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Published on: August 7, 2017
Deep immune profiling of MIS-C demonstrates marked but transient immune activation compared to adult and pediatric
Laura A Vella1,2, Josephine R Giles2,3,4, Amy E Baxter2,3
1Division of Infectious Diseases, Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA. vellal@chop.edu wherry@pennmedicine.upenn.edu.
Insights
Multisystem Inflammatory Syndrome in Children (MIS-C) involves distinct immune responses, including T cell activation, compared to pediatric COVID-19. CD8+ T cells play a key role in MIS-C
Area of Science:
- Immunology
- Pediatrics
- Infectious Diseases
Background:
- Pediatric COVID-19 generally presents milder than adult disease, but a subset develops Multisystem Inflammatory Syndrome in Children (MIS-C).
- Immune system characteristics differentiating MIS-C from pediatric COVID-19 and adult COVID-19 are not well understood.
- MIS-C can lead to severe vascular complications and shock, though fatalities are rare.
Purpose of the Study:
- To compare peripheral blood immune responses between hospitalized pediatric COVID-19 patients and MIS-C patients.
- To elucidate the immune signatures associated with MIS-C and pediatric COVID-19.
- To investigate the role of specific immune cells, such as CD8+ T cells, in MIS-C pathogenesis.
Main Methods:
- Analysis of peripheral blood immune cell profiles in pediatric patients with SARS-CoV-2 infection.
- Comparison of immune responses between patients diagnosed with pediatric COVID-19 and MIS-C.
- Assessment of T cell lymphopenia, T cell activation, and SARS-CoV-2 spike-specific antibodies.
Main Results:
- MIS-C patients exhibited T cell-biased lymphopenia and T cell activation, mirroring patterns seen in severely ill adults.
- All MIS-C patients presented with SARS-CoV-2 spike-specific antibodies upon admission.
- A significant finding was the robust activation of vascular patrolling CX3CR1+ CD8+ T cells in MIS-C patients, correlating with vasoactive medication use. Pediatric COVID-19 patients with ARDS showed sustained immune activation, while MIS-C patients demonstrated decreasing immune activation with clinical improvement.
Conclusions:
- Pediatric COVID-19 and MIS-C exhibit distinct and temporally separated immune signatures.
- CD8+ T cell activation, particularly CX3CR1+ CD8+ T cells, is implicated in the clinical presentation and disease course of MIS-C.
- Understanding these divergent immune profiles is crucial for managing pediatric SARS-CoV-2 related illnesses.
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.
