COVID-19 Vaccination Still Makes Sense: Insights on Pneumonia Risk and Hospitalization from a Large-Scale Study at an Academic Tertiary Center in Italy

COVID-19 vaccines have revolutionized prevention and clinical management by reducing disease severity and mortality. However, their long-term impact on hospitalization is unclear. This retrospective study assessed whether vaccination status, timing, and number of vaccine doses influence the risk of hospitalization and COVID-19 pneumonia in a large cohort in Italy, several years after initial vaccine rollout. From 1 October 2023, to 2 February 2024, at Humanitas Research Hospital (Milan) and two affiliates, we recorded age, sex, comorbidities, vaccination status (number of doses and time since last dose), admission type (urgent vs. elective), and pneumonia diagnosis. Baseline health was quantified by the Charlson Comorbidity Index. Among 16,034 admissions (14,874 patients), vaccination data were available for 5743 cases: 40.8% were in the emergency setting and 59.2% were elective. Patients presented with pneumonia in 6.8% of cases. Laboratory results confirmed COVID-19 pneumonia occurred in 43.7% of pneumonia cases, with a 16.9% mortality. Patients with no vaccine dose had a higher proportion of COVID-19 pneumonia, while COVID-19 pneumonia rates were lower in individuals who had received more vaccine doses. There were no significant differences in COVID-19 pneumonia risk by timing of last vaccination. Moreover, hospitalized unvaccinated patients had overall more frequent emergency admissions (57.3%), while patients with three or more doses had about a ~40% emergency admission rate. COVID-19 positivity during hospitalization was highest in unvaccinated patients (90.7%) and declined with vaccination status. Vaccinated patients, especially those with multiple doses, had significantly lower COVID-19 pneumonia rates and emergency admissions. These findings suggest a possible protective effect of vaccination in modifying the clinical presentation and severity of illness among those who are hospitalized and support continued vaccination efforts for high-risk groups to reduce severe adverse outcomes.