Deep Immune Profiling of MIS-C demonstrates marked but transient immune activation compared to adult and pediatric COVID-19

Vella, L.; Giles, J. R.; Baxter, A. E.; Oldridge, D. A.; Diorio, C.; Alanio, C.; Pampena, M. B.; Wu, J. E.; Chen, Z.; Huang, Y. J.; Anderson, E. M.; Gouma, S.; McNerney, K. O.; Chase, J.; Burudpakdee, C.; Lee, J. H.; Apostolidis, S. A.; Huang, A. C.; Mathew, D.; Kuthuru, O.; Goodwin, E. C.; Weirick, M. E.; Bolton, M. J.; Arevalo, C. P.; Ramos, A.; Jasen, C.; Giannini, H. M.; DAndrea, K.; The UPenn COVID Processing Unit,; Meyer, N. J.; Behrens, E. M.; Bassiri, H.; Hensley, S. E.; Henrickson, S. E.; Teachey, D. T.; Betts, M. M. R.; Wherry, E. J.

Pediatric COVID-19 following SARS-CoV-2 infection is associated with fewer hospitalizations and often milder disease than in adults. A subset of children, however, present with Multisystem Inflammatory Syndrome in Children (MIS-C) that can lead to vascular complications and shock, but rarely death. The immune features of MIS-C compared to pediatric COVID-19 or adult disease remain poorly understood. We analyzed peripheral blood immune responses in hospitalized SARS-CoV-2 infected pediatric patients (pediatric COVID-19) and patients with MIS-C. MIS-C patients had patterns of T cell-biased lymphopenia and T cell activation similar to severely ill adults, and all patients with MIS-C had SARS-CoV-2 spike-specific antibodies at admission. A distinct feature of MIS-C patients was robust activation of vascular patrolling CX3CR1+ CD8 T cells that correlated with use of vasoactive medication. Finally, whereas pediatric COVID-19 patients with acute respiratory distress syndrome (ARDS) had sustained immune activation, MIS-C patients displayed clinical improvement over time, concomitant with decreasing immune activation. Thus, non-MIS-C versus MIS-C SARS-CoV-2 associated illnesses are characterized by divergent immune signatures that are temporally distinct and implicate CD8 T cells in clinical presentation and trajectory of MIS-C.