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

Abstract

Background: A rapidly increasing number of serological surveys for antibodies to SARS-CoV-2 have been reported worldwide. We aimed to synthesise, combine, and assess this large corpus of data.

Methods: In this systematic review and meta-analysis, we searched PubMed, Embase, Web of Science, and five preprint servers for articles published in English between Dec 1, 2019, and Dec 22, 2020. Studies evaluating SARS-CoV-2 seroprevalence in humans after the first identified case in the area were included. Studies that only reported serological responses among patients with COVID-19, those using known infection status samples, or any animal experiments were all excluded. All data used for analysis were extracted from included papers. Study quality was assessed using a standardised scale. We estimated age-specific, sex-specific, and race-specific seroprevalence by WHO regions and subpopulations with different levels of exposures, and the ratio of serology-identified infections to virologically confirmed cases. This study is registered with PROSPERO, CRD42020198253.

Findings: 16 506 studies were identified in the initial search, 2523 were assessed for eligibility after removal of duplicates and inappropriate titles and abstracts, and 404 serological studies (representing tests in 5 168 360 individuals) were included in the meta-analysis. In the 82 studies of higher quality, close contacts (18·0%, 95% CI 15·7-20·3) and high-risk health-care workers (17·1%, 9·9-24·4) had higher seroprevalence than did low-risk health-care workers (4·2%, 1·5-6·9) and the general population (8·0%, 6·8-9·2). The heterogeneity between included studies was high, with an overall I² of 99·9% (p<0·0001). Seroprevalence varied greatly across WHO regions, with the lowest seroprevalence of general populations in the Western Pacific region (1·7%, 95% CI 0·0-5·0). The pooled infection-to-case ratio was similar between the region of the Americas (6·9, 95% CI 2·7-17·3) and the European region (8·4, 6·5-10·7), but higher in India (56·5, 28·5-112·0), the only country in the South-East Asia region with data.

Interpretation: Antibody-mediated herd immunity is far from being reached in most settings. Estimates of the ratio of serologically detected infections per virologically confirmed cases across WHO regions can help provide insights into the true proportion of the population infected from routine confirmation data.

Funding: National Science Fund for Distinguished Young Scholars, Key Emergency Project of Shanghai Science and Technology Committee, Program of Shanghai Academic/Technology Research Leader, National Science and Technology Major project of China, the US National Institutes of Health.

Translation: For the Chinese translation of the abstract see Supplementary Materials section.

Figure 1

Study selection Flowchart of the selection of serological studies of SARS-CoV-2 infection from Dec 1, 2019, to Dec 22, 2020.

Figure 2

Geographical distribution of SARS-CoV-2 serosurveys by study populations from Dec 1, 2019, to Dec 22, 2020 The colours on the maps indicate the cumulative incidence of reported cases, with darker colours representing higher values. Cumulative incidence data are reproduced from the WHO COVID-19 Dashboard.

Figure 3

Estimated seroprevalence by WHO regions and study populations The bar represents the pooled estimates and the error bars represent the 95% CI. Each dot represents the result of one single study. ND=no data.

Figure 4

Estimated seroprevalence by age groups, sex, and race

Figure 5

Estimated ratio of serologically detected infections to confirmed cases of COVID-19 The size of boxes represents the weight for each study. The whisker represents the 95% CI. Values higher than 1 suggest greater under-reporting of infections (due to both mild or asymptomatic infections, care-seeking behaviours, and testing practices).