evidence: Understanding COVID-19 in children: immune determinants and post-infection conditions [...] Nevertheless, collectively, these studies show that the immune response of children and adults to mild SARS-CoV-2 infection are similar, but diverge after the development of severe disease (Fig. 3). Adults with severe COVID-19 might have loss of immune synchrony: T cell lymphopenia, reduced circulating follicular helper T cells, and impaired IFN-mediated signaling juxtaposed with high frequencies of activated SARS-CoV-2-specific T cells, robust humoral responses, and myeloid cell activation. By contrast, children with MIS-C exhibit multilineage immune cell activation beyond that which occurs in pediatric or adult COVID-19, evidenced by greater IFN and inflammasome signaling, widespread T cell activation, and activation of a broad humoral response reactive to common viruses as well as SARS-CoV-2. The association of severe COVID-19 in children and adults with pre-existing medical conditions underscores the contributions of these comorbidities to disease severity. Although studies have started to identify genetic risk factors for MIS-C, the constellation of factors that lead to MIS-C are mostly undefined. The spread of viral variants among unvaccinated pediatric populations may also change the spectrum of disease in children. The solutions to these questions will emerge as investigators continue to develop multicenter studies with larger cohorts alongside new tools for studying SARS-CoV-2 pathogenesis. [...] Consiglio, C. R. et al. The immunology of multisystem inflammatory syndrome in children with COVID-19. Cell183, 968–981.e7 (2020).