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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. 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. 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.

The global surge in the omicron (B.1.1.529) variant has resulted in many individuals with hybrid immunity (immunity developed through a combination of SARS-CoV-2 infection and vaccination). We aimed to systematically review the magnitude and duration of the protective effectiveness of previous SARS-CoV-2 infection and hybrid immunity against infection and severe disease caused by the omicron variant. For this systematic review and meta-regression, we searched for cohort, cross-sectional, and case–control studies in MEDLINE, Embase, Web of Science, ClinicalTrials.gov, the Cochrane Central Register of Controlled Trials, the WHO COVID-19 database, and Europe PubMed Central from Jan 1, 2020, to June 1, 2022, using keywords related to SARS-CoV-2, reinfection, protective effectiveness, previous infection, presence of antibodies, and hybrid immunity. The main outcomes were the protective effectiveness against reinfection and against hospital admission or severe disease of hybrid immunity, hybrid immunity relative to previous infection alone, hybrid immunity relative to previous vaccination alone, and hybrid immunity relative to hybrid immunity with fewer vaccine doses. Risk of bias was assessed with the Risk of Bias In Non-Randomized Studies of Interventions Tool. We used log-odds random-effects meta-regression to estimate the magnitude of protection at 1-month intervals. This study was registered with PROSPERO (CRD42022318605). 11 studies reporting the protective effectiveness of previous SARS-CoV-2 infection and 15 studies reporting the protective effectiveness of hybrid immunity were included. For previous infection, there were 97 estimates (27 with a moderate risk of bias and 70 with a serious risk of bias). The effectiveness of previous infection against hospital admission or severe disease was 74·6% (95% CI 63·1–83·5) at 12 months. The effectiveness of previous infection against reinfection waned to 24·7% (95% CI 16·4–35·5) at 12 months. For hybrid immunity, there were 153 estimates (78 with a moderate risk of bias and 75 with a serious risk of bias). The effectiveness of hybrid immunity against hospital admission or severe disease was 97·4% (95% CI 91·4–99·2) at 12 months with primary series vaccination and 95·3% (81·9–98·9) at 6 months with the first booster vaccination after the most recent infection or vaccination. Against reinfection, the effectiveness of hybrid immunity following primary series vaccination waned to 41·8% (95% CI 31·5–52·8) at 12 months, while the effectiveness of hybrid immunity following first booster vaccination waned to 46·5% (36·0–57·3) at 6 months. All estimates of protection waned within months against reinfection but remained high and sustained for hospital admission or severe disease. Individuals with hybrid immunity had the highest magnitude and durability of protection, and as a result might be able to extend the period before booster vaccinations are needed compared to individuals who have never been infected. WHO COVID-19 Solidarity Response Fund and the Coalition for Epidemic Preparedness Innovations.

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. 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. 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. 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.

Oropouche virus (OROV) is an emerging arbovirus primarily transmitted by biting midges and is increasingly recognized as a public health threat in Central and South America. With over 11,000 confirmed cases reported in 2024, a ten-fold increase from the previous year, its transmission dynamics and true burden remain poorly understood due to diagnostic challenges and fragmented surveillance systems. This systematic review and meta-analysis (SRMA) synthesizes OROV prevalence data in humans and summarizes the available data for vectors and animal hosts sampled between 2000 and 2024 to provide updated estimates and identify key surveillance gaps. We systematically searched Web of Science, PubMed, Embase, Medline, and LILACS for OROV seroprevalence and viral prevalence studies in human, insect, and animal populations, published up to September 12, 2024. The review protocol was registered with PROSPERO (CRD42024551000). Studies were extracted in duplicate, and data were meta-analyzed using generalized linear mixed-effects models. Risk of bias was appraised using a modified Joanna Briggs Institute checklist. We included 71 articles reporting serological or viral prevalence of OROV across nine countries. Between 2000-2024, pooled human seroprevalence among individuals with febrile illness or suspected of Oropouche infection was 12.6% [95% CI 5.3-26.9%] across four South American countries and seroprevalence of 1.1% [95% CI 0.5-2.3%] was observed in asymptomatic groups. Viral prevalence among individuals with febrile illness or suspected of Oropouche infection was 1.5% [0.8-3.0%] across seven South American countries and Haiti. Most studies used convenience sampling and RT-PCR or hemagglutination assays. In vector populations, positive OROV prevalence in Aedes aegypti and Culex quinquefasciatus was reported in two of 18 sources, while 10.0% and 7.5% animal host prevalence was reported in dogs and cattle, respectively. We found high risk of bias in 11.3% of studies in our critical appraisal, with most animal, human, and vector studies falling in the moderate risk of bias range. Despite rising numbers of OROV reported cases, prevalence estimates remain limited by sparse surveillance and variable methodology. This review highlights the urgent need for standardized serological assays, community-based studies, and expanded surveillance in animal and vector reservoirs. A One Health approach is essential to monitor OROV transmission and inform regional preparedness efforts.

During the COVID-19 pandemic, SeroTracker was developed as a dashboard and data platform for SARS-CoV-2 seroprevalence studies.7 Backed by a living systematic review to synthesise these studies, SeroTracker displayed summary data on an interactive online map. ArboTracker offers customisable data filtering options based on pathogen type, sampling frame (age, sex, and location), and laboratory diagnostics (assay type, producer, isotype target, and serotype for dengue estimates). MGW, HW, HR, SK, SS, AS, ET, NB, and RKA report funding for this project from the University of Calgary (Transdisciplinary Connector Grant), Canadian Institutes of Health Research, and the Public Health Agency of Canada (through Canada's COVID-19 Immunity Task Force, 2021-HQ-00056).

Background: Many serological assays to detect SARS-CoV-2 antibodies were developed during the COVID-19 pandemic. Differences in the detection mechanism of SARS-CoV-2 serological assays limited the comparability of seroprevalence estimates for populations being tested. Methods: We conducted a systematic review and meta-analysis of serological assays used in SARS-CoV-2 population seroprevalence surveys, searching for published articles, preprints, institutional sources, and grey literature between 1 January 2020, and 19 November 2021. We described features of all identified assays and mapped performance metrics by the manufacturers, third-party head-to-head, and independent group evaluations. We compared the reported assay performance by evaluation source with a mixed-effect beta regression model. A simulation was run to quantify how biased assay performance affects population seroprevalence estimates with test adjustment. Results: Among 1807 included serosurveys, 192 distinctive commercial assays and 380 self-developed assays were identified. According to manufacturers, 28.6% of all commercial assays met WHO criteria for emergency use (sensitivity [Sn.] >= 90.0%, specificity [Sp.] >= 97.0%). However, manufacturers overstated the absolute values of Sn. of commercial assays by 1.0% [0.1, 1.4%] and 3.3% [2.7, 3.4%], and Sp. by 0.9% [0.9, 0.9%] and 0.2% [−0.1, 0.4%] compared to third-party and independent evaluations, respectively. Reported performance data was not sufficient to support a similar analysis for self-developed assays. Simulations indicate that inaccurate Sn. and Sp. can bias seroprevalence estimates adjusted for assay performance; the error level changes with the background seroprevalence. Conclusions: The Sn. and Sp. of the serological assay are not fixed properties, but varying features depending on the testing population. To achieve precise population estimates and to ensure the comparability of seroprevalence, serosurveys should select assays with high performance validated not only by their manufacturers and adjust seroprevalence estimates based on assured performance data. More investigation should be directed to consolidating the performance of self-developed assays.

The WHO Unity Studies initiative engaged low‐ and middle‐income countries in the implementation of standardised SARS‐CoV‐2 sero‐epidemiological investigation protocols and timely sharing of comparable results for evidence‐based action. To gain a deeper understanding of the methodological challenges faced when conducting seroprevalence studies in the African region, we conducted unstructured interviews with key study teams in five countries. We discuss the challenges identified: participant recruitment and retention, sampling, sample and data management, data analysis and presentation. Potential solutions to aid future implementation include preparedness actions such as the development of new tools, robust planning and practice.

Background Oropouche virus (OROV) is an emerging arbovirus primarily transmitted by biting midges and is increasingly recognized as a public health threat in Central and South America. With over 11,000 confirmed cases reported in 2024, a ten-fold increase from the previous year, its transmission dynamics and true burden remain poorly understood due to diagnostic challenges and fragmented surveillance systems. Objective This systematic review and meta-analysis (SRMA) synthesizes OROV prevalence data in humans and summarizes the available data for vectors and animal hosts sampled between 2000 and 2024 to provide updated estimates and identify key surveillance gaps. Methods We systematically searched Web of Science, PubMed, Embase, Medline, and LILACS for OROV seroprevalence and viral prevalence studies in human, insect, and animal populations, published up to September 12, 2024. The review protocol was registered with PROSPERO (CRD42024551000). Studies were extracted in duplicate, and data were meta-analyzed using generalized linear mixed-effects models. Risk of bias was appraised using a modified Joanna Briggs Institute checklist. Results We included 71 articles reporting serological or viral prevalence of OROV across nine countries. Between 2000-2024, pooled human seroprevalence among individuals with febrile illness or suspected of Oropouche infection was 12.6% [95% CI 5.3-26.9%] across four South American countries and seroprevalence of 1.1% [95% CI 0.5-2.3%] was observed in asymptomatic groups. Viral prevalence among individuals with febrile illness or suspected of Oropouche infection was 1.5% [0.8-3.0%] across seven South American countries and Haiti. Most studies used convenience sampling and RT-PCR or hemagglutination assays. In vector populations, positive OROV prevalence in Aedes aegypti and Culex quinquefasciatus was reported in two of 18 sources, while 10.0% and 7.5% animal host prevalence was reported in dogs and cattle, respectively. We found high risk of bias in 11.3% of studies in our critical appraisal, with most animal, human, and vector studies falling in the moderate risk of bias range. Conclusions Despite rising numbers of OROV reported cases, prevalence estimates remain limited by sparse surveillance and variable methodology. This review highlights the urgent need for standardized serological assays, community-based studies, and expanded surveillance in animal and vector reservoirs. A One Health approach is essential to monitor OROV transmission and inform regional preparedness efforts.

Background Complete reporting of seroepidemiologic studies is critical to their utility in evidence synthesis and public health decision making. The Reporting of Seroepidemiologic studies—SARS‐CoV‐2 (ROSES‐S) guideline is a checklist that aims to improve reporting in SARS‐CoV‐2 seroepidemiologic studies. Adherence to the ROSES‐S guideline has not yet been evaluated. Objectives This study aims to evaluate the completeness of SARS‐CoV‐2 seroepidemiologic study reporting by the ROSES‐S guideline during the COVID‐19 pandemic, determine whether guideline publication was associated with reporting completeness, and identify study characteristics associated with reporting completeness. Methods A random sample from the SeroTracker living systematic review database was evaluated. For each reporting item in the guideline, the percentage of studies that were adherent was calculated, as well as median and interquartile range (IQR) adherence across all items and by item domain. Beta regression analyses were used to evaluate predictors of adherence to ROSES‐S. Results One hundred and ninety‐nine studies were analyzed. Median adherence was 48.1% (IQR 40.0%–55.2%) per study, with overall adherence ranging from 8.8% to 72.7%. The laboratory methods domain had the lowest median adherence (33.3% [IQR 25.0%–41.7%]). The discussion domain had the highest median adherence (75.0% [IQR 50.0%–100.0%]). Reporting adherence to ROSES‐S before and after guideline publication did not significantly change. Publication source (p < 0.001), study risk of bias (p = 0.001), and sampling method (p = 0.004) were significantly associated with adherence. Conclusions Completeness of reporting in SARS‐CoV‐2 seroepidemiologic studies was suboptimal. Publication of the ROSES‐S guideline was not associated with changes in reporting practices. Authors should improve adherence to the ROSES‐S guideline with support from stakeholders.