Elevated risk for psychiatric outcomes in pediatric patients with Multisystem Inflammatory Syndrome (MIS-C): A review of neuroinflammatory and psychosocial stressors

• Published in: Brain, behavior, & immunity. Health behavior, & immunity. Health, 2024-07, Vol.38, p.100760-100760, Article 100760
• Main Authors: Pan, Tracy, Gallo, Meghan E., Donald, Kirsten A., Webb, Kate, Bath, Kevin G.
• Format: Article
• Language: English
• Subjects: Coronavirus; COVID-19; Early life adversity; MIS-C; Multisystem inflammatory syndrome in children; PIMS-TS; Psychiatric risk; Review
• ISSN: 2666-3546; 2666-3546
• DOI: 10.1016/j.bbih.2024.100760

Multisystem Inflammatory Syndrome in Children (MIS-C) is a secondary immune manifestation of COVID-19 involving multiple organ systems in the body, resulting in fever, skin rash, abdominal pain, nausea, shock, and cardiac dysfunction that often lead to hospitalization. Although many of these symptoms resolve following anti-inflammatory treatment, the long-term neurological and psychiatric sequelae of MIS-C are unknown. In this review, we will summarize two domains of the MIS-C disease course, 1) Neuroinflammation in the MIS-C brain and 2) Psychosocial disruptions resulting from stress and hospitalization. In both domains, we present existing clinical findings and hypothesize potential connections to psychiatric outcomes. This is the first review to conceptualize a holistic framework of psychiatric risk in MIS-C patients that includes neuroinflammatory and psychosocial risk factors. As cases of severe COVID-19 and MIS-C subside, it is important for clinicians to monitor outcomes in this vulnerable patient population. An overview of the neurophysiological and psychosocial stress pathways that may contribute to psychiatric risk in MIS-C patients. 1) Immune dysregulation during MIS-C inflammation may lead to leakage of the blood-brain-barrier and unwanted entry of inflammatory markers interleukin-6 (IL-6), IL-10, IL-18, IL-23, IL-27, interferon-alpha (IFN-α), interferon-gamma (IFN-γ), macrophage colony-stimulating factor (M-CSF), IL-17A, and chemokine ligand 9 (CXCL9). In particular, CXCL9 and IL-17A have been found to be uniquely elevated in patients with MIS-C, and we present a potential link between these inflammatory markers and later imbalances of neurotransmitter dynamics. Overall, many of these markers have been associated with psychiatric disorders, but the exact etiology of these outcomes is unknown. 2) MIS-C presents as a multi-hit model of stress by inflicting a combination of universal pandemic stressors (social, financial, and educational disruptions) and hospitalization stressors onto both patients and caretakers. Thus, both 1) neuroinflammatory and 2) psychosocial insults during the MIS-C disease course may negatively impact brain development and lead to elevated psychiatric risk. [Display omitted]