**3.4 Inflammatory mediators**

There is an elevation of interleukin (IL) 1B, IL6, IL8, IL10, IL 17A, IFNy, and a series of chemokines that are present in MIS-C and not in pediatric respiratory infection by COVID-19 [43, 44]. E-selectin is a molecular marker of endothelial cell inflammation and is at high levels in children with MIS-C, so endothelial involvement seems to be a contributor to the inflammatory process of all systems [28]. When measuring inflammatory markers, they differ between patients, probably by genetic susceptibility, severity of the disease, and geographic location [25]. The heterogeneity of inflammatory markers does not allow attributing the disease to a single inflammatory pathway.

In summary, MIS-C is due to a post-infectious immune dysregulation and virusinduced cytopathic effects and inflammation in multiple organ systems. Aberrant immune activation may occur by: particular variants of SARS-CoV-2; genetic predisposition (variants in the genes that encode Fcγ receptors, components of the signaling cascades, mutations in genes such as SOCS1 that regulate the immune response); SARS-CoV-2 spike protein and the formation of a superantigen; dysregulated activation of lymphocytes, with production of IGG; and complement activation and autoantibody-mediated endothelial damage (**Figure 2**).

#### **Figure 2.**

*Theories that would explain the pathophysiology of MIS-C.*
