Mechanism
The pathogenesis is not completely known and could implicate several factors. SARS-CoV-2 could have one of several roles; it could act as an environmental trigger for the condition either directly or indirectly (by somehow paving the way for a different trigger).As with Kawasaki disease, antibody-dependent enhancement, whereby development of antibodies could facilitate viral entry into host cells, has been proposed as a potential mechanism. Epidemiological considerations make a post-infectious mechanism seem likely, possibly coinciding with the development of acquired immune responses to the virus. It has been suggested that the condition may be caused by the cytokine storms induced by COVID-19. The characteristic ability of coronaviruses to block type I and type III interferon responses could help explain a delayed cytokine storm in children whose immune systems struggle to control SARS-CoV-2 viral replication, or are overwhelmed by a high initial viral load. One plausible chain of events leading up to a hyperimmune response could involve early viral triggering of macrophage activation, followed by T helper cell stimulation, in turn leading to cytokine release, stimulation of macrophages, neutrophils, and monocytes, in conjunction with B cell and plasma cell activation, and autoantibody production.It is unknown to what extent the pathophysiology resembles that of other paediatric inflammatory syndromes that share similar clinical features. Clinical overlaps with syndromes that have different causes (Kawasaki disease, toxic shock, macrophage activation syndrome, and secondary haemophagocytic lymphohistiocytosis) may be explained by immunological activation and dysregulation of similar inflammatory pathways. In each of these syndromes, a cytokine storm leads to failure of multiple organs.
The time the syndrome takes to appear following the initial viral infection is debated, though it may develop between the first and second week. Epidemiological data suggest that recognition of the disease may typically be delayed by 2–6 weeks, and usually by 3–4 weeks. By the time of presention, children have often developed antibodies to SARS-CoV-2, but test negative for the virus at RT-PCR.The condition may match some or all of the diagnostic criteria for Kawasaki disease (i.e. the complete or incomplete/atypical subtypes), or for Kawasaki disease shock syndrome. It tends to affect all paediatric age groups, ranging from infancy to adolescence. It can also share clinical features with other paediatric inflammatory conditions, including toxic shock syndrome, and secondary haemophagocytic lymphohistiocytosis or macrophage activation syndrome. Coinfections with other pathogens have been recorded.Affected children always present with persistent fever. Other clinical features at presentation vary. In contrast to acute COVID-19, most children have gastrointestinal symptoms, such as diarrhoea, vomiting, and intense abdominal pain (sometimes severe enough to suggest appendicitis). Muscle pain and feelings of tiredness and general physical weakness are also very common. Some Kawasaki-like symptoms that may be present (especially in children under the age of 5) include mucosal changes around the mouth ("strawberry tongue", cracked lips, etc. ), red eyes (conjunctivitis without pus), widespread rash (consistent with leukocytoclastic vasculitis), red or swollen hands and feet, and enlarged lymph nodes. Chest or neck pain may also be present. Severe headache and altered mental state have been reported, along with various neurological disturbances.