Abstract

The effectiveness of booster bivalent vaccines against the Omicron variant, particularly amongst older patients, remains uncertain. We sought to compare the relative effectiveness of a fourth dose of vaccine using bivalent messenger ribonucleic acid (mRNA), by comparing patients who had and had not received this dose. We conducted a matched retrospective cohort study to assess the risk of COVID-19 infection, hospitalization and death of people aged >60years with four doses as compared to those with only three doses. Cox proportional hazard regression models were used to estimate adjusted hazard ratios (HRs) with 95% confidence intervals (CIs). We adjusted by age, sex, nursing-home, comorbidities, primary care setting and previous episodes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. We also investigated the impact of prior SARS-CoV-2 infection within each cohort, using the same methodology. The administration of a fourth bivalent mRNA vaccine dose conferred significant additional protection against COVID-19 infection (HR: 0.479; 95% CI: 0.454-0.506), hospitalization (HR: 0.393; 95% CI: 0.348-0.443) and 30-day mortality (HR: 0.234; 95% CI: 0.171-0.318), as compared to individuals who had received only a third monovalent vaccine dose. In both cohorts, a prior history of COVID-19 infection involves lower risk of COVID-infection, hospitalization and death. During the period of Omicron predominance, receiving a bivalent booster vaccine as a fourth dose, as compared to receiving only three doses of a monovalent mRNA vaccine, provides significant extra protection against COVID-19 infection, hospitalization and mortality. Antecedents of SARS-CoV-2 prior to vaccination involves a notable reduction in the above COVID-19 outcomes.

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