Despite the need to generate valid and reliable estimates of protection 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. 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. Most participants were seropositive against the spike antigen; 37% of the participants textgreater=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. 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.Competing Interest StatementCK serves as a medical advisor to Centogene and Retromer Therapeutics and has received speaking honoraria from Desitin and Bial.Funding StatementIMMUNEBRIDGE is a research project funded by the Federal Ministry of Education and Research (BMBF) through the Network University Medicine (NUM) (FKZ 01KX1021). The central laboratory analysis in Oldenburg and Greifswald for the population-based cohort studies was financed via the IMMUNEBRIDGE project. Supplement 1 Table S1 gives an overview of the basic funding for data collection for each study. The IMMUNEBRIDGE_ED study was conducted with a hospital-based approach at the Central Emergency Department of the University Medical Center Goettingen and funded by intramural funds. This project was conducted with data from the German National Cohort (NAKO) (www.nako.de). The NAKO is funded by the Federal Ministry of Education and Research (BMBF) [project funding reference numbers: 01ER1301A/B/C, 01ER1511D and 01ER1801A/B/C/D], federal states of Germany and the Helmholtz Association, the participating universities and the institutes of the Leibniz Association. Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:The responsible ethics committees of individual studies approved all study-related analyses: GUIDE: 202/22 approved by the Ethics Committee of the Medical Faculty of the Rheinische Friedrich-Wilhelm-University Bonn ELISA: University of Luebeck (Az. 20-150) NAKO: The study is continuously approved by the responsible local ethics committees of the German Federal States where all study centers are located in (original ethics approvals of the leading ethics committee of the Bayerische Landesaerztekammer (protocol code 13023, Approval Date: 27 March 2013 and 14 February 2014 (rectification of documents, study protocol, consent form)). An external ethics advisory board has been established that accompanies NAKO over the full study period. A ’Code of Ethics’ of NAKO (Ethikkodex) has been developed and the study is under steady surveillance by the ethics committees of the regional study centers (8). STAAB: Ethics committee of the Medical Faculty of the University Wuerzburg (STAAB: ⋕98/13) MuSPAD: Ethics committee of Hannover Medical School (9086_BO_S_2020 for MuSPAD), Dresden paedSAXCOVID: Ethics Committee of the Technische University (TU) Dresden (BO-EK-156042020). Bochum CorKID: Ethics Committee of the Ruhr University Bochum (Nr. 20-6927_7) Wuerzburg Wue-KITa-CoV: Wuerzburg, Kennzeichen 105/21 IMMUNEBRIDGE_ED: Ethics Committee of University Medical Center Goettingen (21/6/22)I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesThe aggregated data for this study will be made available to other academic researchers. The minimum dataset includes study site information, assay information, sample type, demographic information, self-administered diagnostic anamneses and lab results (NC, S Spike, IGRA and NAb). Institutions can apply for the data via serohub@helmholtz-hzi.de. Data were provided to the modelling network for severe infectious diseases in Germany (MONID (13)).