This retrospective cohort study examined the epidemiology of COVID-19 infection among 135794 pediatric patients (<25 years old) undergoing diagnostic testing for the virus in seven US children’s health systems using electronic health records from January 1 through September 8, 2020. The study found that 96% of patients tested had negative results. Rates of severe cardiorespiratory presentation of COVID-19 illness were low and clinical manifestations were typically mild. Black, Hispanic, and Asian race/ethnicity; adolescence and young adulthood; and non-respiratory chronic medical conditions were associated with identified infection. Additionally, Kawasaki disease diagnosis was not an effective proxy for multisystem inflammatory syndrome of childhood. The authors concluded the findings will be critical not only in caring for severely ill patients, but also in constructing sustainable ways to minimize the disease burden caused by COVID-19; however further work is needed in both traditional medical research paradigms and in rapid and highly collaborative science to provide better care for pediatric patients across the spectrum of health.