RARE DISEASE
Multisystem inflammatory syndrome in children and adults
Multisystem inflammatory syndrome in children and adults
Multisystem inflammatory syndrome in children and adults
Synonyms: MIS-C/A
Synonyms: MIS-C/A
Synonyms: MIS-C/A
Drug discovery
0
drugs
With orphan designations
Overview
Multisystem inflammatory syndrome (MIS) is a rare, life-threatening hyperinflammatory condition occurring 2–6 weeks after SARS-CoV-2 infection. It causes systemic inflammation affecting cardiovascular, gastrointestinal, mucocutaneous, and respiratory systems. MIS-C primarily affects children (<21 years), while MIS-A occurs in adults (>21 years), often requiring intensive care due to shock or organ dysfunction [1][5][17].
Categories: rare systemic and rheumatological diseases, rare systemic or rheumatologic diseases of childhood
Research Papers
354 drug discovery papers about Multisystem inflammatory syndrome in children and adults, with 3 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
354 drug discovery papers about Multisystem inflammatory syndrome in children and adults, with 3 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-07-28 | Multisystem inflammatory syndrome in children (MIS-C): an atypical presentation of varicella-zoster virus infection
Mucocutaneous: KD-related symptoms Rash, conjunctivitis, and oral mucositis Vasculitis-like rash Other organs: respiratory, renal, or neurologic Consolidation with pleural effusion Consolidation with pleural effusion III.Infectious triggers Detection by PCR, Ag, or Ab tests PCR (-) and Ab (+) for SARS-CoV-2 PCR (+) and Ab (+) for VZV Close contact with a COVID-19 case within 60 days No contact history of COVID-19 Contact history of COVID-19 (parents) Absence of a more likely alternative diagnosis No pathogens other than SARS-CoV-2 No pathogens other than VZV MIS-C: multisystem inflammatory syndrome in children, ICU: intensive care unit, CT: computed tomography, (+): present, (-): absent or not tested, CRP: C-reactive protein, AST: aspartate transaminase, ALT: alanine transaminase, TG: triglycerides, INR:
2026-07-24 | Measuring the inflammatory response in viral infections with an eye towards MIS-C
Multisystem Inflammatory Syndrome in Children (MIS-C) caused by a recent SARS CoV2 infection in a child, led to broad screening of acutely ill children for widespread inflammation and systemic disease due to need for early diagnosis and therapeutic intervention. This broad laboratory screening to rule-out MIS-C also inadvertently captured the patients who were found to have seasonal viral upper respiratory infections. Thus, this screening provided a unique opportunity to study the inflammatory response to some of the common viral infections. We performed a retrospective chart review for all patients under 18 who presented to the ER or were admitted to the hospital with a positive test for either 1) Viral URI, 2) Acute COVID-19, or 3) positive SARS CoV2 IgG, suggesting previous COVID-19 infection; between March 2020-October 2022. We reviewed 6628 patient encounters with 5312 encounters meeting inclusion criteria. Here we report that patients who had COVID IgG without other infection identified, most frequently showed widespread inflammation, as indicated by 56.7% of patients with 4 or more positive MIS-C criteria suggesting a diagnosis of MIS-C. One patient had a peak of 15 positive MIS-C criteria. Several seasonal viruses showed multisystem inflammatory responses in limited patients with the most frequent occurring in adenovirus (7.6% >= 4 criteria), and peaks of 9 or 10 criteria in sporadic patients for three seasonal viruses (adenovirus, rhinovirus/enterovirus, and parainfluenza viruses). Acute SARS CoV2 demonstrated elevated inflammatory states similar to seasonal cold viruses with a limited number of patients (4.3%) with >= 4 positive criteria markers of MIS-C, and a peak of 9 criteria. The most significant and largest differences between groups were observed in COVID IgG positive patients in comparison to each of the other viral groups followed by adenovirus compared to 5 out of 6 remaining viral pathogens.
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.
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.
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.
2026-07-28 | Multisystem inflammatory syndrome in children (MIS-C): an atypical presentation of varicella-zoster virus infection
Mucocutaneous: KD-related symptoms Rash, conjunctivitis, and oral mucositis Vasculitis-like rash Other organs: respiratory, renal, or neurologic Consolidation with pleural effusion Consolidation with pleural effusion III.Infectious triggers Detection by PCR, Ag, or Ab tests PCR (-) and Ab (+) for SARS-CoV-2 PCR (+) and Ab (+) for VZV Close contact with a COVID-19 case within 60 days No contact history of COVID-19 Contact history of COVID-19 (parents) Absence of a more likely alternative diagnosis No pathogens other than SARS-CoV-2 No pathogens other than VZV MIS-C: multisystem inflammatory syndrome in children, ICU: intensive care unit, CT: computed tomography, (+): present, (-): absent or not tested, CRP: C-reactive protein, AST: aspartate transaminase, ALT: alanine transaminase, TG: triglycerides, INR:
2026-07-24 | Measuring the inflammatory response in viral infections with an eye towards MIS-C
Multisystem Inflammatory Syndrome in Children (MIS-C) caused by a recent SARS CoV2 infection in a child, led to broad screening of acutely ill children for widespread inflammation and systemic disease due to need for early diagnosis and therapeutic intervention. This broad laboratory screening to rule-out MIS-C also inadvertently captured the patients who were found to have seasonal viral upper respiratory infections. Thus, this screening provided a unique opportunity to study the inflammatory response to some of the common viral infections. We performed a retrospective chart review for all patients under 18 who presented to the ER or were admitted to the hospital with a positive test for either 1) Viral URI, 2) Acute COVID-19, or 3) positive SARS CoV2 IgG, suggesting previous COVID-19 infection; between March 2020-October 2022. We reviewed 6628 patient encounters with 5312 encounters meeting inclusion criteria. Here we report that patients who had COVID IgG without other infection identified, most frequently showed widespread inflammation, as indicated by 56.7% of patients with 4 or more positive MIS-C criteria suggesting a diagnosis of MIS-C. One patient had a peak of 15 positive MIS-C criteria. Several seasonal viruses showed multisystem inflammatory responses in limited patients with the most frequent occurring in adenovirus (7.6% >= 4 criteria), and peaks of 9 or 10 criteria in sporadic patients for three seasonal viruses (adenovirus, rhinovirus/enterovirus, and parainfluenza viruses). Acute SARS CoV2 demonstrated elevated inflammatory states similar to seasonal cold viruses with a limited number of patients (4.3%) with >= 4 positive criteria markers of MIS-C, and a peak of 9 criteria. The most significant and largest differences between groups were observed in COVID IgG positive patients in comparison to each of the other viral groups followed by adenovirus compared to 5 out of 6 remaining viral pathogens.
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.
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.
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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