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During the COVID-19 pandemic, it was initially believed that COVID-19 affected children less severely with younger kids being less at risk than adolescents. However, there have been reported cases of children developing a hyperinflammatory condition with symptoms including rashes, swelling and gastrointestinal problems, weeks after the number of COVID-19 cases peaked in their community. This was initially considered to be an atypical form of the previously known ‘Kawasaki disease’ but is now defined by the World Health Organisation (WHO) as a new condition called ‘Multisystem Inflammatory Syndrome in Children’ (MIS-C).

What do we know about Kawasaki disease? 


Approximately 8 in every 100,000 children develop Kawasaki disease in the UK each year. This disease mostly affects very young children, with past research showing 72% of diagnosed children were under the age of 5. Most symptoms include very high fever, rashes, a pink ‘strawberry tongue’, red and swollen eyes (‘conjunctivitis’), swollen hands, feet, and lymph nodes as well as pain.


The disease itself was identified by the Japanese doctor Tomisaku Kawasaki in 1967 and characterised as an acute inflammation of the blood vessels (‘vasculitis’). This hyperinflammation can then lead to the swelling and damage of blood vessels and therefore also affect a child's heartbeat rhythm. Also, antibodies against cells which make up our blood vessels have been observed.  This disease is very much treatable in hospitals, by administering anti-inflammatory drugs that either reduce the production or neutralise the effect of different inflammatory molecules. 


The newly classified disease MIS-C, mostly affects older children above the age of 5 but is still  very similar to Kawasaki disease and was therefore initially thought to be an atypical form of it. However, the WHO has now termed it novel with on-going research trying to tease out the differences and commonalities of both, while the causes are still debated. To date, possible causes range from genetics, to early child-hood infections and most striking in MIS-C: COVID-19 infection.


Autoinflammation and autoantibodies


In general, the immune system protects us against disease using a combination of antibodies and inflammatory responses without harming healthy cells. To do this correctly the immune system must be able to recognise harmful invaders and distinguish them from its own cells. However, in patients with autoimmune diseases, immune cells have lost this ability and mistake healthy cells as foreign, leading them to be targeted and damaged. Autoimmune diseases can lead to short- or long-term damage which can affect the whole body or be more organ-specific. 


This damage can be caused by antibodies targeting the host’s own cells, calledautoantibodies’, and/or through small molecules called ‘cytokines’, this is called ‘autoinflammation’. Cytokines are produced by the body to start, maintain, and finally dampen the immune response once the infection has been fought off. These act on other immune cells that can be either activated or inactivated, depending on the type of cytokine being produced.


The cause of autoimmune diseases, such as MIS-C or Kawasaki Disease, is not fully known, but genetic and environmental factors are known to play a role. Typically, treatment involves anti-inflammatory drugs, immunosuppressants, and sometimes intravenous immunoglobulin (an injection of antibodies taken from healthy donors). These tend to improve symptoms by suppressing autoinflammation and autoantibodies, but do not cure the disease. 


New findings on MIS-C


To understand the differences between the newly defined MIS-C and the established Kawasaki Disease, two recent research studies, one by Camila Rosat Consiglio and colleagues in Stockholm, and one by Conor Gruber and colleagues in New York, compared several factors that are known to be important for the immune response. 


They found that some cytokines, termed ‘Interleukin’ 6, 17 and 18, known to cause inflammation, are more abundant in children with MIS-C. Interleukin 17 in particular, is mainly found in the gastrointestinal tract and mucosal surfaces. This could explain why children with MIS-C suffer from hyperinflammation and especially gastrointestinal symptoms while children with Kawasaki disease do not have gastrointestinal problems.


In particular, both studies try to understand if similar auto-antibodies found in Kawasaki disease might also contribute to MIS-C. The scientists closely analysed antibodies present in children to see if some were directed against parts of the body instead of pathogens. Interestingly, both groups found antibodies that could bind to the children’s blood vessels or heart tissue (different from the ones in Kawasaki Disease) and could be a reason for the strong vascular and cardiac inflammation in MIS-C children.


Why is this important?


By being only a few weeks away school re-openings, it is ever so critical to discover and understand the exact consequences of COVID-19 infection in children and adolescents. In Kawasaki disease, a failure in treatment can lead to a life-long history of heart complications. The long term-consequences of MIS-C are still unknown and only an in-depth characterisation of this disease will ultimately lead to a targeted and correct treatment as well as factual based policies to ensure the safety of children.


Table comparison



Kawasaki disease 


Predominant age range

< 5 years

> 5 years








(red and swollen eyes)



Affecting blood vessels/ heart 



RBPJ & Endoglin

(Autoantibodies to blood vessels/heart)




(blood is unable to clot) 

NO (rare)


Gastrointestinal symptoms 

(anything out of the ordinary within your stomach or gut)

NO (rare)


Increased Interleukin 17 

(a specific immune factor linked to gastrointestinal symptoms)

NO (rare)






Original Papers


NRI summary