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MIS-C More Common, Severe Than Previously Known, Study Suggests

Cases of multisystem inflammatory syndrome in children (MIS-C) may be more common and severe than previously reported, research on hospitalizations from 31 U.S. states suggested.

Examining billing code data for the rare condition turned up 4,107 hospitalizations for MIS-C in 2021, representing roughly 17 cases for every 100 COVID-19 hospitalizations among kids, according to William Encinosa, PhD, of the Agency for Healthcare Research and Quality in Rockville, Maryland.

Deaths occurred in 0.8% of the cases, increasing to 5.8% when six or more organs were involved (MIS-C patients in the study had an average of 3.1 organs involved), the group reported in JAMA Network Open.

In an analysis restricting to the 2,715 MIS-C hospitalizations during the first quarter of 2021, which coincided with the initial Omicron wave, there were 1.48 hospitalizations per 100,000 children per month.

But hospitalization rates were doubled among Black versus non-Hispanic white children (1.99 vs 0.97 per 100,000), a larger disparity than found with COVID-19, the researchers noted, and rates separated even further in areas with increased social vulnerability, as measured by the CDC’s Social Vulnerability Index (SVI).

Since the start of the pandemic, the CDC has received reports on 9,139 cases of the rare condition, which is still not well understood. MIS-C is characterized as a constellation of symptoms among individuals under 21 years of age, including laboratory evidence of inflammation, clinically severe illness requiring hospitalization, multiorgan involvement, “no alternative plausible diagnoses,” and a confirmed SARS-CoV-2 infection in the 4 weeks prior to symptom onset.

During the study period, Encinosa’s group also identified 23,686 hospitalized COVID-19 cases in children among the 31 states included in the analysis. Inpatient deaths occurred in 0.9% of patients in this group, increasing to 17.2% when six or more organs were involved, though the mean organ involvement was 1.5 for the COVID group.

The current research is the first to investigate social vulnerability, race and ethnicity, and the extent of MIS-C and COVID-19 by looking at the number of organ systems involved in relation to outcomes, the researchers noted.

Overall, the MIS-C group was more likely to have six to eight organs involved than the COVID-19 group (8% vs 1%) and adverse medication events (AMEs) were more common in the MIS-C group (most due to glucocorticoids), at 9.8% versus 2.1% in the COVID-19 group (P<0.001).

When more organ systems were involved, AMEs increased for the two groups, while hospital length of stay doubled with MIS-C and tripled for COVID-19 with increasing organ involvement.

“With such similar outcome patterns between MIS-C and COVID-19, one may wonder whether severe MIS-C and COVID-19 cases are actually one and the same,” the researchers mused. “However, we found starkly different patterns between the two diseases with respect to race. In particular, the percentage of patients with MIS-C who were Black doubled from 16.2% to 31.7% as the number of organ systems increased, while with COVID-19 there was no such change.”

Furthermore, they noted, while disparities between Black and white children were found for three of nine outcomes with COVID-19, disparities were observed for seven of nine outcomes with MIS-C.

“We found that Black patients with MIS-C had their length of stay increased by 1 day simply by living in the top 25% of socially vulnerable counties. Thus, severity of MIS-C for Black children was likely exacerbated by socioeconomic factors, even though this was not the case with COVID-19,” the researchers concluded. “Therefore, overall, MIS-C cases were fundamentally different from COVID-19 cases.”

“Moreover, our results corroborate previous studies … that show MIS-C disparities in hospitalization rates go beyond SARS-2-CoV infection rate disparities,” they continued. “We extend this by showing in this study that MIS-C disparities extend even further to outcomes, unlike COVID-19.”

The study from Encinosa and colleagues was performed using data from 4,057 hospitals in 31 states (77% of the U.S. population) through an evaluation of cases documented with ICD-10-CM codes for MIS-C, which was established in 2021 for reimbursement purposes.

Patients with MIS-C were a median age 9 years and 59.5% were male, while 38.1% were white, 27% Hispanic, and 24% were Black. COVID-19 patients had a median age of 15 years and 54.4% were female, while 44.1% white, 27% were Hispanic, and 21% were Black.

While the research sheds light on the risks and impacts of increased organ dysfunction in MIS-C and COVID-19, “the research points to many questions for future investigation,” said Blake Martin, MD, of the University of Colorado School of Medicine in Aurora, and colleagues, writing in an accompanying editorial.

“First, why did Black children compose an increasingly higher proportion of patients with MIS-C as more organ systems were involved? Identifying patient biological or socioeconomic factors that can be targeted for treatment or prevention should be pursued,” they wrote.

“Additional work is needed to identify specific aspects of SVI and mechanisms by which these increases occur,” they continued. “For example, it is unknown whether the prolonged [length of stay] in patients with a high SVI score is a result of slower resolution of disease or discharge planning challenges occurring more frequently within vulnerable populations.”

  • Ingrid Hein is a staff writer for MedPage Today covering infectious disease. She has been a medical reporter for more than a decade. Follow


The study was funded by the Agency for Healthcare Research and Quality and the comment research was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

Encinosa had no disclosures. A co-author reported Dr Figueroa reported receiving personal fees from Navitas Clinical Research, Technical Resources International, The Johns Hopkins University, and Georgetown University Medical Center.

Martin had no disclosures. Co-commenters reported receiving consulting fees from CSL Seqirus, and grants from National Institutes of Health (NIH)/National Institute of Child Health and Human Development, the NIH/National Heart, Lung, and Blood Institute and the NIH/National Center for Advancing Translational Sciences outside the submitted work.

Primary Source

JAMA Network Open

Source Reference: Encinosa W, et al “Complications, adverse drug events, high costs, and disparities in multisystem inflammatory syndrome in children vs COVID-19” JAMA Netw Open 2023; DOI: 10.1001/jamanetworkopen.2022.44975.

Secondary Source

JAMA Network Open

Source Reference: Martin B, et al “Disparities in multisystem inflammatory syndrome in children and COVID-19 across the organ dysfunction continuum” JAMA Netw Open 2023; DOI: 10.1001/jamanetworkopen.2022.49552.

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