Deep immune profiling of MIS-C demonstrates marked but transient immune activation compared with adult and pediatric COVID-19
Open Access
- 4 March 2021
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science Immunology
- Vol. 6 (57)
- https://doi.org/10.1126/sciimmunol.abf7570
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.Keywords
Funding Information
- National Institutes of Health (K08 AI136660)
- National Institutes of Health (AI105343)
- National Institutes of Health (AI082630)
- National Institutes of Health (HL137006)
- National Institutes of Health (HL137915)
- National Institutes of Health (CA230157)
- National Institutes of Health (R01CA193776)
- National Institutes of Health (CA234842)
- National Heart, Lung, and Blood Institute (HL137006)
- National Heart, Lung, and Blood Institute (HL13791)
- National Institutes of Health (T32-AI-007324)
- National Institutes of Health (R01AI121250)
- National Institute of Allergy and Infectious Diseases (AI105343)
- National Cancer Institute (CA009140)
- National Institutes of Health (T32 CA009140)
- National Institutes of Health (HL143613)
- National Institutes of Health (T32 CA009140)
- National Institute of Allergy and Infectious Diseases (K08 AI136660)
- The Parker Foundation
- Mark Foundation For Cancer Research
- University of Pennsylvania Institute for Immunology Glick (COVID-19)
- Paul G. Allen Frontiers Group
- Children's Hospital of Philadelphia
- Elektrobit
- Högskolan i Borås
- Classical Association
- Parker Institute for Cancer Immunotherapy
- National Institute of Allergy and Infectious Diseases (AI08263)
This publication has 81 references indexed in Scilit:
- T-box transcription factor T-bet, a key player in a unique type of B-cell activation essential for effective viral clearanceProceedings of the National Academy of Sciences of the United States of America, 2013
- Pathological Role of Fractalkine/CX3CL1 in Rheumatic Diseases: A Unique Chemokine with Multiple FunctionsFrontiers in Immunology, 2012
- Follicular Helper CD4 T Cells (TFH)Annual Review of Immunology, 2011
- Fractalkine/CX3CL1: A Potential New Target for Inflammatory DiseasesMolecular Interventions, 2010
- Role of PD-1 in regulating acute infectionsCurrent Opinion in Immunology, 2010
- Human Effector and Memory CD8+ T Cell Responses to Smallpox and Yellow Fever VaccinesImmunity, 2008
- PD-1 and Its Ligands in Tolerance and ImmunityAnnual Review of Immunology, 2008
- Molecular Signature of CD8+ T Cell Exhaustion during Chronic Viral InfectionImmunity, 2007
- PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progressionNature, 2006
- Effector and memory T-cell differentiation: implications for vaccine developmentNature Reviews Immunology, 2002