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Serological evidence of human infection with SARS-CoV-2: a systematic review and meta-analysis

Our take —

This systematic review synthesized data from 404 serosurveys globally from December 2019-December 2020, and included seroprevalence, antibody testing data from 5,168,360 individuals. Authors found that close contacts and high risk healthcare workers had a generally higher seroprevalence than low risk healthcare workers and the general population, though there was significant variation across geographic regions. Many of the reviewed studies were determined to be of poor quality, making it difficult to make meaningful comparisons across studies and regions. Within the higher quality studies, combined seroprevalence estimates across studies ranged from 4.2% among low-risk healthcare workers to 18.0% among contacts of known COVID-19 cases.

Study design

Other

Study population and setting

The goal of this study was to collate and synthesize all data from serological surveys for antibodies for SARS-CoV-2 that were published between December 1, 2019 and Dec 22, 2020. The authors systematically searched three databases that house peer-reviewed literature (PubMed, Embase and Web of Science), along with five preprint servers (medRxiv, bioRxiv, SSRN, Wellcome Open Research, and Europe PMC). In order to be included in this review, studies had to include a measure of seroprevalence in non-COVID-19 clinical cases, be conducted after the first reported case in the study area, and report the specific assays used. Only studies in English were included. Seroprevalence was the main outcome, and was defined as the prevalence of seropositive results in each original study.

Summary of Main Findings

A total of 404 of the 10,538 original records identified were included in the study: 8 from the African region, 120 from the region of the Americas, 19 from the Eastern Mediterranean region, 194 from the European region, 19 from the South-East Asia region, and 44 from the Western Pacific region. These 404 studies represented tests done on 5,168,360 unique individuals. 64% (259/404) of studies came from convenience samples (no random sampling). The overall quality of the included studies was low, with only 82 of 404 (20%) classified as of higher quality. Among studies of higher quality, seroprevalence was 18% (95% CI: 15.7-20.3) among close contacts, 17.1% (95% CI: 9.9-24.4) among high-risk health care workers, 4.2% (95% CI: 1.5-6.9) among low-risk health care workers, and 8.0% (95% CI: 6.8-9.2) in the general population. Pooled seroprevalence estimates were highest for the South-East Asia region (19.6% 95%CI 5.5-33.6, all in India). There was a significant variation across the included studies.

Study Strengths

This study is a comprehensive, systematic review of the available evidence at the time of publication. This study incorporated data from a very large body of literature from over 5 million people. The study followed PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and included an assessment of the quality of included papers by adapting existing quality assessment tools for their purposes. These quality assessments highlight the variation in the test performance, immunoglobulin isotypes, and thresholds used.

Limitations

The main limitation of this study is that it attempts to conduct a meta-analysis on heterogenous estimates that are not standardized and utilize different methods of measurement. Serosurveys reviewed in this systematic were conducted at different points in each country’s epidemic trajectory.

Value added

This study synthesizes the available serological evidence on SARS-CoV-2, globally, and sheds light on the generally low quality of the existing seroprevalence studies and the need to standardize methods.

This review was posted on: 2 June 2021