Estimates of protection levels against SARS-CoV-2 infection and severe COVID-19 in Germany before the 2022/2023 winter season: the IMMUNEBRIDGE project

Abstract

Purpose: Despite the need to generate valid and reliable estimates of protection levels against SARS-CoV-2 infection and severe course of COVID-19 for the German population in summer 2022, there was a lack of systematically collected population-based data allowing for the assessment of the protection level in real time.

Methods: In the IMMUNEBRIDGE project, we harmonised data and biosamples for nine population-/hospital-based studies (total number of participants n = 33,637) to provide estimates for protection levels against SARS-CoV-2 infection and severe COVID-19 between June and November 2022. Based on evidence synthesis, we formed a combined endpoint of protection levels based on the number of self-reported infections/vaccinations in combination with nucleocapsid/spike antibody responses ("confirmed exposures"). Four confirmed exposures represented the highest protection level, and no exposure represented the lowest.

Results: Most participants were seropositive against the spike antigen; 37% of the participants ≥ 79 years had less than four confirmed exposures (highest level of protection) and 5% less than three. In the subgroup of participants with comorbidities, 46-56% had less than four confirmed exposures. We found major heterogeneity across federal states, with 4-28% of participants having less than three confirmed exposures.

Conclusion: Using serological analyses, literature synthesis and infection dynamics during the survey period, we observed moderate to high levels of protection against severe COVID-19, whereas the protection against SARS-CoV-2 infection was low across all age groups. We found relevant protection gaps in the oldest age group and amongst individuals with comorbidities, indicating a need for additional protective measures in these groups.

Keywords: Humoral immunity; Neutralizing antibodies; SARS-CoV-2; Seroepidemiological studies.

Fig. 1

A The combined endpoint on the proportion of exposures by infection or vaccination with corresponding humoral immune response, stratified by age; for definition of combined endpoint see Table 1; B the combined endpoint of the proportion of exposures by infection or vaccination regardless of a humoral immune response, stratified by age; C seropositivity against the S-antigen and D against the N-antigen by age, with 95% confidence intervals. Participants from IMMUNEBRIDGE_ED were excluded from this analysis. The combined endpoint could not be formed for 12,185 participants due to missing information from the participants from NAKO (n=10,595) and for additional 1,590 participants from the other cohorts. Vaccination recommendations for children differed from those for adults, recommendations of > 1 dose only currently exist for those > 11 years old

Fig. 2

Age-standardised maps stratified by NUTS 2 region displaying (A–D) the combined endpoint of A no exposures, B 1 to < 3 confirmed exposures, C 3 confirmed exposures, D 3 confirmed exposures and a confirmed exposure in 2022 and (E, F) seropositivity against E the S-antigen and F the N-antigen. Only data from the adult, population-based, cross-sectional studies and cohorts (GUIDE, MuSPAD, NAKO, STAAB) are included in this analysis

Fig. 3

Comparison of (A) the combined endpoint and (B, C) seropositivity against the S- and N-antigen between the population-based studies and IMMUNEBRIDGE_ED in patients with cancer, cardiovascular disease (CVD), diabetes, hypertension, immunosuppression (IS), and lung disease. Post-stratification weights based on the age distribution in IMMUNEBRIDGE_ED comorbidity groups were applied to the population-based data