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Background Our understanding of the global scale of SARS-CoV-2 infection remains incomplete: routine surveillance data underestimates infection, cannot infer on population immunity, there is a predominance of asymptomatic infections, and uneven access to diagnostics. We meta-analyzed standardized SARS-CoV-2 seroprevalence studies after two years in the pandemic to estimate the extent of population infection and remaining susceptibility. Objectives/Methods 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 2020-01-01 and 2021-12-30. Eligible studies - those aligned with the WHO UNITY protocol - 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. Results We identified 431 full texts reporting 803 distinct seroprevalence studies (43% LMIC), including 398 low/moderate risk of bias studies with national/sub-national scope in further analysis. By July 2021, global SARS-CoV-2 seroprevalence was 45.2%, 95% CI [40.7-49.8%]. Seroprevalence rose steeply in the first half of 2021 due to infection in some regions (e.g., 29.9% to 70.1% in Africa) and vaccination and infection in others (e.g., 5.6% to 94.9% in the Americas high-income countries), but remained low in others (e.g., 2.5% in the Western Pacific). In 2021 Q2, median seroprevalence to cumulative incidence ratios were 2.9:1 in HICs and 45.3:1 in LMICs. Children 0-9 years and adults 60+ were at lower risk of seropositivity than adults 20-29. In a multivariate model using pre-vaccination data, stringent public health and social measures were associated with lower seroprevalence. Conclusions Global seroprevalence has risen considerably over time and with regional variation, however much of the global population remains susceptible to SARS-CoV-2 infection. Our estimates of infections based on seroprevalence far exceed reported COVID-19 cases. Quality and standardized seroprevalence studies are essential to inform COVID-19 response, particularly in resource-limited regions.

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