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The Immunology of Multisystem Inflammatory Syndrome in Children with COVID-19.

ABSTRACT: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is typically very mild and often asymptomatic in children. A complication is the rare multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19, presenting 4-6 weeks after infection as high fever, organ dysfunction, and strongly elevated markers of inflammation. The pathogenesis is unclear but has overlapping features with Kawasaki disease suggestive of vasculitis and a likely autoimmune etiology. We apply systems-level analyses of blood immune cells, cytokines, and autoantibodies in healthy children, children with Kawasaki disease enrolled prior to COVID-19, children infected with SARS-CoV-2, and children presenting with MIS-C. We find that the inflammatory response in MIS-C differs from the cytokine storm of severe acute COVID-19, shares several features with Kawasaki disease, but also differs from this condition with respect to T cell subsets, interleukin (IL)-17A, and biomarkers associated with arterial damage. Finally, autoantibody profiling suggests multiple autoantibodies that could be involved in the pathogenesis of MIS-C.

SUBMITTER: Consiglio CR

PROVIDER: S-EPMC7474869 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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The Immunology of Multisystem Inflammatory Syndrome in Children with COVID-19.

Consiglio Camila Rosat CR Cotugno Nicola N Sardh Fabian F Pou Christian C Amodio Donato D Rodriguez Lucie L Tan Ziyang Z Zicari Sonia S Ruggiero Alessandra A Pascucci Giuseppe Rubens GR Santilli Veronica V Campbell Tessa T Bryceson Yenan Y Eriksson Daniel D Wang Jun J Marchesi Alessandra A Lakshmikanth Tadepally T Campana Andrea A Villani Alberto A Rossi Paolo P Landegren Nils N Palma Paolo P Brodin Petter P

Cell 20200906 4

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is typically very mild and often asymptomatic in children. A complication is the rare multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19, presenting 4-6 weeks after infection as high fever, organ dysfunction, and strongly elevated markers of inflammation. The pathogenesis is unclear but has overlapping features with Kawasaki disease suggestive of vasculitis and a likely autoimmune etiology. We appl ...[more]

PMID: 32966765

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Project description:An association between a novel pediatric hyperinflammatory condition and SARS-CoV-2 was recently published and termed pediatric inflammatory multisystem syndrome, temporally associated with SARS-CoV-2 (PIMS-TS) or multisystem inflammatory syndrome (in children) (MIS(-C)). We performed a systematic review and describe the epidemiological, clinical, and prognostic characteristics of 953 PIMS-TS/MIS(-C) cases in 68 records. Additionally, we studied the sensitivity of different case definitions that are currently applied. PIMS-TS/MIS(-C) presents at a median age of 8 years. Epidemiological enrichment for males (58.9%) and ethnic minorities (37.0% Black) is present. Apart from obesity (25.3%), comorbidities are rare. PIMS-TS/MIS(-C) is characterized by fever (99.4%), gastrointestinal (85.6%) and cardiocirculatory manifestations (79.3%), and increased inflammatory biomarkers. Nevertheless, 50.3% present respiratory symptoms as well. Over half of patients (56.3%) present with shock. The majority of the patients (73.3%) need intensive care treatment, including extracorporal membrane oxygenation (ECMO) in 3.8%. Despite severe disease, mortality is rather low (1.9%). Of the currently used case definitions, the WHO definition is preferred, as it is more precise, while encompassing most cases.Conclusion: PIMS-TS/MIS(-C) is a severe, heterogeneous disease with epidemiological enrichment for males, adolescents, and racial and ethnic minorities. However, mortality rate is low and short-term outcome favorable. Long-term follow-up of chronic complications and additional clinical research to elucidate the underlying pathogenesis is crucial. What is Known: • A novel pediatric inflammatory syndrome with multisystem involvement has been described in association with SARS-CoV-2. • To date, the scattered reporting of cases and use of different case definitions provides insufficient insight in the full clinical spectrum, epidemiological and immunological features, and prognosis. What is New: • This systematic review illustrates the heterogeneous spectrum of PIMS-TS/MIS(-C) and its epidemiological enrichment for males, adolescents, and racial and ethnic minorities. • Despite its severe presentation, overall short-term outcome is good. • The WHO MIS definition is preferred, as it is more precise, while encompassing most cases.

Project description:BackgroundA hyperinflammatory immune-mediated shock syndrome has been recognised in children exposed to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19).ObjectiveTo describe typical imaging findings in children with multisystem inflammatory syndrome associated with COVID-19.Materials and methodsDuring the first wave of the COVID-19 pandemic, imaging studies and clinical data from children treated for multisystem inflammatory syndrome were collected from multiple centres. Standardised case templates including demographic, biochemical and imaging information were completed by participating centres and reviewed by paediatric radiologists and paediatricians.ResultsWe included 37 children (21 boys; median age 8.0 years). Polymerase chain reaction (PCR) testing was positive for SARS-CoV-2 in 15/37 (41%) children and immunoglobulins in 13/19 children (68%). Common clinical presentations were fever (100%), abdominal pain (68%), rash (54%), conjunctivitis (38%) and cough (32%). Thirty-three children (89%) showed laboratory or imaging findings of cardiac involvement. Thirty of the 37 children (81%) required admission to the intensive care unit, with good recovery in all cases. Chest radiographs demonstrated cardiomegaly in 54% and signs of pulmonary venous hypertension/congestion in 73%. The most common chest CT abnormalities were ground-glass and interstitial opacities (83%), airspace consolidation (58%), pleural effusion (58%) and bronchial wall thickening (42%). Echocardiography revealed impaired cardiac function in half of cases (51%) and coronary artery abnormalities in 14%. Cardiac MRI showed myocardial oedema in 58%, pericardial effusion in 42% and decreased left ventricular function in 25%. Twenty children required imaging for abdominal symptoms, the commonest abnormalities being free fluid (71%) and terminal ileum wall thickening (57%). Twelve children underwent brain imaging, showing abnormalities in two cases.ConclusionChildren with multisystem inflammatory syndrome showed pulmonary, cardiac, abdominal and brain imaging findings, reflecting the multisystem inflammatory disease. Awareness of the imaging features of this disease is important for early diagnosis and treatment.

Project description:In April 2020, during the peak of the coronavirus disease 2019 (COVID-19) pandemic in Europe, a cluster of children with hyperinflammatory shock with features similar to Kawasaki disease and toxic shock syndrome was reported in England* (1). The patients' signs and symptoms were temporally associated with COVID-19 but presumed to have developed 2-4 weeks after acute COVID-19; all children had serologic evidence of infection with SARS-CoV-2, the virus that causes COVID-19 (1). The clinical signs and symptoms present in this first cluster included fever, rash, conjunctivitis, peripheral edema, gastrointestinal symptoms, shock, and elevated markers of inflammation and cardiac damage (1). On May 14, 2020, CDC published an online Health Advisory that summarized the manifestations of reported multisystem inflammatory syndrome in children (MIS-C), outlined a case definition,† and asked clinicians to report suspected U.S. cases to local and state health departments. As of July 29, a total of 570 U.S. MIS-C patients who met the case definition had been reported to CDC. A total of 203 (35.6%) of the patients had a clinical course consistent with previously published MIS-C reports, characterized predominantly by shock, cardiac dysfunction, abdominal pain, and markedly elevated inflammatory markers, and almost all had positive SARS-CoV-2 test results. The remaining 367 (64.4%) of MIS-C patients had manifestations that appeared to overlap with acute COVID-19 (2-4), had a less severe clinical course, or had features of Kawasaki disease.§ Median duration of hospitalization was 6 days; 364 patients (63.9%) required care in an intensive care unit (ICU), and 10 patients (1.8%) died. As the COVID-19 pandemic continues to expand in many jurisdictions, clinicians should be aware of the signs and symptoms of MIS-C and report suspected cases to their state or local health departments; analysis of reported cases can enhance understanding of MIS-C and improve characterization of the illness for early detection and treatment.

Dataset Information

The Immunology of Multisystem Inflammatory Syndrome in Children with COVID-19.

Publications

The Immunology of Multisystem Inflammatory Syndrome in Children with COVID-19.

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