Seroprevalence of SARS-CoV-2 antibodies prior to the widespread introduction of vaccine programmes in the WHO European Region, January - December 2020: a systematic review

  1. A Vaughan
  2. EF Duffell
  3. GS Friedl
  4. DS Lemos
  5. T Funk
  6. A Nardone
  7. M Valenciano
  8. L Subissi
  9. I Bergeri
  10. E Broberg
  11. P Penttinen
  12. R Pebody
  13. M Keramarou

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Abstract

Background

Seroprevalence surveys are essential to assess the age-specific prevalence of pre-existing cross-reactive antibodies in the population with the emergence of a novel pathogen; to measure population cumulative seroincidence of infection, and to contribute to estimating infection severity. With the emergence of SARS-CoV-2, ECDC and WHO Regional Office for Europe have supported Member States in undertaking standardized population-based SARS-CoV-2 seroprevalence surveys across the WHO European Region.

Objectives

The objective of this study was to undertake a systematic literature review of SARS-CoV-2 population seroprevalence studies undertaken in the WHO European Region to measure pre-existing and cumulative seropositivity prior to the roll out of vaccination programmes.

Methods

We systematically searched MEDLINE, ELSEVIER and the pre-print servers medRxiv and bioRxiv within the “COVID-19 Global literature on coronavirus disease” database using a predefined search strategy. We included seroepidemiology studies published before the widespread implementation of COVID-19 vaccination programmes in January 2021 among the general population and blood donors, at national and regional levels. Study risk of bias was assessed using a quality scoring system based on sample size, sampling and testing methodologies. Articles were supplemented with unpublished WHO-supported Unity-aligned seroprevalence studies and other studies reported directly to WHO Regional Office for Europe and ECDC.

Results

In total, 111 studies from 26 countries published or conducted between 01/01/2020 and 31/12/2020 across the WHO European Region were included. A significant heterogeneity in implementation was noted across the studies, with a paucity of studies from the east of the Region. Eighty-one (73%) studies were assessed to be of low to medium risk of bias. Overall, SARS-CoV-2 seropositivity prior to widespread community circulation was very low. National seroprevalence estimates after circulation started ranged from 0% to 51.3% (median 2.2% (IQR 0.7-5.2%); n=124), while sub-national estimates ranged from 0% to 52% (median 5.8% (IQR 2.3-12%); n=101), with the highest estimates in areas following widespread local transmission.

Conclusions

The review found evidence of low national SARS-CoV-2 seroprevalence (<10%) across the WHO European Region in 2020. The low levels of SARS-CoV-2 antibody in most populations prior to the start of vaccine programmes highlights the critical importance of vaccinating priority groups at risk of severe disease while maintaining reduced levels of transmission to minimize population morbidity and mortality.

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  1. ScreenIT

    SciScore for 10.1101/2021.12.02.21266897: (What is this?)

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

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablenot detected.
    RandomizationThe criteria included: a) the sampling frame (to assess representativeness of the general population); b) stratification (age, sex or population); c) recruitment method (random, convenience), d): adequacy of sample size, e): serological methods and validation; f) and statistical analyses (adjustment of results to account for the sensitivity and specificity of the test).
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Search strategy: We searched MEDLINE, WHO COVID, ELSEVIER and the pre-print servers medRxiv and bioRxiv within the WHO “COVID-19 Global literature on coronavirus disease” database on 21/10/2020 and 12/01/2021.
    MEDLINE
    suggested: (MEDLINE, RRID:SCR_002185)
    ELSEVIER
    suggested: (Elsevier, RRID:SCR_013811)
    bioRxiv
    suggested: (bioRxiv, RRID:SCR_003933)
    Analyses were performed in Microsoft Excel (version 2016) and R version 4.0.4.
    Microsoft Excel
    suggested: (Microsoft Excel, RRID:SCR_016137)

    Results from OddPub: Thank you for sharing your data.

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    This review has some limitations. Firstly, there was significant heterogeneity among the studies, including sampling frame, population and stage of epidemic at time of serosurvey, which makes comparability across studies difficult. Due to such heterogeneity, we opted to not provide one pooled estimate nor conduct a meta-analysis as interpretation would be difficult and may not accurately reflect the picture in the WHO European Region. Secondly, while population-based serological surveys can provide a more accurate estimation of the overall rates of SARS-CoV-2 infection within a population, this approach does not consider antibody waning, which cannot be easily accounted for as antibody levels vary depending on disease severity (85) and longevity is expected to vary greatly across SARS-CoV-2 infected individuals (86). Finally, due to the rapid accumulation of data related to SARS-CoV-2 seroepidemiology and the advent of the ‘preprint era’, not all included studies have been published and may therefore be subject to change upon peer review.

    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.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

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

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  2. Version published to 10.1101/2021.12.02.21266897 on medRxiv