Effect of Influenza Vaccination on the Disease Severity and Viral Load Among Adult Outpatients and Inpatients.

Background

Some studies suggest that, thanks to the mechanisms of immune-mediated attenuation, influenza vaccination reduces severity of influenza illness in breakthrough infections. This study aimed to assess whether influenza vaccination attenuates severity of laboratory-confirmed influenza among Italian adults.

Methods

This secondary analysis included all influenza cases detected during respiratory surveillance studies conducted in outpatient and inpatient settings in Genoa (Italy), throughout the 2023/2024 and 2024/2025 seasons. Here, we compared viral load and the count of influenza-related symptoms in outpatients, alongside all-cause in-hospital mortality and radiologically confirmed pneumonia in inpatients, between vaccinated and unvaccinated adults.

Results

The study included 188 influenza cases diagnosed in primary care and 281 influenza cases identified among inpatients. Of these, 37.2% and 31.7%, respectively, were vaccinated, constituting breakthrough infections. Compared to unvaccinated adults, vaccinated outpatients had a slightly lower viral load (difference in cycle threshold values of 1.36 corresponding to about 0.51 log10 reduction in the number of copies/mL; p = 0.077), primarily driven by influenza A(H1N1)pdm09. Vaccinated outpatients also reported 9% fewer influenza-related symptoms than unvaccinated counterparts [prevalence ratio 0.91; 95% confidence interval (CI): 0.84, 0.99]. Among hospitalized older adults, influenza vaccination was associated with 64% reduced odds of in-hospital death (odds ratio 0.36; 95% CI: 0.12, 0.94). Conversely, no association between vaccination and development of pneumonia was found.

Conclusions

This study corroborates the idea that influenza vaccination attenuates disease severity in breakthrough infections. These effects are, however, dependent on the measure of severity used.