2026-06-24 | Rash, Fever, and a Diagnostic Puzzle: Recognizing MIS-C Among Mimicking Illnesses in a Child After COVID-19 Exposure — A Case Report

Multisystem inflammatory syndrome in children (MIS-C) is a delayed hyperinflammatory condition following SARS-CoV-2 infection that can mimic Kawasaki disease, sepsis, and toxic shock. A previously healthy 9-year-old boy presented on illness day 5 with fever (102.9°F), non-pruritic maculopapular rash, bilateral ankle pain with refusal to walk, and exertional dyspnea. Initial findings included room-air oxygen saturation of 87% with tachypnea (respiratory rate in the 40s), requiring supplemental oxygen via oxymask (2-3 L/min); ICU-level care was not required. Laboratory evaluation revealed markedly elevated C-reactive protein (25.16 mg/dL; reference ≤0.90), erythrocyte sedimentation rate (50 mm/hr; reference 0-15), transaminitis, direct hyperbilirubinemia, positive rapid streptococcal antigen, and anti-streptolysin O titer 1,650 IU/mL (reference <200). Chest radiography showed hypoinflated lungs with prominent vasculature but no consolidation. Echocardiography revealed elevated right ventricular systolic pressure (approximately half to two-thirds systemic) with preserved biventricular function and no coronary artery abnormalities. Despite azithromycin, ceftriaxone, and piperacillin-tazobactam, inflammatory markers and hepatic function worsened. On admission day 4, rheumatology elicited a history of COVID-19 exposure approximately 2 weeks earlier. Additional testing showed elevated D-dimer (6,048 ng/mL FEU; reference 215-499), ferritin (471.8 ng/mL; reference 16-300), lactate dehydrogenase (480 U/L; reference 110-260), and B-type natriuretic peptide (156 pg/mL). Intravenous methylprednisolone 1 mg/kg every 12 hours led to rapid defervescence, respiratory improvement, and laboratory normalization. Anti-nucleocapsid SARS-CoV-2 antibodies later returned positive, consistent with prior natural infection. This case highlights how concurrent streptococcal carriage and hepatic dysfunction may obscure MIS-C and underscores the importance of exposure history, inflammatory testing, and early corticosteroid therapy.

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2026-06-11 | Screening of autoinflammatory genes in patients with SARS-CoV-2-associated MIS-C

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a rare but severe complication of SARS-CoV-2 infection, characterized by systemic hyperinflammation. Evidence indicates innate immunity defects may predispose children to MIS-C. Host genetics may influence MIS-C susceptibility and severity, but underlying mechanisms remain incompletely understood. The aim of this study was to identify rare genetic variants in autoinflammatory genes that may contribute to MIS-C. RESULTS: Whole-exome sequencing was performed in 21 unvaccinated Brazilian children with MIS-C, stratified as non-critical or critical. Variant prioritization focused on single nucleotide variants with minor allele frequency < 0.001 in autoinflammatory genes. Functional impact was inferred using variant pathogenicity metrics, gene constraint scores, and in silico molecular docking. Four heterozygous missense variants were prioritized in three genes (SH3BP2, CARD14, and ADAM17), all in critical patients. ADAM17 was the most constrained gene, with variants in protein maturation (P18L) and substrate recognition (T663N) domains. Docking analyses showed both substitutions could affected ADAM17 interactions. ADAM17-NOTCH1 binding was predicted to be impaired by in silico analysis. CONCLUSIONS: Rare deleterious variants in autoinflammatory genes, especially ADAM17, may influence immune regulation and MIS-C severity. Our results highlight genetic pathways underlying MIS-C and provide a framework for mechanistic studies. Understanding how ADAM17 variants affect immune regulation may improve risk stratification and guide targeted therapies.

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2026-05-08 | Therapy-induced modulation of cellular response in Multisystem Inflammatory Syndrome in Children (MIS-C) - insights into selected immune cells’ markers expression

Multisystem Inflammatory Syndrome in Children (MIS-C) is a rare but serious condition that develops weeks after SARS-CoV-2 exposure and involves systemic inflammation affecting multiple organs. Its exact pathophysiology remains unclear, with proposed mechanisms including cytokine storms, antibody-dependent enhancement, and genetic predispositions. This study aimed to evaluate the effects of immunomodulatory therapy-intravenous immunoglobulins (IVIG) and glucocorticosteroids (GCS) on peripheral immune cell composition in 24 children with MIS-C. Innate and adaptive immune cells populations were analyzed by flow cytometry before and after treatment (IVIG 2 g/kg; GCS 1-2 mg/kg/day). Prior to therapy, patients showed elevated counts and altered phenotypes of neutrophils, monocytes, and T cells. Following treatment, a reduction in CD64 expression on neutrophils and monocytes was observed, along with decreased numbers of inflammatory cells, indicating an immunomodulatory effect of IVIG and GCS. An increase in CD56 expression on monocytes suggested additional phenotypic changes within this compartment. These findings highlight CD64 as a marker of inflammatory activation in MIS-C and demonstrate that therapy reduces its expression, potentially reflecting diminished inflammation. Further research is needed to assess long-term immune effects of treatment in children with MIS-C.

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