We carried out a cohort study on the overall population of the province of Pescara, Italy, to assess the real-world effectiveness of SARS-CoV-2 vaccination against infection, severe, or lethal COVID-19, two years after the start of the vaccination campaign. We included all the resident or domiciled subjects, and extracted the official demographic, vaccination, COVID-19, hospital and co-pay exemption datasets from 1 January 2021, up to 15 February 2023. Cox proportional hazards analyses were adjusted for gender, age, diabetes, hypertension, COPD, major cardio- and cerebrovascular events, cancer, and kidney diseases. Throughout the follow-up (466 days on average), 186,676 subjects received greater than or equal to three vaccine doses (of ChAdOx1 nCoV-19, BNT162b2, mRNA-1273, NVX-CoV2373, or JNJ-78436735), 47,610 two doses, 11,452 one dose, and 44,989 none. Overall, 40.4% of subjects were infected with SARS-CoV-2. Of them, 2.74% had severe or lethal (1.30%) COVID-19. As compared to the unvaccinated, the individuals who received greater than or equal to one booster dose showed a ≥85% lower risk of severe or lethal COVID-19. A massive impact of vaccination was found among the elderly: 22.0% of the unvaccinated, infected individuals died, as opposed to less than 3% of those who received greater than or equal to three vaccine doses. No protection against infection was observed, although this finding was certainly influenced by the Italian restriction policies to control the pandemic. Importantly, during the Omicron predominance period, only the group who received at least a booster dose showed a reduced risk of COVID-19-related death.
Keywords: COVID-19; Italy; SARS-CoV-2; cohort study; vaccine.