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. 2023 Jul 18;15(7):1574.
doi: 10.3390/v15071574.

The Prospective COVID-19 Post-Immunization Serological Cohort in Munich (KoCo-Impf): Risk Factors and Determinants of Immune Response in Healthcare Workers

Christina Reinkemeyer  1 , Yeganeh Khazaei  2 , Maximilian Weigert  2   3 , Marlene Hannes  1 , Ronan Le Gleut  4   5 , Michael Plank  1 , Simon Winter  1 , Ivan Noreña  1 , Theresa Meier  2 , Lisa Xu  2 , Raquel Rubio-Acero  1 , Simon Wiegrebe  2   6 , Thu Giang Le Thi  7 , Christiane Fuchs  4   5   8   9 , Katja Radon  10   11   12 , Ivana Paunovic  1 , Christian Janke  1 , Andreas Wieser  1   13   14   15 , Helmut Küchenhoff  2 , Michael Hoelscher  1   11   13   14 , Noemi Castelletti  1   14   16 ; KoCo-Impf/ORCHESTRA working group
Affiliations

The Prospective COVID-19 Post-Immunization Serological Cohort in Munich (KoCo-Impf): Risk Factors and Determinants of Immune Response in Healthcare Workers

Christina Reinkemeyer et al. Viruses. .

Abstract

Antibody studies analyze immune responses to SARS-CoV-2 vaccination and infection, which is crucial for selecting vaccination strategies. In the KoCo-Impf study, conducted between 16 June and 16 December 2021, 6088 participants aged 18 and above from Munich were recruited to monitor antibodies, particularly in healthcare workers (HCWs) at higher risk of infection. Roche Elecsys® Anti-SARS-CoV-2 assays on dried blood spots were used to detect prior infections (anti-Nucleocapsid antibodies) and to indicate combinations of vaccinations/infections (anti-Spike antibodies). The anti-Spike seroprevalence was 94.7%, whereas, for anti-Nucleocapsid, it was only 6.9%. HCW status and contact with SARS-CoV-2-positive individuals were identified as infection risk factors, while vaccination and current smoking were associated with reduced risk. Older age correlated with higher anti-Nucleocapsid antibody levels, while vaccination and current smoking decreased the response. Vaccination alone or combined with infection led to higher anti-Spike antibody levels. Increasing time since the second vaccination, advancing age, and current smoking reduced the anti-Spike response. The cumulative number of cases in Munich affected the anti-Spike response over time but had no impact on anti-Nucleocapsid antibody development/seropositivity. Due to the significantly higher infection risk faced by HCWs and the limited number of significant risk factors, it is suggested that all HCWs require protection regardless of individual traits.

Keywords: COVID-19; ORCHESTRA; SARS-CoV-2; antibodies; breakthrough infections; health care workers; immunologic response; seroprevalence; vaccination.

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Conflict of interest statement

In addition to the funding disclosed in the funding section, AW and MH report personal fees and non-financial support from Roche Diagnostics, non-financial support from Euroimmun, non-financial support from Viramed, and non-financial support from Mikrogen. AW and MH 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, non-financial support and other from Accenture. MH and AW report personal fees and non-financial support received from Box-Betrobox and non-financial support from Becker MVZ during the conduction of this study. AW is involved in other different patents and companies, not in relation to the serology of SARS-CoV-2. AW reports personal fees and others from Haeraeus Sensors and non-financial 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 this study’s design, data collection, data analyses, data interpretation, writing, or submission of this manuscript.

Figures

Figure 1
Figure 1
Recruitment paths and criteria for inclusion into the analysis. Gray boxes: inclusion criteria and places of recruitment. Orange boxes: information on advertisement modalities for recruiting participants; modalities of the acquisition of informed consent, questionnaire data, and capillary blood samples (acquired in person by study personnel). A triangle diagram describing the exclusion criteria and the final information of the analyzed participants.
Figure 2
Figure 2
Risk factor analysis for SARS-CoV-2 infection, based on positive anti-N serology. Results are based on a logistic regression model and are given as ORs with a 95% CI. The obtained value of model evaluation using pooled AUC was 0.7398. (A) Estimates for categorical variables. (B) Estimates for continuous variables with 95% CI represented by the grey shadowed region.
Figure 3
Figure 3
Anti-N antibody level after infection. Association between quantitative anti-N serology and determinants of antibody response. Results are based on a GLM with gamma distribution and are given as the expected multiplicative changes in anti-N/S antibodies (exponentiated coefficients) with a 95% CI.(A) Estimates for categorical variables. (B) Estimates for continuous variables with 95% CI represented by the grey shadowed region.
Figure 4
Figure 4
Anti-S antibody level after infection and vaccination. Association between quantitative anti-S serology and determinants of antibody response. Results are based on a GLM with gamma distribution and are given as the expected multiplicative changes in anti-N/S antibodies (exponentiated coefficients) with a 95% CI. (A) Estimates for categorical variables. (B) Estimates for continuous variables with 95% CI represented by the grey shadowed region.
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