Differentiating between MIS-C and severe COVID-19

February 25, 2021
Miranda Hester

Ms. Hester is Content Specialist with Contemporary OB/GYN and Contemporary Pediatrics.

A case series offers insight on how to separate multisystem inflammatory syndrome in children (MIS-C) and severe acute coronavirus 2019 disease (COVID-19).

In April 2020, the first cases of multisystem inflammatory syndrome in children (MIS-C) were found. The current hypothesis is that MIS-C is mostly post-infection and distinct from coronavirus 2019 disease (COVID-19) because many of the cases had COVID-19 negative respiratory samples and MIS-C also peaked after reported COVID-19 cases. An investigation in JAMA examines how the characteristics and outcomes of MIS-C compare with severe COVID-19.1

Investigators created a case series of patients aged younger than 21 years who were hospitalized between March 15, 2020, and October 31, 2020, at 66 hospitals in 31 states in the United States. The last date of follow-up was January 5, 2021. The patients with COVID-19 had a positive reverse transcriptase–polymerase chain reaction (RT-PCR) and severe organ system involvement. Patients with MIS-C had inflammation; multisystem involvement; fever; and a positive severe acute respiratory syndrome coronavirus 2 RT-PCR test or antibody test results or recent exposure with no alternate diagnosis.

A total of 1116 patients were included and 539 diagnosed with MIS-C and 577 diagnosed with COVID-19. When compared with patients who had COVID-19, patients with MIS-C were more likely to be non-Hispanic Black (32.3% vs 21.5%; absolute risk difference [RD], 10.8% [95% CI, 5.6%-16.0%]; adjusted risk ratios [aRR], 1.43 [95% CI, 1.17-1.76] vs White) and be 6 to 12 years of age (40.8% vs 19.4%; RD, 21.4% [95% CI, 16.1%-26.7%]; aRR, 1.51 [95% CI, 1.33-1.72] vs 0-5 years). Additionally, they were more likely to have cardiovascular without respiratory involvement (10.6% vs 2.9%; RD, 7.7% [95% CI, 4.7%-10.6%]; aRR, 2.49 [95% CI, 2.05-3.02] vs respiratory involvement), cardiorespiratory involvement (56.0% vs 8.8%; RD, 47.2% [95% CI, 42.4%-52.0%]; aRR, 2.99 [95% CI, 2.55-3.50] vs respiratory involvement), and mucocutaneous without cardiorespiratory involvement (7.1% vs 2.3%; RD, 4.8% [95% CI, 2.3%-7.3%]; aRR, 2.29 [95% CI, 1.84-2.85] vs respiratory involvement) when compared to patients with COVID-19. The MIS-C patients also had a higher C-reactive protein level (median, 152 mg/L vs 33 mg/L; P < .001), a higher neutrophil to lymphocyte ratio (median, 6.4 vs 2.7, P < .001), and a lower platelet count (<150 ×103 cells/μL [212/523 {41%} vs 84/486 {17%}, P < .001]). Three hundred ninety-eight of the patients with MIS-C required admission to the intensive care unit in comparison with 253 patients with COVID-19 who were admitted to one. Eight patients with COVID-19 died during hospitalization and 10 MIS-C patients died in the hospital. Among the patients with reduced left ventricular systolic function and coronary artery aneurysm, roughly e 91.0% (95% CI, 86.0%-94.7%) and 79.1% (95% CI, 67.1%-89.1%), respectively, normalized within 30 days.

Investigators concluded that their case series illustrate patterns of organ involvement and clinical presentation that could potentially distinguish between patients who have severe acute COVID-19 and those with MIS-C.


1. Feldstein L, Tenforde M, Friedman K, et al. Characteristics and outcomes of US children and adolescents with multisystem inflammatory syndrome in children (MIS-C) compared with severe acute COVID-19. JAMA. February 24, 2021. Epub ahead of print. doi:10.1001/jama.2021.2091