Multisystem inflammatory syndrome in children during the coronavirus disease pandemic of 2019: a review of clinical features and acute phase management.
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SUBMITTER: Shioji N
PROVIDER: S-EPMC8164829 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundThe serologic and cytokine responses of children hospitalized with multisystem inflammatory syndrome (MIS-C) vs coronavirus disease 2019 (COVID-19) are poorly understood.MethodsWe 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.ResultsChildren 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]).ConclusionsMIS-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.
| S-EPMC8883592 | biostudies-literature
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.
| S-EPMC8324361 | biostudies-literature
Project description:Kawasaki-like disease (KLD) and multisystem inflammatory syndrome in children (MIS-C) are considered as challenges for pediatric patients under the age of 18 infected with coronavirus disease 2019 (COVID-19). A systematic search was performed on July 2, 2020, and updated on December 1, 2020, to identify studies on KLD/MIS-C associated with COVID-19. The databases of Scopus, PubMed, Web of Science, Embase, and Scholar were searched. The hospitalized children with a presentation of Kawasaki disease (KD), KLD, MIS-C, or inflammatory shock syndromes were included. A total number of 133 children in 45 studies were reviewed. A total of 74 (55.6%) cases had been admitted to pediatric intensive care units (PICUs). Also, 49 (36.8%) patients had required respiratory support, of whom 31 (23.3%) cases had required mechanical ventilation/intubation, 18 (13.5%) cases had required other oxygen therapies. In total, 79 (59.4%) cases had been discharged from hospitals, 3 (2.2%) had been readmitted, 9 (6.7%) had been hospitalized at the time of the study, and 9 (6.7%) patients had expired due to the severe heart failure, shock, brain infarction. Similar outcomes had not been reported in other patients. Approximately two-thirds of the children with KLD associated with COVID-19 had been admitted to PICUs, around one-fourth of them had required mechanical ventilation/intubation, and even some of them had been required readmissions. Therefore, physicians are strongly recommended to monitor children that present with the characteristics of KD during the pandemic as they can be the dominant manifestations in children with COVID-19.
| S-EPMC8242327 | biostudies-literature
Project description:BackgroundAlthough neutralizing antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) correlate with protection against coronavirus disease 2019 (COVID-19), little is known about the neutralizing and antibody-dependent cell-mediated cytotoxicity (ADCC) responses to COVID-19, multisystem inflammatory syndrome in children (MIS-C), and COVID-19 vaccination in children.MethodsWe enrolled children 0-21 years of age with a history of COVID-19 (n = 13), MIS-C (n = 13), or 2 doses of BNT162b2 vaccination (n = 14) into a phlebotomy protocol. We measured pseudovirus neutralizing and functional ADCC antibodies to SARS-CoV-2 variants, including Omicron (B.1.1.529).ResultsThe primary BNT162b2 vaccination series elicited higher neutralizing and ADCC responses with greater breadth to SARS-CoV-2 variants than COVID-19 or MIS-C, although these were diminished against Omicron.ConclusionsSerologic responses were significantly reduced against variants, particularly Omicron.
| S-EPMC9213873 | biostudies-literature
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.
| S-EPMC8089028 | biostudies-literature
Project description:While fewer cases of severe Coronavirus Disease 2019 (COVID-19) are reported globally in children, a small proportion of SARS-CoV-2 infected children develop a novel pediatric febrile entity called multisystem inflammatory syndrome in children (MIS-C) that develops 2 to 5 weeks after initial SARS-CoV-2 exposure. MIS-C primarily effects male children and children of Hispanic or black descent. MIS-C manifests as a severe and uncontrolled inflammatory response with multiorgan involvement. A hyperinflammatory state is evidenced by clinical makers of inflammation including high levels of C-reactive protein (CRP), ferritin, and D-dimers, and an increased expression of pro-inflammatory cytokines. Children often present with persistent fever, severe gastrointestinal symptoms, cardiovascular manifestations, respiratory symptoms and neurological symptoms6-11,13. Cardiovascular manifestations include hypotension, shock, cardiac dysfunction, myocarditis and pericardial effusion. In the united states, admission to the intensive care unit occurs in approximately 58% of cases. To understand disease pathogenesis of MIS-C and proteins associated with the severe form of disease we performed proteomics analysis of serum or plasma samples. We collected serum from healthy children (SARS-CoV-2 negative, n=20), mild MIS-C (non-ICU, n=5) and severe MIS-C (ICU, n = 20) patients. MIS-C definition and diagnosis was performed according to CDC guidelines. Healthy adult serum (n = 4) was also used for reference ranges quality control and we obtained plasma samples from Kawasaki Disease (KD; n=7) patients that were recruited before the Coronavirus Disease 2019 (COVID-19) pandemic.
2021-09-29 | PXD025462 | Pride
Project description:ObjectiveTo develop a more comprehensive description of multisystem inflammatory syndrome in children (MIS-C), a novel syndrome linked to severe acute respiratory syndrome coronavirus 2, by conducting a systematic analysis of studies from different settings that used various inclusion criteria.Study designMIS-C studies were identified by searching PubMed and Embase as well as preprint repositories and article references to identify studies of MIS-C cases published from April 25, 2020, through June 29, 2020. MIS-C study metadata were assessed and information on case demographics, clinical symptoms, laboratory measurements, treatments, and outcomes were summarized and contrasted between studies.ResultsEight studies were identified representing a total of 440 MIS-C cases. Inclusion criteria varied by study: 3 studies selected patients diagnosed with Kawasaki disease, 2 required cardiovascular involvement, and 3 had broader multisystem inclusion criteria. Median age of patients by study ranged from 7.3 to 10 years, and 59% of patients were male. Across all studies, the proportion of patients with positive results for severe acute respiratory syndrome coronavirus 2 reverse transcriptase-polymerase chain reaction tests ranged from 13% to 69% and for serology, from 75% to 100%. Patients with MIS-C had high prevalence of gastrointestinal (87%), dermatologic/mucocutaneous (73%), and cardiovascular (71%) symptoms. Prevalence of cardiovascular, neurologic, and respiratory system involvement significantly differed by study inclusion criteria. All studies reported elevated C-reactive protein, interleukin-6, and fibrinogen levels for at least 75% of patients in each study.ConclusionsThis systematic review of MIS-C studies assists with understanding this newly identified syndrome and may be useful in developing a refined, universal case definition of MIS-C.
| S-EPMC7403869 | biostudies-literature
Project description:ImportanceTo date, no study has characterized the mucocutaneous features seen in hospitalized children with multisystem inflammatory syndrome in children (MIS-C) or the temporal association of these findings with the onset of systemic symptoms.ObjectiveTo describe the mucocutaneous findings seen in children with MIS-C during the height of the coronavirus disease 2019 (COVID-19) pandemic in New York City in 2020.Design, setting, and participantsA retrospective case series was conducted of 35 children admitted to 2 hospitals in New York City between April 1 and July 14, 2020, who met Centers for Disease Control and Prevention and/or epidemiologic criteria for MIS-C.Main outcomes and measuresLaboratory and clinical characteristics, with emphasis on mucocutaneous findings, of children who met criteria for MIS-C. The characterization of mucocutaneous features was verified by 2 board-certified pediatric dermatologists.ResultsTwenty-five children (11 girls [44%]; median age, 3 years [range, 0.7-17 years]) were identified who met definitional criteria for MIS-C; an additional 10 children (5 girls [50%]; median age, 1.7 years [range, 0.2-15 years]) were included as probable MIS-C cases (patients met all criteria with the exception of laboratory test evidence of severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] infection or known exposure). The results of polymerase chain reaction tests for SARS-CoV-2 were positive for 10 patients (29%), and the results of SARS-CoV-2 immunoglobulin G tests were positive for 19 patients (54%). Of the 35 patients, 29 (83%) exhibited mucocutaneous changes, with conjunctival injection (n = 21), palmoplantar erythema (n = 18), lip hyperemia (n = 17), periorbital erythema and edema (n = 7), strawberry tongue (n = 8), and malar erythema (n = 6) being the most common findings. Recognition of mucocutaneous findings occurred a mean of 2.7 days (range, 1-7 days) after the onset of fever. The duration of mucocutaneous findings varied from hours to days (median duration, 5 days [range, 0-11 days]). Neither the presence nor absence of mucocutaneous findings was significantly associated with overall disease severity.Conclusions and relevanceIn this case series of hospitalized children with suspected MIS-C during the COVID-19 pandemic, a wide spectrum of mucocutaneous findings was identified. Despite their protean and transient nature, these mucocutaneous features serve as important clues in the recognition of MIS-C.
| S-EPMC7726702 | biostudies-literature
Project description:Objectivesmulti-system ınflammatory syndrome in children (MIS-C) is an immune-mediated process that develops after infections like SARS-CoV-2. The authors aimed to reveal the mucocutaneous findings of patients diagnosed with MIS-C at presentation and evaluate the frequency of these mucocutaneous findings and their possible relationship with the severity of the disease.MethodsA prospective study was conducted of 43 children admitted to a tertiary hospitals between January 2021 and January 2022 who met Centers for Disease Control and Prevention criteria for MIS-C.Results43 children (25 [58.1%] male); median age, 7.5 years [range 0.5‒15 years]) met the criteria for MIS-C. The most common symptom was cutaneous rash 81.4%, followed by gastrointestinal symptoms 67.4%, oral mucosal changes 65.1%, and conjunctival hyperemia 58.1%. The most common mucosal finding was fissured lips at 27.9%, diffuse hyperemia of the oral mucosa at 18.6%, and strawberry tongue at 13.9%. Urticaria (48.8%) was the most common type of cutaneous rash in the present study's patients. The most common rash initiation sites were the trunk (32.6%) and the palmoplantar region (20.9%). The presence or absence of mucocutaneous findings was not significantly associated with disease severity.Study limitationsThe number of patients in the this study was small.ConclusionsThe present study's prospective analysis detected mucocutaneous symptoms in almost 9 out of 10 patients in children diagnosed with MIS-C. Due to the prospective character of the present research, the authors think that the characteristic features of cutaneous and mucosal lesions the authors obtained will contribute to the literature on the diagnosis and prognosis of MIS-C.
| S-EPMC9666380 | biostudies-literature
Project description:BackgroundMultisystem inflammatory syndrome in children (MIS-C) is a severe clinical phenotype of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection that remains poorly understood.MethodsHospitalized children <18 years of age with suspected coronavirus disease 2019 (COVID-19) (N = 53) were recruited into a prospective cohort study; 32 had confirmed COVID-19, with 16 meeting the US Centers for Disease Control criteria for MIS-C. Differences in nasopharyngeal viral ribonucleic acid (RNA) levels, SARS-CoV-2 seropositivity, and cytokine/chemokine profiles were examined, including after adjustments for age and sex.ResultsThe median ages for those with and without MIS-C were 8.7 years (interquartile range [IQR], 5.5-13.9) and 2.2 years (IQR, 1.1-10.5), respectively (P = .18), and nasopharyngeal levels of SARS-CoV-2 RNA did not differ significantly between the 2 groups (median 63 848.25 copies/mL versus 307.1 copies/mL, P = .66); 75% of those with MIS-C were antibody positive compared with 44% without (P = .026). Levels of 14 of 37 cytokines/chemokines (interleukin [IL]-1RA, IL-2RA, IL-6, IL-8, tumor necrosis factor-α, IL-10, IL-15, IL-18, monocyte chemoattractant protein [MCP]-1, IP-10, macrophage-inflammatory protein [MIP]-1α, MCP-2, MIP-1β, eotaxin) were significantly higher in children with MIS-C compared to those without, irrespective of age or sex (false discovery rate <0.05; P < .05).ConclusionsThe distinct pattern of heightened cytokine/chemokine dysregulation observed with MIS-C, compared with acute COVID-19, occurs across the pediatric age spectrum and with similar levels of nasopharyngeal SARS-CoV-2 RNA.
| S-EPMC8241418 | biostudies-literature