Dataset Information

A descriptive study on multisystem inflammatory syndrome in children in a single center in West Michigan.

ABSTRACT:

Background

Multisystem Inflammatory Syndrome in Children (MIS-C) is a rare hyperinflammatory condition that occurs following SARS-CoV-2 infection. There is a paucity of research describing risk factors, optimal management, and outcomes of this life-threatening condition.

Methods

This is a case series of 26 patients diagnosed with MIS-C in a West Michigan pediatric tertiary care center from April 2020 to February 2021. We describe the clinical, imaging, and laboratory characteristics of these patients and detail their treatments and outcomes with comparisons between Pediatric Intensive Care Unit (PICU) and non-PICU patients. Categorical testing utilized Chi-square and Fisher's Exact tests. Comparison between groups used T-tests or Kruskal-Wallis.

Results

Fifteen patients (57%) required intensive care. There was no statistically significant difference in demographics between PICU and non-PICU patients, however all Black patients required intensive care. Gastrointestinal symptoms were present in 22 patients (84%). Seventeen patients (65%) had Kawasaki-like features and 12 (46%) developed coronary artery dilation. Patients requiring intensive care were less likely to have a reported history of COVID-19 disease or exposure (p = 0.0362). Statistically significant differences were also noted in peak ferritin (p = 0.0075), procalcitonin, and BNP in those who required intensive care.

Conclusions

Although overlap exists with other hyperinflammatory conditions, our study provides further evidence that MIS-C is a distinct, albeit heterogenous, disorder with various degrees of cardiac involvement. Anakinra, in conjunction with steroid use, appears to be effective and safe in the treatment of MIS-C. This report identifies procalcitonin, peak ferritin, and BNP as potentially useful biomarkers for severity of disease.

SUBMITTER: Shabab J

PROVIDER: S-EPMC8675109 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background and aims:A newly recognized multisystem inflammatory syndrome in children (MIS-C) has had a paradigm-shifting effect on the perception of severe acute respiratory syndrome, coronavirus-2 (SARS-CoV-2) illness severity in children. We report the clinical and biochemical features of liver involvement, and the comorbidities that present with hepatitis, in a substantial cohort of patients.Approach and results:This is a retrospective cohort study of 44 patients with MIS-C admitted at Morgan Stanley Children's Hospital of New York-Presbyterian during April and May 2020. We evaluated the number of patients who developed hepatitis and examined both demographics and inflammatory laboratory values to ascertain those that were at higher risk for liver involvement and more severe disease. Hepatitis was present in 19 subjects (43%) and was associated with more severe disease. Persons with hepatitis had significantly higher rates of shock at presentation (21.1% vs. 0%; P = 0.008), greater respiratory support requirement (42.1% vs. 12%; P = 0.005), and longer hospitalization times (median, 7 [interquartile range {IQR}, 5, 10] vs. 4 days [IQR, 3.5, 6.5]; P < 0.05). Patients with hepatitis also had significantly higher levels of ferritin (706.9 vs. 334.2 mg/mL; P < 0.01), interleukin-6 (233.9 vs. 174.7 pg/mL; P < 0.05), troponin (83.0 vs. 28.5 ng/L; P < 0.05), and B-type natriuretic peptide (7,424.5 vs. 3,209.5 pg/mL; P < 0.05). The single patient with liver failure also developed multiorgan failure requiring vasopressors, hemodialysis, and mechanical ventilation. All patients were discharged, though >50% had persistent hepatitis up to 1 month after discharge.Conclusions:Hepatitis is common in children with MIS-C and is associated with a more severe presentation and persistent elevation of liver function tests in many. Despite the positive outcomes reported here, close follow-up is warranted given the limited knowledge of the long-term impact of SARS-CoV-2 on the liver.

Project description:Background: Most children and adolescents infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) develop a mild coronavirus disease 2019 (COVID-19) that usually does not require medical intervention. However, a small proportion of pediatric patients develop a severe clinical condition, Multisystem Inflammatory Syndrome in Children (MIS-C). The involvement of epigenetics in the control of the immune response and viral activity prompted us to carry out an epigenomic study to uncover target loci regulated by DNA methylation that could be altered upon the appearance of MIS-C. Methods: Peripheral blood samples were recruited from 43 confirmed MIS-C patients with a median age of 7.7 years, most of whom were of West-Eurasian origin. Four or more organ systems were involved in the majority of patients. 69 non-COVID-19 pediatric samples and 15 COVID-19 pediatric samples without MIS-C were used as controls. The cases in the two groups were mixed and divided into discovery (MIS-C = 29 and non-MIS-C = 56) and validation (MIS-C = 14 and non-MIS-C = 28) cohorts, and balanced for age, gender and ethnic background. We interrogated 850,000 CpG sites of the human genome for DNA methylation variants. Findings: The DNA methylation content of 33 CpG loci was linked with the presence of MIS-C. Of these sites, 18 (54.5%) were located in described genes. The top candidate gene was the immune T-cell mediator ZEB2; and others highly ranked candidates included the regulator of natural killer cell functional competence SH2D1B; VWA8, which contains a domain of the Von Willebrand factor A involved in the pediatric hemostasis disease; and human leukocyte antigen complex member HLA-DRB1; in addition to pro-inflammatory genes such as CUL2 and AIM2. The identified loci were used to construct a DNA methylation profile (EPIMISC) that was associated with MIS-C in both cohorts. The EPIMISC signature was also overrepresented in Kawasaki disease patients, a childhood pathology with also a possible viral trigger, that shares many of the clinical features of MIS-C. Interpretation: We have characterized DNA methylation loci that are associated with the onset of MIS-C. The identified genes are likely contributors to the characteristic exaggerated host inflammatory response observed in these patients. The described epigenetic signature could also provide new targets for more specific therapies for the disorder.

Project description:BackgroundEvidence is urgently needed to support treatment decisions for children with multisystem inflammatory syndrome (MIS-C) associated with severe acute respiratory syndrome coronavirus 2.MethodsWe performed an international observational cohort study of clinical and outcome data regarding suspected MIS-C that had been uploaded by physicians onto a Web-based database. We used inverse-probability weighting and generalized linear models to evaluate intravenous immune globulin (IVIG) as a reference, as compared with IVIG plus glucocorticoids and glucocorticoids alone. There were two primary outcomes: the first was a composite of inotropic support or mechanical ventilation by day 2 or later or death; the second was a reduction in disease severity on an ordinal scale by day 2. Secondary outcomes included treatment escalation and the time until a reduction in organ failure and inflammation.ResultsData were available regarding the course of treatment for 614 children from 32 countries from June 2020 through February 2021; 490 met the World Health Organization criteria for MIS-C. Of the 614 children with suspected MIS-C, 246 received primary treatment with IVIG alone, 208 with IVIG plus glucocorticoids, and 99 with glucocorticoids alone; 22 children received other treatment combinations, including biologic agents, and 39 received no immunomodulatory therapy. Receipt of inotropic or ventilatory support or death occurred in 56 patients who received IVIG plus glucocorticoids (adjusted odds ratio for the comparison with IVIG alone, 0.77; 95% confidence interval [CI], 0.33 to 1.82) and in 17 patients who received glucocorticoids alone (adjusted odds ratio, 0.54; 95% CI, 0.22 to 1.33). The adjusted odds ratios for a reduction in disease severity were similar in the two groups, as compared with IVIG alone (0.90 for IVIG plus glucocorticoids and 0.93 for glucocorticoids alone). The time until a reduction in disease severity was similar in the three groups.ConclusionsWe found no evidence that recovery from MIS-C differed after primary treatment with IVIG alone, IVIG plus glucocorticoids, or glucocorticoids alone, although significant differences may emerge as more data accrue. (Funded by the European Union's Horizon 2020 Program and others; BATS ISRCTN number, ISRCTN69546370.).

Project description:BACKGROUND:Understanding the epidemiology and clinical course of multisystem inflammatory syndrome in children (MIS-C) and its temporal association with coronavirus disease 2019 (Covid-19) is important, given the clinical and public health implications of the syndrome. METHODS:We conducted targeted surveillance for MIS-C from March 15 to May 20, 2020, in pediatric health centers across the United States. The case definition included six criteria: serious illness leading to hospitalization, an age of less than 21 years, fever that lasted for at least 24 hours, laboratory evidence of inflammation, multisystem organ involvement, and evidence of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) based on reverse-transcriptase polymerase chain reaction (RT-PCR), antibody testing, or exposure to persons with Covid-19 in the past month. Clinicians abstracted the data onto standardized forms. RESULTS:We report on 186 patients with MIS-C in 26 states. The median age was 8.3 years, 115 patients (62%) were male, 135 (73%) had previously been healthy, 131 (70%) were positive for SARS-CoV-2 by RT-PCR or antibody testing, and 164 (88%) were hospitalized after April 16, 2020. Organ-system involvement included the gastrointestinal system in 171 patients (92%), cardiovascular in 149 (80%), hematologic in 142 (76%), mucocutaneous in 137 (74%), and respiratory in 131 (70%). The median duration of hospitalization was 7 days (interquartile range, 4 to 10); 148 patients (80%) received intensive care, 37 (20%) received mechanical ventilation, 90 (48%) received vasoactive support, and 4 (2%) died. Coronary-artery aneurysms (z scores ?2.5) were documented in 15 patients (8%), and Kawasaki's disease-like features were documented in 74 (40%). Most patients (171 [92%]) had elevations in at least four biomarkers indicating inflammation. The use of immunomodulating therapies was common: intravenous immune globulin was used in 144 (77%), glucocorticoids in 91 (49%), and interleukin-6 or 1RA inhibitors in 38 (20%). CONCLUSIONS:Multisystem inflammatory syndrome in children associated with SARS-CoV-2 led to serious and life-threatening illness in previously healthy children and adolescents. (Funded by the Centers for Disease Control and Prevention.).