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Diagnostic accuracy of serological tests for covid-19: systematic review and meta-analysis

BMJ 2020; 370 doi: https://doi.org/10.1136/bmj.m2516 (Published 01 July 2020) Cite this as: BMJ 2020;370:m2516

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  1. Mayara Lisboa Bastos, postdoctoral fellow12,
  2. Gamuchirai Tavaziva, research assistant1,
  3. Syed Kunal Abidi, medical student1,
  4. Jonathon R Campbell, postdoctoral fellow16,
  5. Louis-Patrick Haraoui, assistant professor3,
  6. James C Johnston, clinical associate professor4,
  7. Zhiyi Lan, consultant1,
  8. Stephanie Law, postdoctoral fellow5,
  9. Emily MacLean, doctoral student6,
  10. Anete Trajman, visiting researcher12,
  11. Dick Menzies, full professor16,
  12. Andrea Benedetti, associate professor16,
  13. Faiz Ahmad Khan, associate professor16
  1. 1Respiratory Epidemiology and Clinical Research Unit, Centre for Outcomes Research and Evaluation, Research Institute of the McGill University Health Centre, Montreal, Canada
  2. 2Social Medicine Institute, State University of Rio de Janeiro, Rio de Janeiro, Brazil
  3. 3Department of Microbiology and Infectious Diseases, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Québec, Canada
  4. 4University of British Columbia, Vancouver, Canada
  5. 5Department of Global Health and Social Medicine, Harvard Medical School, Boston, MA, USA
  6. 6Departments of Epidemiology, Biostatistics and Occupational Health, and Medicine, McGill University, Montreal, Canada
  1. Correspondence to: F Ahmad Khan faiz.ahmadkhan{at}mcgill.ca
  • Accepted 23 June 2020

Abstract

Objective To determine the diagnostic accuracy of serological tests for coronavirus disease-2019 (covid-19).

Design Systematic review and meta-analysis.

Data sources Medline, bioRxiv, and medRxiv from 1 January to 30 April 2020, using subject headings or subheadings combined with text words for the concepts of covid-19 and serological tests for covid-19.

Eligibility criteria and data analysis Eligible studies measured sensitivity or specificity, or both of a covid-19 serological test compared with a reference standard of viral culture or reverse transcriptase polymerase chain reaction. Studies were excluded with fewer than five participants or samples. Risk of bias was assessed using quality assessment of diagnostic accuracy studies 2 (QUADAS-2). Pooled sensitivity and specificity were estimated using random effects bivariate meta-analyses.

Main outcome measures The primary outcome was overall sensitivity and specificity, stratified by method of serological testing (enzyme linked immunosorbent assays (ELISAs), lateral flow immunoassays (LFIAs), or chemiluminescent immunoassays (CLIAs)) and immunoglobulin class (IgG, IgM, or both). Secondary outcomes were stratum specific sensitivity and specificity within subgroups defined by study or participant characteristics, including time since symptom onset.

Results 5016 references were identified and 40 studies included. 49 risk of bias assessments were carried out (one for each population and method evaluated). High risk of patient selection bias was found in 98% (48/49) of assessments and high or unclear risk of bias from performance or interpretation of the serological test in 73% (36/49). Only 10% (4/40) of studies included outpatients. Only two studies evaluated tests at the point of care. For each method of testing, pooled sensitivity and specificity were not associated with the immunoglobulin class measured. The pooled sensitivity of ELISAs measuring IgG or IgM was 84.3% (95% confidence interval 75.6% to 90.9%), of LFIAs was 66.0% (49.3% to 79.3%), and of CLIAs was 97.8% (46.2% to 100%). In all analyses, pooled sensitivity was lower for LFIAs, the potential point-of-care method. Pooled specificities ranged from 96.6% to 99.7%. Of the samples used for estimating specificity, 83% (10 465/12 547) were from populations tested before the epidemic or not suspected of having covid-19. Among LFIAs, pooled sensitivity of commercial kits (65.0%, 49.0% to 78.2%) was lower than that of non-commercial tests (88.2%, 83.6% to 91.3%). Heterogeneity was seen in all analyses. Sensitivity was higher at least three weeks after symptom onset (ranging from 69.9% to 98.9%) compared with within the first week (from 13.4% to 50.3%).

Conclusion Higher quality clinical studies assessing the diagnostic accuracy of serological tests for covid-19 are urgently needed. Currently, available evidence does not support the continued use of existing point-of-care serological tests.

Study registration PROSPERO CRD42020179452.

Footnotes

  • Contributors: MLB and FAK (equally) and AB, DM, and JC conceived the study and study design. MLB drafted the initial search strategy and executed the search. MLB, GT, and FAK screened the studies. MLB, GT, SL, EM, AT, ZL, and SA extracted data extraction and performed the quality assessment. MLB, AB, FAK, and ZL analysed the data. MLB and FAK wrote the first draft of the manuscript. FAK is the guarantor. All authors interpreted the data and wrote and critically reviewed the manuscript and all revisions. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted.

  • Funding: This study was funded (publication costs) by a grant (ECRF-R1-30) from the McGill Interdisciplinary Initiative in Infection and Immunity (MI4). MB is supported by the Canadian Institutes of Health Research (award #FRD143350). JRC is supported by Fonds de Recherche Sante Quebec (FRSQ award #258907 and #287869). SL holds a research training award from the FRSQ. AB holds a research salary award from the FRSQ. AT is supported by Conselho Nacional de Ensino, Pesquisa e Desenvolvimento Tecnológico (award #303267/2018-6). FAK receives salary support from the McGill University Department of Medicine. MI4 and these agencies had no input into the study design, data collection, data analysis or interpretation, report writing, or the decision to submit the paper for publication.

  • Competing interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: SL reports personal fees from Carebook Technologies, outside the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

  • Ethical approval: Not required.

  • Data sharing: Data can be requested from the corresponding author.

  • The study guarantor (FAK) affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

  • Dissemination to participants and related patient and public communities: The results of the meta-analysis will be disseminated to patients, providers, policy makers through social media, and academic and institutional networks.

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