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      Antibody Response After SARS-CoV-2 Infection and Implications for Immunity : A Rapid Living Review

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          Abstract

          Antibody tests for SARS-CoV-2, the virus that causes COVID-19, are widely available. This living review summarizes the evidence on the prevalence, levels, and durability of detectable antibodies after SARS-CoV-2 infection and whether antibodies to SARS-CoV-2 confer protective immunity. The review will be updated as more evidence becomes available.

          Abstract

          Background:

          The clinical significance of the antibody response after SARS-CoV-2 infection remains unclear.

          Purpose:

          To synthesize evidence on the prevalence, levels, and durability of detectable antibodies after SARS-CoV-2 infection and whether antibodies to SARS-CoV-2 confer natural immunity.

          Data Sources:

          MEDLINE (Ovid), Embase, CINAHL, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, World Health Organization global literature database, and Covid19reviews.org from 1 January through 15 December 2020, limited to peer-reviewed publications available in English.

          Study Selection:

          Primary studies characterizing the prevalence, levels, and duration of antibodies in adults with SARS-CoV-2 infection confirmed by reverse transcriptase polymerase chain reaction (RT-PCR); reinfection incidence; and unintended consequences of antibody testing.

          Data Extraction:

          Two investigators sequentially extracted study data and rated quality.

          Data Synthesis:

          Moderate-strength evidence suggests that most adults develop detectable levels of IgM and IgG antibodies after infection with SARS-CoV-2 and that IgG levels peak approximately 25 days after symptom onset and may remain detectable for at least 120 days. Moderate-strength evidence suggests that IgM levels peak at approximately 20 days and then decline. Low-strength evidence suggests that most adults generate neutralizing antibodies, which may persist for several months like IgG. Low-strength evidence also suggests that older age, greater disease severity, and presence of symptoms may be associated with higher antibody levels. Some adults do not develop antibodies after SARS-CoV-2 infection for reasons that are unclear.

          Limitation:

          Most studies were small and had methodological limitations; studies used immunoassays of variable accuracy.

          Conclusion:

          Most adults with SARS-CoV-2 infection confirmed by RT-PCR develop antibodies. Levels of IgM peak early in the disease course and then decline, whereas IgG peaks later and may remain detectable for at least 120 days.

          Primary Funding Source:

          Agency for Healthcare Research and Quality. (PROSPERO: CRD42020207098)

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          Most cited references75

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          Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.

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            QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies.

            In 2003, the QUADAS tool for systematic reviews of diagnostic accuracy studies was developed. Experience, anecdotal reports, and feedback suggested areas for improvement; therefore, QUADAS-2 was developed. This tool comprises 4 domains: patient selection, index test, reference standard, and flow and timing. Each domain is assessed in terms of risk of bias, and the first 3 domains are also assessed in terms of concerns regarding applicability. Signalling questions are included to help judge risk of bias. The QUADAS-2 tool is applied in 4 phases: summarize the review question, tailor the tool and produce review-specific guidance, construct a flow diagram for the primary study, and judge bias and applicability. This tool will allow for more transparent rating of bias and applicability of primary diagnostic accuracy studies.
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              Antibody responses to SARS-CoV-2 in patients of novel coronavirus disease 2019

              Abstract Background The novel coronavirus SARS-CoV-2 is a newly emerging virus. The antibody response in infected patient remains largely unknown, and the clinical values of antibody testing have not been fully demonstrated. Methods A total of 173 patients with SARS-CoV-2 infection were enrolled. Their serial plasma samples (n=535) collected during the hospitalization were tested for total antibodies (Ab), IgM and IgG against SARS-CoV-2. The dynamics of antibodies with the disease progress was analyzed. Results Among 173 patients, the seroconversion rate for Ab, IgM and IgG was 93.1%, 82.7% and 64.7%, respectively. The reason for the negative antibody findings in 12 patients might due to the lack of blood samples at the later stage of illness. The median seroconversion time for Ab, IgM and then IgG were day-11, day-12 and day-14, separately. The presence of antibodies was <40% among patients within 1-week since onset, and rapidly increased to 100.0% (Ab), 94.3% (IgM) and 79.8% (IgG) since day-15 after onset. In contrast, RNA detectability decreased from 66.7% (58/87) in samples collected before day-7 to 45.5% (25/55) during day 15-39. Combining RNA and antibody detections significantly improved the sensitivity of pathogenic diagnosis for COVID-19 (p<0.001), even in early phase of 1-week since onset (p=0.007). Moreover, a higher titer of Ab was independently associated with a worse clinical classification (p=0.006). Conclusions The antibody detection offers vital clinical information during the course of SARS-CoV-2 infection. The findings provide strong empirical support for the routine application of serological testing in the diagnosis and management of COVID-19 patients.
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                Author and article information

                Journal
                Ann Intern Med
                Ann Intern Med
                aim
                Annals of Internal Medicine
                American College of Physicians
                0003-4819
                1539-3704
                16 March 2021
                : M20-7547
                Affiliations
                [1 ]Scientific Resource Center for the AHRQ Evidence-based Practice Center Program, Portland VA Research Foundation, and VA Portland Health Care System, Portland, Oregon (I.A., C.A., E.G., R.A.P.)
                [2 ]Scientific Resource Center for the AHRQ Evidence-based Practice Center Program, Portland VA Research Foundation, VA Evidence Synthesis Program, and VA Portland Health Care System, Portland, Oregon (M.H.)
                [3 ]VA Evidence Synthesis Program and VA Portland Health Care System, Portland, Oregon (J.A., K.M.)
                Author notes
                Disclaimer: The views expressed in this article are those of the authors and do not necessarily represent the views of ACP, nor do they necessarily represent the official views of or imply endorsement by AHRQ or the U.S. Department of Health and Human Services.
                Acknowledgment: The authors thank Edwin Reid and Elizabeth Stoeger for editorial support.
                Financial Support: By contract no. HHSA290201700003C from AHRQ, U.S. Department of Health and Human Services.
                Corresponding Author: Mark Helfand, MD, 3710 SW U.S. Veterans Hospital Road, P3-MED, Portland, OR 97239; e-mail, mark.helfand@ 123456va.gov .
                Current Author Addresses: Dr. Arkhipova-Jenkins: 3710 SW U.S. Veterans Hospital Road, Portland VA Research Foundation Building 106, R212, Portland, OR 97239.
                Drs. Helfand and Mackey: VA Portland Health Care System, 3710 SW U.S. Veterans Hospital Road, Mail Code P3MED, Portland, OR 97239.
                Ms. Armstrong, Dr. Gean, Ms. Anderson, and Ms. Paynter: VA Portland Health Care System, 3710 SW U.S. Veterans Hospital Road, Mail Code R&D 71, Portland, OR 97239.
                Author Contributions: Conception and design: I. Arkhipova-Jenkins, M. Helfand, C. Armstrong, K. Mackey.
                Analysis and interpretation of the data: I. Arkhipova-Jenkins, M. Helfand, E. Gean, K. Mackey.
                Drafting of the article: I. Arkhipova-Jenkins, C. Armstrong, R.A. Paynter, K. Mackey.
                Critical revision of the article for important intellectual content: I. Arkhipova-Jenkins, M. Helfand, K. Mackey.
                Final approval of the article: I. Arkhipova-Jenkins, M. Helfand, C. Armstrong, E. Gean, J. Anderson, R.A. Paynter, K. Mackey.
                Obtaining of funding: M. Helfand.
                Administrative, technical, or logistic support: I. Arkhipova-Jenkins, M. Helfand, C. Armstrong, E. Gean, J. Anderson, R.A. Paynter.
                Collection and assembly of data: I. Arkhipova-Jenkins, C. Armstrong, E. Gean, J. Anderson, R.A. Paynter, K. Mackey.
                Author information
                https://orcid.org/0000-0001-7918-5228
                https://orcid.org/0000-0003-4749-5664
                Article
                aim-olf-M207547
                10.7326/M20-7547
                8025942
                33721517
                71849590-3a50-41c4-a54c-63521821fdae

                This article is made available via the PMC Open Access Subset for unrestricted re-use for research, analyses, and text and data mining through PubMed Central. Acknowledgement of the original source shall include a notice similar to the following: "© 2020 American College of Physicians. Some rights reserved. This work permits non-commercial use, distribution, and reproduction in any medium, provided the original author and source are credited." These permissions are granted for the duration of the COVID-19 pandemic or until permissions are revoked in writing. Upon expiration of these permissions, PMC is granted a perpetual license to make this article available via PMC and Europe PMC, consistent with existing copyright protections.

                History
                Categories
                Reviews
                10444, Antibody production
                3122457, COVID-19
                2553, Immunity
                , Systematic rev
                early, Currently Online First
                coronavirus, Coronavirus Disease 2019 (COVID-19)
                poc-eligible, POC Eligible

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