Group A Streptococcal Disease in Sudden Unexpected Death in Youth in the Pre- and Post-COVID-19 Era

Background: An upsurge in pediatric invasive group A streptococcal infection (iGAS) has been observed in the Netherlands along with a suspected increase in iGAS-related sudden death. Sudden unexplained deaths in youth (SUDY) are investigated nationally through a standardized procedure [(Postmortem Evaluation of Sudden Unexplained Death in Youth (PESUDY)]. We investigate epidemiological differences between pediatric iGAS-related sudden deaths (iGAS-PESUDY) and surviving iGAS cases. Methods: This observational study used data from the COPP-iGAS study on pediatric iGAS infections in Dutch hospitals and the PESUDY database. Children 0–18 years of age were included between August 2016 and December 2022. Results: Twenty-one iGAS-PESUDY cases and 156 iGAS survivors were included. iGAS-PESUDY cases tended to be older compared to survivors. iGAS-PESUDY cases significantly increased in 2022 compared to the pre-COVID period. Pre- and/or coinciding infections were present in 66% of iGAS-PESUDY cases, predominantly varicella zoster (19%) and influenza (24%). In survivors, 13% had varicella zoster virus and 3% had influenza virus (P ≤ 0.001). C-reactive protein levels tended to be lower in iGAS-PESUDY cases (81 mg/L; interquartile range, 26.8–307.5) compared to survivors (266 mg/L; interquartile range, 218.0–302.0). Conclusion: iGAS is currently a prevalent cause of SUDY. The finding of moderately elevated C-reactive protein levels compared to high levels in survivors might suggest children dying suddenly of iGAS have a rapid and fulminant disease course. Children with a pre- and/or coinciding infection of varicella zoster or influenza virus may be at greater risk of succumbing to iGAS infections.