Dataset Information

Serologic and Cytokine Signatures in Children With Multisystem Inflammatory Syndrome and Coronavirus Disease 2019.

ABSTRACT:

Background

The serologic and cytokine responses of children hospitalized with multisystem inflammatory syndrome (MIS-C) vs coronavirus disease 2019 (COVID-19) are poorly understood.

Methods

We performed a prospective, multicenter, cross-sectional study of hospitalized children who met the Centers for Disease Control and Prevention case definition for MIS-C (n = 118), acute COVID-19 (n = 88), or contemporaneous healthy controls (n = 24). We measured severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike receptor-binding domain (RBD) immunoglobulin G (IgG) titers and cytokine concentrations in patients and performed multivariable analysis to determine cytokine signatures associated with MIS-C. We also measured nucleocapsid IgG and convalescent RBD IgG in subsets of patients.

Results

Children with MIS-C had significantly higher SARS-CoV-2 RBD IgG than children with acute COVID-19 (median, 2783 vs 146; P < .001), and titers correlated with nucleocapsid IgG. For patients with MIS-C, RBD IgG titers declined in convalescence (median, 2783 vs 1135; P = .010) in contrast to patients with COVID-19 (median, 146 vs 4795; P < .001). MIS-C was characterized by transient acute proinflammatory hypercytokinemia, including elevated levels of interleukin (IL) 6, IL-10, IL-17A, and interferon gamma (IFN-γ). Elevation of at least 3 of these cytokines was associated with significantly increased prevalence of prolonged hospitalization ≥8 days (prevalence ratio, 3.29 [95% CI, 1.17-9.23]).

Conclusions

MIS-C was associated with high titers of SARS-CoV-2 RBD IgG antibodies and acute hypercytokinemia with IL-6, IL-10, IL-17A, and IFN-γ.

SUBMITTER: Lapp SA

PROVIDER: S-EPMC8883592 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Publications

Serologic and Cytokine Signatures in Children With Multisystem Inflammatory Syndrome and Coronavirus Disease 2019.

Lapp Stacey A SA Abrams Joseph J Lu Austin T AT Hussaini Laila L Kao Carol M CM Hunstad David A DA Rosenberg Robert B RB Zafferani Marc J MJ Ede Kaleo C KC Ballan Wassim W Laham Federico R FR Beltran Yajira Y Hsiao Hui-Mien HM Sherry Whitney W Jenkins Elan E Jones Kaitlin K Horner Anna A Brooks Alyssa A Bryant Bobbi B Meng Lu L Hammett Teresa A TA Oster Matthew E ME Bamrah-Morris Sapna S Godfred-Cato Shana S Belay Ermias E Chahroudi Ann A Anderson Evan J EJ Jaggi Preeti P Rostad Christina A CA

Open forum infectious diseases 20220224 3

<h4>Background</h4>The serologic and cytokine responses of children hospitalized with multisystem inflammatory syndrome (MIS-C) vs coronavirus disease 2019 (COVID-19) are poorly understood.<h4>Methods</h4>We performed a prospective, multicenter, cross-sectional study of hospitalized children who met the Centers for Disease Control and Prevention case definition for MIS-C (n = 118), acute COVID-19 (n = 88), or contemporaneous healthy controls (n = 24). We measured severe acute respiratory syndrom ...[more]

PMID: 35237703

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Project description:BackgroundThis study aimed to describe the clinical symptoms, laboratory findings, treatment, and outcomes of coronavirus disease 2019-related multisystem inflammatory syndrome in children to provide a reference for clinical practice.MethodsWe employed a literature search of databases such as PubMed, Web of Science, EMBASE, and Johns Hopkins University for articles on COVID-19-related multisystem inflammatory syndrome in children published between April 1, 2020, and January 15, 2021. High-quality articles were selected for analysis on the basis of their quality standard scores. Using R3.6.3 software, meta-analyses of random- or fixed-effects models were used to determine the prevalence of comorbidities. Subgroup analysis was also performed to determine heterogeneity.ResultsA total of 57 articles (2,290 pediatric patients) were included in the study. Clinical Manifestations. :ncidences of fever, gastrointestinal symptoms, respiratory symptoms, and musculoskeletal symptoms (myalgias or arthralgias) were 99.91% (95% CI: 99.67-100%), 82.72% (95% CI: 78.19-86.81%), 53.02% (45.28-60.68%), and 14.16% (95% CI: 8.4-21.12%), respectively. The incidences of rash, conjunctival injection, lymphadenopathy, dry cracked lips, neurologic symptoms (headache, altered mental status, or confusion), swollen hands and feet, typical Kawasaki disease, and atypical Kawasaki disease were 59.34% (95% CI: 54.73-63.87%), 55.23% (95% CI: 50.22-60.19%), 27.07% (95% CI: 19.87-34.93%), 46.37% (95% CI: 39.97-52.83%), 28.87% (95% CI: 22.76-35.40%), 28.75% (95% CI: 21.46-36.64%), 17.32% (95% CI: 15.44-19.29%), and 36.19% (95% CI: 21.90-51.86%), respectively. The incidences of coronary artery dilation, aneurysm, pericardial effusion, myocarditis, myocardial dysfunction, high troponin, and N-terminal pro-B-type natriuretic peptide were 17.83%, 6.85%, 20.97%, 35.97%, 56.32%, 76.34%, and 86.65%, respectively. The incidences of reduced lymphocytes, thrombocytopenia, hypoalbuminemia, elevated C-reactive protein, ferritin, LDH, interleukin-6, PCT, and FIB were 61.51%, 26.42%, 77.92%, 98.5%, 86.79%, 80.59%, 89.30%, 85.10%, and 87.01%, respectively. PICU Hospitalization Rate and Mortality. The incidences of PICU hospitalization or with shock were 72.79% and 55.68%, respectively. The mortality rate was 1.00%. Conclusion and Relevance. PICU hospitalization and shock rates of multisystem inflammatory syndrome in children associated with COVID-19 were high, and its cumulative multiorgans and inflammatory indicators are increased, but if treated in time, the mortality rate was low.

Project description:BackgroundMany cases have been reported recently on multisystem inflammatory syndrome in children (MIS-C), a newly emerged disease that seemed to correlate with coronavirus disease 2019 (COVID-19). The aim of this review was to describe the clinical features, treatment and outcomes of MIS-C, as well as to assess the risk of bias of published case studies, analyzing their reporting quality.MethodsWe searched all articles reporting on multisystem inflammatory condition in children and adolescents in the context of COVID-19 through MEDLINE (via PubMed), Web of Science, China Biology Medicine disc (CBM) and China National Knowledge Infrastructure (CNKI) from their inception to June 17, 2020. We used CARE and IHE checklists to evaluate the risk of bias and quality of the included studies. We combined the data of clinical manifestations, imaging findings, treatments and outcomes using STATA version 15.ResultsTwenty-four studies were included, with a total of 270 participants. Most cases were from Europe and the United States, and the terms of MIS-C in different articles were varied. Fever and gastrointestinal symptoms were the most experienced symptoms. Shock, rash, conjunctivitis, lips or oral cavity changes, hand and feet anomalies, and lymphadenopathy were observed, while respiratory symptoms seemed relatively infrequent. Seventy-eight percent to 100% of patients had evidence of SARS-CoV-2 infection, and patients positive for SARS-CoV-2 by serology [86% (95% CI: 78%, 95%)] were more than those by RT-PCR [36% (95% CI: 26%, 46%)]. Most patients had one or more increased inflammatory markers including C-reactive protein (CRP), procalcitonin (PCT), erythrocyte sedimentation rate (ESR), ferritin, interleukin-6 (IL-6), and D-dimer, accompanied by neutrophilia and lymphopenia. Impaired cardiac function was seen from elevated biomarkers and abnormal echocardiography. Intravenous immunoglobulin (IVIG), anticoagulants, inotropic agents and glucocorticoids were the main treatments, along with other intensive supportive care. Overall, the outcomes of MIS-C were favorable, and only one death was recorded. In terms of the quality assessment of included studies, most of the case studies did not follow the standard reporting checklist, so that they failed to get higher scores in the risk of bias assessment.ConclusionsPatients with MIS-C present with symptoms more severe than children with COVID-19, with fever and gastrointestinal symptoms as the primary manifestations and multisystem involvement, particularly cardiovascular system. Longer follow-up and further researches for the pathophysiology of MIS-C are urgently needed. In addition, attention should be paid to the quality of case studies to improve the completeness and transparency of scientific reports.

Project description:BackgroundMultisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 causes significant cardiovascular involvement, which can be a determinant of clinical course and outcome. The aim of this study was to investigate whether echocardiographic measures of ventricular function were independently associated with adverse clinical course and cardiac sequelae in patients with MIS-C.MethodsIn a longitudinal observational study of 54 patients with MIS-C (mean age, 6.8 ± 4.4 years; 46% male; 56% African American), measures of ventricular function and morphometry at initial presentation, predischarge, and at a median of 3- and 10-week follow-up were retrospectively analyzed and were compared with those in 108 age- and gender-matched normal control subjects. The magnitude of strain is expressed as an absolute value. Risk stratification for adverse clinical course and outcomes were analyzed among the tertiles of clinical and echocardiographic data using analysis of variance and univariate and multivariate regression.ResultsMedian left ventricular apical four-chamber peak longitudinal strain (LVA4LS) and left ventricular global longitudinal strain (LVGLS) at initial presentation were significantly decreased in patients with MIS-C compared with the normal cohort (16.2% and 15.1% vs 22.3% and 22.0%, respectively, P < .01). Patients in the lowest LVA4LS tertile (<13%) had significantly higher C-reactive protein and high-sensitivity troponin, need for intensive care, and need for mechanical life support as well as longer hospital length of stay compared with those in the highest tertile (>18.5%; P < .01). Initial LVA4LS and LVGLS were normal in 13 of 54 and 10 of 39 patients, respectively. There was no mortality. In multivariate regression, only LVA4LS was associated with both the need for intensive care and length of stay. At median 10-week follow-up to date, seven of 36 patients (19%) and six of 25 patients (24%) had abnormal LVA4LS and LVGLS, respectively. Initial LVA4LS < 16.2% indicated abnormal LVA4LS at follow-up with 100% sensitivity.ConclusionImpaired LVGLS and LVA4LS at initial presentation independently indicate a higher risk for adverse acute clinical course and persistent subclinical left ventricular dysfunction at 10-week follow-up, suggesting that they could be applied to identify higher risk children with MIS-C.

Dataset Information

Serologic and Cytokine Signatures in Children With Multisystem Inflammatory Syndrome and Coronavirus Disease 2019.

Background

Methods

Results

Conclusions

Publications

Serologic and Cytokine Signatures in Children With Multisystem Inflammatory Syndrome and Coronavirus Disease 2019.

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