The Trilogy of SARS-CoV-2 in Pediatrics (Part 2): Multisystem Inflammatory Syndrome in Children

Multisystem Inflammatory Syndrome in Children (MIS-C) was first recognized as a novel illness in 2020 with manifestations similar to other hyperinflammatory syndromes, such as Kawasaki disease or macrophage activation syndrome. Severity varies from a self-limited febrile illness to shock requiring inotropes and mechanical ventilation. Gastrointestinal symptoms and persistent fevers are the most common clinical symptoms, with the addition of cardiac manifestations inclusive of ventricular dysfunction and coronary artery aneurysms. With no controlled trials or comparative effectiveness studies evaluating treatment of MIS-C to date, current treatment with immunomodulatory agents has mainly been derived from previous experience treating Kawasaki disease. This article provides a comprehensive review summarizing published data for the evaluation and management of MIS-C, with a focus on pharmacotherapy treatment considerations.

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Diversity of Cardiac and Gastrointestinal Presentations of Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with COVID-19: A Case Series

Global Pediatric Health ◽

10.1177/2333794x21996613 ◽

2021 ◽

Vol 8 ◽

pp. 2333794X2199661

Author(s):

Anuja R. Shikhare ◽

Rimsha M. Iqbal ◽

Rabail Tariq ◽

Daniel R. Turner ◽

Bassam M. Gebara ◽

...

Keyword(s):

Kawasaki Disease ◽

Gastrointestinal Symptoms ◽

Case Series ◽

Asymptomatic Infection ◽

Cardiac Monitoring ◽

Delayed Presentation ◽

Terminal Ileitis ◽

Serologic Evidence ◽

Cardiac Manifestations ◽

Inflammatory Syndrome

COVID-19 is generally a benign or asymptomatic infection in children, but can occasionally be severe or fatal. Delayed presentation of COVID-19 with hyperinflammation and multi-organ involvement was recently recognized, designated the Multisystem Inflammatory Syndrome in Children (MIS-C). Six children with MIS-C with molecular and serologic evidence of SARS-CoV-2 infection were admitted to our hospital between May 5, 2020 and June 25, 2020. All had fever and weakness; 4/6 presented with gastrointestinal symptoms. Two children had features of complete Kawasaki disease, 3 had incomplete Kawasaki disease, while 1 had terminal ileitis with delayed onset of circulatory shock. Treatment consisted of intravenous immunoglobulin and aspirin for Kawasaki-like disease. Remdesivir, corticosteroids, and infliximab were used when indicated. Median hospitalization was 7 days. Immediate treatment resulted in rapid clinical improvement. In children presenting with hyperinflammatory syndromes without cardiac manifestations, testing for SARS-CoV-2 RNA and antibodies, with close cardiac monitoring should be pursued due to the manifold presentations of SARS-CoV-2 infection in children.

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Coronavirus Disease 2019-Related Multisystem Inflammatory Syndrome in Children: A Systematic Review and Meta-Analysis

Biochemistry Research International ◽

10.1155/2021/5596727 ◽

2021 ◽

Vol 2021 ◽

pp. 1-11

Author(s):

Ji-Gan Wang ◽

Zhi-Juan Zhong ◽

Meng Li ◽

Jun Fu ◽

Yu-Heng Su ◽

...

Keyword(s):

Mortality Rate ◽

Kawasaki Disease ◽

Fixed Effects ◽

Clinical Symptoms ◽

Myocardial Dysfunction ◽

Clinical Manifestations ◽

Gastrointestinal Symptoms ◽

Musculoskeletal Symptoms ◽

Hands And Feet ◽

Inflammatory Syndrome

Background. This study aimed to describe the clinical symptoms, laboratory findings, treatment, and outcomes of coronavirus disease 2019-related multisystem inflammatory syndrome in children to provide a reference for clinical practice. Methods. We employed a literature search of databases such as PubMed, Web of Science, EMBASE, and Johns Hopkins University for articles on COVID-19-related multisystem inflammatory syndrome in children published between April 1, 2020, and January 15, 2021. High-quality articles were selected for analysis on the basis of their quality standard scores. Using R3.6.3 software, meta-analyses of random- or fixed-effects models were used to determine the prevalence of comorbidities. Subgroup analysis was also performed to determine heterogeneity. Results. A total of 57 articles (2,290 pediatric patients) were included in the study. Clinical Manifestations. :ncidences of fever, gastrointestinal symptoms, respiratory symptoms, and musculoskeletal symptoms (myalgias or arthralgias) were 99.91% (95% CI: 99.67–100%), 82.72% (95% CI: 78.19–86.81%), 53.02% (45.28–60.68%), and 14.16% (95% CI: 8.4–21.12%), respectively. The incidences of rash, conjunctival injection, lymphadenopathy, dry cracked lips, neurologic symptoms (headache, altered mental status, or confusion), swollen hands and feet, typical Kawasaki disease, and atypical Kawasaki disease were 59.34% (95% CI: 54.73–63.87%), 55.23% (95% CI: 50.22–60.19%), 27.07% (95% CI: 19.87–34.93%), 46.37% (95% CI: 39.97–52.83%), 28.87% (95% CI: 22.76–35.40%), 28.75% (95% CI: 21.46–36.64%), 17.32% (95% CI: 15.44–19.29%), and 36.19% (95% CI: 21.90–51.86%), respectively. The incidences of coronary artery dilation, aneurysm, pericardial effusion, myocarditis, myocardial dysfunction, high troponin, and N-terminal pro-B-type natriuretic peptide were 17.83%, 6.85%, 20.97%, 35.97%, 56.32%, 76.34%, and 86.65%, respectively. The incidences of reduced lymphocytes, thrombocytopenia, hypoalbuminemia, elevated C-reactive protein, ferritin, LDH, interleukin-6, PCT, and FIB were 61.51%, 26.42%, 77.92%, 98.5%, 86.79%, 80.59%, 89.30%, 85.10%, and 87.01%, respectively. PICU Hospitalization Rate and Mortality. The incidences of PICU hospitalization or with shock were 72.79% and 55.68%, respectively. The mortality rate was 1.00%. Conclusion and Relevance. PICU hospitalization and shock rates of multisystem inflammatory syndrome in children associated with COVID-19 were high, and its cumulative multiorgans and inflammatory indicators are increased, but if treated in time, the mortality rate was low.

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COVID-19 and Multisystem Inflammatory Syndrome in Children: A Systematic Review and Meta-analysis

10.22541/au.160571540.02057981/v1 ◽

2020 ◽

Author(s):

Jun Yasuhara ◽

Kae Watanabe ◽

Hisato Takagi ◽

Naokata Sumitomo ◽

Toshiki Kuno

Keyword(s):

Kawasaki Disease ◽

Clinical Symptoms ◽

Myocardial Dysfunction ◽

Meta Analysis ◽

Gastrointestinal Symptoms ◽

Multiple Organ ◽

Coronary Abnormalities ◽

Cardiovascular Involvement ◽

Distinct Features ◽

Inflammatory Syndrome

Background: Multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 has been increasingly recognized. However, the clinical features of MIS-C and the differences from Kawasaki disease remain unknown. The study aims to investigate the epidemiology and clinical course of MIS-C. Methods: PubMed and EMBASE were searched through August 30, 2020. Observational studies describing MIS-C were included. Data regarding demographic features, clinical symptoms, laboratory, echocardiography and radiology findings, treatments, and outcomes were extracted. Study-specific estimates were combined using one-group meta-analysis in a random-effects model. Results: A total of 27 studies were identified including 917 MIS-C patients. The mean age was 9.3 (95% confidence interval [CI], 8.4-10.1). The pooled proportions of Hispanic and Black cases were 34.6% (95% CI, 28.3-40.9) and 31.5% (95% CI, 24.8-38.1), respectively. The common manifestations were gastrointestinal symptoms (87.3%; 95% CI, 82.9-91.6) and cardiovascular involvement such as myocardial dysfunction (55.3%; 95% CI, 42.4-68.2), coronary artery aneurysms (21.7%; 95% CI, 12.8-30.1) and shock (65.8%; 95% CI, 51.1-80.4), with marked elevated inflammatory and cardiac markers. The majority of patients received intravenous immunoglobulin (81.0%; 95% CI, 75.0-86.9), aspirin (67.3%; 95% CI, 48.8-85.7), and corticosteroids (63.6%; 95% CI, 53.4-73.8) with a variety of anti-inflammatory agents. Although myocardial dysfunction improved in 55.1% (95% CI, 33.4-76.8) at discharge, the rate of extracorporeal membrane oxygenation use was 6.3% (95% CI, 2.8-9.8) and the mortality was 1.9% (95% CI, 1.0-2.8). Conclusion: Our findings suggest that MIS-C leads to multiple organ failure, including gastrointestinal manifestations, myocardial dysfunction and coronary abnormalities, and has distinct features from Kawasaki disease.

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Perspective of Immunopathogenesis and Immunotherapies for Kawasaki Disease

Frontiers in Pediatrics ◽

10.3389/fped.2021.697632 ◽

2021 ◽

Vol 9 ◽

Author(s):

Lung Chang ◽

Horng-Woei Yang ◽

Tang-Yu Lin ◽

Kuender D. Yang

Keyword(s):

Kawasaki Disease ◽

Macrophage Activation ◽

Clinical Symptoms ◽

Human Leukocyte ◽

T Helper 17 ◽

Leukocyte Antigen ◽

Ivig Resistance ◽

Risk Patients ◽

Phenotypic Variations ◽

Inflammatory Syndrome

Kawasaki Disease (KD) is an acute inflammatory illness that mostly occurs in children below 5 years of age, with intractable fever, mucocutaneous lesions, lymphadenopathy, and lesions of the coronary artery (CAL). KD is sharing clinical symptoms with systemic inflammatory syndrome in children (MIS-C) which is related to COVID-19. Certain genes are identified to be associated with KD, but the findings usually differ between countries and races. Human Leukocyte Antigen (HLA) allele types and toll-like receptor (TLR) expression are also correlated to KD. The acute hyperinflammation in KD is mediated by an imbalance between augmented T helper 17 (Th17)/Th1 responses with high levels of interleukin (IL)-6, IL-10, IL-17A, IFN-γ, and IP-10, in contrast to reduced Th2/Treg responses with lower IL-4, IL-5, FoxP3, and TGF-β expression. KD has varying phenotypic variations regarding age, gender, intravenous immunoglobulin (IVIG) resistance, macrophage activation and shock syndrome. The signs of macrophage activation syndrome (MAS) can be interpreted as hyperferritinemia and thrombocytopenia contradictory to thrombocytosis in typical KD; the signs of KD with shock syndrome (KDSS) can be interpreted as overproduction of nitric oxide (NO) and coagulopathy. For over five decades, IVIG and aspirin are the standard treatment for KD. However, some KD patients are refractory to IVIG required additional medications against inflammation. Further studies are proposed to delineate the immunopathogenesis of IVIG-resistance and KDSS, to identify high risk patients with genetic susceptibility, and to develop an ideal treatment regimen, such as by providing idiotypic immunoglobulins to curb cytokine storms, NO overproduction, and the epigenetic induction of Treg function.

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KAWASAKI DISEASE AND MULTISYSTEM INFLAMMATORY SYNDROME IN CHILDREN WITH COVID-19 INFECTION

PEDIATRIA Journal named after G N SPERANSKY ◽

10.24110/0031-403x-2020-99-6-209-219 ◽

2020 ◽

Vol 99 (6) ◽

pp. 209-219

Author(s):

L.V. Bregel ◽

◽

M.M. Kostik ◽

L.Z. Fell ◽

O.S. Efremova ◽

...

Keyword(s):

Kawasaki Disease ◽

Hemophagocytic Syndrome ◽

Early Recognition ◽

Gastrointestinal Symptoms ◽

The United States ◽

Interleukin 10 ◽

Left Ventricular ◽

Urgent Care ◽

High Dose ◽

Inflammatory Syndrome

During the COVD-19 pandemic, some pediatric patients in many countries around the world experienced a syndrome resembling a severe Kawasaki disease (KD), often accompanied by shock. Due to the incomplete signs of the classic KD in the era before the present pandemic, in many publications from European countries and the United States, this condition was called «multisystem inflammatory syndrome in children – MIS-C» or «hyperinflammatory shock» or «Kawasaki-like syndrome». This syndrome with a new coronavirus infection is characterized by refractory fever, frequent gastrointestinal symptoms, heart damage (including coronary dilation in some patients, and acute left ventricular failure in the majority), increased ESR and CRP levels, neutrophilia, extremely high troponin levels, increased ferritin, AST, ALT, lactate dehydrogenase, creatine phosphate kinase, interleukin-6 and interleukin-10, coagulopathy with an increase in D-dimer and fibrinogen, thrombocytopenia, sometimes procalcitonin increase. The manifestations of a cytokine storm may meet the criteria for secondary hemophagocytic syndrome. The mechanism of myocardial damage remains unclear. Treatment with high-dose intravenous immunoglobulin is effective, and in the presence of signs of hemophagocytic syndrome, dexamethasone or methylprednisolone. Further research is needed to understand the pathogenesis, resemblance and differences of this syndrome with classic KD, understanding of heart injuiry and early recognition for the need of urgent care.

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Abstract 16566: Presentation and Outcome of Pediatric Multisystem Inflammatory Syndrome Temporally Associated With Sars-cov-2 Pandemic: An International Survey

Circulation ◽

10.1161/circ.142.suppl_3.16566 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Carles Bautista ◽

Joan Sanchez-de-Toledo ◽

Clark C Bradley ◽

Jetrho Herberg ◽

Fanny Bajolle ◽

...

Keyword(s):

Kawasaki Disease ◽

Cardiac Involvement ◽

Gastrointestinal Symptoms ◽

Duration Of Symptoms ◽

Entire Cohort ◽

Common Presentation ◽

Increased Risk ◽

Life Threatening ◽

The Mean ◽

Inflammatory Syndrome

Introduction: Following the SARS-CoV-2 pandemic peak, children suffering from a multiorgan inflammatory disease that often leads to shock have been reported. This condition shares features with Kawasaki disease, but its etiopathogenesis is unknown. Hypothesis: We aimed to describe presentation and hospital course for this pediatric inflammatory multisystemic syndrome associated with COVID-19 (PIMS-TS). Methods: Data were collected from a retrospective review of children from 33 participating European, Asian and American sites. Results: We included 183 patients (109 males, 59·6%) with PIMS-TS, at a mean age of 7·0 (±4·7) years. Fifty-six (30·6%) had black ethnicity and obesity was present in 48 (26·2%) cases. Overall, 114/183 (62·3%) had biological evidence of current or recent SARS-CoV-2 infection. At admission, all presented with fever, 117/183 (63·9%) with gastrointestinal symptoms and 79/183 (43·2%) with shock, that was associated with more frequent black ethnicity, higher inflammatory markers and more cardiac involvement. Twenty-seven patients (14·7%) fulfilled criteria for Kawasaki disease. They were younger with no shock, fewer gastrointestinal, cardio-respiratory and neurological symptoms. Among the remaining PIMS-TS patients, 77 (49·3%) had mainly fever and inflammation with less cardiac involvement. For the entire cohort of 183 patients, the mean duration of admission was 8·6 (±5·6) days. Inotropic support, mechanical ventilation and ECMO were indicated in 72 (39·3%), 43 (23·5%) and 4 (2·2%) patients, respectively. Three patients (1·6%) died. A shorter duration of symptoms before admission was a risk factor for worse outcome and for ECMO/death, with 63% increased risk per day reduction (95%CI 0·39-0·93, p=0·03) and with 51·4% increased risk per day reduction (95%CI 0·36-0·9, p=0·03), respectively. Conclusions: We describe the first largest international series of children with PIMS-TS. Life-threatening shock is a common presentation. A shorter duration of symptoms prior to admission characterizes the fulminant form of the disease with potentially worse outcome.

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Multisystem Inflammatory Syndrome in Children (MIS-C), a Post-viral Myocarditis and Systemic Vasculitis—A Critical Review of Its Pathogenesis and Treatment

Frontiers in Pediatrics ◽

10.3389/fped.2020.626182 ◽

2020 ◽

Vol 8 ◽

Author(s):

Jeremy C. McMurray ◽

Joseph W. May ◽

Madeleine W. Cunningham ◽

Olcay Y. Jones

Keyword(s):

Kawasaki Disease ◽

Critical Review ◽

Acute Rheumatic Fever ◽

Systemic Vasculitis ◽

Viral Myocarditis ◽

Current Treatment ◽

Clinical Perspective ◽

Treatment Regimens ◽

Inflammatory Syndrome ◽

Post Infectious

MIS-C is a newly defined post-viral myocarditis and inflammatory vasculopathy of children following COVID-19 infection. This review summarizes the literature on diagnosis, parameters of disease severity, and current treatment regimens. The clinical perspective was analyzed in light of potential immunopathogenesis and compared to other post-infectious and inflammatory illnesses of children affecting the heart. In this paradigm, the evidence supports the importance of endothelial injury and activation of the IL-1 pathway as a common determinant among MIS-C, Kawasaki disease, and Acute Rheumatic fever.

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Phenotype, Susceptibility, Autoimmunity, and Immunotherapy Between Kawasaki Disease and Coronavirus Disease-19 Associated Multisystem Inflammatory Syndrome in Children

Frontiers in Immunology ◽

10.3389/fimmu.2021.632890 ◽

2021 ◽

Vol 12 ◽

Author(s):

Men-Ren Chen ◽

Ho-Chang Kuo ◽

Yann-Jinn Lee ◽

Hsin Chi ◽

Sung Chou Li ◽

...

Keyword(s):

Kawasaki Disease ◽

Genetic Susceptibility ◽

Protective Factor ◽

Transforming Growth Factor ◽

Gastrointestinal Symptoms ◽

Treatment Resistance ◽

Human Leukocyte ◽

T Helper 17 ◽

Inducible Protein ◽

Inflammatory Syndrome

Coronavirus disease-19 (COVID-19) in children is usually mild but some are susceptible to a Kawasaki disease (KD)-like multisystem inflammatory syndrome in children (MIS-C) in the convalescent stage, posing a need to differentiate the phenotype, susceptibility, autoimmunity, and immunotherapy between KD and MIS-C, particularly in the upcoming mass vaccination of COVID-19. Patients with MIS-C are prone to gastrointestinal symptoms, coagulopathy, and shock in addition to atypical KD syndrome with fever, mucocutaneous lesions, lymphadenopathy, and/or cardiovascular events. MIS-C manifests KD-like symptoms that alert physicians to early recognize and adopt the KD treatment regimen for patients with MIS-C. MIS-C linked to COVID-19 teaches us infection-associated autoimmune vasculitis and vice versa. Studies on genetic susceptibility have identified certain human leukocyte antigen (HLA) locus and toll-like receptor (TLR) associated with KD and/or COVID-19. Certain HLA subtypes, such as HLA-DRB1 and HLA-MICA A4 are associated with KD. HLA-B*46:01 is proposed to be the risk allele of severe COVID-19 infection, and blood group O type is a protective factor of COVID-19. The autoimmune vasculitis of KD, KD shock syndrome (KDSS), or MIS-C is mediated by a genetic variant of HLA, FcγR, and/or antibody-dependent enhancement (ADE) resulting in hyperinflammation with T helper 17 (Th17)/Treg imbalance with augmented Th17/Th1 mediators: interleukin-6 (IL-6), IL-10, inducible protein-10 (IP-10), Interferon (IFNγ), and IL-17A, and lower expression of Treg-signaling molecules, FoxP3, and transforming growth factor (TGF-β). There are certain similarities and differences in phenotypes, susceptibility, and pathogenesis of KD, KDSS, and MIS-C, by which a physician can make early protection, prevention, and precision treatment of the diseases. The evolution of immunotherapies for the diseases has shown that intravenous immunoglobulin (IVIG) alone or combined with corticosteroids is the standard treatment for KD, KDSS, and MIS-C. However, a certain portion of patients who revealed a treatment resistance to IVIG or IVIG plus corticosteroids, posing a need to early identify the immunopathogenesis, to protect hosts with genetic susceptibility, and to combat Th17/Treg imbalance by anti-cytokine or pro-Treg for reversal of the hyperinflammation and IVIG resistance. Based on physiological and pathological immunity of the diseases under genetic susceptibility and host milieu conditions, a series of sequential regimens are provided to develop a so-called “Know thyself, enemy (pathogen), and ever-victorious” strategy for the prevention and immunotherapy of KD and/or MIS-C.

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Case Report: Changes in Cytokine Kinetics During the Course of Disease in a Japanese Patient With Multisystem Inflammatory Syndrome in Children

Frontiers in Pediatrics ◽

10.3389/fped.2021.702318 ◽

2021 ◽

Vol 9 ◽

Author(s):

Satoshi Takasago ◽

Aiko Sakai ◽

Masaya Sugiyama ◽

Masashi Mizokami ◽

Hiromichi Hamada ◽

...

Keyword(s):

Kawasaki Disease ◽

Acute Myocarditis ◽

Severe Disease ◽

Gastrointestinal Symptoms ◽

Disease Status ◽

Classical Trajectory ◽

Course Of Disease ◽

Old Japanese ◽

Cervical Swelling ◽

Inflammatory Syndrome

Multisystem inflammatory syndrome in children (MIS-C) is a severe disease that is reportedly linked to coronavirus disease 2019. Affected patients present with gastrointestinal symptoms and cardiovascular dysfunction, in addition to Kawasaki disease-like features, suggesting the potential for overlapping disease mechanisms. Kawasaki disease has been reported among individuals of East Asian ethnicities, whereas there is minimal clinical literature regarding the occurrence of MIS-C among individuals of Asian ethnicities. A few reports thus far have described changes in cytokine kinetics during the course of disease in patients with MIS-C. We followed the temporal cytokine kinetics in a 9-year-old Japanese girl who exhibited a classical trajectory of MIS-C. The patient exhibited right cervical swelling and pain, abdominal pain, vomiting, and lip reddening, which developed 31 days after she was diagnosed with severe acute respiratory syndrome coronavirus-2 infection. The patient was diagnosed with Kawasaki disease on her fifth day of illness; because she fulfilled the criteria for MIS-C, she was also diagnosed with this disease on her fifth day of illness. Her fever rapidly resolved upon administration of intravenous immunoglobulin, aspirin, and prednisolone. On the patient's sixth day of illness, she developed acute myocarditis, which was treated with two diuretics and one vasodilator; the myocarditis ameliorated within a few days. Analyses of temporal kinetics for 71 serum cytokines revealed several patterns of cytokine changes that were consistent with the patient's clinical course of disease. Importantly, there was a clear distinction between cytokines that did and did not decrease rapidly following post-treatment fever resolution. These findings may be useful for the assessment of disease status and selection of therapy in patients with similar symptoms; they may also provide insights for basic and clinical research regarding MIS-C.

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Laboratory parameters between multisystem inflammatory syndrome in children and Kawasaki disease

10.22541/au.162657937.78880867/v1 ◽

2021 ◽

Author(s):

Chunling Zhou ◽

Yan Zhao ◽

Xia Wang ◽

Ying Huang ◽

Xuewen Tang ◽

...

Keyword(s):

Kawasaki Disease ◽

Inflammatory Markers ◽

Clinical Symptoms ◽

Meta Analysis ◽

Absolute Lymphocyte Count ◽

Cardiac Markers ◽

C Reactive Protein ◽

Laboratory Parameters ◽

Reactive Protein ◽

Inflammatory Syndrome

Multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 (COVID-19) has been described to partially overlap with Kawasaki disease (KD) with regard to clinical symptoms, but they are unlikely to share the same disease entity. We conducted a systematic review and meta-analysis to characterize the laboratory parameters of MIS-C compared with those of KD and Kawasaki disease shock syndrome (KDSS). Databases were searched for studies on laboratory parameters of MIS-C (hematology, inflammatory markers, cardiac markers and biochemistry) through May 31, 2021. Twelve studies with 3073 participants yielded 969 MIS-C patients. In terms of hematology, MIS-C patients had lower levels of leukocytes, absolute lymphocyte count and platelet count (PLT) than KD patients and had similar absolute neutrophil count (ANC) and hemoglobin (Hb) levels. In terms of inflammatory markers, MIS-C patients had higher levels of C-reactive protein, D-dimer and ferritin than KD patients and had similar levels of procalcitonin and ESR. In terms of cardiac markers, MIS-C patients had higher CPK levels than KD patients. The levels of NT-proBNP, troponin and AST were not significantly different between MIS-C and KD patients. In terms of biochemistry, MIS-C patients had lower levels of albumin, sodium and ALT and higher levels of creatinine than KD patients. In addition, MIS-C patients had lower levels of PLT, Hb and ESR and higher levels of ANC than KDSS patients. Measurement of laboratory parameters might assist clinicians with accurate evaluation of MIS-C and further mechanistic research.

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