Background Many studies report the seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies. We aimed to synthesize seroprevalence data to better estimate the level and distribution of SARS-CoV-2 infection, identify high-risk groups, and inform public health decision making. Methods In this systematic review and meta-analysis, we searched publication databases, preprint servers, and grey literature sources for seroepidemiological study reports, from January 1, 2020 to December 31, 2020. We included studies that reported a sample size, study date, location, and seroprevalence estimate. We corrected estimates for imperfect test accuracy with Bayesian measurement error models, conducted meta-analysis to identify demographic differences in the prevalence of SARS-CoV-2 antibodies, and meta-regression to identify study-level factors associated with seroprevalence. We compared region-specific seroprevalence data to confirmed cumulative incidence. PROSPERO: CRD42020183634. Results We identified 968 seroprevalence studies including 9.3 million participants in 74 countries. There were 472 studies (49%) at low or moderate risk of bias. Seroprevalence was low in the general population (median 4.5%, IQR 2.4–8.4%); however, it varied widely in specific populations from low (0.6% perinatal) to high (59% persons in assisted living and long-term care facilities). Median seroprevalence also varied by Global Burden of Disease region, from 0.6% in Southeast Asia, East Asia and Oceania to 19.5% in Sub-Saharan Africa (p<0.001). National studies had lower seroprevalence estimates than regional and local studies (p<0.001). Compared to Caucasian persons, Black persons (prevalence ratio [RR] 3.37, 95% CI 2.64–4.29), Asian persons (RR 2.47, 95% CI 1.96–3.11), Indigenous persons (RR 5.47, 95% CI 1.01–32.6), and multi-racial persons (RR 1.89, 95% CI 1.60–2.24) were more likely to be seropositive. Seroprevalence was higher among people ages 18–64 compared to 65 and over (RR 1.27, 95% CI 1.11–1.45). Health care workers in contact with infected persons had a 2.10 times (95% CI 1.28–3.44) higher risk compared to health care workers without known contact. There was no difference in seroprevalence between sex groups. Seroprevalence estimates from national studies were a median 18.1 times (IQR 5.9–38.7) higher than the corresponding SARS-CoV-2 cumulative incidence, but there was large variation between Global Burden of Disease regions from 6.7 in South Asia to 602.5 in Sub-Saharan Africa. Notable methodological limitations of serosurveys included absent reporting of test information, no statistical correction for demographics or test sensitivity and specificity, use of non-probability sampling and use of non-representative sample frames. Discussion Most of the population remains susceptible to SARS-CoV-2 infection. Public health measures must be improved to protect disproportionately affected groups, including racial and ethnic minorities, until vaccine-derived herd immunity is achieved. Improvements in serosurvey design and reporting are needed for ongoing monitoring of infection prevalence and the pandemic response.
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.
Background. As the world grapples with the COVID-19 pandemic, there is increasing global interest in the role of serological testing for population monitoring and to inform public policy. However, limitations in serological study designs and test standards raise concerns about the validity of seroprevalence estimates and their utility in decision-making. There is now a critical window of opportunity to learn from early SARS-CoV-2 serology studies. We aimed to synthesize the results of SARS-CoV-2 serosurveillance projects from around the world and provide recommendations to improve the coordination, strategy, and methodology of future serosurveillance efforts.Methods. This was a rapid systematic review of cross-sectional and cohort studies reporting seroprevalence outcomes for SARS-CoV 2. We included completed, ongoing, and proposed serosurveys. The search included electronic databases (PubMed, MedRXIV, BioRXIV, and WHO ICTPR); five medical journals (NEJM, BMJ, JAMA, The Lancet, Annals of Internal Medicine); reports by governments, NGOs, and health systems; and media reports (Google News) from December 1, 2019 to May 1, 2020. We extracted data on study characteristics and critically appraised prevalence estimates using Joanna Briggs Institute criteria.Results. Seventy records met inclusion criteria, describing 73 studies. Of these, 23 reported prevalence estimates: eight preprints, 14 news articles, and one government report. These studies had a total sample size of 35,784 and reported 42 prevalence estimates. Seroprevalence estimates ranged from 0.4% to 59.3%. No estimates were found to have a low risk of bias (43% high risk, 21% moderate risk, 36% unclear). Fifty records reported characteristics of ongoing or proposed serosurveys. Overall, twenty countries have completed, ongoing, or proposed serosurveys. Discussion.Study design, quality, and prevalence estimates of early SARS-CoV2 serosurveys are heterogeneous, suggesting that the urgency to examine seroprevalence may have compromised methodological rigour. Based on the limitations of included studies, future serosurvey investigators and stakeholders should ensure that: i) serological tests used undergo high-quality independent evaluations that include cross-reactivity; ii) all reports of serosurvey results, including media, describe the test used, sample size, and sampling method; and iii) initiatives are coordinated to prevent test fatigue, minimize redundant efforts, and encourage better study methodology.
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.
Perceptual training is generally assumed to improve perception by modifying the encoding or decoding of sensory information. However, this assumption is incompatible with recent demonstrations that transfer of learning can be enhanced by across-trial variation of training stimuli or task. Here we present three lines of evidence from healthy adults in support of the idea that the enhanced transfer of auditory discrimination learning is mediated by working memory (WM). First, the ability to discriminate small differences in tone frequency or duration was correlated with WM measured with a tone n-back task. Second, training frequency discrimination around a variable frequency transferred to and from WM learning, but training around a fixed frequency did not. The transfer of learning in both directions was correlated with a reduction of the influence of stimulus variation in the discrimination task, linking WM and its improvement to across-trial stimulus interaction in auditory discrimination. Third, while WM training transferred broadly to other WM and auditory discrimination tasks, variable-frequency training on duration discrimination did not improve WM, indicating that stimulus variation challenges and trains WM only if the task demands stimulus updating in the varied dimension. The results provide empirical evidence as well as a theoretic framework for interactions between cognitive and sensory plasticity during perceptual experience.
Population-level immune surveillance, which includes monitoring exposure and assessing vaccine-induced immunity, is a crucial component of public health decision-making during a pandemic. Serosurveys estimating the prevalence of SARS-CoV-2 antibodies in the population played a key role in characterizing SARS-CoV-2 epidemiology during the early phases of the pandemic. Existing serosurveys provide infrastructure to continue immune surveillance, but must be adapted to remain relevant in the SARS-CoV-2 vaccine era. Here, we delineate how SARS-CoV-2 serosurveys should be designed to distinguish infection- and vaccine-induced humoral immune responses to efficiently monitor the evolution of the pandemic. We discuss how serosurvey results can inform vaccine distribution to improve allocation efficiency in countries with scarce vaccine supplies and help assess the need for booster doses in countries with substantial vaccine coverage.
BackgroundStudies reporting estimates of the seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies have rapidly emerged. We aimed to synthesize seroprevalence data to better estimate the burden of SARS-CoV-2 infection, identify high-risk groups, and inform public health decision making.MethodsIn this systematic review and meta-analysis, we searched publication databases, preprint servers, and grey literature sources for seroepidemiological study reports, from January 1, 2020 to August 28, 2020. We included studies that reported a sample size, study date, location, and seroprevalence estimate. Estimates were corrected for imperfect test accuracy with Bayesian measurement error models. We conducted meta-analysis to identify demographic differences in the prevalence of SARS-CoV-2 antibodies, and meta-regression to identify study-level factors associated with seroprevalence. We compared region-specific seroprevalence data to confirmed cumulative incidence. PROSPERO: CRD42020183634.FindingsWe identified 338 seroprevalence studies including 2.3 million participants in 50 countries. Seroprevalence was low in the general population (median 3.2%, IQR 1.0-6.4%) and slightly higher in at-risk populations (median 5.4%, IQR 1.5-18.4%). Median seroprevalence varied by WHO Global Burden of Disease region (p < 0.01), from 1.0% in Southeast Asia, East Asia and Oceania to 18.8% in South Asia. National studies had lower seroprevalence estimates than local (p = 0.02) studies. Compared to White persons, Black persons (prevalence ratio [RR] 2.34, 95% CI 1.60-3.43) and Asian persons (RR 1.56, 95% CI 1.22-2.01) were more likely to be seropositive. Seroprevalence was higher among people ages 18-64 compared to 65 and over (RR 1.26, 95% CI 1.04-1.52). Health care workers had a 1.74x (95% CI: 1.18-2.58) higher risk compared to the general population. There was no difference in seroprevalence between sexes. There were 123 studies (36%) at low or moderate risk of bias. Seroprevalence estimates from national studies were median 11.9 (IQR 8.0 - 16.6) times higher than the corresponding SARS-CoV-2 cumulative incidence.InterpretationMost of the population remains susceptible to SARS-CoV-2 infection. Public health measures must be improved to protect disproportionately affected groups, including non-White people and adults. Measures taken in SE Asia, E Asia and Oceania, and Latin America and Caribbean may have been more effective in controlling virus transmission than measures taken in other regions.FundingPublic Health Agency of Canada through the COVID-19 Immunity Task Force.
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