It has been noted that a leading hypothesis for the pathogenesis of Kawasaki disease also involves a hyperinflammatory response to viral infection (such as by a novel RNA virus) in some genetically predisposed children, and that SARS-CoV-2 is now "added to the list" of implicated viral triggers. Hopes have been expressed that study of the new condition may help understand the hidden mechanisms behind Kawasaki disease. But current evidence suggest that MIS-C and Kawasaki disease represent two distinct disease entities

Proposed role of the STING pathway
A possible role of the stimulator of interferon genes known as STING has been proposed. SARS-CoV-2 is capable of upregulating the STING protein (encoded by TMEM173 transmembrane protein, and expressed in alveoli, endothelial cells, and the spleen), resulting in massive release of interferon-beta and cytokines derived from activation of NF-κB and IRF-3. In MIS-C, such a scenario could lead to a clinical picture similar to STING-associated vasculopathy with onset in infancy (also known as SAVI) – a condition characterized by fever, lung injury, vascular inflammation, myositis, skin lesions (occasionally acral necrosis), and arterial aneurysms. Variations in the presentation and severity of MIS-C might at least partially be explained by characteristic differences in polymorphisms of TMEM173 found in various populations. Epidemiology
Epidemiological information is limited, and clinical statistics currently derive from review of case series. This emerging condition is considered rare. Its incidence is not known.
History
Cases of Kawasaki disease with concurrent SARS-CoV-2 infection have been recorded among children in Europe and in the United States since 7 April 2020, when a report was published by the American Academy of Pediatrics regarding a case of classic Kawasaki disease in a six-month old girl who tested positive for COVID-19 in California. In this case, COVID-19 did not appear to have significant clinical implications.On 25 April, concerns were initially raised in the United Kingdom regarding a cluster of children of various ages presenting with a multisystem inflammatory state who required intensive care, and who all displayed "overlapping features of toxic shock syndrome and atypical Kawasaki disease with blood parameters consistent with severe COVID-19 in children." Details of the eight cases which helped trigger this alert (not all with confirmed exposure to COVID-19) were later reported in The Lancet, where the authors summarized the clinical picture as "a hyperinflammatory syndrome with multiorgan involvement similar to Kawasaki disease shock syndrome." Accounts of analogous cases – including some that appeared less clinically severe – were also being informally shared among clinicians around Europe. The EUs Early Warning and Response System flagged suspected cases in Austria, Germany and Portugal that had tested positive for SARS-CoV-2. In Bergamo, at the heart of the COVID-19 epidemic in Lombardy, a cluster of 20 cases of Kawasaki disease appeared to be roughly equivalent to the number commonly recorded there over the course of three years.