CD64, CD11a and CD18 leukocytes expression in children with SARS-CoV-2 multisystem inflammatory syndrome versus children with Kawasaki disease: Similar but not the same

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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Current Understanding of Multisystem Inflammatory Syndrome (MIS-C) Following COVID-19 and Its Distinction from Kawasaki Disease

Current Rheumatology Reports ◽

10.1007/s11926-021-01028-4 ◽

2021 ◽

Vol 23 (8) ◽

Author(s):

Hulya Bukulmez

Keyword(s):

Kawasaki Disease ◽

Current Understanding ◽

Inflammatory Syndrome

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Potential New Treatments for Kawasaki Disease, Its Variations, and Multisystem Inflammatory Syndrome

SN Comprehensive Clinical Medicine ◽

10.1007/s42399-021-00872-w ◽

2021 ◽

Author(s):

Kevin Roe

Keyword(s):

Kawasaki Disease ◽

New Treatments ◽

Inflammatory Syndrome

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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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Superantigenic TCR Vbeta 21.3 signature in Multisystem Inflammatory Syndrome in Children

10.1101/2021.02.11.21251166 ◽

2021 ◽

Author(s):

Marion Moreews ◽

Kenz Le Gouge ◽

Alicia Bellomo ◽

Christophe Malcus ◽

Rémi Pescarmona ◽

...

Keyword(s):

Immune Response ◽

T Cells ◽

T Cell ◽

Kawasaki Disease ◽

T Cell Activation ◽

Toxic Shock Syndrome ◽

Healthy Children ◽

Toxic Shock ◽

Hla Dr ◽

Inflammatory Syndrome

AbstractObjectivesMultiple Inflammatory Syndrome in Children (MIS-C) is the most severe pediatric form of COVID-19 and occurs in previously healthy children. MIS-C combines features of Kawasaki disease and Toxic Shock Syndrome (TSS).MethodsChildren with suspected MIS-C were included within the first week of diagnosis and a large scale immunoassay was performed to determein the immunologic signature of these patients.ResultsWe characterized the immunological profile of 27 MIS-C cases in comparison with 4 KD and 4 TSS cases. Similarly to TSS, an increase of serum inflammatory cytokines (IL-6, TNF-a, CD25s) was observed in MIS-C contrasting with low expression of HLA-DR monocytes, a feature often associated with immune paralysis. Expansions of T cells expressing the Vβ21.3 T cell receptor β chain variable region were detected in both CD4 and CD8 subsets in almost 50% of patients and Vβ21.3-positive T cells expressed high level of HLA-DR highlighting their specific activation. TCR sequencing uncovered the polyclonal nature of the Vβ 21.3+ population. SARS-CoV2 antigene-specific production of interferon gamma in T cells was not increased in MIS-C T cells compared to COVID-19 patients suggesting the antigen-specific immune response in MIS-C patients is not pivotal to the manifestation.ConclusionsOur findings argue in favor of a strong activation of the immune system related to a superantigenic immune response in MIS-C with a specific polyclonal Vβ21.3 T cell expansion.Key messagesWhat is already known about this subject ?MIS-C occurs 3-5 weeks after acute SARS-CoV2 infection and overlap features of Toxic Shock syndrome and Kawasaki disease.MIS-C appears different in term of cytokine and autoantibodies generation from KD with subtle signs of T cells activationWhat does this study add?This study demonstrates that Vβ21.3+ CD4 and CD8 T cells are highly increased in about 50% of MIS-C and distinctive of the Vβ2+ expansion observed in toxic shock syndrome in This reflects a specific T cell activation and cytokine release syndrome similar to toxic shock syndromeHow mich this impact on clinical practice or future developments?Vβ21.3+ signature can be available on a short term basis by flowcytometry and represents a signature of the MIS-C.As for TSS, immunomodulating therapies may revert the superantigenic activation and resolve this life threatening pediatric condition.

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