ObjectiveThis study focused on Bulgarian patient cohorts harbouring a single documented chronic comorbidity–cardiovascular pathology, an oncological disease or a chronic pulmonary diseases (CPD) comparing the outcomes in fully vaccinated and non-vaccinated populations classified by sex and age groups in ambulatory, hospital and intensive care unit (ICU) settings at the national level.DesignRetrospective analysisSettings, participants and outcome measuresIn total, 1 126 946 patients with confirmed COVID-19, on a national level, were retrospectively analysed between March 2020 and April 2022, using data from the Ministry of Health’s United Information Portal, launched in March 2020.ResultsOf all the confirmed 247 441 hospitalised cases of COVID-19, 67 723 (27.3%) had documented cardiovascular disease (CVD), 2140 (0.9%) had confirmed solid malignancy (regardless of stage) and 3243 (1.3%) had established CPD as their only chronic pathology. The number of cumulative deaths in each subgroup was 10 165 (in-hospital=5812 and ICU=4353); 4.0% vaccinated (410/10 165, p<0.001), 344 (in-hospital=196 and ICU=148), 4.9% vaccinated (17/344, p<0.001), 494 (in-hospital=287 and ICU=207) and 5.2% vaccinated (26/494, p<0.001), respectively. Statistical significance (p<0.001) was obtained in favour of reduced ambulatory, hospitalisation and both in-hospital and ICU-related mortality in the vaccinated cohorts, and BNT162b2 was the most effective at preventing mortality in all age groups.ConclusionsThis retrospective analysis shows that patients vaccinated against COVID-19 demonstrated trends of reduced hospitalisations and premature mortality in patients with CVD, solid malignancy or CPD as a single comorbidity.