Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.
Multisystem inflammatory syndrome in children (MIS-C) is a systemic inflammatory condition seen in children following SARS-CoV-2 infection or exposure. Symptoms are highly variable and include fever, diarrhoea, cardiogenic shock, respiratory compromise and Kawasaki disease (KD)-like features.1 2 Compared with acute COVID-19, MIS-C is characterised by distinct immune responses, including increased monocyte/macrophage-derived cytokines such as interleukin (IL)-6 and IL-18, T-cell-derived cytokines including IL-10 and IL-17A, and TRBV11-2 expressing T cells.3 4 However, the relationship between MIS-C-related immunophenotypes and clinical heterogeneity is unknown.
We determined clinical associations of MIS-C immunophenotypes in a cohort of 76 MIS-C patients.4 All patients met the Centers for Disease Control and Prevention definition for MIS-C and had documented SARS-CoV2 serologies (online supplemental table S3). Clinical characteristics of the cohort were previously reported4 and used to identify patients with diarrhoea, cardiac, respiratory, neurological and KD-like symptoms (online supplemental tables S1–S3). MIS-C patients who met criteria for complete or incomplete KD were labelled MIS-C/KD. Serum biomarkers (n=69) and T cell receptor repertoire (n=58) were measured as previously reported.4 To quantify SARS-CoV-2-specific T cell responses (n=24), we stimulated peripheral blood mononuclear cells with spike, membrane or nucleocapsid SARS-CoV-2 peptides; cytokine expression was measured using intracellular staining and flow cytometry. Groups were compared using Mann-Whitney with multiple comparison adjustment.
Serum biomarkers associated with macrophage and Th1 activation, including IFN-γ, were elevated in patients with shock, consistent with previous reports3–5 (figure 1A, online supplemental figure S1). Accordingly, significantly increased SARS-CoV-2-induced IFN-γ, IL-2 and TNF-α were seen in memory CD4+ T cells from patients with neurological involvement and respiratory failure (figure …
Handling editor Josef S Smolen
Contributors CJR and DMS performed experiments, analysed data, wrote and reviewed the manuscript and prepared the figures. MMK, AS, MS and CO performed experiments and contributed to the manuscript. KS, OD and RC performed experiments, analysed data and reviewed the manuscript, FL consented patients and provided biological specimens and clinical metadata, MCP, GAMS, YE and CA consented patients, provided biological specimens and clinical metadata, and reviewed the manuscript, SEW, MM, KD, YZ and HM assisted with sample collection, sample analysis, and manuscript review, KSB and MM reviewed clinical metadata. HCS coordinated, with LDN, collection and processing of the samples and the research project overall.
Funding This work was supported by the intramural research programmes of NIAID (1-ZIA-AI001274) and NIAMS (1-ZIA-AR041204). This research was supported (in part) by the Intramural Research Programme of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health.
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review Not commissioned; externally peer reviewed.
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.