Serology detection is recognized for its sensitivity in convalescent patients with COVID-19, in comparison with nucleic acid amplification tests(NAATs), which is considered as the gold standard for diagnosing acute infection. However, when and how serology detection performs the best remains unknown. This article aimed to evaluate the diagnostic accuracy of serologic methods for COVID-19 based on assay design and post-symptom-onset intervals. Two authors independently searched PubMed, Cochrane library, Ovid, EBSCO for case-control, longitudinal and cohort studies that determined the diagnostic accuracy of serology tests in comparison with NAATs for SARS-CoV-2 RNA in COVID-19 cases and used QUADAS-2 for quality ... More
Serology detection is recognized for its sensitivity in convalescent patients with COVID-19, in comparison with nucleic acid amplification tests(NAATs), which is considered as the gold standard for diagnosing acute infection. However, when and how serology detection performs the best remains unknown. This article aimed to evaluate the diagnostic accuracy of serologic methods for COVID-19 based on assay design and post-symptom-onset intervals. Two authors independently searched PubMed, Cochrane library, Ovid, EBSCO for case-control, longitudinal and cohort studies that determined the diagnostic accuracy of serology tests in comparison with NAATs for SARS-CoV-2 RNA in COVID-19 cases and used QUADAS-2 for quality assessment. Pooled accuracy was analyzed using INLA method. A total of 27 studies were included in this meta-analysis, with 4 cohort, 16 case-control and 7 longitudinal studies and 4,565 participants. The overall sensitivity of IgG, IgM, and total antibody(TAB) was 0.76(95%CI 0.65-0.86), 0.69(95%CI 0.59-0.78), 0.78(95%CI 0.70-0.85). The overall specificity was 0.98(95%CI 0.96-0.99), 0.95(95%CI 0.91-0.98), 0.97(95%CI 0.93-0.99). Serology tests had the lowest sensitivity at 0-7 days after symptom onset and the highest at >14 days. TAB had a better sensitivity than IgG or IgM only. Using combined nucleocapsid(N) and spike(S) protein had a better sensitivity compared to N or S protein only. Lateral flow immunoassay(LFIA) had a lower sensitivity than enzyme-linked immunoassay(ELISA) and chemiluminescent immunoassay(CLIA). Serology tests will play an important role in the clinical diagnosis for later stage COVID-19 patients. ELISA tests, detecting TAB or targeting combined N and S proteins had a higher diagnostic sensitivity compared to other methods.
