Emerging Insights into the Pathophysiology of Multi-system Inflammatory Syndrome in Children Associated with COVID-19
The Canadian journal of cardiology
Multisystem inflammatory syndrome in children (MIS-C) has emerged as a rare, delayed hyperinflammatory response to SARS-CoV-2 infection, and causes severe morbidity in the pediatric age group. While MIS-C shares many clinical similarities to Kawasaki disease (KD), important differences in epidemiologic, clinical, immunologic and potentially genetic factors exist and suggest potential differences in pathophysiology and points to be explored and explained. Epidemiologic features include male predominance, peak age of 6-12 years, and specific racial and/or ethnicity predilections. MIS-C is characterized by fever, prominent gastrointestinal symptoms, mucocutaneous manifestations, respiratory symptoms, and neurological complaints, and patients often present with shock. Cardiac complications are frequent and include ventricular dysfunction, valvular regurgitation, pericardial effusion, coronary artery dilation and aneurysms, conduction abnormalities, and arrhythmias. Emerging evidence regarding potential immunologic mechanisms suggest that an exaggerated T-cell response to a superantigen on the SARS-CoV-2 spike glycoprotein, as well as the formation of autoantibodies against cardiovascular, gastrointestinal, and endothelial antigens, are major contributors to the inflammatory milieu of MIS-C. Further studies are needed to determine both shared and distinct immunologic pathway(s) that underlie the pathogenesis of MIS-C versus both acute SARS-CoV-2 infcction and KD. There is evidence to suggest that the rare risk of more benign mRNA vaccine -associated myopericarditis is outweighed by a reduced risk of more severe MIS-C. In the current review, we synthesize the published literature to describe associated factors and potential mechanisms regarding an increased risk of MIS-C and cardiac complications, provide insights into the underlying immunologic pathophysiology, and define similarities and differences with KD.
Lin, Justin; Harahsheh, Ashraf S.; Raghuveer, Geetha; Jain, Supriya; Chouieter, Nadine F.; Garrido-Garcia, Luis Martin; Dahdah, Nagib; Portman, Michael A.; Misra, Nilanjana; Khoury, Michael; Fabi, Marianna; Elias, Matthew D.; Dionne, Audrey; Lee, Simon; Selamet Tierney, Elif Seda; Ballweg, Jean A.; Manlhiot, Cedric; and McCrindle, Brian W., "Emerging Insights into the Pathophysiology of Multi-system Inflammatory Syndrome in Children Associated with COVID-19" (2023). GW Authored Works. Paper 2291.