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. 2023 Jul 13;23(1):466.
doi: 10.1186/s12879-023-08435-1.

The representative COVID-19 cohort Munich (KoCo19): from the beginning of the pandemic to the Delta virus variant

Ronan Le Gleut #  1   2 , Michael Plank #  3 , Peter Pütz  4 , Katja Radon  5   6   7 , Abhishek Bakuli  3 , Raquel Rubio-Acero  3 , Ivana Paunovic  3 , Friedrich Rieß  3 , Simon Winter  3 , Christina Reinkemeyer  3 , Yannik Schälte  1   8   9 , Laura Olbrich  3 , Marlene Hannes  3 , Inge Kroidl  3 , Ivan Noreña  3 , Christian Janke  3 , Andreas Wieser #  3   10   11   12 , Michael Hoelscher #  3   6   10   11 , Christiane Fuchs #  1   2   8   13 , Noemi Castelletti #  14   15   16 ; KoCo19/ORCHESTRA-study group
Collaborators, Affiliations

The representative COVID-19 cohort Munich (KoCo19): from the beginning of the pandemic to the Delta virus variant

Ronan Le Gleut et al. BMC Infect Dis. .

Abstract

Background: Population-based serological studies allow to estimate prevalence of SARS-CoV-2 infections despite a substantial number of mild or asymptomatic disease courses. This became even more relevant for decision making after vaccination started. The KoCo19 cohort tracks the pandemic progress in the Munich general population for over two years, setting it apart in Europe.

Methods: Recruitment occurred during the initial pandemic wave, including 5313 participants above 13 years from private households in Munich. Four follow-ups were held at crucial times of the pandemic, with response rates of at least 70%. Participants filled questionnaires on socio-demographics and potential risk factors of infection. From Follow-up 2, information on SARS-CoV-2 vaccination was added. SARS-CoV-2 antibody status was measured using the Roche Elecsys® Anti-SARS-CoV-2 anti-N assay (indicating previous infection) and the Roche Elecsys® Anti-SARS-CoV-2 anti-S assay (indicating previous infection and/or vaccination). This allowed us to distinguish between sources of acquired antibodies.

Results: The SARS-CoV-2 estimated cumulative sero-prevalence increased from 1.6% (1.1-2.1%) in May 2020 to 14.5% (12.7-16.2%) in November 2021. Underreporting with respect to official numbers fluctuated with testing policies and capacities, becoming a factor of more than two during the second half of 2021. Simultaneously, the vaccination campaign against the SARS-CoV-2 virus increased the percentage of the Munich population having antibodies, with 86.8% (85.5-87.9%) having developed anti-S and/or anti-N in November 2021. Incidence rates for infections after (BTI) and without previous vaccination (INS) differed (ratio INS/BTI of 2.1, 0.7-3.6). However, the prevalence of infections was higher in the non-vaccinated population than in the vaccinated one. Considering the whole follow-up time, being born outside Germany, working in a high-risk job and living area per inhabitant were identified as risk factors for infection, while other socio-demographic and health-related variables were not. Although we obtained significant within-household clustering of SARS-CoV-2 cases, no further geospatial clustering was found.

Conclusions: Vaccination increased the coverage of the Munich population presenting SARS-CoV-2 antibodies, but breakthrough infections contribute to community spread. As underreporting stays relevant over time, infections can go undetected, so non-pharmaceutical measures are crucial, particularly for highly contagious strains like Omicron.

Keywords: Breakthrough infections; COVID-19; ORCHESTRA; Population-based cohort study; SARS-CoV-2; Sero-incidence; Sero-prevalence; Vaccination status.

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Conflict of interest statement

In addition to the funding disclosed in the funding section, L.O. received non-financial support from Dr. Box Betrobox and grants from the Bavarian State Ministry of Science and the Arts during the conduct of the study. AW and MH report personal fees and non-financial support from Roche Diagnostics, LO reports non-financial support from Roche Diagnostics. AW, MH and LO report non-financial support from Euroimmun, non-financial support from Viramed, non-financial support from Mikrogen. AW, MH, LO report grants, non-financial support and other from German Centre for Infection Research DZIF, grants and non-financial support from Government of Bavaria, non-financial support from BMW, non-financial support from Munich Police, nonfinancial support and other from Accenture. MH and AW report personal fees and nonfinancial support from Dr. Box-Betrobox, non-financial support from Dr. Becker MVZ during the conduct of the study. AW is involved in other different patents and companies not in relation with the serology of SARS-CoV-2. AW reports personal fees and other from Haeraeus Sensors, nonfinancial support from Bruker Daltonics, all of which are outside the submitted work, and non-related to SARS-CoV-2. The funders had no role in study design, data collection, data analyses, data interpretation, writing, or submission of this manuscript. All other authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Epidemic evolution in Munich with description of the sample analysis. A Black: number of new daily SARS-CoV-2 cases officially reported by the Robert Koch Institute (RKI). Blue: number of blood/DBS samples of the KoCo19 collected daily. B Description of the lab analysis. With anti-N, anti-S and the response to the questionnaire item on vaccination it was possible to define the participants as: infected and vaccinated, infected and non-vaccinated, non-infected and vaccinated and non-infected and non-vaccinated. Blue shaded regions denote a negative response while orange regions a positive one
Fig. 2
Fig. 2
Cohort description based on the ever-positive principle, i.e. anti-N sero-positivity remains for all rounds after sero-conversion, independently of other blood results or if missing. A Change of serological status of participants: only infected (anti-N ever positive and stated to be non-vaccinated in the questionnaire), naïve (anti-N and anti-S always negative), vaccinated (only anti-S ever positive), infected & vaccinated (in previous round only anti-S positive, or stated to be vaccinated in the questionnaire), infected without information on vaccination (infected, undefined vaccination) and non-responders/missing. B Observed responder behaviours. Left legend: number of participants. Right legend: number of missing rounds. Bottom legend: number of missing samples per round
Fig. 3
Fig. 3
A Weighted and unweighted cumulative anti-N sero-prevalence in private households and official numbers of cases reported by the authorities for the Munich population older than 13 years. B Weighted and unweighted anti-N sero-incidence. C Anti-N sero-prevalence estimates calibrated on the number of vaccinated people split according to the vaccination status of the same round. D Calibrated estimates for the infection of naïve subjects and breakthrough infections. E Prevalence and incidence of vaccination in Munich (official numbers). F Relative frequencies according to the infection and vaccination status
Fig. 4
Fig. 4
Association between potential risk factors and SARS-CoV-2 sero-positivity taking into account time between baseline and Follow-up 4; events are thus right-censored. Results are based on multiple imputation. The main individual level risk factors were country of birth outside Germany and being employed in a job more in contact with the epidemic. Living in an apartment with a living area of 30–40 square meters per inhabitant revealed a slightly higher risk, while for 40–55 square meters per inhabitant the hazard ratio decreased
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