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Meta-Analysis
. 2020 Dec;9(1):2200-2211.
doi: 10.1080/22221751.2020.1826362.

Meta-analysis of diagnostic performance of serology tests for COVID-19: impact of assay design and post-symptom-onset intervals

Hongyu Wang  1 , Jingwen Ai  1 , Michael J Loeffelholz  2 , Yi-Wei Tang  2 , Wenhong Zhang  1
Affiliations
Meta-Analysis

Meta-analysis of diagnostic performance of serology tests for COVID-19: impact of assay design and post-symptom-onset intervals

Hongyu Wang et al. Emerg Microbes Infect. 2020 Dec.

Abstract

Serology detection is recognized for its sensitivity in convalescent patients with COVID-19, in comparison with nucleic acid amplification tests (NAATs). 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 in COVID-19 cases and used QUADAS-2 for quality assessment. Pooled accuracy was analysed 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 4565 participants. 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.

Keywords: COVID-19; SARS-CoV-2; immunoassays; metanalysis; serology.

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Conflict of interest statement

No potential conflict of interest was reported by the author(s).

MJL and YWT are employees of Cepheid, the commercial manufacturer of the Xpert Xpress SARS-CoV-2 test. HYW, JWA and WHZ declare no competing interests.

Figures

Figure 1.
Figure 1.
Search process of the meta-analysis.
Figure 2.
Figure 2.
Risk of bias and application concerns of included studies assessed using QUADAS-2 tool. Red spots refer to high risk of bias or high concern, yellow refer to unclear and green refer to low.
Figure 3.
Figure 3.
Overall Sensitivity and Specificity of Serology test in NAAT-confirmed COVID-19 cases. (A) Histogram of sensitivity and specificity in IgG, IgM, total antibody. Median (column) and 95% CI (error bar) were shown in the histogram. (B–D) forest plots of sensitivity (Right) and specificity (Left) in IgG, IgM, total antibody. Abbreviations: TAB: Total antibody.
Figure 4.
Figure 4.
Summary receiver-operating characteristic of IgG (A), IgM (B), TAB (C).
Figure 5.
Figure 5.
Dynamic change of the sensitivity of serology test at 0–7, 8–14, >14 days since symptom onset.
Figure 6.
Figure 6.
Sensitivity of serology test in different method or targeted antigen. (A) Histogram of the sensitivity of serology test in ELISA, CLIA, and LFIA. (B) Histogram of the specificity of serology test in ELISA, CLIA, and LFIA. (C) Histogram of the sensitivity of serology test when targeted on spike protein (S), nucleoprotein (N) or both (N + S). Abbreviations: ELISA: Enzyme linked immune sorbent assay; CLIA: Chemiluminescent immunoassay; LFIA: Lateral flow (immuno)assay.
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