United States influenza 2022-2023 season characteristics as inferred from wastewater solids, influenza hospitalization and syndromic data

Influenza A virus (IAV) causes significant morbidity and mortality in the United States and has pandemic potential. Identifying IAV epidemic patterns is essential to inform the timing of vaccines and non-pharmaceutical interventions. In a prospective, longitudinal study design, we measured IAV RNA in wastewater settled solids at 163 wastewater treatment plants across 33 states to characterize the 2022-2023 influenza season at the state, health and human services (HHS) regional, and national scales. Influenza season onset, offset, duration, peak, and intensity using IAV RNA in wastewater were compared with those determined using laboratory-confirmed influenza hospitalization rates and outpatient visits for influenza-like illness (ILI). The onset for HHS regions as determined by IAV RNA in wastewater roughly corresponded with those determined using ILI when the annual geometric mean of IAV RNA concentration was used as baseline (i.e., the threshold that triggers onset), although offsets between the two differed. IAV RNA in wastewater provided early warning of onset, compared to the ILI estimate, when the baseline was set at twice the limit of IAV RNA detection in wastewater. Peak when determined by IAV RNA in wastewater generally preceded peak determined by IAV hospitalization rate by two weeks or less. Wastewater settled solids data is an IAV-specific indicator that can be used to augment clinical surveillance for seasonal influenza epidemic timing and intensity.