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      How to detect and reduce potential sources of biases in studies of SARS-CoV-2 and COVID-19

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          Abstract

          In response to the coronavirus disease (COVID-19) pandemic, public health scientists have produced a large and rapidly expanding body of literature that aims to answer critical questions, such as the proportion of the population in a geographic area that has been infected; the transmissibility of the virus and factors associated with high infectiousness or susceptibility to infection; which groups are the most at risk of infection, morbidity and mortality; and the degree to which antibodies confer protection to re-infection. Observational studies are subject to a number of different biases, including confounding, selection bias, and measurement error, that may threaten their validity or influence the interpretation of their results. To assist in the critical evaluation of a vast body of literature and contribute to future study design, we outline and propose solutions to biases that can occur across different categories of observational studies of COVID-19. We consider potential biases that could occur in five categories of studies: (1) cross-sectional seroprevalence, (2) longitudinal seroprotection, (3) risk factor studies to inform interventions, (4) studies to estimate the secondary attack rate, and (5) studies that use secondary attack rates to make inferences about infectiousness and susceptibility.

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          The online version of this article (10.1007/s10654-021-00727-7) contains supplementary material, which is available to authorized users.

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          Most cited references56

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          Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection

          Understanding immune memory to SARS-CoV-2 is critical for improving diagnostics and vaccines, and for assessing the likely future course of the COVID-19 pandemic. We analyzed multiple compartments of circulating immune memory to SARS-CoV-2 in 254 samples from 188 COVID-19 cases, including 43 samples at ≥ 6 months post-infection. IgG to the Spike protein was relatively stable over 6+ months. Spike-specific memory B cells were more abundant at 6 months than at 1 month post symptom onset. SARS-CoV-2-specific CD4+ T cells and CD8+ T cells declined with a half-life of 3-5 months. By studying antibody, memory B cell, CD4+ T cell, and CD8+ T cell memory to SARS-CoV-2 in an integrated manner, we observed that each component of SARS-CoV-2 immune memory exhibited distinct kinetics.
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            Systematic review of COVID‐19 in children shows milder cases and a better prognosis than adults

            Abstract Aim The coronavirus disease 2019 (COVID‐19) pandemic has affected hundreds of thousands of people. Data on symptoms and prognosis in children are rare. Methods A systematic literature review was carried out to identify papers on COVID‐19, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), using the MEDLINE and Embase databases between January 1 and March 18, 2020. Results The search identified 45 relevant scientific papers and letters. The review showed that children have so far accounted for 1%‐5% of diagnosed COVID‐19 cases, they often have milder disease than adults and deaths have been extremely rare. Diagnostic findings have been similar to adults, with fever and respiratory symptoms being prevalent, but fewer children seem to have developed severe pneumonia. Elevated inflammatory markers were less common in children, and lymphocytopenia seemed rare. Newborn infants have developed symptomatic COVID‐19, but evidence of vertical intrauterine transmission was scarce. Suggested treatment included providing oxygen, inhalations, nutritional support and maintaining fluids and electrolyte balances. Conclusions The coronavirus disease 2019 has occurred in children, but they seemed to have a milder disease course and better prognosis than adults. Deaths were extremely rare.
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              COVID-19 and Racial/Ethnic Disparities

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                Author and article information

                Contributors
                eaccorsi@g.harvard.edu
                xuetingqiu@hsph.harvard.edu
                erumpler@hsph.harvard.edu
                lkennedyshaffer@vassar.edu
                rek160@mail.harvard.edu
                keyajoshi@g.harvard.edu
                egoldste@hsph.harvard.edu
                mats.stensrud@epfl.ch
                rniehus@hsph.harvard.edu
                mc349@st-andrews.ac.uk
                mlipsitc@hsph.harvard.edu
                Journal
                Eur J Epidemiol
                Eur J Epidemiol
                European Journal of Epidemiology
                Springer Netherlands (Dordrecht )
                0393-2990
                1573-7284
                25 February 2021
                25 February 2021
                : 1-18
                Affiliations
                [1 ]GRID grid.38142.3c, ISNI 000000041936754X, Center for Communicable Disease Dynamics, Department of Epidemiology, , Harvard T.H. Chan School of Public Health, ; Boston, MA 02115 USA
                [2 ]GRID grid.267778.b, ISNI 0000 0001 2290 5183, Department of Mathematics and Statistics, , Vassar College, ; Poughkeepsie, NY 12604 USA
                [3 ]GRID grid.5333.6, ISNI 0000000121839049, Department of Mathematics, , École Polytechnique Fédérale de Lausanne, ; Lausanne, Switzerland
                [4 ]GRID grid.11914.3c, ISNI 0000 0001 0721 1626, Division of Infection and Global Health Research, School of Medicine, , University of St Andrews, ; St Andrews, UK
                [5 ]GRID grid.418716.d, ISNI 0000 0001 0709 1919, Specialist Virology Laboratory, , Royal Infirmary of Edinburgh, ; Edinburgh, UK
                [6 ]GRID grid.417068.c, ISNI 0000 0004 0624 9907, Regional Infectious Diseases Unit, , Western General Hospital, ; Edinburgh, UK
                [7 ]GRID grid.38142.3c, ISNI 000000041936754X, Department of Immunology and Infectious Diseases, , Harvard T.H. Chan School of Public Health, ; Boston, MA 02115 USA
                Author information
                http://orcid.org/0000-0002-7443-7921
                Article
                727
                10.1007/s10654-021-00727-7
                7906244
                33634345
                9fae5ea4-ab05-41b5-aedb-84e31b7cdde8
                © The Author(s) 2021

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 12 November 2020
                : 4 February 2021
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100000060, National Institute of Allergy and Infectious Diseases;
                Award ID: T32AI007535
                Award Recipient :
                Funded by: National Institute of General Medical Sciences (US)
                Award ID: U54GM088558
                Award ID: U54GM088558
                Award ID: U54GM088558
                Award Recipient :
                Funded by: Morris-Singer Fund
                Funded by: National Institutes of Health (US)
                Award ID: U01 CA261277
                Award Recipient :
                Categories
                Review

                Public health
                epidemiological biases,selection bias,misclassification,measurement error,covid-19,observational data

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