BackgroundHeart failure (HF) patients are at higher risk of severe coronavirus disease 2019 (COVID-19). The Omicron variant has many novel mutations including those in the spike protein, leading to questions about vaccine effectiveness. The aim of this analysis was to evaluate the effectiveness of the COVID-19 vaccine with or without a booster (i.e., after the third dose) during the Omicron variant wave. MethodsChronic heart failure patients in the Czech Republic were included in the analysis. COVID-19 infection was monitored from January 1st 2022 to March 31st 2022. The analysis was conducted on data collected in the National Health Information System. Vaccine effectiveness of vaccinated (with or without booster) vs. unvaccinated patients was analyzed for incidence of COVID-19, COVID-19-related hospitalizations, COVID-19 related intensive care unit admissions, and COVID-19 related mechanical ventilation/extracorporeal membrane oxygenation treatment. FindingsFrom a total 165,453 HF patients in the Czech Republic, 9,728 contracted COVID-19 (22.9% of them not vaccinated, 23.2% vaccinated and 53.8% vaccinated and boosted). Risk of intensive care unit (ICU) hospitalization was 7.6% in the unvaccinated group, 4.8% in the vaccinated group and 2.9% in the boosted group. The calculated effectiveness of the COVID-19 vaccine in prevention of ICU hospitalization in the vaccinated group was 41.9 and 76.6% in the boosted group. InterpretationThe results demonstrated moderate vaccine effectiveness in the prevention of severe COVID-19 in vaccinated but not boosted HF patients. Much stronger effectiveness was found in those who were vaccinated and boosted.