Multisystem inflammatory syndrome in children (MIS-C) and sepsis differentiation by a clinical and analytical score: MISSEP score

Abstract

Differential diagnosis between Multisystem Inflammatory Syndrome in Children (MIS-C) and other causes of systemic inflammatory response such as sepsis is complex. The aims were to evaluate the differences between pediatric patients with MIS-C and sepsis and to develop a score to distinguish both entities. This was a retrospective study that compared demographic, clinical, diagnostic, and therapeutic data of pediatric patients with MIS-C (cohort 2020-2022) and sepsis (cohorts 2010-2014 and 2017-2018) admitted to a Pediatric Intensive Care Unit (PICU) of a tertiary care hospital. A diagnostic score was developed with variables that differentiated the two conditions. Twenty-nine patients with MIS-C were identified, who were matched 1:3 with patients with sepsis (n = 87). Patients with MIS-C were older (10 vs. 4 years old), and the majority were male (69%). Clinical characteristics that demonstrated differences were prolonged fever and signs and symptoms affecting skin-mucosa and gastrointestinal system. Leukocytes, PCT, and ferritin were higher in sepsis, while thrombocytopenia, lymphopenia, and elevated fibrinogen and adrenomedullin (biomarker with a role for the detection of invasive infections) were more frequent in MIS-C. MIS-C patients presented greater myocardial dysfunction (p < 0.001). Five criteria were selected and included in the MISSEP score after fitting them into a multivariate logistic regression model: fever > 48 hours (20 points), thrombocytopenia < 150 × 10³/µL (6 points), abdominal pain (15 points), conjunctival erythema (11 points), and Vasoactive Inotropic Score (VIS) > 10 (7 points). The cutoff > 25 points allowed to discriminate MIS-C from sepsis with a sensitivity of 0.89 and specificity of 0.95. Conclusion: MIS-C phenotype overlaps with sepsis. MISSEP score could be useful to distinguish between both entities and direct specific treatment. What is Known: • Differential diagnosis between Multisystem Inflammatory Syndrome in Children (MIS-C) and other causes of systemic inflammatory response such as sepsis is complex. • It is essential to establish an accurate initial diagnosis and early specific treatment in both cases of MIS-C and sepsis to improve the prognosis of these patients. What is New: • Patients with MIS-C are older and have characteristic symptoms of prolonged fever, gastrointestinal symptoms, skin-mucosal involvement, and greater myocardial dysfunction, compared to patients with sepsis. • The use of diagnostic scores, such as the MISSEP score, can be very useful to distinguish between the two entities and help direct specific treatment.

Keywords: Biomarkers; COVID-19; Diagnostic score; MIS-C; SARS-CoV-2; Sepsis.

Fig. 1

Score distribution of all available patients. Sepsis patients are shown in yellow and MIS-C patients in blue. Dashed line shows the cutoff point. Sensitivity of the model: 0.89 and specificity: 0.95