Background: We analysed data garnered during the ongoing Italian nationwide coronavirus disease 2019 (COVID-19) vaccination campaign for comparing early COVID-19 monovalent vaccine efficacy in older persons who received the primary vaccination cycle, the first vaccine booster, and the second vaccine booster. Methods: We conducted a retrospective analysis of early COVID-19 monovalent vaccine efficacy (i.e., within 120 days) against COVID-19 related hospitalizations, intensive care unit (ICU) admissions and deaths in older persons (i.e., aged ≥ 80 years), by accessing official data of the COVID-19 national integrated surveillance program instituted by the Italian National Institute of Health. Vaccine efficacy was compared (odds ratio; OR) among cohorts receiving the primary vaccination cycle, the first vaccine booster, and the second vaccine booster. Results: A consistent decline could be seen in the rate of COVID-19 hospitalizations, ICU admissions and deaths with increasing number of monovalent immunizations. Within 120 days of administration, the first and second vaccine boosters had superior efficacy compared to the primary vaccination cycle, reducing the odds of all endpoints between 62%-71% and 69%-84%, respectively. A modestly superior early efficacy could also be noted for the second versus the first monovalent vaccine booster (ORs of all endpoints further reduced by 18%-48%). Conclusion: Since an increasing number of immunizations is associated with a lower risk of unfavourable COVID-19 outcomes, vaccine boosters may be useful for limiting the clinical burden of this infectious disease in elderly populations.
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