Predictors of Severe Multisystem Inflammatory Syndrome in Children Identified

Key clinical and laboratory parameters of MIS-C were identified as risk factors for severe disease.

In multisystem inflammatory disease in children (MIS-C), key clinical and laboratory parameters have been identified as risk factors for severe disease, according to the results of a study published in Rheumatology (Oxford).

Data are lacking on the risk factors that may be associated with a more severe clinical course and outcomes among those with MIS-C.

Researchers of a retrospective cohort study sought to identify the predictors of a severe clinical course of MIS-C (defined by the need for inotropic support).

The study included children who were hospitalized in Israeli and US medical centers between July 2020 and March 2021 and who had been admitted to a pediatric ward or an intensive care unit (ICU) with a suspected diagnosis of MIS-C, based on the criteria used by the US Centers for Disease Control and Prevention (CDC).

The CDC case definition of MIS-C includes younger than 21 years; fever; laboratory evidence of inflammation; the requirement of hospital admission; multisystem (ie, ≥2) organ involvement (cardiac, pulmonary, renal, hematologic, gastrointestinal [GI], dermatologic, neurologic); absence of an alternative diagnosis; and a known exposure to COVID-19 within 4 weeks prior to symptom-onset or laboratory confirmation of a SARS-CoV-2 infection by reverse transcription polymerase chain reaction (RT-PCR), serology, or antigen test.

Among 111 individuals who were clinically suspected of having MIS-C during the study period, 100 fulfilled the CDC criteria. Overall, 78% of the patients were admitted to an Israeli medical center and 22% were admitted to the US medical center. The mean participant age was 9.65±4.48 years and 61% were boys. A total of 11% of the participants met the criteria for Kawasaki disease (ie, ≥4 clinical signs in addition to the mandatory criterion of fever), and 87% experienced GI symptoms (abdominal pain, vomiting, or diarrhea) on admission.

Identification of patients at high risk to develop a severe disease course may lead to earlier, more aggressive treatment decisions.

Overall, 65% of the patients were hypotensive and 44% required inotropic support. A total of 63% of patients were admitted to the ICU All participants received immunosuppressive therapy; 78% received treatment with intravenous immunoglobulin and 91% received corticosteroids.

Echocardiographic examination showed that 10% of patients had acute coronary ectasia or aneurysm and 37% had left ventricular dysfunction (LVD) during the acute phase of the disease.

According to the univariate model, LVD was strongly associated with severe disease (odds ratio [OR], 4.178; 95% CI, 1.760-9.917), whereas the presence of conjunctivitis (OR, 0.403; 95% CI, 0.173-0.938) and mucosal changes on admission (OR, 0.333; 95% CI, 0.119-0.931) were protective. Laboratory markers indicative of a severe disease course included low hemoglobin and platelet counts, low albumin and potassium levels, high leukocyte and neutrophil counts, and high troponin and brain natriuretic peptide levels.

According to the multivariate analysis, central nervous system involvement and fever of greater than 39.5 °C were linked to severe disease. In addition, mucosal involvement demonstrated a 6.2-fold decreased risk for severe disease. Further, low hemoglobin and platelet counts, as well as elevated C-reactive protein and troponin levels, were all identified as risk factors for severe disease.

Study limitations included the retrospective design and the retrieval of data from multiple centers that may have resulted in different clinical approaches, including no uniform policy for inotropic support. Further, because of the inability to retrospectively standardize timelines of data collection from multiple centers, risk factors might have been identified from data that were accessed during hospitalization and not at admission.

The study authors concluded, “Identification of patients at high risk to develop a severe disease course may lead to earlier, more aggressive treatment decisions. While the pandemic continues, future larger prospective cohorts will be needed to validate these findings.”


Kaidar K, Dizitzer Y, Hashkes PJ, et al. Risk factors for haemodynamic compromise in multisystem inflammatory syndrome in children: a multicentre retrospective study. Rheumatology (Oxford). Published online December 30, 2022. doi:10.1093/rheumatology/keac692