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      Multisystem inflammatory syndrome in 1.2 million children: longitudinal cohort study of risk factors

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          Abstract

          Background

          We identified patient characteristics associated with an increased risk of developing MIS-C.

          Methods

          We conducted a longitudinal cohort study of 1,195,327 patients aged 0–19 years between 2006 and 2021, including the first two waves of the pandemic (February 25–August 22, 2020 and August 23, 2020-March 31, 2021). Exposures included prepandemic morbidity, birth outcomes, and family history of maternal disorders. Outcomes included MIS-C, Kawasaki disease, and other Covid-19 complications during the pandemic. We calculated risk ratios (RRs) and 95% confidence intervals (CIs) for the association between patient exposures and these outcomes using log-binomial regression models adjusted for potential confounders.

          Results

          Among 1,195,327 children, 84 developed MIS-C, 107 Kawasaki disease, and 330 other Covid-19 complications during the first year of the pandemic. Prepandemic hospitalizations for metabolic disorders (RR 11.3, 95% CI 5.61–22.6), atopic conditions (RR 3.34, 95% CI 1.60–6.97), and cancer (RR 8.11, 95% CI 1.13–58.3) were strongly associated with the risk of MIS-C, compared with no exposure. These same exposures were also associated with Kawasaki disease and other Covid-19 complications. However, birth characteristics and history of maternal morbidity were not associated with MIS-C development.

          Conclusions

          Children with pre-existing morbidity have a considerably elevated risk of MIS-C.

          Impact

          • Morbidities that predispose children to multisystem inflammatory syndrome (MIS-C) are unclear.

          • In this study, prepandemic hospitalizations for metabolic disorders, atopic conditions, and cancer were associated with an elevated risk of MIS-C.

          • Birth characteristics and family history of maternal morbidity were not, however, associated with MIS-C.

          • Pediatric morbidities may play a greater role in MIS-C onset than maternal or perinatal characteristics, and may help clinicians better recognize children at risk for this complication.

          Related collections

          Most cited references34

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          Sex differences in immune responses

          Males and females differ in their immunological responses to foreign and self-antigens and show distinctions in innate and adaptive immune responses. Certain immunological sex differences are present throughout life, whereas others are only apparent after puberty and before reproductive senescence, suggesting that both genes and hormones are involved. Furthermore, early environmental exposures influence the microbiome and have sex-dependent effects on immune function. Importantly, these sex-based immunological differences contribute to variations in the incidence of autoimmune diseases and malignancies, susceptibility to infectious diseases and responses to vaccines in males and females. Here, we discuss these differences and emphasize that sex is a biological variable that should be considered in immunological studies.
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            The Immunology of Multisystem Inflammatory Syndrome in Children with COVID-19

            Highlights Hyperinflammation in MIS-C differs from that of acute COVID-19 T-cell subsets discriminate Kawasaki disease patients from MIS-C IL-17A drives Kawasaki, but not MIS-C hyperinflammation. Global profiling reveals candidate autoantibodies with pathogenic potential
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              Characteristics and Outcomes of US Children and Adolescents With Multisystem Inflammatory Syndrome in Children (MIS-C) Compared With Severe Acute COVID-19

              Refinement of criteria for multisystem inflammatory syndrome in children (MIS-C) may inform efforts to improve health outcomes.
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                Author and article information

                Contributors
                nathalie.auger@inspq.qc.ca
                Journal
                Pediatr Res
                Pediatr Res
                Pediatric Research
                Nature Publishing Group US (New York )
                0031-3998
                1530-0447
                17 May 2023
                : 1-9
                Affiliations
                [1 ]GRID grid.410559.c, ISNI 0000 0001 0743 2111, Health Innovation and Evaluation Hub, , University of Montreal Hospital Research Centre, ; Montreal, QC Canada
                [2 ]GRID grid.434819.3, ISNI 0000 0000 8929 2775, Bureau d’information et d’études en santé des populations, , Institut national de santé publique du Québec, ; Montreal, QC Canada
                [3 ]GRID grid.14848.31, ISNI 0000 0001 2292 3357, Department of Social and Preventive Medicine, School of Public Health, , University of Montreal, ; Montreal, QC Canada
                [4 ]GRID grid.14709.3b, ISNI 0000 0004 1936 8649, Department of Epidemiology, Biostatistics and Occupational Health, , McGill University, ; Montreal, QC Canada
                [5 ]Department of Rheumatology, Cité-de-la-Santé Hospital, Laval, QC Canada
                [6 ]GRID grid.14848.31, ISNI 0000 0001 2292 3357, Department of Microbiology, Infectious Diseases, and Immunology, , University of Montreal, ; Montreal, QC Canada
                [7 ]GRID grid.411418.9, ISNI 0000 0001 2173 6322, Infection Prevention and Control, Clinical Department of Laboratory Medicine, , Sainte-Justine Hospital Research Centre, ; Montreal, QC Canada
                [8 ]GRID grid.14848.31, ISNI 0000 0001 2292 3357, Department of Pediatrics, Sainte-Justine Hospital Research Centre, , University of Montreal, ; Montreal, QC Canada
                Article
                2633
                10.1038/s41390-023-02633-y
                10191400
                37198405
                5e79c4aa-b4e6-4380-90f7-8af9b48c5f87
                © The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                : 19 October 2022
                : 14 February 2023
                : 18 February 2023
                Categories
                Population Study Article

                Pediatrics
                Pediatrics

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