Multisystem inflammatory disorder in children (MIS-C) is a recently identified rare disease process seen in some children after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. As a new disease entity, there have been efforts to clarify the diagnostic criteria for MIS-C to most accurately identify patients with this disease, while differentiating them from those with severe acute coronavirus disease 2019 (COVID-19). In this study, the researchers aimed to compare the clinical characteristics and outcomes of children and adolescents with MIS-C and those with severe COVID-19 to better distinguish between these disease states.

In this case series, 1116 patients were included who were ≤21 years of age hospitalized between March and October 2020 from 66 hospitals across 31 states. A total of 539 of these patients had MIS-C, and 577 patients had severe acute COVID-19. The Centers for Disease Control and Prevention definition for MIS-C was used in this study, which includes children <21 years old, fevers >38°C for >24 hours, clinically severe illness of ≥2 organs (multisystem involvement), no other plausible diagnosis, and evidence of current or recent SARS-CoV-2 infection or recent exposure. Severe acute COVID-19 was defined by clinical consensus criteria, including a positive reverse-transcriptase polymerase chain reaction test for SARS-CoV-2 and severe involvement of ≥1 organ systems.

Patient surveillance data in the Overcoming COVID-19 network registry for hospitalized patients <12 years old with MIS-C and severe acute COVID-19 were included in the analysis. Sex, race, ethnicity, comorbid conditions, presenting signs and symptoms, laboratory values within 48 hours of admission, severe complications, and clinical outcomes were compared between the 2 groups in the registry. Multivariable regression was used to compute adjusted risk ratios of factors associated with COVID-19 versus those associated with MIS-C.

Compared with patients with severe COVID-19, patients with MIS-C were more likely to be 6 to 12 years of age and of non-Hispanic Black race. Patients with MIS-C also had a higher neutrophil to lymphocyte ratio, higher C-reactive protein, and lower platelet count, when compared with those with severe COVID-19. Clinical syndromes, including cardiorespiratory involvement, cardiovascular without respiratory involvement, and mucocutaneous without cardiorespiratory involvement, were more likely in the MIS-C group, compared with the severe COVID-19 group. Both groups had similar rates of severe respiratory involvement without cardiovascular involvement and death rates during hospitalization. In patients with MIS-C who received echocardiograms, 34% of them had depressed left ventricular ejection fraction (LVEF); however, 91% had returned to a normal LVEF by 30 days, and 99% of those evaluated had a normal LVEF by 90 days. A total of 13% of patients with MIS-C who were evaluated for coronary aneurysms had aneurysms identified; 79% of those aneurysms resolved by 30 days, and 100% resolved by 90 days.

There are patterns of clinical presentation in MIS-C and severe COVID-19 in a large cohort that can help differentiate these 2 disease processes and inform appropriate treatment. The cardiac involvement seen in MIS-C has a high likelihood of resolving over time.

MIS-C and severe acute COVID-19 are currently understood to be discrete disease entities but often have overlapping clinical features, making it difficult to differentiate the 2 in some instances. Given that MIS-C is newly identified, in this study, the authors sought to clarify the defining features that discriminates between these 2 disease states. In this large case series, the authors were able to find differentiating factors including age, race, and clinical presentations. Mucocutaneous findings were more likely seen in MIS-C and may be a defining feature that is easy for the clinician to identify to support a diagnosis of MIS-C. Finally, laboratory values suggesting an inflammatory state such as elevated C-reactive protein and an increased neutrophil to lymphocyte ratio can help clinicians differentiate MIS-C from severe COVID-19.