing in SARS-CoV-2 strain that could alter viral attachment and infectivity. We propose that the interplay of these mutations could be one of the factors driving global variations in COVID-19 spread. In addition, the mutations identified in this study could be an important indicator in predicting efficacies of vaccines, antibodies SERO and therapeutics that target SARS-CoV-2 RBD-ACE2 interface.

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Human Phenotype

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