Obesity appears to be more prevalent in patients with multisystem inflammatory syndrome in children (MIS-C) than in children with Kawasaki disease, according to a new study.
In addition, obesity is associated with more severe presentation, laboratory results, and outcomes of MIS-C than Kawasaki disease. The results suggest that obesity as a comorbid factor should be considered at the clinical presentation of MIS-C associated with COVID-19, according to the researchers.
"In children with MIS-C, obesity was associated with a more severe disease presentation and worsened outcomes, including important factors such as a higher proportion admitted to the intensive care unit [ICU], worsened heart function parameters, and worsened inflammatory markers," study author Michael Khoury, MD, pediatric cardiologist at the University of Alberta in Edmonton, told Medscape Medical News.
"Conversely, obesity status was largely not associated with presentation and outcomes in children with Kawasaki disease," he said. "These findings suggest that obesity status should be considered for children presenting with MIS-C."
The study was published online on December 8, 2023, in JAMA Network Open.
Distinct Inflammatory Processes
Although children tend to have mild disease with SARS-CoV-2 infections, they may also present with a more serious postinfectious inflammatory syndrome called MIS-C. The cardiac and vascular symptoms of MIS-C can resemble those of Kawasaki disease, a medium-vessel vasculitis that remains a leading cause of pediatric-acquired heart disease. To treat MIS-C at the beginning of the COVID-19 pandemic, clinicians relied on treatments used for similar diseases, such as Kawasaki disease.
Despite the similarities, however, MIS-C and Kawasaki disease display certain differences. Patients with Kawasaki disease may develop coronary artery aneurysms, whereas those with MIS-C may develop myocardial dysfunction. Researchers have analyzed various demographic, lab, and clinical characteristics, such as obesity, to understand the associations with MIS-C and severe clinical presentation.
Khoury and colleagues analyzed data from the International Kawasaki Disease Registry between January 2020 and July 2022, which included patients with MIS-C (defined by US Centers for Disease Control and Prevention [CDC] criteria) and Kawasaki disease (defined by American Heart Association criteria) across 42 sites in eight countries. The researchers excluded patients with Kawasaki disease who had evidence of a recent COVID-19 infection or had unknown COVID-19 status.
For this study, the degree of adiposity was determined using the World Health Organization weight normative values for patients under the age of 2 years and CDC body mass index (BMI) for ages 2 years or older. Initially expressed as an adiposity z score, adiposity categories were converted to percentiles and defined as overweight (BMI/weight ≥ 85th to < 95th percentile), obesity (BMI/weight ≥ 95th percentile), and severe obesity (BMI/weight > 99th percentile).
Among 1767 children, 338 had Kawasaki disease and 1429 had MIS-C. Overall, 89.7% came from the United States or Canada. Patients with MIS-C had a higher prevalence of overweight than those with Kawasaki disease (17.1% vs 11.5%), as well as a higher prevalence of obesity (23.7% vs 11.5%) and severe obesity (10.4% vs 3.8%).
Overall, patients with MIS-C had more severe presentations and worse clinical outcomes than those with Kawasaki disease. Among patients with MIS-C, higher adiposity was associated with worse lab test values and outcomes, including a greater likelihood of shock, ICU admission and inotrope requirement, and increased inflammatory markers, creatinine levels, and alanine aminotransferase levels.
Among patients with Kawasaki disease, adiposity wasn't associated with lab test features or outcomes, apart from ICU admission rate. Obesity also wasn't associated with important clinical outcomes of Kawasaki disease, such as coronary artery involvement.
"These findings further highlight that Kawasaki disease and MIS-C, while similar in many ways, represent two distinct inflammatory processes with unique risk factors and varying outcomes," said Khoury.
The investigators noted that the lower prevalence of obesity in patients with Kawasaki disease in this study may reflect the lower rates of obesity in younger children, because the patients with Kawasaki disease were significantly younger than those with MIS-C.
The differences in the prevalence of obesity related to race and ethnicity may have been a confounding factor as well, the authors wrote, because race and ethnicity data were missing for 31% of the study population. At the same time, the adiposity z-score remained higher for patients with MIS-C after adjusting for age, sex, and race and ethnicity.
Greater Vigilance Needed
Commenting on the findings for Medscape, E. Ann Yeh, MD, director of the pediatric multiple sclerosis and neuroinflammatory disorders program at the Hospital for Sick Children in Toronto, said, "This important study provides evidence for the central role of obesity in shaping outcomes in children with MIS-C, in comparison to Kawasaki disease."
Yeh, who wasn't involved with this study, has researched symptoms and sequalae of hospitalized pediatric patients with SARS-CoV-2, as well as predictors of severe illness in children with MIS-C.
"The results should alert clinicians to the need for greater vigilance with children presenting with COVID and obesity," she said. "Future studies should evaluate preventive strategies that can be put into place for this population."
Several authors reported support from National Institutes of Health grants for studies related to MIS-C and post-acute sequalae of SARS-CoV-2 infection. Khoury and Yeh reported no relevant financial relationships.
Carolyn Crist is a health and medical journalist who reports on the latest studies for Medscape, MDedge, and WebMD.
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