Findings from a multi-cohort analysis indicate that levels of neutrophil extracellular trap (NET) remnants are elevated in paediatric patients affected by multi-system inflammatory syndrome in children or chilblain-like lesions (also known as ‘COVID toes’), as well as in adults with symptomatic COVID-19, and were associated with clinical outcomes. Impaired NET degradation was observed in both adult and paediatric populations; these impairments did not seem to be genetically driven and were considered to be multifactorial.