Mortality, Adverse Medication Events, Length of Hospital Stay Rises as More Organ Systems are Impacted by MIS-C Post-COVID-19


Multisystem inflammatory syndrome typically presents approximately 1 month after a COVID infection, occasionally resulting in cardiac complications in previously healthy children.

With the arrival of the third anniversary of the COVID-19 pandemic, research efforts have increasingly turned toward understanding the post-COVID-19 condition, otherwise known as long COVID. Children have been particularly impacted by multisystem inflammatory syndrome (MIS-C), a relatively novel hyperinflammatory syndrome that usually presents approximately 1 month after a COVID infection, occasionally resulting in cardiac complications in previously healthy children.

However, there is not yet a complete picture of MIS-C across US hospitals as the surveillance currently relies on hospitals voluntarily reporting the data to state health departments. Most CDC studies have been limited to 66 hospitals across 31 studies, with incidence of up to 1700 MIS-C cases.

A recent retrospective cross-sectional study used reporting data from the Agency for Healthcare Research and Quality (AHRQ) to compare outcomes across MIS-C and COVID-19 as of October 20, 2022. The study authors examined 2 clinical outcomes: inpatient death and adverse medication events (AMEs) during treatment with a particular focus on glucocorticoids and immunoglobulin—the 2 main treatments for MIS-C—as coded by the hospitals.

Additionally, the authors investigated 2 usage outcomes: length of stay and costs. The hospital costs were evaluated by applying the 2021 hospital-level Centers for Medicaid & Medicare Cost Report Information System cost-to-charge ratios. These were then adjusted with the Centers for Medicaid and Medicare Wage Index. Cost was defined by the expenses incurred in the production of hospital services, such as wages, supplies, and utility, but excluding physician fees.

Due to the range in severity of MIS-C and COVID-19, the study investigators compared clinical and usage outcomes by stratifying both the MIS-C and COVID-19 subsamples by the number of organ systems affected by complications. Authors identified and examined more than 50 complications comprising 8 different organ dysfunction categories related to MIS-C hospitalizations: cardiac, respiratory, neurological, hematologic, gastrointestinal, musculoskeletal, kidney, and mucocutaneous complications. MIS-C and COVID-19 were then stratified into 5 categories: 0 to 2 systems, 3 systems, 4 systems, 5 systems, and 6 to 8 systems affected by complications.

The study identified 4107 billed MIS-C hospitalizations (median age, 9 [IQR, 5-13] years; 2443 [59.5%] male; 1664 [40.5%] female; 881 [24.3%] Black). Patients with COVID-19 without MIS-C included 23,686 individuals (median age, 15 [IQR, 5-18] years; 12,878 [54.4%] female; 10,808 (45.6%) male; 4472 [20.5%] Black). The share of hospitalized children with MIS-C who were Black was higher than in those with COVID-19 (MIS-C: 24%; 95% CI, 23%-26% vs COVID-19: 21%; 95% CI, 20%-21%; P = .001).

The MIS-C hospitalization rate was 1.48 (95% CI, 1.35-1.62) per 100,000 children per month. The overall incidence varied 2-fold by race: 0.97 for White children and 1.99 for Black children (P=.01). This is a larger disparity than found with COVID-19, in which the incidence varied from 4.4 for white children to 6.6 for Black children (P=.01).

The study found that patients with MIS-C had more organ systems affected 3.1 (95% CI, 3.0-3.2) vs 1.5 (95% CI, 1.4-1.5) for COVID-19 (P <.001). Individually, MIS-C was more severe than COVID-19 for 7 of the 8 complications—all but neurological, where there was no significant difference).

Nearly 8% of patients with MIS-C had 6 or more of the 8 organ systems mentioned affected by complications, compared with 1% of patients with COVID-19. Additionally, outcomes worsened as the number of organ system dysfunctions increased from 0 to 2 to 6 to 8 organs.

Inpatient death for MIS-C increased from less than 1% to 5.8% (95% CI, 3.3%-8.4%), and from less than 1% to 17.2% (95% CI, 11.7%-22.7%) for COVID-19. AMEs for MIS-C increased from 4.9% (95% CI, 3.8%-6.0%) to 17.8% (95% CI, 13.7%-22.0%) and from 1.2% (95% CI, 1.0%-1.3%) to 13.4% (95% CI, 8.4%-18.3%) for COVID-19.

Median length of stay doubled from 4 (IQR, 2-5) to 8 (IQR, 5-12) days for MIS-C and tripled from 3 (IQR, 2-5) to 16 (IQR, 7-23) days for COVID-19. Median costs increased from $16,225 (IQR, $9244-$26 822) to $53,359 (IQR, $35 920-$86 882) for MIS-C and from $6474 (IQR, $3741-$12 103) to $98,643 (IQR, $30 675-$204 956) for COVID-19.

“While the CDC reports an MIS-C death rate of 0.8% and 0.7% for pediatric COVID-19, we found that, when 6 or more organ systems were affected, the death rate increased to 5.8% for MIS-C and 17.2% for COVID-19,” the authors wrote.

To the authors’ knowledge, this study included the first analysis of AMEs in the treatment of MIS-C and COVID-19. These AMEs increased significantly over the number of organ systems involved for both MIS-C and COVID-19.

Overall, this study found that average outcome rates reported in previous MIS-C studies can be misleading. The number of organ system dysfunctions matters, with outcome rates diverging significantly from the averages as multiple organ systems fail.

Finally, racial and ethnic disparities in outcomes were seen with MIS-C, but not with COVID-19, and Black children in more vulnerable socioeconomic areas experienced greater severity in MIS-C outcomes but not for COVID-19.


Encinosa W, Moon K, Figueroa J, et al. Complications, adverse drug events, high costs, and disparities in multisystem inflammatory syndrome in children vs COVID-19. JAMA Netw Open. 2023;6(1):e2244975. doi:10.1001/jamanetworkopen.2022.44975

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