Researchers identified novel MIS-C subtypes

Black and Latino children were over-represented in a cohort of kids with Covid-19-related multisystem inflammatory syndrome reported by researchers from the Children’s National Hospital in Washington DC, and the disease was identified in children with and without detectable SARS-CoV-2 virus.

In a newly reported study, researchers from Children’s National identified key clinical, biomarker, and other features associated with the Covid-19 disorder multisystem inflammatory syndrome in children (MIS-C), which had been diagnosed in approximately 4,000 children in the United States as of early June.

The study, published online June 25 in The Journal of Pediatrics, included 124 children treated at the hospital between March and September of 2020, including 63 with a diagnosis of MIS-C (39 confirmed and 24 probable).

Black children in the cohort had the highest risk for a diagnosis of MIS-C, accounting for 46% of confirmed or probable cases. A total of 35% and 11% of cases, respectively, involved Latino and White children (8% from other ethnicities).

The median patient age was 7.25 years. Just 5 (8%) of the confirmed or probable MIS-C cases occurred among children younger than age 1 year, with 18 (29%) cases occurring in ages 1-5, 19 (30%) occurring in ages 5-10, 15 (24%) occurring in ages 10-15, and 6 (10%) occurring in adolescents age 15 and older.

The analysis revealed that heart complications, including systolic myocardial dysfunction and valvular regurgitation, occurred more often in the roughly half (52%) of MIS-C patients who became critically ill.

In all, 55% of children in the MIS-C cohort who became critically ill had cardiac complications compared to 28% who did not become critically ill.

This rate of cardiac complications was lower than has been reported in previously published studies of MIS-C.

Researcher Roberta DeBiasi, MD, and colleagues also identified novel subtypes of the newly identified Covid-19 disorder in children, including MIS-C with and without detectable SARS-CoV-2 virus, MIS-C with and without the clinical features of Kawasaki disease and MIS-C with and without new onset cardiac abnormalities.

Patients with MIS-C with detectable virus were found to have lower viral load than patients with primary SARS -CoV-2 infections, with viral loads similar to controls who had detectable virus and other diagnoses.

More children with confirmed or probable multisystem inflammatory syndrome had antibodies for SARS-CoV-2 than controls, consistent with the hypothesis that MIS-C most often occurs immediately following primary infection as a result of immune system hyperresponse to the virus.

The finding that roughly half of the MIS-C cohort had symptoms inconsistent with Kawasaki disease or were not critically ill illustrates the challenges for the diagnosis and management of the disease, DeBiasi and colleagues wrote.

“Failing to identify these children not only underestimates the prevalence of the disease, but may result in sub-optimal outcomes, because presumably, earlier identification and treatment could prevent progression to critically ill status and/or ameliorate the likelihood of initial and/or subsequent cardiovascular complications,” the researcher wrote.

A recently reported cohort study involving 248 children with Covid-19-related multisystem inflammatory syndrome located in 7 U.S. states suggested a disease incidence of 5.1 per million person months and 316 per million SARS-CoV-2 infections among those younger than 21 years of age.

In that study, researchers also reported a higher incidence of MIS-C among Black and Latino children, with an estimated adjusted incidence rate ratio compared to White children of 9.26 (95% CI, 6.15-13.93) for Black children and 8.92 (95% CI, 6.00-13.26) among Latino children.

Recently reported observational studies examining treatments for MIS-C appeared to show conflicting findings regarding the efficacy of immunomodulation with IVIG and/or glucocorticoids, with the Overcoming Covid Consortium study suggesting a lower risk for cardiovascular dysfunction in patients initially treated with intravenous immunoglobulin (IVIG) plus glucocorticoids, while observational data from the Best Available Treatment Study (BATS) consortium showed no statistically significant difference between patients treated with a combination of IVIG and glucocorticoids and those receiving either therapy alone.

In an editorial in New England Journal of Medicine, DeBiasi wrote that key differences in the patient populations and the trial dates could explain the seemingly discordant findings.

DeBiasi further noted that while both groups of researchers used propensity-score adjustment and other statistical methods in an attempt to control for confounding related to treatment or variations in care, “these modeling approaches cannot fully compensate for such variations.”

“In a triumph of collaboration, experts achieved consensus about diagnostic criteria and the need to induce rapid immunomodulation aimed at limiting the course of illness. However, in the absence of randomized, controlled clinical trials, consensus around specific immunomodulatory therapies has been more elusive, given the speed with which centers have had to establish cohorts and deliver treatment,” she wrote.

  1. Black children in the cohort had the highest risk for a diagnosis of multisystem inflammatory syndrome, accounting for 46% of confirmed or probable cases. A total of 35% and 11% of cases, respectively, involved Latino and White children (8% from other ethnicities).
  2. The analysis revealed that heart complications, including systolic mycocardial dysfunction and valvular regurgitation, occurred more often in the roughly half (52%) of MIS-C patients who became critically ill.

Salynn Boyles, Contributing Writer, BreakingMED™

Funded in part by the Ikaria Fund, who had no role in the design, collection, analysis and interpretation of data, writing of the report, or decision to submit the manuscript for publication. The authors declared no conflicts of interest.

 

Cat ID: 190

Topic ID: 79,190,730,933,190,926,192,927,151,928,925,934

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