Mortality for causes unrelated to COVID-19 by number of doses and time since administration of COVID-19 vaccines: a retrospective cohort analysis in the Treviso Province, Italy (2021-2025)

OBJECTIVES: Safety concerns might explain the low uptake of COVID-19 vaccination recently observed in several countries. This study aims to compare COVID-19-unrelated mortality between vaccinated and unvaccinated people. METHODS: We conducted a retrospective cohort analysis over 2021-2025 among 735,473 residents aged ≥12 years in the Treviso Province of Italy. We used Cox regression models, including vaccination as time-dependent exposure and adjusting for socio-demographic and clinical characteristics, to estimate the hazard ratios (HRs) of COVID-19-related and -unrelated death by number of doses and time since administration of COVID-19 vaccines. RESULTS: Despite decreasing over time, the HR of COVID-19-related death in vaccinated compared with unvaccinated participants showed a significant vaccine-induced protection after the primary cycle or any booster dose. To a lesser extent, we also observed a reduced COVID-19-unrelated mortality associated with vaccination, with the HR ranging from 0.72 (95% confidence interval [CI]: 0.69-0.75) after two or more booster doses to 0.83 (95% CI: 0.77-0.89) after the first dose. We estimated a lower HR of COVID-19-unrelated death ≤30 days after a vaccine dose (HR = 0.48, 95% CI: 0.44-0.51) than >30 days later (HR = 0.80, 95% CI: 0.77-0.83). CONCLUSIONS: These results are reassuring about safety of COVID-19 vaccines and confirm their high effectiveness against COVID-19-related death, thus supporting seasonal COVID-19 vaccination campaigns.