Global SARS-CoV-2 seroprevalence from January 2020 to April 2022: A systematic review and meta-analysis of standardized population-based studies

  1. Isabel Bergeri
  2. Mairead G. Whelan
  3. Harriet Ware
  4. Lorenzo Subissi
  5. Anthony Nardone
  6. Hannah C. Lewis
  7. Zihan Li
  8. Xiaomeng Ma
  9. Marta Valenciano
  10. Brianna Cheng
  11. Lubna Al Ariqi
  12. Arash Rashidian
  13. Joseph Okeibunor
  14. Tasnim Azim
  15. Pushpa Wijesinghe
  16. Linh-Vi Le
  17. Aisling Vaughan
  18. Richard Pebody
  19. Andrea Vicari
  20. Tingting Yan
  21. Mercedes Yanes-Lane
  22. Christian Cao
  23. David A. Clifton
  24. Matthew P. Cheng
  25. Jesse Papenburg
  26. David Buckeridge
  27. Niklas Bobrovitz
  28. Rahul K. Arora
  29. Maria D. Van Kerkhove
  30. Unity Studies Collaborator Group

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Abstract

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.

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  1. Version published to 10.1371/journal.pmed.1004107
  2. ScreenIT

    SciScore for 10.1101/2021.12.14.21267791: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    NIH rigor criteria are not applicable to paper type.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    We designed a search strategy in MEDLINE, Embase, Web of Science, and Europe PMC using key terms such as SARS-COV-2, COVID-19, seroprevalence, and serology; We included published research articles, preprints, institutional reports, grey literature, and media reports (full strategy in Supplementary file S.3.1).
    MEDLINE
    suggested: (MEDLINE, RRID:SCR_002185)
    Embase
    suggested: (EMBASE, RRID:SCR_001650)
    Standardized results uploaded to Zenodo by UNITY study collaborators additionally included information on the proportion of asymptomatic seropositive individuals.
    Zenodo
    suggested: (ZENODO, RRID:SCR_004129)

    Results from OddPub: Thank you for sharing your code and data.

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    A few limitations were encountered during the course of this study.. First, although we conducted meta-regression to explore heterogeneity of the included studies, there remained some residual heterogeneity that could not be explained quantitatively — likely driven by differences in disease transmission in the different countries and time points that serosurveys were conducted. Second, we did not account for waning of population immunity, so the present study likely underestimates the extent of past infection and case ascertainment. Thirdly, seroprevalence studies are cumulative, meaning that results reflect all COVID-19 countermeasures implemented up to the time of participant sampling and, thus, we cannot isolate the contributions of particular PHSM. Fourthly, while we screened study eligibility based on high assay performance criteria, different serological assays may yield varying results which should be taken into account when interpreting seroprevalence data. Finally, at certain points in time, our meta-analysis estimates were driven by studies from specific countries — either very populous countries (i.e. SEAR: India, AMR HIC: USA, AMR LMIC: Brazil, WPR: China), or countries in regions with scarce data during the time in question (e.g. EMR: 2 countries in early 2021). We also could not produce global estimates for mid to late 2021 due to the delays between when seroprevalence studies sampled participants and released results. Our global estimates of infections based on...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • No funding statement was detected.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

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  3. Version published to 10.1101/2021.12.14.21267791 on medRxiv