SARS-CoV-2 seroprevalence in Germany - a population based sequential study in five regions

  1. Daniela Gornyk
  2. Manuela Harries
  3. Stephan Glöckner
  4. Monika Strengert
  5. Tobias Kerrinnes
  6. Gerhard Bojara
  7. Stefanie Castell
  8. Kerstin Frank
  9. Knut Gubbe
  10. Jana-Kristin Heise
  11. Pilar Hernandez
  12. Oliver Kappert
  13. Winfried Kern
  14. Thomas Illig
  15. Norman Klopp
  16. Henrike Maaß
  17. Julia Ortmann
  18. Barbora Kessel
  19. Gottfried Roller
  20. Monike Schlüter
  21. Torsten Tonn
  22. Michael Ziemons
  23. Yvonne Kemmling
  24. Berit Lange
  25. Gérard Krause

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Abstract

Prevalence of SARS-CoV-2 antibodies is an essential indicator to guide measures. Few population-based estimates are available in Germany. We determine seroprevalence allowing comparison between regions, time points, socio-demographic and health-related factors.

MuSPAD is a sequential multi-local seroprevalence study. We randomly recruited adults in five counties with differing cumulative SARS-CoV-2 incidence July 2020 - February 2021. Serostatus was determined using Spike S1-specific IgG ELISA. We determined county-wise proportions of seropositivity. We assessed underestimation of infections, county and age specific infection fatality risks, and association of seropositivity with demographic, socioeconomic and health factors.

We found seroprevalence of 2.4 % (95%CI: 1.8-3.1%) for Reutlingen in June 2020 (stage 1) which increased to 2.9% (95%CI: 2.1-3.8%) in October (stage 2), Freiburg stage 1 1.5% (95% CI: 1.1-2.1%) vs. 2.5% (95%CI: 1.8-3.4%), Aachen stage 1 2.3% (95% CI: 1.7-3.1%) vs. 5.4% (95%CI: 4.4-6.6%), Osnabrück 1.3% (95% CI: 1.0-1.9%) and Magdeburg in Nov/Dec 2020. 2.4% (95%CI 1.9-3.1%). Number needed to quarantine to have one infected person quarantined was 8.2. The surveillance detection ratio (SDR) between number of infections based on our results and number reported to health authorities ranged from 2.5-4.5. Participants aged 80+ had lower SDR. Infection fatality estimates ranged from 0.2-2.4%. Lower education was associated with higher, smoking with lower seropositivity.

Seroprevalence remained low until December 2020 with high underdetection. The second wave from November 2020 to February 2021 resulted in additional 2-5% of the population being infected. Detected age specific differences of SDR should be taken into account in modelling and forecasting COVID-19 morbidity.

Highlights

Evidence before this study

Seroepidemiological surveys on SARS-CoV-2 are a useful tool to track the transmission during the epidemic. We searched PubMed/the pre-print server medRxiv and included web-based reports from German health organizations using the keywords “seroprevalence”, “SARS-CoV-2”, “Germany” and similar other English and German terms in the period from January 1st, 2020 until March 2021. We identified 30 published studies in Germany which mostly report low SARS-CoV-2 seroprevalence (<5%). Most of these surveys were so-called hotspot studies which assessed seroprevalence after localized outbreaks or examined seroprevalence of specific population groups such as e.g. medical staff. Few studies are either population-based or blood donor-based, but do not allow comparisons between regions. To date, we only consider the Corona sub-study of the Rhineland study similar to MuSPAD. It reports a low SARS-CoV-2 seroprevalence (46/4755; 0.97%; 95% CI: 0.72−1.30). Based on this, almost the entire German population remained susceptible to a SARS-CoV-2 infection by the end of 2020.

Added value of this study

We provide the first comprehensive, high-precision multi-region population-based SARS-CoV-2 seroprevalence study with representative sampling following the WHO protocol in Germany. By measuring SARS-CoV-2 IgG, we explore immunity at regional and national level over time. We also assess risk factors and sample each region twice, which permits to monitor seroprevalence progression throughout the epidemic in different exemplary German regions.

Implications of all the available evidence

Our results show low seroprevalence (<3%) until Mid-December 2020 in all regions. While estimates in Reutlingen, Aachen, Freiburg and Osnabrück reflect low seroprevalence mostly after the first wave, the survey in Magdeburg cumulatively already represents the beginning of the second wave. The number needed to quarantine to ensure one infected person was quarantined was 8.2 in our study. We also show that for the first wave reported infections reflected overall around 25% of those actually infected rising to 40-50% in the second wave. A slightly raised infection risk could be shown for persons with lower education.

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  1. Version published to 10.1101/2021.05.04.21256597v2 on medRxiv
  2. ScreenIT

    SciScore for 10.1101/2021.05.04.21256597: (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
    Analyses were done using STATA (Version 14 and 16) and R Version 4.0.2.
    STATA
    suggested: (Stata, RRID:SCR_012763)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Limitations include the serial design in that it does not measure seroprevalence in all places at the same time. This means that compared to the measurements from July 2020 (three months after the peak of the epidemic) more antibody waning has taken place in those regions sampled later and up to major infection dynamics of the second wave in October/ November 2020. An additional limitation is since we did not include individuals younger than 18 years of age, our results can only be generalised for the adult population. All study materials were only provided in German and sufficient knowledge of the language was required to give written informed consent. Hence, this study cannot detect possible differences in the subgroup of the German population that does not fulfil these requirements. Still, we believe that five main conclusions can be drawn from the estimates presented: First, our estimates of both seroprevalence and our infection fatality estimates are in line with those few other available population-based reports and reports based on blood donor samples from Germany. These existing seroprevalence studies indicate low seroprevalences between 0.4 to 1.4% with an underreporting ratio of 2 to 8 and infection fatality estimates of 0.5 to 1.5% in studies up to November 202010,20,21. Pooling all current population-based estimates for Germany yields a pooled seroprevalence of 1.3% (0.9 -1.7%) with high heterogeneity (I2: 92%)22. Underreporting estimates over time from both exist...

    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.

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  3. Version published to 10.1101/2021.05.04.21256597v1 on medRxiv