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      Clinical applications of detecting IgG, IgM, or IgA antibody for the diagnosis of COVID-19: A meta-analysis and systematic review

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          Highlights

          • The investigated positive results provided mark heterogeneity of sensitivity.

          • Diagnosing COVID-19 with either IgM + or IgG + presents a favorable diagnostic accuracy.

          • The sensitivity of antibody test might be improved by prolonged testing time.

          • IgA might be a surrogate providing a better diagnostic accuracy compared to IgG or IgM.

          Abstract

          Background

          Coronavirus disease 2019 is a global pandemic. Serological antibody test is one important diagnostic method increasingly used in the clinic, although its clinical application is still under investigation.

          Methods

          We conducted a meta-analysis to compare the diagnostic performances of severe acute respiratory syndrome coronavirus 2 specific antibody tests in COVID-19 patients. Test results analyzed included (1) IgM-positive but IgG-negative (IgM +IgG-), (2) IgG-positive but IgM-negative (IgG +IgM-), (3) both IgM and IgG-positive (IgM +IgG +), (4) IgM-positive without IgG information (IgM +IgG +/-), (5) IgG-positive without IgM information (IgG +IgM +/-), (6) either IgM or IgG-positive (IgM + or IgG +), and (7) IgA-positive (IgA +).

          Results

          Sixty-eight studies were included. The pooled sensitivities of IgM +IgG-, IgG +IgM-, IgM +IgG +, IgM +IgG +/-, IgG +IgM +/-, and IgM + or IgG + were 6%, 7%, 53%, 68%, 73%, and 79% respectively. The pooled specificity ranged from 98% to 100%. The IgA + had a pooled sensitivity of 78%, but a relatively low specificity of 88%. Tests conducted two weeks after symptom onset provided improved diagnostic accuracy. Chemiluminescence immunoassay and detection of S protein as the antigen could offer a more accurate diagnostic result.

          Discussion

          Our findings support the supplemental role of serological antibody tests in COVID-19 diagnosis. However, their capacity to diagnose COVID-19 early in the disease course could be limited.

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          Most cited references31

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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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              Detection of SARS-CoV-2 in Different Types of Clinical Specimens

              This study describes results of PCR and viral RNA testing for SARS-CoV-2 in bronchoalveolar fluid, sputum, feces, blood, and urine specimens from patients with COVID-19 infection in China to identify possible means of non-respiratory transmission.
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                Author and article information

                Journal
                Int J Infect Dis
                Int J Infect Dis
                International Journal of Infectious Diseases
                The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.
                1201-9712
                1878-3511
                12 January 2021
                12 January 2021
                Affiliations
                [a ]Department of Otorhinolaryngology Head and Neck surgery, The First Affiliated Hospital, Sun Yat-Sen University, 2nd Zhongshan Road 58#, Guangzhou, 510080, Guangdong, PR China
                [b ]Department of Allergy and Clinical Immunology, State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
                [c ]Guangzhou Key Laboratory of Otorhinolaryngology, Guangzhou, China
                Author notes
                [* ]Corresponding author at: Department of Allergy and Clinical Immunology, State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, 151 Yan Jing Road, Guangzhou 510120, China.
                [** ]Corresponding author at: Department of Otorhinolaryngology Head and Neck surgery, the First Affiliated Hospital of Sun Yat-sen University, No.58 Zhongshan Er Road, 510080 Guangzhou, China.
                [1]

                Mengyu Chen and Rundong Qin contributed equally to this paper.

                Article
                S1201-9712(21)00026-6
                10.1016/j.ijid.2021.01.016
                7833601
                33450372
                880e6db1-3f7d-4139-8738-ded15e7e689b
                © 2021 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                : 19 October 2020
                : 4 January 2021
                : 6 January 2021
                Categories
                Article

                Infectious disease & Microbiology
                covid-19,sars-cov-2,antibody tests,specificity,sensitivity,diagnostic accuracy

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