Examining Clinical Features and Severe Neurologic Disease of Parechovirus Infection in Young Infants: A Multistate Cohort Study

Background: Human parechovirus (HPeV) infection can result in severe disease in infants, including sepsis, seizures, brain injury, and death. In 2022, a resurgence of HPeV was noted in young infants. The spectrum of illness and outcomes remain to be fully described. Methods: A multistate retrospective cohort study was conducted to evaluate hospitalizations and outcomes of infants aged ≤6 months admitted in 2022 with laboratory-confirmed HPeV infection. Infants with severe disease were defined as having clinical seizures, or abnormalities on magnetic resonance imaging or electroencephalogram during admission. Infants with severe versus nonsevere disease were compared using descriptive statistics. Results: A total of 124 U.S. infants were identified with HPeV in 11 states. Cases of HPeV peaked in May and presented at a median of 25.8 days of life (0-194 d) with fever, fussiness, and poor feeding. Bacterial and other viral co-infections were rare. Thirty-three (27%) of infants had severe neurologic disease, were more likely to present at an earlier age (13.9 vs 30 days of life, P <. 01), have preterm gestation (12% vs 1%, P =. 02), and present with respiratory symptoms (26% vs 8%, P =. 01) or apnea (41% vs 1%, P <. 001). Subcortical white matter cytoxic cerebral edema was common in severe cases. Two infants with HPeV died during admission with severe neurologic HPeV disease; no infant with mild HPeV disease died. Conclusions: This is the largest, geographically diverse U.S. study to describe the 2022 HPeV outbreak among infants. Longitudinal follow up of infants is needed to define predictors and outcomes of severe HPeV disease.