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Introduction: At the end of April 2020, three European pediatric societies published an alert on a new hyperinflammatory disorder linked to SARS-CoV-2. This disease has alternatively been called Kawasaki-like disease, pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 infection (PIMS-TS), and multisystem inflammatory syndrome in children (MIS-C). These alerts provide a clear starting point from which to study the early response of the medical and scientific community to a new disease in terms of scientific publications, and to compare the timeline of this response with levels of general public interest. To this aim, we conducted a bibliometric analysis of articles on this disease published between 1 April and 5 July 2020., Method: A literature search was performed using PubMed and in three preprint repositories. For each article, the name used for the disease in the title, the number of authors, the number of patients, the citations according to Google Scholar, the journal impact factor, and the Altmetric score were retrieved. Google search trends for the terms "Kawasaki" and "COVID," "COVID-19," and "coronavirus" were also retrieved, as was the number of Reuters news articles published on the topic. These data were compared longitudinally on a weekly basis. The quality of the reporting of the study was evaluated using the STROBE guidelines for observational studies with more than three patients and using the CARE guidelines for case reports of three or fewer patients., Results: Eighty-six articles were included, among which ten were preprints (three of which were subsequently published) and 49 were clinical articles (57%). A total of 857 patients were described. The median number of authors per article was five (range, 1-45), the median number of patients was four (1-186), the median number of citations was one (0-170), the median Altmetric score was 12 (0-7242), and the median journal impact factor was 3.7 (1-74.7). For the clinical articles, the median percentage of STROBE or CARE checklist items satisfied was 70% (IQR, 56.75-79.25; range, 40-90). Guideline adherence was significantly higher for observational studies than for case reports (median percentage of checklist items satisfied, 78.5% vs 61.5%; P<0.001); however, guideline adherence did not differ significantly between peer-reviewed and preprint articles (median percentage of checklist items satisfied, 57% vs 72%; P=0.205). The only statistically significant difference between clinical articles and other types of articles was the number of authors (median, 7 vs 2; P=2.53E-9). Fifty-seven of the 86 articles were authored by researchers from just three countries (the USA, 31; France, 14; and the UK, 12). The names most frequently used in the title were Kawasaki-like disease (n=37), followed by MIS-C (n=27), PIM-TS (n=14), and other names involving the term "inflammatory" (n=12). Google searches for related terms peaked between weeks 18 and 21, following the initial alerts and decreased rapidly thereafter. The number of Reuters articles on the subject was correlated with Google search trends (ρ: 0.86, 95% CI [0.59; 0.96]; P=0.00016), but the number of medical articles published was not (ρ: -0.54, 95% CI [-0.87; 0.14]; P=0.11). The first small case series was published less than 2 weeks after the initial alert; however, if all articles had been deposited as preprints when they were submitted to journals, the cumulative number of reported cases would have been 300% higher in week 18 (3 vs 1), 400% higher in week 19 (44 vs 11), 70% higher in week 20 (124 vs 73), and 54% higher in week 21 (129 vs 84)., Conclusion: In a period of 9 weeks after the initial alerts from European pediatric societies, 85 medical articles were published, involving 856 patients (one case report was published before the alerts), allowing rapid dissemination of research information. However, general public interest followed the news cycle rather than scientific releases. The quality of the reporting, as assessed by adherence to STROBE or CARE guidelines, was adequate with more than two-thirds of checklist items satisfied. Learned societies play an important role in the early dissemination of up-to-date peer-reviewed information. Preprint deposition should be encouraged to accelerate the dissemination of research information., (Copyright © 2021 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.)

Multiple Inflammatory Syndrome in Children (MIS-C) is a delayed and severe complication of SARS-CoV-2 infection that strikes previously healthy children. As MIS-C combines clinical features of Kawasaki disease and Toxic Shock Syndrome (TSS), we aimed to compare the immunological profile of pediatric patients with these different conditions. We analyzed blood cytokine expression, and the T cell repertoire and phenotype in 36 MIS-C cases, which were compared to 16 KD, 58 TSS, and 42 COVID-19 cases. We observed an increase of serum inflammatory cytokines (IL-6, IL-10, IL-18, TNF-α, IFNγ, CD25s, MCP1, IL-1RA) in MIS-C, TSS and KD, contrasting with low expression of HLA-DR in monocytes. We detected a specific expansion of activated T cells expressing the Vβ21.3 T cell receptor β chain variable region in both CD4 and CD8 subsets in 75% of MIS-C patients and not in any patient with TSS, KD, or acute COVID-19; this correlated with the cytokine storm detected. The T cell repertoire returned to baseline within weeks after MIS-C resolution. Vβ21.3+ T cells from MIS-C patients expressed high levels of HLA-DR, CD38 and CX3CR1 but had weak responses to SARS-CoV-2 peptides in vitro . Consistently, the T cell expansion was not associated with specific classical HLA alleles. Thus, our data suggested that MIS-C is characterized by a polyclonal Vβ21.3 T cell expansion not directed against SARS-CoV-2 antigenic peptides, which is not seen in KD, TSS and acute COVID-19., (Copyright © 2021, American Association for the Advancement of Science.)

This is a Brighton Collaboration Case Definition of the term "Multisystem Inflammatory Syndrome in Children and Adults (MIS-C/A)" to be utilized in the evaluation of adverse events following immunization. The case definition was developed by topic experts convened by the Coalition for Epidemic Preparedness Innovations (CEPI) in the context of active development of vaccines for SARS-CoV-2. The format of the Brighton Collaboration was followed, including an exhaustive review of the literature, to develop a consensus definition and defined levels of certainty. The document underwent peer review by the Brighton Collaboration Network and by selected expert external reviewers prior to submission. The comments of the reviewers were taken into consideration and edits incorporated into this final manuscript., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: NP Klein has received research support from Pfizer for COVID-19 vaccine clinical trials and from Pfizer, Merck, GSK, Sanofi Pasteur and Protein Science (now Sanofi Pasteur) for unrelated studies. FM Munoz is a consultant for the Coalition for Epidemic Preparedness Innovations (CEPI) for the development of Brighton Collaboration Case Definitions for the Safety Platform for Emergency vACcines (SPEAC) Project. The following authors have no conflict of interests to disclose: TP Vogel, KA Top, C Karatzios, DC Hilmers, LI Tapia, P Moceri, L Giovannini-Chami, N Wood, R Chandler, EP Schlaudecker, MC Poli, E Muscal. The findings, opinions and assertions contained in the consensus document are those of the individual scientific professional members of the working group. They do not necessarily represent the official positions of each participant’s organization (e.g., government, university or corporation). Specifically, the findings and conclusions in the paper are those of the authors and do not necessarily represent the views of their respective institutions., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)