Distinguishing Multisystem Inflammatory Syndrome in Children From COVID-19, Kawasaki Disease and Toxic Shock Syndrome

Abstract

Background: Distinguishing multisystem inflammatory syndrome in children (MIS-C) from coronavirus disease 2019 (COVID-19), Kawasaki disease (KD), and toxic shock syndrome (TSS) can be challenging. Because clinical management of these conditions can vary, timely and accurate diagnosis is essential.

Methods: Data were collected from patients <21 years of age hospitalized with MIS-C, COVID-19, KD, and TSS in 4 major health care institutions. Patient demographics and clinical and laboratory data were compared among the 4 conditions, and a diagnostic scoring tool was developed to assist in clinical diagnosis.

Results: A total of 233 patients with MIS-C, 102 with COVID-19, 101 with KD, and 76 with TSS were included in the analysis. Patients with MIS-C had the highest prevalence of decreased cardiac function (38.6%), myocarditis (34.3%), pericardial effusion (38.2%), mitral regurgitation (31.8%) and pleural effusion (34.8%) compared with patients with the other conditions. Patients with MIS-C had increased peak levels of C-reactive protein and decreased platelets and lymphocyte nadir counts compared with patients with COVID-19 and KD and elevated levels of troponin, brain natriuretic peptide and pro-brain natriuretic peptide compared with COVID-19. Diagnostic scores utilizing clinical findings effectively distinguished MIS-C from COVID-19, KD, and TSS, with internal validation showing area under the curve ranging from 0.87 to 0.97.

Conclusions: Compared with COVID-19, KD, and TSS, patients with MIS-C had significantly higher prevalence of cardiac complications, elevated markers of inflammation and cardiac damage, thrombocytopenia, and lymphopenia. Diagnostic scores can be a useful tool for distinguishing MIS-C from COVID-19, KD, and TSS.

FIGURE 1.

Proportions with signs and symptoms and clinical findings of interest for patients with MIS-C, COVID-19, KD, and TSS. Proportions with signs and symptoms (A) and clinical findings (B). P values from Fisher exact tests for difference in proportions compared with MIS-C patients denoted as ns (not significant),* (P < 0.05), ** (P < 0.01), and *** (P < 0.001).

FIGURE 2.

Laboratory markers of interest in patients with MIS-C, COVID-19, KD, and TSS. D-dimer, troponin, BNP, and proBNP (panels F-I), do not include comparisons with KD and TSS due to insufficient sample size.

FIGURE 3.

Four diagnostic scores using clinical criteria to help optimally distinguish between MIS-C, COVID-19, KD, and TSS. Panel A: MIS-C and COVID-19, panel B: MIS-C and KD, panel C: MIS-C and TSS, and panel D: MIS-C and COVID-19, KD, and TSS. The probability calculation assumes a similar number of patients with MIS-C and the other conditions are compared. The following number (and percent) of patients were missing laboratory test results: CRP, 53 (10.3%); lymphocytes, 34 (6.6%); platelets, 6 (1.2%); fibrinogen, 46 (13.7%); troponin, 58 (17.3%); ferritin, 31 (9.3%) and BNP/proBNP, 43 (12.8%). For patients with missing values, multiple imputation was used to determine the likelihood of abnormal lab values. Criteria with negative coefficients indicate that the presence of the criterion decreases the probability that the patient has MIS-C (ie, the absence of the criterion increases the probability that the patient has MIS-C). For a given patient, their plausible diagnoses determine which diagnostic score would be most applicable. ¹The summed score: all criteria that applies to the patient is added together for the total score. ²pMIS-C is the estimated probability that a patient with each given summed score has MIS-C. ARDS indicates acute respiratory distress syndrome; BNP, brain natriuretic peptide; pMIS-C, probability of MIS-C.