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

BackgroundDue 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. MethodsWe 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-naive participants, we compared COVID-19 hospitalisation risk by mRNA vaccine dose and/or prior infection (pre-omicron or omicron) history. FindingsDuring 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. InterpretationElderly 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-naive older adults remain up-to-date with vaccination may further reduce COVID-19 hospitalisations most efficiently. FundingMinistere de la Sante et des Services sociaux du Quebec.