Prior infection- and/or vaccine-induced protection against Omicron BA.1, BA.2 and BA.4/BA.5-related hospitalisations in older adults: a test-negative case-control study in Quebec, Canada

Background Due to severe outcomes, elderly adults 60 years or older are prioritized for COVID-19 vaccination but accumulated SARS-CoV-2 infection and vaccination likely modifies their risk. We estimated vaccine effectiveness against omicron-associated hospitalisation among elderly adults, by number of doses, prior infection history and time since last immunological event. Methods We conducted a test-negative case-control study among symptomatic elderly adults tested for SARS-CoV-2 in Quebec, Canada during BA.1-, BA.2- and BA.4/5-dominant periods. Relative to unvaccinated, infection-naïve participants, we compared COVID-19 hospitalisation risk by mRNA vaccine dose and/or prior infection (pre-omicron or omicron) history. Findings During BA.1, BA.2 and BA.4/5 periods, two- vs. four-dose vaccine effectiveness alone against hospitalisation was: 78% (95%CI:75-80) vs. 96% (95%CI:93-98); 60% (95%CI:50-97) vs. 84% (95%CI:81-87); and 40% (95%CI:30-49) vs. 68% (95%CI:63-72), respectively, consistent with longer median time since second vs fourth dose. By respective period, effectiveness of pre-omicron vs. omicron infection alone against hospitalisation was: 93% (95%CI:80-97) vs. [not estimable]; 88% (95%CI:50-97) vs. 96% (95%CI:68-99); and 69% (95%CI:30-85) vs. 90% (95%CI:79-95). Regardless of doses (2-5) or prior infection type, hybrid protection was ≥90%, lasting at least 6-8 months during the BA.4/5 period. Prior omicron infection alone reduced BA.4/5 hospitalisation risk by >80% for at least 6-8 months. Interpretation Elderly adults with history of both prior SARS-CoV-2 infection and ≥2 vaccine doses appear well-protected for a prolonged period against omicron hospitalisation, including BA.4/5. Ensuring infection-naïve older adults remain up-to-date with vaccination may further reduce COVID-19 hospitalisations most efficiently. Funding Ministère de la Santé et des Services sociaux du Québec. ### Competing Interest Statement SC, MO and GDS report that the Ministère de la Santé et des Services sociaux du Québec gave financial support to their institution for this work. DT is supported by a research career award from the Fonds de recherche du Québec - Santé. JF reports grants from Ministère de la Santé et des Services sociaux du Québec for sequencing of SARS-CoV-2 positive samples, grants and receipt of sequencing consumables from the Public health agency of Canada for integral innovation in sequencing SARS-CoV-2, and grants from Genome Canada for sequencing of SARS-CoV-2 positive samples unrelated to the current work. DMS reports grants paid to her institution and unrelated to current work from Public Health Agency of Canada, from Michael Smith Foundation for Health Research, from Canadian Institutes of Health Research and from British Columbia CDC Foundation for Public Health. Others authors declare that they have no conflicts of interest. ### Funding Statement This work was supported by the Ministère de la Santé et des Services sociaux du Québec. ### 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: The study was conducted under the legal mandate of the National Director of Public Health of Quebec under the Public Health Act and was also approved by the Research Ethics Board of the Centre hospitalier universitaire de Québec-Université Laval. 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 The databases used in this study are a property of the Ministère de la Santé et des Services sociaux du Québec that was shared with the researchers under the legal mandate of the National Director of Public Health of Quebec under the Public Health Act, precluding data sharing with a third party. Aggregate data are available within the manuscript and the supplementary material.