COVID-19 mortality in Italy varies by patient age, sex and pandemic wave

SARS-CoV-2 has caused a worldwide epidemic of enormous proportions, which resulted in different mortality rates in different countries for unknown reasons. We analyzed factors associated with mortality using data from the Italian national database of more than 4 million SARS-CoV-2-positive cases diagnosed between January 2020 and July 2021, including > 415 thousand hospitalized for coronavirus disease-19 (COVID-19) and > 127 thousand deceased. For patients for whom age, sex and date of infection detection were available, we determined the impact of these variables on mortality 30 days after the date of diagnosis or hospitalization. Multivariable weighted Cox analysis showed that each of the analyzed variables independently affected COVID-19 mortality. Specifically, in the overall series, age was the main risk factor for mortality, with HR > 100 in the age groups older than 65 years compared with a reference group of 15-44 years. Male sex presented a two-fold higher risk of death than female sex. Patients infected after the first pandemic wave (i.e. after 30 June 2020) had an approximately threefold lower risk of death than those infected during the first wave. Thus, in a series of all confirmed SARS-CoV-2-infected cases in an entire European nation, elderly age was by far the most significant risk factor for COVID-19 mortality, confirming that protecting the elderly should be a priority in pandemic management. Male sex and being infected during the first wave were additional risk factors associated with COVID-19 mortality.