Background: While influenza A(H3N2)-predominant seasons tend to have increased rates of influenza-associated hospitalizations and deaths, little is known about differences in clinical presentation and hospitalization outcomes by influenza type and subtype.

Methods: Data from hospitalized adults aged ≥18 years in four U.S. states from 2017-2020 were used to evaluate the association between influenza type/subtype and severe influenza presentation and outcomes. Log binomial regression and modified Poisson regression with robust error variance were used to estimate adjusted risk ratios (aRR) for clinical indicators within 24 hours of hospital admission and severity outcomes. Multivariable Cox proportional hazard models were used to estimate adjusted hazard ratios for length of hospital stay and intensive care unit (ICU) stay. All models were adjusted for underlying conditions, age group, influenza vaccination, and site.

Results: Patients with influenza A(H1N1) were more likely to be admitted to an ICU (aRR=1.42) than patients with A(H3N2). Patients with influenza A(H1N1) had higher risk of hypoxemia (SpO2 <90%) than patients with A(H3N2) (aRR=1.24) and B (aRR=1.43). Patients with influenza A(H1N1) compared with A(H3N2) also had higher risk of hyponatremia (sodium <135 mmol/L, aRR=1.19) and compared with B had higher risk of fever (>38°C, aRR=1.56).

Conclusions: Adult patients hospitalized with influenza A(H1N1) had a higher risk of multiple severity indicators. Better understanding of influenza severity related to both host and virus type are important for reducing the burden of severe influenza in adults.