Seropositivity rate and diagnostic accuracy of serological tests in 2019-nCoV cases: a pooled analysis of individual studies.

OBJECTIVE

Currently, detection of SARS-CoV-2 RNA is standard in the diagnosis of COVID-19 (2019-nCoV). However, reliable and rapid serological diagnostic methods to screen SARS-CoV-2 infected patients, including those who do not have overt symptoms, are urgently needed. Most studies have described serological tests based on the detection of SARS-CoV-2-specific IgM and IgG. Here, we attempted to systematically analyze the positive rates and comprehensive diagnostic efficacy of IgM and IgG in response to SARS-CoV-2 infection.

MATERIALS AND METHODS

By systematically searching PubMed, medRxiv, bioRxiv and other databases, studies regarding the detection of peripheral blood IgM and/or IgG related to SARS-CoV-2 were collected. The positive rate, sensitivity (SEN), specificity (SPE), area under the curve (AUC) and corresponding 95% CIs were obtained by weighted quantitative mergence, and the source of heterogeneity was explored by performing a subgroup study and sensitivity analysis.

RESULTS

A total of 30 studies were included, which were comprised of 3856 confirmed SARS-CoV-2 RNA positive cases, 368 suspected RNA negative cases, 1167 asymptomatic carriers, and 2526 RNA negative controls. The corresponding meta-analysis showed that in confirmed cases with 2019-nCoV, the positive rates of single IgM, single IgG and their joint detection related to SARS-CoV-2 were 61.2% (95% CI: 53.4%-69.0%), 58.8% (95% CI: 49.6%-68.0%) and 62.1% (52.7%-71.4%), respectively. In suspected RNA negative cases, the positive rates of single IgM, single IgG and their joint detection were 29.0% (95% CI: 14.0%-44.0%), 37.0% (95% CI: 20.0%-55.0%) and 55.0% (95% CI: 19.0%-90.0%), respectively. Interestingly, IgM/IgG detection also demonstrated a positive rate of 19% (95% CI: 10.0%-27.0%) in asymptomatic cases. Using RT-PCR test as reference, the AUCs of IgM, IgG and IgM/IgG in the diagnosis of 2019-nCoV infection were 0.9656, 0.9766, and 0.9838, respectively. The stratified analyses showed that among confirmed cases with 2019-nCoV, the positive rates of IgM and IgG were 27.3% (95%CI: 19.8%-34.8%) and 22.3% (95% CI: 11.3%-33.3%), respectively, 0-7days following the onset of symptoms, whereas the positive rate of parallel IgM/IgG testing attained 39.3% (95% CI: 24.2%-54.4%). Moreover, the efficacy of antibody testing based on CLIA (chemiluminescence enzyme immunoassays) in diagnosing 2019-nCoV infection was higher than that of LFIA (lateral flow immunoassays) and ELISA (enzyme linked immunosorbent assay).

CONCLUSIONS

IgM, IgG and their joint testing exhibited high clinical value in the diagnosis of 2019-nCoV, which may assist in making up for the deficiency of throat swab RNA tests.