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Serologic and Cytokine Signatures in Children With Multisystem Inflammatory Syndrome and Coronavirus Disease 2019
Stacey A Lapp1,2, Joseph Abrams3, Austin T Lu1,2
1Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, USA.
Insights
Children with multisystem inflammatory syndrome (MIS-C) have higher SARS-CoV-2 antibody levels and acute inflammation compared to COVID-19. Elevated cytokines in MIS-C patients were linked to longer hospital stays.
Area of Science:
- Pediatric immunology
- Infectious diseases
- Virology
Background:
- The immune response in children with multisystem inflammatory syndrome (MIS-C) compared to COVID-19 is not well understood.
- Investigating serologic and cytokine differences is crucial for understanding MIS-C pathogenesis.
Purpose of the Study:
- To compare the serologic and cytokine profiles of children hospitalized with MIS-C versus acute COVID-19.
- To identify specific cytokine signatures associated with MIS-C and clinical outcomes.
Main Methods:
- A prospective, cross-sectional study involving hospitalized children with MIS-C, acute COVID-19, and healthy controls.
- Measurement of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike receptor-binding domain (RBD) immunoglobulin G (IgG) titers and cytokine levels.
- Multivariable analysis to identify cytokine signatures linked to MIS-C and prolonged hospitalization.
Main Results:
- Children with MIS-C exhibited significantly higher SARS-CoV-2 RBD IgG titers than those with acute COVID-19.
- MIS-C was characterized by acute hypercytokinemia, with elevated levels of IL-6, IL-10, IL-17A, and IFN-γ.
- Elevated levels of at least three key cytokines were associated with a higher prevalence of prolonged hospitalization (≥8 days).
Conclusions:
- MIS-C is associated with elevated SARS-CoV-2 RBD IgG antibody titers and acute hypercytokinemia.
- Specific cytokines (IL-6, IL-10, IL-17A, IFN-γ) are characteristic of the acute phase of MIS-C.
- Cytokine profiles may serve as biomarkers for disease severity and duration in MIS-C.
Background:
The serologic and cytokine responses of children hospitalized with multisystem inflammatory syndrome (MIS-C) vs coronavirus disease 2019 (COVID-19) are poorly understood.
Methods:
We performed a prospective, multicenter, cross-sectional study of hospitalized children who met the Centers for Disease Control and Prevention case definition for MIS-C (n = 118), acute COVID-19 (n = 88), or contemporaneous healthy controls (n = 24). We measured severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike receptor-binding domain (RBD) immunoglobulin G (IgG) titers and cytokine concentrations in patients and performed multivariable analysis to determine cytokine signatures associated with MIS-C. We also measured nucleocapsid IgG and convalescent RBD IgG in subsets of patients.
Results:
Children with MIS-C had significantly higher SARS-CoV-2 RBD IgG than children with acute COVID-19 (median, 2783 vs 146; P < .001), and titers correlated with nucleocapsid IgG. For patients with MIS-C, RBD IgG titers declined in convalescence (median, 2783 vs 1135; P = .010) in contrast to patients with COVID-19 (median, 146 vs 4795; P < .001). MIS-C was characterized by transient acute proinflammatory hypercytokinemia, including elevated levels of interleukin (IL) 6, IL-10, IL-17A, and interferon gamma (IFN-γ). Elevation of at least 3 of these cytokines was associated with significantly increased prevalence of prolonged hospitalization ≥8 days (prevalence ratio, 3.29 [95% CI, 1.17-9.23]).
Conclusions:
MIS-C was associated with high titers of SARS-CoV-2 RBD IgG antibodies and acute hypercytokinemia with IL-6, IL-10, IL-17A, and IFN-γ.
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