Importance:
Multisystem Inflammatory Syndrome in Children (MIS-C) associated with
SARS-CoV-2 infection is thought to be driven by a post-viral dysregulated immune response, where
interleukin 6 (IL-6) might have a central role. In this setting,
IL-6 inhibitors are prescribed as
immunomodulation in cases refractory to standard
therapy. Objective: To compare plasma
IL-6 concentration between
critically ill children with MIS-C and
sepsis. Design: A retrospective cohort study from previously collected data. Setting: Individual patient data were gathered from three different international datasets. Participants:
Critically ill children between 1 month-old and 18 years old, with an
IL-6 level measured within 48 h of admission to
intensive care. Septic patients were diagnosed according to Surviving
Sepsis Campaign definition and MIS-C cases by CDC criteria. We excluded children with immunodeficiency or immunosuppressive therapy. Exposure: None. Main Outcome(s) and Measure(s): The primary outcome was
IL-6 plasma concentration in MIS-C and
sepsis group at admission to the intensive care unit. We described demographics, inflammatory
biomarkers, and clinical outcomes for both groups. A subgroup analysis for
shock in each group was done. Results: We analyzed 66 patients with MIS-C and 44 patients with
sepsis. MIS-C cases were older [96 (48, 144) vs. 20 (5, 132) months old, p < 0.01], but no differences in sex (41 vs. 43% female, p = 0.8) compared to septic group.
Mechanical ventilation use was 48.5 vs. 93% (p < 0.001), vasoactive
drug use 79 vs. 66% (p = 0.13), and mortality 4.6 vs. 34.1% (p < 0.01) in MIS-C group compared to
sepsis.
IL-6 was 156 (36, 579) ng/dl in MIS-C and 1,432 (122, 6,886) ng/dl in
sepsis (p < 0.01), while no significant differences were observed in
procalcitonin (PCT) and
c-reactive protein (CRP). 52/66 (78.8%) patients had
shock in MIS-C group, and 29/44 (65.9%) had
septic shock in
sepsis group.
Septic shock had a significantly higher plasma
IL-6 concentration than the three other sub-groups. Differences in
IL-6, CRP, and PCT were not statistically different between MIS-C with and without
shock. Conclusions and Relevance:
IL-6 plasma concentration was elevated in
critically ill MIS-C patients but at levels much lower than those of
sepsis. Furthermore,
IL-6 levels don't discriminate between MIS-C cases with and without
shock. These results lead us to question the role of
IL-6 in the pathobiology of MIS-C, its diagnosis, clinical outcomes, and, more importantly, the
off-label use of
IL-6 inhibitors for these cases.