Balancing Benefits and Harms of COVID-19 Vaccines: Lessons from the Ongoing Mass Vaccination Campaign in Lombardy, Italy.

Background. Limited evidence exists on the balance between the benefits and harms of the COVID-19 vaccines. The aim of this study is to compare the benefits and safety of mRNA-based (Pfizer-BioNTech and Moderna) and adenovirus-vectored (Oxford-AstraZeneca) vaccines in subpopulations defined by age and sex. Methods. All citizens who are newly vaccinated from 27 December 2020 to 3 May 2021 are matched to unvaccinated controls according to age, sex, and vaccination date. Study outcomes include the events that are expected to be avoided by vaccination (i.e., hospitalization and death from COVID-19) and those that might be increased after vaccine inoculation (i.e., venous thromboembolism). The incidence rate ratios (IRR) of vaccinated and unvaccinated citizens are separately estimated within strata of sex, age category and vaccine type. When suitable, number needed to treat (NNT) and number needed to harm (NNH) are calculated to evaluate the balance between the benefits and harm of vaccines within each sex and age category. Results. In total, 2,351,883 citizens are included because they received at least one dose of vaccine (755,557 Oxford-AstraZeneca and 1,596,326 Pfizer/Moderna). A reduced incidence of COVID-19-related outcomes is observed with a lowered incidence rate ranging from 55% to 89% and NNT values ranging from 296 to 3977. Evidence of an augmented incidence of harm-related outcomes is observed only for women aged <50 years within 28 days after Oxford-AstraZeneca (being the corresponding adjusted IRR of 2.4, 95% CI 1.1−5.6, and NNH value of 23,207, 95% CI 10,274−89,707). Conclusions. A favourable balance between benefits and harms is observed in the current study, even among younger women who received Oxford-AstraZeneca.