Deep immune profiling of MIS-C demonstrates marked but transient immune activation compared with adult and pediatric COVID-19
Laura A. Vella, Josephine R. Giles, Amy E. Baxter, Derek A. Oldridge, Caroline Diorio, Leticia Kuri-Cervantes, Cécile Alanio, M. Betina Pampena, Jennifer E. Wu, Zeyu Chen, Yinghui Huang, Elizabeth M. Anderson, Sigrid Gouma, Kevin O. McNerney, Julie Chase, Chakkapong Burudpakdee, Jessica H. Lee, Sokratis A. Apostolidis, Alexander C. Huang, Divij Mathew, Oliva Kuthuru, Eileen C. Goodwin, Madison E. Weirick, Marcus J. Bolton, Claudia P. Arevalo, André Ramos, Cristina Jasen, Peyton Conrey, Samir Sayed, H.M. Giannini, Kurt D’Andrea, The UPenn COVID Processing Unit, Nuala J. Meyer, Edward M. Behrens, Hamid Bassiri, Scott E. Hensley, Sarah E. Henrickson, David T. Teachey, Michael R. Betts, E. John Wherry, Sharon Adamski, Zahidul Alam, Mary M. Addison, Katelyn T. Byrne, Aditi Chandra, Hélène C. Descamps, Nicholas Han, Yaroslav Kaminskiy, Shane Kammerman, Justin Kim, Allison R. Greenplate, Jacob T. Hamilton, Nune Markosyan, Julia Han Noll, Dalia K. Omran, Ajinkya Pattekar, Eric Perkey, Elizabeth M. Prager, Dana Pueschl, Austin K. Rennels, Jennifer Shah, Jake Shilan, Nils Wellhausen, Ashley Vanderbeck
Abstract
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 the 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 from one another and implicate CD8+ T cells in the clinical presentation and trajectory of MIS-C.