Diagnostic performance of COVID‐19 serological assays during early infection: A systematic review and meta‐analysis of 11 516 samples

OBJECTIVE: The use of coronavirus disease 2019 (COVID‐19) serological testing to diagnose acute infection or determine population seroprevalence relies on understanding assay accuracy during early infection. We aimed to evaluate the diagnostic performance of serological testing in COVID‐19 by providing summary sensitivity and specificity estimates with time from symptom onset. METHODS: A systematic search of Ovid MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL) and PubMed was performed up to May 13, 2020. All English language, original peer‐reviewed publications reporting the diagnostic performance of serological testing vis‐à‐vis virologically confirmed SARS‐CoV‐2 infection were included. RESULTS: Our search yielded 599 unique publications. A total of 39 publications reporting 11 516 samples from 8872 human participants met eligibility criteria for inclusion in our study. Pooled percentages of IgM and IgG seroconversion by Day 7, 14, 21, 28 and after Day 28 were 37.5%, 73.3%, 81.3%, 72.3% and 73.3%, and 35.4%, 80.6%, 93.3%, 84.4% and 98.9%, respectively. By Day 21, summary estimate of IgM sensitivity was 0.872 (95% CI: 0.784‐0.928) and specificity 0.973 (95% CI: 0.938‐0.988), while IgG sensitivity was 0.913 (95% CI: 0.823‐0.959) and specificity 0.960 (95% CI: 0.919‐0.980). On meta‐regression, IgM and IgG test accuracy was significantly higher at Day 14 using enzyme‐linked immunosorbent assay (ELISA) compared to other methods. CONCLUSIONS: Serological assays offer imperfect sensitivity for the diagnosis of acute SARS‐CoV‐2 infection. Estimates of population seroprevalence during or shortly after an outbreak will need to adjust for the delay between infection, symptom onset and seroconversion.