NOTCH4 and COVID-19: In particular, while Notch4 was also upregulated on circulating Tregs in children with acute COVID-19 as a function of disease severity, the Tregs in those with MIS-C additionally showed upregulation of Notch1 expression, a pathway previously implicated in Th1-skewed immune dysregulation, autoimmunity, graft-versus-host disease, and solid organ rejection (41, 42).