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Meta-Analysis
. 2022 Apr 21;12(4):e053912.
doi: 10.1136/bmjopen-2021-053912.

Meta-analysis of the robustness of COVID-19 diagnostic kit performance during the early pandemic

Chandrakumar Shanmugam #  1 , Michael Behring #  2 , Vishwas Luthra  3 , Sixto M Leal  4 , Sooryanarayana Varambally  4 , George J Netto  4 , Upender Manne  5
Affiliations
Meta-Analysis

Meta-analysis of the robustness of COVID-19 diagnostic kit performance during the early pandemic

Chandrakumar Shanmugam et al. BMJ Open. .

Abstract

Background: Accurate detection of SARS-CoV-2 is necessary to mitigate the COVID-19 pandemic. However, the test reagents and assay platforms are varied and may not be sufficiently robust to diagnose COVID-19.

Methods: We reviewed 85 studies (21 530 patients), published from five regions of the world, to highlight issues involved in the diagnosis of COVID-19 in the early phase of the pandemic. All relevant articles, published up to 31 May 2020, in PubMed, BioRiXv, MedRiXv and Google Scholar, were included. We evaluated the qualitative (9749 patients) and quantitative (10 355 patients) performance of RT-PCR and serologic diagnostic tests for real-world samples, and assessed the concordance (5538 patients) between test performance in meta-analyses. Synthesis of results was done using random effects modelling and bias was evaluated according to QUADAS-2 guidelines.

Results: The RT-PCR tests exhibited heterogeneity in the primers and reagents used. Of 1957 positive RT-PCR COVID-19 participants, 1585 had positive serum antibody (IgM±IgG) tests (sensitivity 0.81, 95% CI 0.66 to 0.90). While 3509 of 3581 participants RT-PCR negative for COVID-19 were found negative by serology testing (specificity 0.98, 95% CI 0.94 to 0.99). The chemiluminescent immunoassay exhibited the highest sensitivity, followed by ELISA and lateral flow immunoassays. Serology tests had higher sensitivity and specificity for laboratory approval than for real-world reporting data.

Discussion: The robustness of the assays/platforms is influenced by variability in sampling and reagents. Serological testing complements and may minimise false negative RT-PCR results. Lack of standardised assay protocols in the early phase of pandemic might have contributed to the spread of COVID-19.

Keywords: COVID-19; Molecular diagnostics; Public health.

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Conflict of interest statement

Competing interests: None declared.

Figures

Figure 1
Figure 1
Comparison of performance (sensitivity and specificity) of serology tests (IgM/IgG) based on assay platforms. CLIA, chemiluminescent immunoassay; LFIA, lateral flow immunoassay.
Figure 2
Figure 2
Comparison of sensitivity of laboratory setting versus real-world setting of RT-PCR and serology (IgM/IgG) kits.
Figure 3
Figure 3
The effect of primer choice in RT-PCR referent on sensitivity of tests based on serum IgG.
See this image and copyright information in PMC

Update of

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