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Background Our understanding of the global scale of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection remains incomplete: Routine surveillance data underestimate infection and cannot infer on population immunity; there is a predominance of asymptomatic infections, and uneven access to diagnostics. We meta-analyzed SARS-CoV-2 seroprevalence studies, standardized to those described in the World Health Organization’s Unity protocol (WHO Unity) for general population seroepidemiological studies, to estimate the extent of population infection and seropositivity to the virus 2 years into the pandemic. Methods and findings We conducted a systematic review and meta-analysis, searching MEDLINE, Embase, Web of Science, preprints, and grey literature for SARS-CoV-2 seroprevalence published between January 1, 2020 and May 20, 2022. The review protocol is registered with PROSPERO (CRD42020183634). We included general population cross-sectional and cohort studies meeting an assay quality threshold (90% sensitivity, 97% specificity; exceptions for humanitarian settings). We excluded studies with an unclear or closed population sample frame. Eligible studies—those aligned with the WHO Unity protocol—were extracted and critically appraised in duplicate, with risk of bias evaluated using a modified Joanna Briggs Institute checklist. We meta-analyzed seroprevalence by country and month, pooling to estimate regional and global seroprevalence over time; compared seroprevalence from infection to confirmed cases to estimate underascertainment; meta-analyzed differences in seroprevalence between demographic subgroups such as age and sex; and identified national factors associated with seroprevalence using meta-regression. We identified 513 full texts reporting 965 distinct seroprevalence studies (41% low- and middle-income countries [LMICs]) sampling 5,346,069 participants between January 2020 and April 2022, including 459 low/moderate risk of bias studies with national/subnational scope in further analysis. By September 2021, global SARS-CoV-2 seroprevalence from infection or vaccination was 59.2%, 95% CI [56.1% to 62.2%]. Overall seroprevalence rose steeply in 2021 due to infection in some regions (e.g., 26.6% [24.6 to 28.8] to 86.7% [84.6% to 88.5%] in Africa in December 2021) and vaccination and infection in others (e.g., 9.6% [8.3% to 11.0%] in June 2020 to 95.9% [92.6% to 97.8%] in December 2021, in European high-income countries [HICs]). After the emergence of Omicron in March 2022, infection-induced seroprevalence rose to 47.9% [41.0% to 54.9%] in Europe HIC and 33.7% [31.6% to 36.0%] in Americas HIC. In 2021 Quarter Three (July to September), median seroprevalence to cumulative incidence ratios ranged from around 2:1 in the Americas and Europe HICs to over 100:1 in Africa (LMICs). Children 0 to 9 years and adults 60+ were at lower risk of seropositivity than adults 20 to 29 (p < 0.001 and p = 0.005, respectively). In a multivariable model using prevaccination data, stringent public health and social measures were associated with lower seroprevalence (p = 0.02). The main limitations of our methodology include that some estimates were driven by certain countries or populations being overrepresented. Conclusions In this study, we observed that global seroprevalence has risen considerably over time and with regional variation; however, over one-third of the global population are seronegative to the SARS-CoV-2 virus. Our estimates of infections based on seroprevalence far exceed reported Coronavirus Disease 2019 (COVID-19) cases. Quality and standardized seroprevalence studies are essential to inform COVID-19 response, particularly in resource-limited regions.

IntroductionEstimating COVID-19 cumulative incidence in Africa remains problematic due to challenges in contact tracing, routine surveillance systems and laboratory testing capacities and strategies. We undertook a meta-analysis of population-based seroprevalence studies to estimate SARS-CoV-2 seroprevalence in Africa to inform evidence-based decision making on public health and social measures (PHSM) and vaccine strategy.MethodsWe searched for seroprevalence studies conducted in Africa published 1 January 2020–30 December 2021 in Medline, Embase, Web of Science and Europe PMC (preprints), grey literature, media releases and early results from WHO Unity studies. All studies were screened, extracted, assessed for risk of bias and evaluated for alignment with the WHO Unity seroprevalence protocol. We conducted descriptive analyses of seroprevalence and meta-analysed seroprevalence differences by demographic groups, place and time. We estimated the extent of undetected infections by comparing seroprevalence and cumulative incidence of confirmed cases reported to WHO.PROSPERO: CRD42020183634.ResultsWe identified 56 full texts or early results, reporting 153 distinct seroprevalence studies in Africa. Of these, 97 (63%) were low/moderate risk of bias studies. SARS-CoV-2 seroprevalence rose from 3.0% (95% CI 1.0% to 9.2%) in April–June 2020 to 65.1% (95% CI 56.3% to 73.0%) in July–September 2021. The ratios of seroprevalence from infection to cumulative incidence of confirmed cases was large (overall: 100:1, ranging from 18:1 to 954:1) and steady over time. Seroprevalence was highly heterogeneous both within countries—urban versus rural (lower seroprevalence for rural geographic areas), children versus adults (children aged 0–9 years had the lowest seroprevalence)—and between countries and African subregions.ConclusionWe report high seroprevalence in Africa suggesting greater population exposure to SARS-CoV-2 and potential protection against COVID-19 severe disease than indicated by surveillance data. As seroprevalence was heterogeneous, targeted PHSM and vaccination strategies need to be tailored to local epidemiological situations.

BackgroundCOVID-19 case data underestimates infection and immunity, especially in low- and middle-income countries (LMICs). We meta-analyzed standardized SARS-CoV-2 seroprevalence studies to estimate global seroprevalence.Objectives/MethodsWe conducted a systematic review and meta-analysis, searching MEDLINE, Embase, Web of Science, preprints, and grey literature for SARS-CoV-2 seroprevalence studies aligned with the WHO UNITY protocol published between 2020-01-01 and 2021-10-29. Eligible studies were extracted and critically appraised in duplicate. We meta-analyzed seroprevalence by country and month, pooling to estimate regional and global seroprevalence over time; compared seroprevalence from infection to confirmed cases to estimate under-ascertainment; meta-analyzed differences in seroprevalence between demographic subgroups; and identified national factors associated with seroprevalence using meta-regression. PROSPERO: CRD42020183634.ResultsWe identified 396 full texts reporting 736 distinct seroprevalence studies (41% LMIC), including 355 low/moderate risk of bias studies with national/sub-national scope in further analysis. By April 2021, global SARS-CoV-2 seroprevalence was 26.1%, 95% CI [24.6-27.6%]. Seroprevalence rose steeply in the first half of 2021 due to infection in some regions (e.g., 18.2% to 45.9% in Africa) and vaccination and infection in others (e.g., 11.3% to 57.4% in the Americas high-income countries), but remained low in others (e.g., 0.3% to 1.6% in the Western Pacific). In 2021 Q1, median seroprevalence to case ratios were 1.9:1 in HICs and 61.9:1 in LMICs. Children 0-9 years and adults 60+ were at lower risk of seropositivity than adults 20-29. In a multivariate model using data pre-vaccination, more stringent public health and social measures were associated with lower seroprevalence.ConclusionsGlobal seroprevalence has risen considerably over time and with regional variation, however much of the global population remains susceptible to SARS-CoV-2 infection. True infections far exceed reported COVID-19 cases. Standardized seroprevalence studies are essential to inform COVID-19 control measures, particularly in resource-limited regions.

IntroductionEstimating COVID-19 cumulative incidence in Africa remains problematic due to challenges in contact tracing, routine surveillance systems and laboratory testing capacities and strategies. We undertook a meta-analysis of population-based seroprevalence studies to estimate SARS-CoV-2 seroprevalence in Africa to inform evidence-based decision making on Public Health and Social Measures (PHSM) and vaccine strategy.MethodsWe searched for seroprevalence studies conducted in Africa published 01-01-2020 to 30-12-2021 in Medline, Embase, Web of Science, and Europe PMC (preprints), grey literature, media releases and early results from WHO Unity studies. All studies were screened, extracted, assessed for risk of bias and evaluated for alignment with the WHO Unity protocol for seroepidemiological investigations. We conducted descriptive analyses of seroprevalence and meta-analysed seroprevalence differences by demographic groups, place and time. We estimated the extent of undetected infections by comparing seroprevalence and cumulative incidence of confirmed cases reported to WHO. PROSPERO: CRD42020183634.ResultsWe identified 54 full texts or early results, reporting 151 distinct seroprevalence studies in Africa Of these, 95 (63%) were low/moderate risk of bias studies. SARS-CoV-2 seroprevalence rose from 3.0% [95% CI: 1.0-9.2%] in Q2 2020 to 65.1% [95% CI: 56.3-73.0%] in Q3 2021. The ratios of seroprevalence from infection to cumulative incidence of confirmed cases was large (overall: 97:1, ranging from 10:1 to 958:1) and steady over time. Seroprevalence was highly heterogeneous both within countries - urban vs. rural (lower seroprevalence for rural geographic areas), children vs. adults (children aged 0-9 years had the lowest seroprevalence) - and between countries and African sub-regions (Middle, Western and Eastern Africa associated with higher seroprevalence).ConclusionWe report high seroprevalence in Africa suggesting greater population exposure to SARS-CoV-2 and protection against COVID-19 disease than indicated by surveillance data. As seroprevalence was heterogeneous, targeted PHSM and vaccination strategies need to be tailored to local epidemiological situations.