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. 2022 Dec;92(6):1805-1814.
doi: 10.1038/s41390-022-02029-4. Epub 2022 Mar 29.

The difference of the inflammatory milieu in MIS-C and severe COVID-19

Sibel Lacinel Gurlevik  1 , Yasemin Ozsurekci  1 , Erdal Sağ  2   3 , P Derin Oygar  1 , Selman Kesici  4 , Ümmüşen Kaya Akca  5 , Muserref Kasap Cuceoglu  5 , Ozge Basaran  5 , Sultan Göncü  4 , Jale Karakaya  6 , Ali Bülent Cengiz  1 , Seza Özen  7   8
Affiliations

The difference of the inflammatory milieu in MIS-C and severe COVID-19

Sibel Lacinel Gurlevik et al. Pediatr Res. 2022 Dec.

Abstract

Background: Coronavirus disease 19 (COVID-19) may have a severe course in children. Multisystem inflammatory syndrome in children (MIS-C) is the post-COVID complication characterized by an exaggerated inflammation, observed in children. However, data on the underlying pathophysiology are sparse. We therefore aimed to assess the cytokine and chemokine profiles of children with MIS-C and compare these to life-threatening severe SARS-CoV-2 and healthy controls (HCs) to shed light on disease pathophysiology.

Methods: Samples of 31 children with MIS-C, 10 with severe/critical COVID-19 and 11 HCs were included. Cytokine and chemokine profiles were studied and compared in between groups.

Results: Most cytokines and chemokines related to IL-1 family and IFN-γ pathway (including IL-18 and MIG/CXCL9) and IL-17A were significantly higher in the MIS-C group when compared to the severe/critical COVID-19 group and HCs. IP-10/CXCL10 and IL-10 were higher in both MIS-C patients and severe/critical COVID-19 compared to HCs.

Conclusion: Our results suggest that IL-1 and IFN-γ pathways play an important role in the pathophysiology of MIS-C.

Impact: This study defines a pattern of distinctive immune responses in children with MIS-C and in patients with severe/critical COVID-19. As the COVID-19 pandemic continues, biomarkers to identify MIS-C risk are needed to guide our management that study results may shed light on it.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Comparison of laboratory test results on admission.
Statistically significant differences of laboratory values are given. WBC white blood cell, PNL polymorphonuclear lymphocyte, CRP C-reactive protein, BNP B-type natriuretic peptide, CK-MB creatine kinase myocardial band. *P < 0.05; **P < 0.01.
Fig. 2
Fig. 2. Quantitative circulating levels of selected cytokines.
*P < 0.05; **P < 0.01; ***P < 0.001.
Fig. 3
Fig. 3. Quantitative circulating levels of selected chemokines.
*P < 0.05; **P < 0.01; ***P < 0.001.
Fig. 4
Fig. 4. Heatmap and the ROC curve of cytokines and chemokines.
a Heatmap representing the selected cytokines and chemokines. Every column represents a patient. Asterisk (*) identifies the cytokines and chemokines with significant differences between MIS-C and severe/critical COVID-19. Color gradient represents the normalized percentages of cytokine and chemokine levels. MIS-C multisystem inflammatory syndrome in children (n = 31), COVID-19 coronavirus disease 19 (n = 10). b The ROC curve of IL-17A, IL-18 and MIG/CXCL9 concentrations in differentiating MIS-C from severe/critical COVID-19. The utility of IL-17A, IL-18 and MIG/CXCL9 concentrations in differentiating MIS-C from severe/critical COVID-19 were assessed by ROC curve analysis and performed well with area under curve of 0.816 (P = 0.003), 0.819 (P = 0.003) and 0.897 (P < 0.001), respectively.
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