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:
categories:
Small molecules
antibodies
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.
2026-05-08 | 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.
2026-04-24 | Multisystem Inflammatory Syndrome in Children, United States, 2023–2024
Multisystem inflammatory syndrome in children (MIS-C) is rare following SARS-CoV-2 infection, but sporadic cases continue to be reported. This analysis of cases from 2023-2024 shows little change in clinical presentation between years. Among vaccine age-eligible children, 99% of cases occurred in children who were not up-to-date with COVID-19 vaccination.
2026-03-17 | Autoimmune Response in Children with Multisystem Inflammatory Syndrome in Children (MIS-C): Clinical Significance of ANA Positivity
zGiri: Bu almada, iddetli akut solunum sendromu koronavirs tip 2 enfeksiyonu sonrasnda ocuklarda gelien multisistem enflamatuvar sendrom (MIS-C) hastalarnda otoimmn yantlar incelendi ve antinkleer antikor (ANA) pozitifliinin klinik
proteins
2026-01-10 | Multisystem Inflammatory Syndrome in Children with tailored therapy and six-month outcome
BACKGROUND: Multisystem Inflammatory Syndrome in Children (MIS-C) is a hyperinflammatory condition with multi-organ involvement, particularly affecting the cardiac and gastrointestinal systems. Although immunomodulatory therapy is standard, treatment approaches vary. This study aimed to evaluate treatment modalities in MIS-C such as methylprednisolone (MP), intravenous immunoglobulin (IVIG), anakinra and therapeutic plasma exchange (TPE) based on clinical severity and laboratory parameters in a prospectively followed cohort. METHODS: A total of 125 MIS-C patients were included in the study and followed for at least 6 months after discharge. Patients were stratified by severity and treated with various immunomodulatory regimens, including IVIG+MP, IVIG+MP+anakinra, and IVIG+MP+anakinra+TPE. RESULTS: Patients with mild disease and low inflammatory markers (median CRP 9 mg/dL, ferritin 192 µg/dL) received IVIG+MP. Those with higher inflammation (CRP 20-24 mg/dL, ferritin 308-846 µg/dL) without cardio-pulmonary support were treated with IVIG+low-dose-MP+anakinra. Patients with shock, macrophage activation syndrome, or bicytopenia received IVIG+high-dose-MP+anakinra. TPE was added in cases requiring cardio-pulmonary support. Most were discharged without corticosteroids or anakinra; only 11% received a short outpatient prednisolone taper. CONCLUSION: The mid-term longitudinal assessment of MIS-C patients suggests that timely immunomodulatory therapies, guided by laboratory parameters, promote safe resolution of systemic inflammation and cardiac complications, and shorten treatment duration. IMPACT: Demonstrates that short-term, biomarker-guided use of anakinra and corticosteroids effectively controls hyperinflammation in MIS-C. Highlights that prolonged corticosteroid therapy may not be necessary, even in severe cases. Provides evidence of early cardiac recovery, including resolution of CAAs, without post-discharge steroids. Supports a steroid-sparing treatment approach, reducing risks of long-term immunosuppression. May inform future MIS-C treatment guidelines by minimizing the need for escalation therapy, ECMO, and related complications.
2025-08-27 | Pediatric and Adult Inborn Errors of Immunity and COVID-19: A Comparative Study.
COVID-19 has worse clinical outcomes in inborn errors of immunity (IEI) patients. We aimed to determine COVID-19-related hospitalization/ICU admission/mortality risk in patients with IEI. We included 62 COVID-19 (29 children and 33 adults) in a referral center. F/M ratio was 0.94 with median age, 19 (8 months-64 years) years. 53.2% had primary antibody deficiency. Hospitalization rate was 11/29 in children, 21/33 in adults and 7/11 in patients with combined immunodeficiency diseases. Myalgia was more common in adults compared to children (p = 0.013). Inpatients have more cough compared to outpatients (p = 0.002). D-dimer and ferritin levels were higher in inpatients (p = 0.033 and p = 0.046, respectively). Cough (OR: 6.05; [95% CI: 1.76-20.74], p = 0.004) and immunoglobulin replacement therapy use in IEI (OR: 5.15; [95% CI: 1.46-18.11], p = 0.010) were related to hospitalization risk. Inpatients with intensive care unit (ICU) admission had higher ferritin levels (p = 0.02). 77.4% had at least one comorbidity like pulmonary (45.2%), autoimmune (38.7%), and gastrointestinal diseases (32.3%). ICU admission was high in agammaglobulinemia (40%) and immune dyseregulation (ID) (16.6%). An LRBA deficiency patient experienced MIS-C (Multisystem Inflammatory Syndrome in Children) and another died. Eight patients, four in the present center, received convalescent plasma (X-linked agammaglobulinemia [XLA] [n = 3], autosomal recessive agammaglobulinemia [n = 1], LRBA deficiency [n = 1], and CTLA4 deficiency [n = 1], CVID [n = 1], and STAT1 deficiency [n = 1]). Overall mortality was 6.5%, high in ID (16.6%), none in children. Higher D-dimer and ferritin levels is associated with a higher hospitalization ratio- twice in adults compared to children. Overall mortality (6.5%) was about six times the general population with no mortality in children. A high ICU ratio in agammaglobulinemia, suggesting the importance of mucosal IgA in COVID-19 defense. Convalescent plasma helps shorten hospitalization period in agammaglobulinemia.
2024-11-04 | Post-COVID-19 Multisystem Inflammatory Syndrome in Adults (MIS-A) With Elevated Levels of Soluble Urokinase Plasminogen Activator Receptor (suPAR) Treated With Anakinra: A Case Report.
The COVID-19 pandemic has brought attention to a newly identified syndrome of multisystem inflammation. This potentially fatal complication of the disease was initially observed in children and later in adults. It affects primarily unvaccinated patients and may manifest within a timeframe of 2-12 weeks following infection. Soluble urokinase plasminogen activator receptor (suPAR), a novel biomarker, highlights the severity of inflammation and the degree of immune system activation. Herein, we report a case of a patient with multisystem inflammatory syndrome in adults (MIS-A) and markedly elevated suPAR levels, successfully treated with interleukin-1 (IL-1) receptor antagonist. A 59-year-old female was admitted to our hospital due to febrile illness (up to 40°C) with chills, vomiting, non-bloody diarrhea, and abdominal pain for four days prior to her admission. She tested positive for SARS-CoV-2 12 weeks before her presentation. During hospitalization, the patient deteriorated clinically with multiorgan involvement and hemodynamically instability, with concomitant markedly elevated inflammatory markers. Extensive workup with high suPAR levels led to post-COVID-19 MIS-A diagnosis, and treatment with dexamethasone and an interleukin-1 receptor antagonist (IL-1ra), anakinra, was administered. The subcutaneous injection of anakinra effectively and safely deterred MIS-A. Further research is needed to investigate the role of interleukin-1 inhibitors for the management of this potentially life-threatening condition.
2024-03-06 | MIS-C, inherited metabolic diseases and methylmalonic acidemia: a case report and review of the literature
Abstract Bacground Methylmalonic acidemia (MMA) secondary to mutase deficiency, mut0 , is an inborn error of metabolism causing complete enzyme deficiency. Multisystem Inflammatory Syndrome in Children (MIS-C) is a hyperinflammatory syndrome characterized by fever, inflammation, multiorgan impairment that manifests 14–60 days after the SARS-CoV-2 infection in patients aged < 21 years. Case presentation We describe the clinical case of a 2-year-old child with MMA secondary to mutase deficiency, with the documented homozygous mutation c.2179 C > T of MMUT gene, associated to mut0 phenotype. One month after SARS-CoV-2 infection, he presented fever, rash, significant increase of C-reactive protein (CRP), ferritin, triglycerides, (interleukin) IL-6, PRO-BNP, compatible with the diagnosis of MIS-C. He was treated with intravenous immunoglobulins (2gr/Kg), methylprednisolone (2 mg/Kg/day), with rapid clinical improvement. Ten days later, he showed the worsening of clinical conditions, with the recurrence of fever, vasculitic rash with palmoplantar extension, further increase of ferritin (1033 ug/l), IL-6 (146 pg/ml), PRO-BNP (5117 pg/ml), triglycerides, anemia, thrombocytopenia, metabolic acidosis with hyperlactatemia (180 mg/dl), increased urinary methylmalonic acid (200 mmol/mCreat), multiorgan failure. He was treated with sodium bicarbonate, thiamine, coenzyme Q, vitamin C, methylprednisolone and anakinra (2 mg/Kg/day). Three days after the start of anakinra, he showed a significant improvement of clinical and biochemical parameters and defervescence. 20 days later, a sepsis from Staphylococcus Aureus and Candida Albicans required the interruption of anakinra, with the worsening of the clinical and haematological parameters and the exitus. Conclusions Only a few cases of patients with inherited metabolic diseases (IMD) and MIS-C are described. However, to our knowledge, this is the first case of MIS-C in MMA described. The description of these clinical cases is a precious lesson for pediatricians to manage IMD therapeutic emergencies. Anakinra must be considered as a safe treatment of choice in IMD patients with MIS-C. The use of anakinra in patients with a severe form of MMA is safe and can be employed to treat MIS-C, gaining a substantial clinical and biochemical improvement.
2024-02-23 | Subcutaneous anakinra in the management of refractory MIS-C in France
Introduction Multisystemic inflammatory syndrome in children (MIS-C) is a therapeutic emergency and can lead to myocardial dysfunction (17%–75%) and heart failure (52%–53%). Intravenous immunoglobulins (IVIG) and corticosteroids (CST) have been validated for the management of this condition. Recent reports suggest that an interleukin-1 (IL-1) receptor antagonist, namely anakinra, may be a valuable add-on to the 2019 novel coronavirus disease (COVID-19) treatment for refractory patients. The purpose of this study was to describe the clinico-biological characteristics of patients treated with anakinra as well as the efficacy and safety of subcutaneous anakinra therapy in this condition. Methods The prospective multicentre study of children hospitalized for MIS-C between March 2020 and September 2022, including 23 international paediatric centres, followed for a mean duration of 3.072 ± 3.508 months. The patient data were extracted from the Juvenile Inflammatory Rheumatism (JIR) cohort. The clinico-pathological characteristics, cardiac ultrasound data, and adverse events were reported in patients receiving anakinra. Results Of the 470 children admitted with MIS-C, 18 French patients (50% girls) with a mean age of 10.06 ± 3.9 years were treated with subcutaneous anakinra. Anakinra was used in two situations, macrophage activation syndrome (MAS) (4 patients) and heart failure (14 patients) with a median left ventricular ejection fraction (LVEF) of 39.5% (30%–45%). The average dose of anakinra received was 2.53 ± 1.3 mg/kg/day for a median duration of 3 days. Prior to introduction, 78% ( n = 14/18) of the patients had received CST and 56% ( n = 10/18) had received IVIG. Only two patients received IVIG alone and six received CST alone plus anakinra. In 10% of cases, IVIG was poorly tolerated from a cardiovascular point of view and was discontinued. Transient elevations in serum transaminases were noted in four patients on anakinra without the need for treatment or dose modification. In all patients, rapid (48 h) improvement in myocardial function was observed (LVEF > 55%) with a concomitant significant decrease in myocardial enzymes ( p < 0.05). All patients survived with complete recovery of cardiac function without sequelae. Conclusions Subcutaneous anakinra appears to be a safe and effective treatment for the management of heart failure or MAS in MIS-C patients. The value of IVIG in these two situations remains to be reviewed.
small molecules
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.
2025-09-24 | Policy Adherence to Antithrombotic Therapy for Prophylactic Anticoagulation in Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with COVID-19
Overall, 40 (80%) patients were started on enoxaparin per our center's institutional guidelines. Our study demonstrated an empiric enoxaparin dose of 0.5 mg/kg (maximum initial dose 60 mg) every 12 hours resulted in zero venous thromboembolism events. In conjunction with a median dose of 3.1 mg/kg/d of aspirin, these doses resulted in one bleeding event.
2025-09-13 | Macrophage activation syndrome associated with multi-system inflammatory syndrome in children: a case report and cytokine profile
Macrophage activation syndrome (MAS) is a potentially life-threatening complication requiring early diagnosis and prompt treatment in rheumatic diseases such as systemic juvenile idiopathic arthritis (sJIA). Recently, multisystem inflammatory syndrome in children (MIS-C) associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was reported to be complicated by MAS. The diagnostic criteria for MAS-associated MIS-C (MIS-C/MAS) remain unknown. We report the case of a 12-year-old boy who presented with fever for 4 days, swollen cervical lymph nodes, conjunctival congestion, red lips, strawberry tongue, irregular erythematous lesions, abdominal pain, and diarrhoea; he had coronavirus disease 2019 (COVID-19) 1 month prior. The patient was diagnosed MIS-C/MAS based on the criteria for sJIA/MAS, treated with intravenous immunoglobulin, glucocorticoids, and cyclosporine without any coronary artery sequelae. Evaluation of the patient's serum cytokine profile revealed that CXCL9 level (14259 pg/mL, reference range <31-83 pg/mL) was significantly elevated, as in sJIA/MAS. Based on cytokine profiles, the diagnostic criteria for MIC-S/MAS may be consistent with those for sJIA/MAS. No previous studies have reported on the cytokine profiles of MIS-C/MAS. Pediatricians should consider that MIS-C may complicate MAS, such as sJIA. Glucocorticoids and cyclosporine may be considered in cases of MIS-C complicated by MAS.
2025-08-12 | Both Corticosteroids and Intravenous Immunoglobulin Protect From Aneurysms in Children With Multisystem Inflammatory Syndrome: A Multicenter Ambispective Study
Corticosteroids, IVIG and their combination appear to be protective against aneurysms in children with MIS-C compared with no immunomodulatory treatment. Although the 3 therapies showed no significant differences when compared with each other, only the combination significantly reduced the risk. Corticosteroids may still be a useful option when IVIG is limited.
cell therapies
2024-10-11 | NK Cell and Monocyte Dysfunction in Multisystem Inflammatory Syndrome in Children
Abstract Multisystem inflammatory syndrome in children (MIS-C) is a severe complication of SARS-CoV-2 infection characterized by multiorgan involvement and inflammation. Testing of cellular function ex vivo to understand the aberrant immune response in MIS-C is limited. Despite strong Ab production in MIS-C, SARS-CoV-2 nucleic acid testing can remain positive for 4–6 wk postinfection. Therefore, we hypothesized that dysfunctional cell-mediated Ab responses downstream of Ab production may be responsible for delayed clearance of viral products in MIS-C. In MIS-C, monocytes were hyperfunctional for phagocytosis and cytokine production, whereas NK cells were hypofunctional for both killing and cytokine production. The decreased NK cell cytotoxicity correlated with an NK exhaustion marker signature and systemic IL-6 levels. Potentially providing a therapeutic option, cellular engagers of CD16 and SARS-CoV-2 proteins were found to rescue NK cell function in vitro. Taken together, our results reveal dysregulation in Ab-mediated cellular responses of myeloid and NK cells that likely contribute to the immune pathology of this disease.
2024-04-18 | Antibody-mediated cellular responses are dysregulated in Multisystem Inflammatory Syndrome in Children (MIS-C)
Multisystem Inflammatory Syndrome in Children (MIS-C) is a severe complication of SARS-CoV-2 infection characterized by multi-organ involvement and inflammation. Testing of cellular function ex vivo to understand the aberrant immune response in MIS-C is limited. Despite strong antibody production in MIS-C, SARS-CoV-2 nucleic acid testing can remain positive for 4-6 weeks after infection. Therefore, we hypothesized that dysfunctional cell-mediated antibody responses downstream of antibody production may be responsible for delayed clearance of viral products in MIS-C. In MIS-C, monocytes were hyperfunctional for phagocytosis and cytokine production, while natural killer (NK) cells were hypofunctional for both killing and cytokine production. The decreased NK cell cytotoxicity correlated with an NK exhaustion marker signature and systemic IL-6 levels. Potentially providing a therapeutic option, cellular engagers of CD16 and SARS-CoV-2 proteins were found to rescue NK cell function in vitro. Together, our results reveal dysregulation in antibody-mediated cellular responses unique to MIS-C that likely contribute to the immune pathology of this disease.
2024-01-05 | “Extracorporeal membrane oxygenation outcomes in multisystem inflammatory syndrome of childhood – An extracorporeal life support organization registry study”,
Multisystem inflammatory disease in childhood (MIS-C) is a novel pediatric syndrome after a COVID-19 infection that causes systemic injury, with potential life-threatening hemodynamic compromise requiring Extracorporeal Membrane Oxygenation (ECMO) support. We performed an observational retrospective cohort study in children aged 0-18 years with MIS-C and non-MIS-C myocarditis on ECMO between January 2020 and December 2021, using the ELSO Registry database. We aimed to compare the outcomes of both populations and to identify factors for decreased survival in MIS-C patients on ECMO. The Extracorporeal Life Support Organization (ELSO) Registry reported 310 pediatric ECMO patients with MIS-C (56.1%) and non-MIS-C myocarditis (43.9%). No difference was found in survival to hospital discharge between groups (67.2% for MIS-C vs 69.1% for non-MIS-C myocarditis, p 0.725). Multivariable analysis demonstrated that ECPR and co-infection were significantly associated with decreased survival to hospital discharge in MIS-C patients (OR 0.138, p 0.01 and OR 0.44, p 0.02, respectively). Outcomes of children with MIS-C on ECMO support are similar to those of non-MIS-C myocarditis despite higher infectious, multiorgan dysfunction and respiratory complications accompanying COVID-19 infections. The use of ECMO for MIS-C patients seems to be feasible and safe. Prospective studies on the use of ECMO support in MIS-C patients may improve outcomes in this pediatric population.
2023-06-13 | Successful Use of Granulocyte and Monocyte Adsorptive Apheresis in a Patient with Post-COVID-19 Multisystem Inflammatory Syndrome in Adults
Multisystem inflammatory syndrome in adults (MIS-A) is a life-threatening disease that can develop weeks after coronavirus disease 2019 (COVID-19). MIS-A symptoms include multiorgan involvement, especially gastrointestinal tract and heart involvement, and Kawasaki disease-like symptoms. We herein report a 44-year-old Japanese man with MIS-A who had contracted COVID-19 five weeks ago and went into shock after acute gastroenteritis, acute kidney injury, and Kawasaki disease-like symptoms. Methylprednisone pulse and high-dose intravenous immunoglobulin resulted in recovery of shock and his renal function, but diffuse ST-segment elevation on electrocardiography and pericardial effusion with a fever emerged after therapy. Additional granulocyte-monocyte adsorptive apheresis successfully ameliorated the cardiac involvement.
2023-04-26 | Extracorporeal Membrane Oxygenation in an Adolescent with Multisystem Inflammatory Syndrome in Children
Multisystem inflammatory syndrome in children is a rare and potentially life-threatening disease that is associated with SARS-CoV-2 infection, characterized by hyperinflammation and multiorgan involvement. Cardiovascular involvement is common, including myocardial dysfunction often leading to cardiogenic shock. We present the case of a 17-year-old boy with fever, odynophagia, maculopapular rash and abdominal pain who developed a cardiogenic shock. Due to progressive deterioration of cardiac function despite optimized vasoactive support, veno-arterial extracorporeal membrane oxygenation support was initiated 12 hours after admission, with successful decannulation after seven days and discharge after 23 days, with normal cardiac function. The patient received corticosteroids and intravenous immunoglobulin. Early recognition and intensive care support are crucial for ensuring a successful outcome in severe cases of multisystem inflammatory syndrome. In cases of severe cardiogenic shock, extracorporeal membrane oxygenation support can be critical for survival and rapid recovery.
other
2023-12-01 | Neutralization of SARS-CoV-2 Omicron BQ.1, BQ.1.1 and XBB.1 variants following SARS-CoV-2 infection or vaccination in children
Emergence of highly transmissible Omicron subvariants led to increased SARS-CoV-2 infection and disease in children. However, minimal knowledge exists regarding the neutralization capacity against circulating Omicron BA.4/BA.5, BA.2.75, BQ.1, BQ.1.1 and XBB.1 subvariants following SARS-CoV-2 vaccination in children versus during acute or convalescent COVID-19, or versus multisystem inflammatory syndrome (MIS-C). Here, we evaluate virus-neutralizing capacity against SARS-CoV-2 variants in 151 age-stratified children ( <5, 5-11, 12-21 years old) hospitalized with acute severe COVID-19 or MIS-C or convalescent mild (outpatient) infection compared with 62 age-stratified vaccinated children. An age-associated effect on neutralizing antibodies is observed against SARS-CoV-2 following acute COVID-19 or vaccination. The primary series BNT162b2 mRNA vaccinated adolescents show higher vaccine-homologous WA-1 neutralizing titers compared with <12 years vaccinated children. Post-infection antibodies did not neutralize BQ.1, BQ.1.1 and XBB.1 subvariants. In contrast, monovalent mRNA vaccination induces more cross-neutralizing antibodies in young children <5 years against BQ.1, BQ.1.1 and XBB.1 variants compared with ≥5 years old children. Our study demonstrates that in children, infection and monovalent vaccination-induced neutralization activity is low against BQ.1, BQ.1.1 and XBB.1 variants. These findings suggest a need for improved SARS-CoV-2 vaccines to induce durable, more cross-reactive neutralizing antibodies to provide effective protection against emerging variants in children.
2022-11-20 | Serologic Responses to COVID-19 Vaccination in Children with History of Multisystem Inflammatory Syndrome (MIS-C)
ABSTRACT Understanding the serological responses to COVID-19 vaccination in children with history of MIS-C could inform vaccination recommendations. We prospectively enrolled five children hospitalized with MIS-C and measured SARS-CoV-2 binding IgG antibodies to spike protein variants longitudinally pre- and post-Pfizer-BioNTech BNT162b2 primary series COVID-19 vaccination. We found that SARS-CoV-2 variant cross-reactive IgG antibodies waned following acute MIS-C, but were significantly boosted with vaccination and maintained for at least 3 months. We then compared post-vaccination binding, pseudovirus neutralizing, and functional antibody-dependent cell-mediated cytotoxicity (ADCC) titers to the reference strain (Wuhan-hu-1) and Omicron variant (B.1.1.529) among previously healthy children (n=6) and children with history of MIS-C (n=5) or COVID-19 (n=5). Despite the breadth of binding antibodies elicited by vaccination in all three groups, pseudovirus neutralizing and ADCC titers were reduced to the Omicron variant. Vaccination after MIS-C or COVID-19 (hybrid immunity) conferred advantage in generating pseudovirus neutralizing and functional ADCC antibodies to Omicron.
2022-11-04 | Pitfalls in Understanding and Handling of Covid-19 Vaccination (“Any Fool Can Know. The Point Is to Understand”)
The aim of this article is to critically review the managing of vaccination over the course of the present COVID-19 pandemic against the knowledge that had already been at hand and the scientific data that had yet to be learned. In the period before vaccines for COVID-19 became available, the startling similarity in epidemiologic behavior between COVID-19 and the Spanish flu could be observed. The development of vaccines against COVID-19 has evolved at an unprecedented speed resulting in highly immunogenic vaccines with incredible protective characteristics covering a relatively short follow-up time in clinical trials. The rollout in the general population turned out to take significantly longer time than the duration of immunity conferred by a 2-dose vaccination schedule (about 3-4 months). Therefore, the SARS-CoV-2 was left with the opportunity for random mutations with each replication cycle, resulting in immune evasion, shortened incubation, shortened serial interval, and increased transmissibility. The short incubation period of COVID-19 requires a steady protective antibody titer to be maintained to avert infection, achieve herd immunity, and terminate the pandemic spread. The protective neutralization titer needed to avert symptomatic infection and infection altogether is about 3% and 20%, respectively, of the mean convalescent titer. The latter corresponds to an absolute titer of 1:10–1:30. The intensity and duration of protective vaccinal and hybrid humoral immunity are explored. From the present perspective, it was naive to believe that a 2-dose vaccination would suffice to counter COVID-19 primarily due to its short incubation and a roll-out that was not catching up with the waning protective vaccinal antibody levels. Besides, the spacing of doses and boosters with respect to previous infection or vaccination, and differences in natural immunity and vaccine-induced immunity (adenovirus-vectored and mRNA) are discussed. The issue of vaccination and multisystem inflammatory syndrome in children is briefly presented. Finally, ethical points are discussed as some vaccine production platforms and neutralization tests use human cell lines derived from aborted fetuses.Conclusion – If the COVID-19 vaccines had been licensed as 3-dose vaccines, with more generous spacing, e.g. 0-2-6 months, providing for quantitatively larger and temporally more durable humoral immunity, that would have enabled attaining a steadier herd immunity and probably a paradoxical earlier effect on stopping the transmission.
2022-09-01 | The Attitudes of the Patients with the Multisystem Inflammatory Syndrome in Children Secondary to SARS-CoV-2 Regarding COVID-19 Vaccines
Objective: Multisystem inflammatory syndrome (MIS-C) in children is an abnormal immune response that occurs after exposure to SARS-CoV-2. To our knowledge, there is no study demonstrating the efficacy and safety of the BNT162b2 mRNA vaccine in children who were diagnosed with MIS-C previously. In this study, we aimed to present the attitudes of MIS-C patients over the age of 12 years towards the COVID-19 vaccine, and the side effects of the vaccine in vaccinated patients.Materials and Methods: The files of patients who were followed up with the diagnosis of MIS-C between May 2020 and January 2022 aged 12 years and over were reviewed retrospectively.Results: Thirty-six patients (12 girls, 24 boys) were included in the study. The median age was 13.5 (12-17) years. Eight of the 36 patients (22.2%) were vaccinated at a median of 3 (3-6) months after the diagnosis of MIS-C. No side effects or disease reactivation was observed following vaccination. The most common reasons for patients' refusal to be vaccinated were having had the disease and being concerned about a recurrence.Conclusion: This study showed that COVID-19 vaccination was safe in children who were diagnosed with MIS-C, although most of our patients were against it.
2022-08-22 | Maternal COVID-19 Vaccine May Reduce the Risk of MIS-C in Infants: A Narrative Review
COVID-19 infection in the pediatric population usually leads to a mild illness, however, a rare but serious complication of MIS-C has been seen in children. MIS-C usually presents 2-4 weeks after COVID-19 infection or exposure, and rare reports have been documented in neonates. Vaccinations for COVID-19 have been approved for children 6 months and above in the United States, and recent reports suggest significantly low prevalence and risk of complications of MIS-C in vaccinated children compared to unvaccinated children. Vaccinations for COVID-19 are safe and recommended during pregnancy and prevent severe maternal morbidity and adverse birth outcomes. Evidence from other vaccine-preventable diseases suggests that through passive transplacental antibody transfer, maternal vaccinations are protective against infections in infants during the first 6 months of life. Various studies have demonstrated that maternal COVID-19 vaccination is associated with the presence of anti-spike protein antibodies in infants, persisting even at 6 months of age. Further, completion of a 2-dose primary mRNA COVID-19 vaccination series during pregnancy is associated with reduced risk for COVID-19–associated hospitalization among infants aged 6 months or less. Therefore, it can be hypothesized that maternal COVID-19 vaccination can reduce the risk of and severity of MIS-C in infants. In this article, we review the literature to support this hypothesis.
antibodies
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.
2026-05-08 | 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.
2026-04-24 | Multisystem Inflammatory Syndrome in Children, United States, 2023–2024
Multisystem inflammatory syndrome in children (MIS-C) is rare following SARS-CoV-2 infection, but sporadic cases continue to be reported. This analysis of cases from 2023-2024 shows little change in clinical presentation between years. Among vaccine age-eligible children, 99% of cases occurred in children who were not up-to-date with COVID-19 vaccination.
2026-03-17 | Autoimmune Response in Children with Multisystem Inflammatory Syndrome in Children (MIS-C): Clinical Significance of ANA Positivity
zGiri: Bu almada, iddetli akut solunum sendromu koronavirs tip 2 enfeksiyonu sonrasnda ocuklarda gelien multisistem enflamatuvar sendrom (MIS-C) hastalarnda otoimmn yantlar incelendi ve antinkleer antikor (ANA) pozitifliinin klinik
proteins
2026-01-10 | Multisystem Inflammatory Syndrome in Children with tailored therapy and six-month outcome
BACKGROUND: Multisystem Inflammatory Syndrome in Children (MIS-C) is a hyperinflammatory condition with multi-organ involvement, particularly affecting the cardiac and gastrointestinal systems. Although immunomodulatory therapy is standard, treatment approaches vary. This study aimed to evaluate treatment modalities in MIS-C such as methylprednisolone (MP), intravenous immunoglobulin (IVIG), anakinra and therapeutic plasma exchange (TPE) based on clinical severity and laboratory parameters in a prospectively followed cohort. METHODS: A total of 125 MIS-C patients were included in the study and followed for at least 6 months after discharge. Patients were stratified by severity and treated with various immunomodulatory regimens, including IVIG+MP, IVIG+MP+anakinra, and IVIG+MP+anakinra+TPE. RESULTS: Patients with mild disease and low inflammatory markers (median CRP 9 mg/dL, ferritin 192 µg/dL) received IVIG+MP. Those with higher inflammation (CRP 20-24 mg/dL, ferritin 308-846 µg/dL) without cardio-pulmonary support were treated with IVIG+low-dose-MP+anakinra. Patients with shock, macrophage activation syndrome, or bicytopenia received IVIG+high-dose-MP+anakinra. TPE was added in cases requiring cardio-pulmonary support. Most were discharged without corticosteroids or anakinra; only 11% received a short outpatient prednisolone taper. CONCLUSION: The mid-term longitudinal assessment of MIS-C patients suggests that timely immunomodulatory therapies, guided by laboratory parameters, promote safe resolution of systemic inflammation and cardiac complications, and shorten treatment duration. IMPACT: Demonstrates that short-term, biomarker-guided use of anakinra and corticosteroids effectively controls hyperinflammation in MIS-C. Highlights that prolonged corticosteroid therapy may not be necessary, even in severe cases. Provides evidence of early cardiac recovery, including resolution of CAAs, without post-discharge steroids. Supports a steroid-sparing treatment approach, reducing risks of long-term immunosuppression. May inform future MIS-C treatment guidelines by minimizing the need for escalation therapy, ECMO, and related complications.
2025-08-27 | Pediatric and Adult Inborn Errors of Immunity and COVID-19: A Comparative Study.
COVID-19 has worse clinical outcomes in inborn errors of immunity (IEI) patients. We aimed to determine COVID-19-related hospitalization/ICU admission/mortality risk in patients with IEI. We included 62 COVID-19 (29 children and 33 adults) in a referral center. F/M ratio was 0.94 with median age, 19 (8 months-64 years) years. 53.2% had primary antibody deficiency. Hospitalization rate was 11/29 in children, 21/33 in adults and 7/11 in patients with combined immunodeficiency diseases. Myalgia was more common in adults compared to children (p = 0.013). Inpatients have more cough compared to outpatients (p = 0.002). D-dimer and ferritin levels were higher in inpatients (p = 0.033 and p = 0.046, respectively). Cough (OR: 6.05; [95% CI: 1.76-20.74], p = 0.004) and immunoglobulin replacement therapy use in IEI (OR: 5.15; [95% CI: 1.46-18.11], p = 0.010) were related to hospitalization risk. Inpatients with intensive care unit (ICU) admission had higher ferritin levels (p = 0.02). 77.4% had at least one comorbidity like pulmonary (45.2%), autoimmune (38.7%), and gastrointestinal diseases (32.3%). ICU admission was high in agammaglobulinemia (40%) and immune dyseregulation (ID) (16.6%). An LRBA deficiency patient experienced MIS-C (Multisystem Inflammatory Syndrome in Children) and another died. Eight patients, four in the present center, received convalescent plasma (X-linked agammaglobulinemia [XLA] [n = 3], autosomal recessive agammaglobulinemia [n = 1], LRBA deficiency [n = 1], and CTLA4 deficiency [n = 1], CVID [n = 1], and STAT1 deficiency [n = 1]). Overall mortality was 6.5%, high in ID (16.6%), none in children. Higher D-dimer and ferritin levels is associated with a higher hospitalization ratio- twice in adults compared to children. Overall mortality (6.5%) was about six times the general population with no mortality in children. A high ICU ratio in agammaglobulinemia, suggesting the importance of mucosal IgA in COVID-19 defense. Convalescent plasma helps shorten hospitalization period in agammaglobulinemia.
2024-11-04 | Post-COVID-19 Multisystem Inflammatory Syndrome in Adults (MIS-A) With Elevated Levels of Soluble Urokinase Plasminogen Activator Receptor (suPAR) Treated With Anakinra: A Case Report.
The COVID-19 pandemic has brought attention to a newly identified syndrome of multisystem inflammation. This potentially fatal complication of the disease was initially observed in children and later in adults. It affects primarily unvaccinated patients and may manifest within a timeframe of 2-12 weeks following infection. Soluble urokinase plasminogen activator receptor (suPAR), a novel biomarker, highlights the severity of inflammation and the degree of immune system activation. Herein, we report a case of a patient with multisystem inflammatory syndrome in adults (MIS-A) and markedly elevated suPAR levels, successfully treated with interleukin-1 (IL-1) receptor antagonist. A 59-year-old female was admitted to our hospital due to febrile illness (up to 40°C) with chills, vomiting, non-bloody diarrhea, and abdominal pain for four days prior to her admission. She tested positive for SARS-CoV-2 12 weeks before her presentation. During hospitalization, the patient deteriorated clinically with multiorgan involvement and hemodynamically instability, with concomitant markedly elevated inflammatory markers. Extensive workup with high suPAR levels led to post-COVID-19 MIS-A diagnosis, and treatment with dexamethasone and an interleukin-1 receptor antagonist (IL-1ra), anakinra, was administered. The subcutaneous injection of anakinra effectively and safely deterred MIS-A. Further research is needed to investigate the role of interleukin-1 inhibitors for the management of this potentially life-threatening condition.
2024-03-06 | MIS-C, inherited metabolic diseases and methylmalonic acidemia: a case report and review of the literature
Abstract Bacground Methylmalonic acidemia (MMA) secondary to mutase deficiency, mut0 , is an inborn error of metabolism causing complete enzyme deficiency. Multisystem Inflammatory Syndrome in Children (MIS-C) is a hyperinflammatory syndrome characterized by fever, inflammation, multiorgan impairment that manifests 14–60 days after the SARS-CoV-2 infection in patients aged < 21 years. Case presentation We describe the clinical case of a 2-year-old child with MMA secondary to mutase deficiency, with the documented homozygous mutation c.2179 C > T of MMUT gene, associated to mut0 phenotype. One month after SARS-CoV-2 infection, he presented fever, rash, significant increase of C-reactive protein (CRP), ferritin, triglycerides, (interleukin) IL-6, PRO-BNP, compatible with the diagnosis of MIS-C. He was treated with intravenous immunoglobulins (2gr/Kg), methylprednisolone (2 mg/Kg/day), with rapid clinical improvement. Ten days later, he showed the worsening of clinical conditions, with the recurrence of fever, vasculitic rash with palmoplantar extension, further increase of ferritin (1033 ug/l), IL-6 (146 pg/ml), PRO-BNP (5117 pg/ml), triglycerides, anemia, thrombocytopenia, metabolic acidosis with hyperlactatemia (180 mg/dl), increased urinary methylmalonic acid (200 mmol/mCreat), multiorgan failure. He was treated with sodium bicarbonate, thiamine, coenzyme Q, vitamin C, methylprednisolone and anakinra (2 mg/Kg/day). Three days after the start of anakinra, he showed a significant improvement of clinical and biochemical parameters and defervescence. 20 days later, a sepsis from Staphylococcus Aureus and Candida Albicans required the interruption of anakinra, with the worsening of the clinical and haematological parameters and the exitus. Conclusions Only a few cases of patients with inherited metabolic diseases (IMD) and MIS-C are described. However, to our knowledge, this is the first case of MIS-C in MMA described. The description of these clinical cases is a precious lesson for pediatricians to manage IMD therapeutic emergencies. Anakinra must be considered as a safe treatment of choice in IMD patients with MIS-C. The use of anakinra in patients with a severe form of MMA is safe and can be employed to treat MIS-C, gaining a substantial clinical and biochemical improvement.
2024-02-23 | Subcutaneous anakinra in the management of refractory MIS-C in France
Introduction Multisystemic inflammatory syndrome in children (MIS-C) is a therapeutic emergency and can lead to myocardial dysfunction (17%–75%) and heart failure (52%–53%). Intravenous immunoglobulins (IVIG) and corticosteroids (CST) have been validated for the management of this condition. Recent reports suggest that an interleukin-1 (IL-1) receptor antagonist, namely anakinra, may be a valuable add-on to the 2019 novel coronavirus disease (COVID-19) treatment for refractory patients. The purpose of this study was to describe the clinico-biological characteristics of patients treated with anakinra as well as the efficacy and safety of subcutaneous anakinra therapy in this condition. Methods The prospective multicentre study of children hospitalized for MIS-C between March 2020 and September 2022, including 23 international paediatric centres, followed for a mean duration of 3.072 ± 3.508 months. The patient data were extracted from the Juvenile Inflammatory Rheumatism (JIR) cohort. The clinico-pathological characteristics, cardiac ultrasound data, and adverse events were reported in patients receiving anakinra. Results Of the 470 children admitted with MIS-C, 18 French patients (50% girls) with a mean age of 10.06 ± 3.9 years were treated with subcutaneous anakinra. Anakinra was used in two situations, macrophage activation syndrome (MAS) (4 patients) and heart failure (14 patients) with a median left ventricular ejection fraction (LVEF) of 39.5% (30%–45%). The average dose of anakinra received was 2.53 ± 1.3 mg/kg/day for a median duration of 3 days. Prior to introduction, 78% ( n = 14/18) of the patients had received CST and 56% ( n = 10/18) had received IVIG. Only two patients received IVIG alone and six received CST alone plus anakinra. In 10% of cases, IVIG was poorly tolerated from a cardiovascular point of view and was discontinued. Transient elevations in serum transaminases were noted in four patients on anakinra without the need for treatment or dose modification. In all patients, rapid (48 h) improvement in myocardial function was observed (LVEF > 55%) with a concomitant significant decrease in myocardial enzymes ( p < 0.05). All patients survived with complete recovery of cardiac function without sequelae. Conclusions Subcutaneous anakinra appears to be a safe and effective treatment for the management of heart failure or MAS in MIS-C patients. The value of IVIG in these two situations remains to be reviewed.
small molecules
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.
2025-09-24 | Policy Adherence to Antithrombotic Therapy for Prophylactic Anticoagulation in Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with COVID-19
Overall, 40 (80%) patients were started on enoxaparin per our center's institutional guidelines. Our study demonstrated an empiric enoxaparin dose of 0.5 mg/kg (maximum initial dose 60 mg) every 12 hours resulted in zero venous thromboembolism events. In conjunction with a median dose of 3.1 mg/kg/d of aspirin, these doses resulted in one bleeding event.
2025-09-13 | Macrophage activation syndrome associated with multi-system inflammatory syndrome in children: a case report and cytokine profile
Macrophage activation syndrome (MAS) is a potentially life-threatening complication requiring early diagnosis and prompt treatment in rheumatic diseases such as systemic juvenile idiopathic arthritis (sJIA). Recently, multisystem inflammatory syndrome in children (MIS-C) associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was reported to be complicated by MAS. The diagnostic criteria for MAS-associated MIS-C (MIS-C/MAS) remain unknown. We report the case of a 12-year-old boy who presented with fever for 4 days, swollen cervical lymph nodes, conjunctival congestion, red lips, strawberry tongue, irregular erythematous lesions, abdominal pain, and diarrhoea; he had coronavirus disease 2019 (COVID-19) 1 month prior. The patient was diagnosed MIS-C/MAS based on the criteria for sJIA/MAS, treated with intravenous immunoglobulin, glucocorticoids, and cyclosporine without any coronary artery sequelae. Evaluation of the patient's serum cytokine profile revealed that CXCL9 level (14259 pg/mL, reference range <31-83 pg/mL) was significantly elevated, as in sJIA/MAS. Based on cytokine profiles, the diagnostic criteria for MIC-S/MAS may be consistent with those for sJIA/MAS. No previous studies have reported on the cytokine profiles of MIS-C/MAS. Pediatricians should consider that MIS-C may complicate MAS, such as sJIA. Glucocorticoids and cyclosporine may be considered in cases of MIS-C complicated by MAS.
2025-08-12 | Both Corticosteroids and Intravenous Immunoglobulin Protect From Aneurysms in Children With Multisystem Inflammatory Syndrome: A Multicenter Ambispective Study
Corticosteroids, IVIG and their combination appear to be protective against aneurysms in children with MIS-C compared with no immunomodulatory treatment. Although the 3 therapies showed no significant differences when compared with each other, only the combination significantly reduced the risk. Corticosteroids may still be a useful option when IVIG is limited.
cell therapies
2024-10-11 | NK Cell and Monocyte Dysfunction in Multisystem Inflammatory Syndrome in Children
Abstract Multisystem inflammatory syndrome in children (MIS-C) is a severe complication of SARS-CoV-2 infection characterized by multiorgan involvement and inflammation. Testing of cellular function ex vivo to understand the aberrant immune response in MIS-C is limited. Despite strong Ab production in MIS-C, SARS-CoV-2 nucleic acid testing can remain positive for 4–6 wk postinfection. Therefore, we hypothesized that dysfunctional cell-mediated Ab responses downstream of Ab production may be responsible for delayed clearance of viral products in MIS-C. In MIS-C, monocytes were hyperfunctional for phagocytosis and cytokine production, whereas NK cells were hypofunctional for both killing and cytokine production. The decreased NK cell cytotoxicity correlated with an NK exhaustion marker signature and systemic IL-6 levels. Potentially providing a therapeutic option, cellular engagers of CD16 and SARS-CoV-2 proteins were found to rescue NK cell function in vitro. Taken together, our results reveal dysregulation in Ab-mediated cellular responses of myeloid and NK cells that likely contribute to the immune pathology of this disease.
2024-04-18 | Antibody-mediated cellular responses are dysregulated in Multisystem Inflammatory Syndrome in Children (MIS-C)
Multisystem Inflammatory Syndrome in Children (MIS-C) is a severe complication of SARS-CoV-2 infection characterized by multi-organ involvement and inflammation. Testing of cellular function ex vivo to understand the aberrant immune response in MIS-C is limited. Despite strong antibody production in MIS-C, SARS-CoV-2 nucleic acid testing can remain positive for 4-6 weeks after infection. Therefore, we hypothesized that dysfunctional cell-mediated antibody responses downstream of antibody production may be responsible for delayed clearance of viral products in MIS-C. In MIS-C, monocytes were hyperfunctional for phagocytosis and cytokine production, while natural killer (NK) cells were hypofunctional for both killing and cytokine production. The decreased NK cell cytotoxicity correlated with an NK exhaustion marker signature and systemic IL-6 levels. Potentially providing a therapeutic option, cellular engagers of CD16 and SARS-CoV-2 proteins were found to rescue NK cell function in vitro. Together, our results reveal dysregulation in antibody-mediated cellular responses unique to MIS-C that likely contribute to the immune pathology of this disease.
2024-01-05 | “Extracorporeal membrane oxygenation outcomes in multisystem inflammatory syndrome of childhood – An extracorporeal life support organization registry study”,
Multisystem inflammatory disease in childhood (MIS-C) is a novel pediatric syndrome after a COVID-19 infection that causes systemic injury, with potential life-threatening hemodynamic compromise requiring Extracorporeal Membrane Oxygenation (ECMO) support. We performed an observational retrospective cohort study in children aged 0-18 years with MIS-C and non-MIS-C myocarditis on ECMO between January 2020 and December 2021, using the ELSO Registry database. We aimed to compare the outcomes of both populations and to identify factors for decreased survival in MIS-C patients on ECMO. The Extracorporeal Life Support Organization (ELSO) Registry reported 310 pediatric ECMO patients with MIS-C (56.1%) and non-MIS-C myocarditis (43.9%). No difference was found in survival to hospital discharge between groups (67.2% for MIS-C vs 69.1% for non-MIS-C myocarditis, p 0.725). Multivariable analysis demonstrated that ECPR and co-infection were significantly associated with decreased survival to hospital discharge in MIS-C patients (OR 0.138, p 0.01 and OR 0.44, p 0.02, respectively). Outcomes of children with MIS-C on ECMO support are similar to those of non-MIS-C myocarditis despite higher infectious, multiorgan dysfunction and respiratory complications accompanying COVID-19 infections. The use of ECMO for MIS-C patients seems to be feasible and safe. Prospective studies on the use of ECMO support in MIS-C patients may improve outcomes in this pediatric population.
2023-06-13 | Successful Use of Granulocyte and Monocyte Adsorptive Apheresis in a Patient with Post-COVID-19 Multisystem Inflammatory Syndrome in Adults
Multisystem inflammatory syndrome in adults (MIS-A) is a life-threatening disease that can develop weeks after coronavirus disease 2019 (COVID-19). MIS-A symptoms include multiorgan involvement, especially gastrointestinal tract and heart involvement, and Kawasaki disease-like symptoms. We herein report a 44-year-old Japanese man with MIS-A who had contracted COVID-19 five weeks ago and went into shock after acute gastroenteritis, acute kidney injury, and Kawasaki disease-like symptoms. Methylprednisone pulse and high-dose intravenous immunoglobulin resulted in recovery of shock and his renal function, but diffuse ST-segment elevation on electrocardiography and pericardial effusion with a fever emerged after therapy. Additional granulocyte-monocyte adsorptive apheresis successfully ameliorated the cardiac involvement.
2023-04-26 | Extracorporeal Membrane Oxygenation in an Adolescent with Multisystem Inflammatory Syndrome in Children
Multisystem inflammatory syndrome in children is a rare and potentially life-threatening disease that is associated with SARS-CoV-2 infection, characterized by hyperinflammation and multiorgan involvement. Cardiovascular involvement is common, including myocardial dysfunction often leading to cardiogenic shock. We present the case of a 17-year-old boy with fever, odynophagia, maculopapular rash and abdominal pain who developed a cardiogenic shock. Due to progressive deterioration of cardiac function despite optimized vasoactive support, veno-arterial extracorporeal membrane oxygenation support was initiated 12 hours after admission, with successful decannulation after seven days and discharge after 23 days, with normal cardiac function. The patient received corticosteroids and intravenous immunoglobulin. Early recognition and intensive care support are crucial for ensuring a successful outcome in severe cases of multisystem inflammatory syndrome. In cases of severe cardiogenic shock, extracorporeal membrane oxygenation support can be critical for survival and rapid recovery.
other
2023-12-01 | Neutralization of SARS-CoV-2 Omicron BQ.1, BQ.1.1 and XBB.1 variants following SARS-CoV-2 infection or vaccination in children
Emergence of highly transmissible Omicron subvariants led to increased SARS-CoV-2 infection and disease in children. However, minimal knowledge exists regarding the neutralization capacity against circulating Omicron BA.4/BA.5, BA.2.75, BQ.1, BQ.1.1 and XBB.1 subvariants following SARS-CoV-2 vaccination in children versus during acute or convalescent COVID-19, or versus multisystem inflammatory syndrome (MIS-C). Here, we evaluate virus-neutralizing capacity against SARS-CoV-2 variants in 151 age-stratified children ( <5, 5-11, 12-21 years old) hospitalized with acute severe COVID-19 or MIS-C or convalescent mild (outpatient) infection compared with 62 age-stratified vaccinated children. An age-associated effect on neutralizing antibodies is observed against SARS-CoV-2 following acute COVID-19 or vaccination. The primary series BNT162b2 mRNA vaccinated adolescents show higher vaccine-homologous WA-1 neutralizing titers compared with <12 years vaccinated children. Post-infection antibodies did not neutralize BQ.1, BQ.1.1 and XBB.1 subvariants. In contrast, monovalent mRNA vaccination induces more cross-neutralizing antibodies in young children <5 years against BQ.1, BQ.1.1 and XBB.1 variants compared with ≥5 years old children. Our study demonstrates that in children, infection and monovalent vaccination-induced neutralization activity is low against BQ.1, BQ.1.1 and XBB.1 variants. These findings suggest a need for improved SARS-CoV-2 vaccines to induce durable, more cross-reactive neutralizing antibodies to provide effective protection against emerging variants in children.
2022-11-20 | Serologic Responses to COVID-19 Vaccination in Children with History of Multisystem Inflammatory Syndrome (MIS-C)
ABSTRACT Understanding the serological responses to COVID-19 vaccination in children with history of MIS-C could inform vaccination recommendations. We prospectively enrolled five children hospitalized with MIS-C and measured SARS-CoV-2 binding IgG antibodies to spike protein variants longitudinally pre- and post-Pfizer-BioNTech BNT162b2 primary series COVID-19 vaccination. We found that SARS-CoV-2 variant cross-reactive IgG antibodies waned following acute MIS-C, but were significantly boosted with vaccination and maintained for at least 3 months. We then compared post-vaccination binding, pseudovirus neutralizing, and functional antibody-dependent cell-mediated cytotoxicity (ADCC) titers to the reference strain (Wuhan-hu-1) and Omicron variant (B.1.1.529) among previously healthy children (n=6) and children with history of MIS-C (n=5) or COVID-19 (n=5). Despite the breadth of binding antibodies elicited by vaccination in all three groups, pseudovirus neutralizing and ADCC titers were reduced to the Omicron variant. Vaccination after MIS-C or COVID-19 (hybrid immunity) conferred advantage in generating pseudovirus neutralizing and functional ADCC antibodies to Omicron.
2022-11-04 | Pitfalls in Understanding and Handling of Covid-19 Vaccination (“Any Fool Can Know. The Point Is to Understand”)
The aim of this article is to critically review the managing of vaccination over the course of the present COVID-19 pandemic against the knowledge that had already been at hand and the scientific data that had yet to be learned. In the period before vaccines for COVID-19 became available, the startling similarity in epidemiologic behavior between COVID-19 and the Spanish flu could be observed. The development of vaccines against COVID-19 has evolved at an unprecedented speed resulting in highly immunogenic vaccines with incredible protective characteristics covering a relatively short follow-up time in clinical trials. The rollout in the general population turned out to take significantly longer time than the duration of immunity conferred by a 2-dose vaccination schedule (about 3-4 months). Therefore, the SARS-CoV-2 was left with the opportunity for random mutations with each replication cycle, resulting in immune evasion, shortened incubation, shortened serial interval, and increased transmissibility. The short incubation period of COVID-19 requires a steady protective antibody titer to be maintained to avert infection, achieve herd immunity, and terminate the pandemic spread. The protective neutralization titer needed to avert symptomatic infection and infection altogether is about 3% and 20%, respectively, of the mean convalescent titer. The latter corresponds to an absolute titer of 1:10–1:30. The intensity and duration of protective vaccinal and hybrid humoral immunity are explored. From the present perspective, it was naive to believe that a 2-dose vaccination would suffice to counter COVID-19 primarily due to its short incubation and a roll-out that was not catching up with the waning protective vaccinal antibody levels. Besides, the spacing of doses and boosters with respect to previous infection or vaccination, and differences in natural immunity and vaccine-induced immunity (adenovirus-vectored and mRNA) are discussed. The issue of vaccination and multisystem inflammatory syndrome in children is briefly presented. Finally, ethical points are discussed as some vaccine production platforms and neutralization tests use human cell lines derived from aborted fetuses.Conclusion – If the COVID-19 vaccines had been licensed as 3-dose vaccines, with more generous spacing, e.g. 0-2-6 months, providing for quantitatively larger and temporally more durable humoral immunity, that would have enabled attaining a steadier herd immunity and probably a paradoxical earlier effect on stopping the transmission.
2022-09-01 | The Attitudes of the Patients with the Multisystem Inflammatory Syndrome in Children Secondary to SARS-CoV-2 Regarding COVID-19 Vaccines
Objective: Multisystem inflammatory syndrome (MIS-C) in children is an abnormal immune response that occurs after exposure to SARS-CoV-2. To our knowledge, there is no study demonstrating the efficacy and safety of the BNT162b2 mRNA vaccine in children who were diagnosed with MIS-C previously. In this study, we aimed to present the attitudes of MIS-C patients over the age of 12 years towards the COVID-19 vaccine, and the side effects of the vaccine in vaccinated patients.Materials and Methods: The files of patients who were followed up with the diagnosis of MIS-C between May 2020 and January 2022 aged 12 years and over were reviewed retrospectively.Results: Thirty-six patients (12 girls, 24 boys) were included in the study. The median age was 13.5 (12-17) years. Eight of the 36 patients (22.2%) were vaccinated at a median of 3 (3-6) months after the diagnosis of MIS-C. No side effects or disease reactivation was observed following vaccination. The most common reasons for patients' refusal to be vaccinated were having had the disease and being concerned about a recurrence.Conclusion: This study showed that COVID-19 vaccination was safe in children who were diagnosed with MIS-C, although most of our patients were against it.
2022-08-22 | Maternal COVID-19 Vaccine May Reduce the Risk of MIS-C in Infants: A Narrative Review
COVID-19 infection in the pediatric population usually leads to a mild illness, however, a rare but serious complication of MIS-C has been seen in children. MIS-C usually presents 2-4 weeks after COVID-19 infection or exposure, and rare reports have been documented in neonates. Vaccinations for COVID-19 have been approved for children 6 months and above in the United States, and recent reports suggest significantly low prevalence and risk of complications of MIS-C in vaccinated children compared to unvaccinated children. Vaccinations for COVID-19 are safe and recommended during pregnancy and prevent severe maternal morbidity and adverse birth outcomes. Evidence from other vaccine-preventable diseases suggests that through passive transplacental antibody transfer, maternal vaccinations are protective against infections in infants during the first 6 months of life. Various studies have demonstrated that maternal COVID-19 vaccination is associated with the presence of anti-spike protein antibodies in infants, persisting even at 6 months of age. Further, completion of a 2-dose primary mRNA COVID-19 vaccination series during pregnancy is associated with reduced risk for COVID-19–associated hospitalization among infants aged 6 months or less. Therefore, it can be hypothesized that maternal COVID-19 vaccination can reduce the risk of and severity of MIS-C in infants. In this article, we review the literature to support this hypothesis.
Access all drug discovery papers and probability of success in trials forecasts:
Access all drug discovery papers and probability of success in trials forecasts:
Drug Discovery Landscape
0 orphan drug designations.
0 orphan drug designations.
Let's accelerate rare disease drug discovery
Let's accelerate drug discovery
Get access to Explority AI’s forecasts to outperform average preclinical success rates. Whether you’re expanding your R&D pipeline, evaluating a partnership, or simply have a question — we’d love to hear from you.