Severity of Influenza-Associated Hospitalizations by Influenza Virus Type and Subtype in the United States, 2010─2019

Introduction: Influenza burden varies across seasons, due in part to differences in circulating influenza virus types/subtypes. Using the U.S. Influenza Hospitalization Surveillance Network (FluSurv-NET), we assessed severity of influenza-associated outcomes among individuals hospitalized with influenza A(H3N2), A(H1N1)pdm09, and B virus infections during the 2010─11 through 2018─19 influenza seasons.Methods: To evaluate the association between influenza virus type/subtype and in-hospital severe outcomes (intensive care unit [ICU] admission, mechanical ventilation [MV] or extracorporeal membrane oxygenation [ECMO] use, and death), we used logistic regression adjusted for influenza season, influenza vaccination status, age, and FluSurv-NET site. When missing, influenza A subtypes were imputed using chained equations of known subtypes by season.Findings: Among 104,969 hospitalized individuals with laboratory-confirmed influenza, after imputation, 57·7% had A(H3N2), 24·6% A(H1N1)pdm09, and 17·7% B virus infections; 16·7% required ICU admission, 6·5% received MV/ECMO, and 3·0% died. Individuals with A(H1N1)pdm09 versus A(H3N2) had higher odds of in-hospital severe outcomes: ICU admission adjusted odds ratio (aOR):1·42 (95% CI:1·32─1·52); MV/ECMO aOR:1·79 (95% CI:1·60─2·00); and death aOR:1·25 (95% CI:1·07─1·46). Individuals infected with influenza B versus A(H3N2) had 1·06 (95% CI: 1·01─1·12) times the odds of ICU admission, 1·14 (95% CI: 1·05─1·24) times the odds of MV/ECMO use, and 1·18 (95% CI: 1·07─1·31) times the odds of death.Interpretation: Over one in six individuals hospitalized with influenza had in-hospital severe outcomes. While a higher proportion of influenza hospitalizations had A(H3N2), individuals hospitalized with A(H1N1)pdm09 and B viruses experienced more severe outcomes compared to those with A(H3N2).Funding: This work was funded by grant CK17-1701 from the CDC through an Emerging Infections Program cooperative agreement, grant 5U38HM000414 from a 2008─13 Influenza Hospitalization Surveillance Project (IHSP) cooperative agreement, grant 5U38OT000143 from a 2013─18 IHSP cooperative agreement, and grant 5NU38OT000297 from a 2018─23 IHSP cooperative agreement. The project was supported by CTSA award No. UL1 TR002243 from the National Center for Advancing Translational Sciences at Vanderbilt University Medical Center. Declaration of Interest: EJA has consulted for Pfizer, Sanofi Pasteur, GSK, Janssen, Moderna, and Medscape, and his institution receives funds to conduct clinical research unrelated to this manuscript from MedImmune, Regeneron, PaxVax, Pfizer, GSK, Merck, Sanofi-Pasteur, Janssen, and Micron. EJA serves on a safety monitoring board for Kentucky BioProcessing, Inc. and Sanofi Pasteur. EJA serves on a data adjudication board for WCG and ACI Clinical. EJA’s institution has also received funding from NIH to conduct clinical trials of COVID-19 vaccines. ES notes only the agency grant funding supporting the data collection for this project, and agency grant funding from the Centers for Disease Control and Prevention to support other epidemiology projects. HKT, WS, NBA, JM, KY-H, RKH, RL have received CDC grant funding. JH and LL have received grants from the Michigan Department of Health and Human Services. ES reports grants from Council for State and Territorial Epidemiologists (CSTE) during the conduct of the study and grants from CDC outside the submitted work. AG reports grants from CSTE. All other co-authors had no conflicts of interest.Ethical Approval: FluSurv-NET sites obtained human subjects and ethics approvals from their respective state health department and academic partner Institutional Review Boards (IRBs) as needed. CDC determined this activity met the requirement for public health surveillance; therefore, the CDC’s IRB approval was not required.