Influenza Vaccine Effectiveness for Prevention of Severe Influenza-Associated Illness Among Adults in the United States, 2019–2020: A Test-Negative Study

Abstract Background Influenza vaccine effectiveness (VE) against a spectrum of severe disease, including critical illness and death, remains poorly characterized. Methods We conducted a test-negative study in an intensive care unit (ICU) network at 10 US hospitals to evaluate VE for preventing influenza-associated severe acute respiratory infection (SARI) during the 2019–2020 season, which was characterized by circulation of drifted A/H1N1 and B-lineage viruses. Cases were adults hospitalized in the ICU and a targeted number outside the ICU (to capture a spectrum of severity) with laboratory-confirmed, influenza-associated SARI. Test-negative controls were frequency-matched based on hospital, timing of admission, and care location (ICU vs non-ICU). Estimates were adjusted for age, comorbidities, and other confounders. Results Among 638 patients, the median (interquartile) age was 57 (44–68) years; 286 (44.8%) patients were treated in the ICU and 42 (6.6%) died during hospitalization. Forty-five percent of cases and 61% of controls were vaccinated, which resulted in an overall VE of 32% (95% CI: 2–53%), including 28% (−9% to 52%) against influenza A and 52% (13–74%) against influenza B. VE was higher in adults 18–49 years old (62%; 95% CI: 27–81%) than those aged 50–64 years (20%; −48% to 57%) and ≥65 years old (−3%; 95% CI: −97% to 46%) ( P = .0789 for interaction). VE was significantly higher against influenza-associated death (80%; 95% CI: 4–96%) than nonfatal influenza illness. Conclusions During a season with drifted viruses, vaccination reduced severe influenza-associated illness among adults by 32%. VE was high among young adults. During the 2019–2020 influenza season, characterized by circulation of drifted viruses with limited antigenic similarity to administered vaccines, influenza vaccination was moderately effective in preventing severe influenza disease, with 32% vaccine effectiveness in this multicenter study in the United States.