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.

Keywords: critical illness; immunization; influenza; vaccination; vaccine effectiveness.

Figure 1.

Flow diagram of patient enrollment. Abbreviation: LAR, legally authorized representative.

Figure 2.

Secondary analyses of influenza VE for the prevention of influenza-associated severe acute respiratory infection. Abbreviations: CI, confidence interval; VE, vaccine effectiveness.

Figure 3.

Sensitivity analyses for the assessment of influenza vaccine effectiveness for the prevention of influenza-associated severe acute respiratory infection. These secondary estimates evaluating vaccine sequence were restricted to the subset of patients with verified vaccination for the current and previous season. Note all comparisons used those patients who were not vaccinated in either season as reference. Current season estimates included all participants vaccinated during the current season. Current season only estimates include participants vaccinated during the current season who were not vaccinated during the previous season. Current and previous season estimates include participants who were vaccinated during both seasons. Previous season only estimates include participants who were vaccinated during the previous season; patients vaccinated in the current season were not included in this estimation. Abbreviations: CI, confidence interval; IPTW, inverse probability of treatment weighting; PS, propensity scores; VE, vaccine effectiveness.