COVID-19, caused by SARS-CoV-2, is significantly more severe in adults than in children. The biological reasons for this difference remain to be elucidated. We have compared the most recent virological and immunological data related to COVID-19 between adults and children and contrasted this with earlier data from severe acute respiratory syndrome (SARS) caused by the related SARS-CoV-1 in 2003. Based on these available data, a number of hypotheses are proposed to explain the difference in COVID-19 clinical outcomes between adults and children. NF-kB may be a key factor that could explain the severe clinical manifestations of COVID-19 in adults as well as rare complications associated with paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) in paediatric COVID-19 patients.