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

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....

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Bibliographic Details
Published in:Science Immunology 2021-03, Vol.6 (57)
Main Authors: Vella, Laura A, Giles, Josephine R, Baxter, Amy E, Oldridge, Derek A, Diorio, Caroline, Kuri-Cervantes, Leticia, Alanio, Cécile, Pampena, M Betina, Wu, Jennifer E, Chen, Zeyu, Huang, Yinghui Jane, Anderson, Elizabeth M, Gouma, Sigrid, McNerney, Kevin O, Chase, Julie, Burudpakdee, Chakkapong, Lee, Jessica H, Apostolidis, Sokratis A, Huang, Alexander C, Mathew, Divij, Kuthuru, Oliva, Goodwin, Eileen C, Weirick, Madison E, Bolton, Marcus J, Arevalo, Claudia P, Ramos, Andre, Jasen, C J, Conrey, Peyton E, Sayed, Samir, Giannini, Heather M, D'Andrea, Kurt, Meyer, Nuala J, Behrens, Edward M, Bassiri, Hamid, Hensley, Scott E, Henrickson, Sarah E, Teachey, David T, Betts, Michael R, Wherry, E John
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aging - immunology
Child
Child, Preschool
Coronavirus
COVID-19 - immunology
Female
Flow Cytometry
Humans
Leukopenia - immunology
Lymphocyte Activation
Male
Systemic Inflammatory Response Syndrome - immunology
T-Lymphocytes - immunology
Young Adult
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Summary: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.
ISSN:2470-9468
2470-9468
DOI:10.1126/sciimmunol.abf7570