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Updated: Dec 13, 2025
Author Spotlight: Advancements in Multiplex Detection of Respiratory Viruses
Published on: November 10, 2023
Multisystem inflammatory syndrome in children and COVID-19 are distinct presentations of SARS-CoV-2
Caroline Diorio1,2, Sarah E Henrickson1,3, Laura A Vella1,4
1Immune Dysregulation Frontier Program.
Insights
Distinguishing pediatric COVID-19 from multisystem inflammatory syndrome in children (MIS-C) is crucial. Unique cytokine profiles and blood smear findings like burr cells help differentiate severe COVID-19 from MIS-C in children.
Area of Science:
- Pediatric Infectious Diseases
- Immunology
- Hematology
Background:
- Initial reports indicated lower susceptibility to SARS-CoV-2 in children compared to adults.
- Emergence of a severe pediatric condition, multisystem inflammatory syndrome in children (MIS-C), distinct from COVID-19.
- Need for understanding unique hematologic and immunologic parameters differentiating pediatric COVID-19 and MIS-C.
Purpose of the Study:
- To identify distinct hematologic and immunologic markers between pediatric COVID-19 and MIS-C.
- To provide insights into the pathophysiology of these distinct conditions in children.
- To aid in the clinical differentiation of severe COVID-19 from MIS-C in pediatric patients.
Main Methods:
- Prospective enrollment of hospitalized pediatric patients with confirmed SARS-CoV-2 infection.
- Classification of patients into MIS-C, severe COVID-19, or minimal COVID-19 groups.
- Analysis of cytokine profiles (IFN-γ, IL-10, IL-6, IL-8, TNF-α), viral cycle thresholds (Cts), peripheral blood smear morphology (including burr cells), and soluble C5b-9 levels.
Main Results:
- Five key cytokines were analyzed; TNF-α and IL-10 levels differentiated MIS-C from severe COVID-19.
- Presence of burr cells on blood smears and viral cycle thresholds (Cts) distinguished severe COVID-19 from MIS-C.
- Study included 20 pediatric patients: 9 severe COVID-19, 5 minimal COVID-19, and 6 MIS-C.
Conclusions:
- Pediatric patients with SARS-CoV-2 infection are susceptible to critical illness, presenting as either severe COVID-19 or MIS-C.
- Cytokine profiling and peripheral blood smear examination are valuable tools for distinguishing MIS-C from severe COVID-19 in children.
- These findings contribute to understanding the distinct clinical and biological profiles of COVID-19 and MIS-C in pediatric populations.
Abstract:
BACKGROUNDInitial reports from the severe acute respiratory coronavirus 2 (SARS-CoV-2) pandemic described children as being less susceptible to coronavirus disease 2019 (COVID-19) than adults. Subsequently, a severe and novel pediatric disorder termed multisystem inflammatory syndrome in children (MIS-C) emerged. We report on unique hematologic and immunologic parameters that distinguish between COVID-19 and MIS-C and provide insight into pathophysiology.METHODSWe prospectively enrolled hospitalized patients with evidence of SARS-CoV-2 infection and classified them as having MIS-C or COVID-19. Patients with COVID-19 were classified as having either minimal or severe disease. Cytokine profiles, viral cycle thresholds (Cts), blood smears, and soluble C5b-9 values were analyzed with clinical data.RESULTSTwenty patients were enrolled (9 severe COVID-19, 5 minimal COVID-19, and 6 MIS-C). Five cytokines (IFN-γ, IL-10, IL-6, IL-8, and TNF-α) contributed to the analysis. TNF-α and IL-10 discriminated between patients with MIS-C and severe COVID-19. The presence of burr cells on blood smears, as well as Cts, differentiated between patients with severe COVID-19 and those with MIS-C.CONCLUSIONPediatric patients with SARS-CoV-2 are at risk for critical illness with severe COVID-19 and MIS-C. Cytokine profiling and examination of peripheral blood smears may distinguish between patients with MIS-C and those with severe COVID-19.FUNDINGFinancial support for this project was provided by CHOP Frontiers Program Immune Dysregulation Team; National Institute of Allergy and Infectious Diseases; National Cancer Institute; the Leukemia and Lymphoma Society; Cookies for Kids Cancer; Alex's Lemonade Stand Foundation for Childhood Cancer; Children's Oncology Group; Stand UP 2 Cancer; Team Connor; the Kate Amato Foundations; Burroughs Wellcome Fund CAMS; the Clinical Immunology Society; the American Academy of Allergy, Asthma, and Immunology; and the Institute for Translational Medicine and Therapeutics.
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