Humoral Immunity to SARS-CoV-2 and Inferred Protection from Infection in a French Longitudinal Community Cohort

Population-level immunity to SARS-CoV-2 is growing through vaccination as well as ongoing circulation. Given waning immunity and emergence of new variants, it is important to dynamically determine the risk of re-infection in the population. For estimating immune protection, neutralization titers are most informative, but these assays are difficult to conduct at a population level. Measurement of antibody levels can be implemented at high throughput, but has not been robustly validated as a correlate of protection. Here, we have developed a method that predicts neutralization and protection based on variant-specific antibody measurements to SARS-CoV-2 antigens. This approach allowed us to estimate population-immunity in a longitudinal cohort from France followed for up to 2 years. Participants with a single vaccination or immunity caused by infection only are especially vulnerable to COVID-19 or hospitalization due to SARS-CoV-2. While the median reduced risk to COVID-19 in participants with 3 vaccinations was 96%, the median reduced risk among participants with infection-acquired immunity only was 42%. The results presented here are consistent with data from vaccine-effectiveness studies indicating robustness of our approach. Our multiplex serological assay can be readily optimized and employed to study any new variant and provides a framework for development of an assay that would include protection estimates. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by the Fondation pour la Recherche Medicale (CorPopImm to MW), and the French Governments Laboratoire d'Excellence Integrative Biology of Emerging Infectious Diseases(Investissement dAvenir grant ANR-10-LABX-62-IBEID), and INCEPTION programs (Investissement dAvenir grant ANR-16-CONV-0005), and URGENCE COVID-19 fundraising campaign of Institut Pasteur (TooLab project awarded to M.B.). The COVID-Oise cohort is funded by Alliance Tous Unis contre le virus Institut Pasteur, AP-HP and Fondation de France. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study combines samples collected from different cohorts. All of these have been evaluated by ethical committees. The Comite de Protection des Personnes Ile de France IV ([NCT04750720][1]) gave ethical approval for the collection of samples used in this study. Institutional Review Board of Strasbourg University Hospital ([NCT04441684][2]) gave ethical approval for the collection of samples used in this study. The Comite de Protection des Personnes Nord Ouest IV gave approval for the study called COVID-Oise ([NCT04644159][3]). The Comite de Protection des Personnes Ile de France III gave permission for the Corser studies registered by [NCT04325646][4]. 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. Yes I 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. Yes All data produced in the present study are available upon reasonable request to the authors. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT04750720&atom=%2Fmedrxiv%2Fearly%2F2022%2F05%2F25%2F2022.05.23.22275460.atom [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT04441684&atom=%2Fmedrxiv%2Fearly%2F2022%2F05%2F25%2F2022.05.23.22275460.atom [3]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT04644159&atom=%2Fmedrxiv%2Fearly%2F2022%2F05%2F25%2F2022.05.23.22275460.atom [4]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT04325646&atom=%2Fmedrxiv%2Fearly%2F2022%2F05%2F25%2F2022.05.23.22275460.atom