Multisystem Inflammatory Syndrome in Children (MIS-C)

Multisystem inflammatory syndrome in children (MIS-C) is a rare multisystem inflammatory condition that affects children & adolescents. It is associated with exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and illness with COVID-19. It is similar to Kawasaki disease.

Multisystem Inflammatory SyndromeImage Credit: Bernard Chantal/

What is MIS-C?

Multisystem inflammatory syndrome in children (MIS-C) is a rare systemic inflammatory disease that affects children & adolescents and is linked to COVID-19.

In the UK and Europe, the condition is referred to as pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS), whereas in the US it is referred to as MIS-C.

MIS-C/PIMS-TS is very similar to Kawasaki disease. Kawasaki disease is a rare disease that affects children under the age of 5 primarily and is characterized by a fever that can last around 5 days alongside a bodily rash, swollen glands, red fingers & toes, and red eyes. It is not transmissible between individuals.

MIS-C/PIMS-TS also shares clinical and pathological features with other pediatric inflammatory syndromes that are non-Kawasaki.

MIS-C/PIMS-TS tends to affect a very small population of children and adolescents between the ages of 0 and 21 years of age, whereas Kawasaki disease affects children around the age of 4-5 years. A recent study in the US suggested MIS-C was most likely to occur in children aged 6 to 12.

What are the symptoms and features of MIS-C?

The symptoms of MIS-C/PIMS-TS match many features of Kawasaki disease, but also symptoms of other pediatric inflammatory conditions including toxic shock syndrome, septic shock, and macrophage activation syndrome.

A healthcare professional should be contacted if a child shows symptoms of MIS-C. According to the Centers for Disease Control and Prevention (CDC), these include:

  • Abdominal pain
  • Fever
  • Diarrhea
  • Vomiting
  • Rash
  • Neck pain
  • Feeling extra tired
  • Bloodshot eyes

Different symptoms will be shown by different children.

The CDC advises that if symptoms any of the following severe symptoms are shown, emergency care should be sought straight away:

  • New confusion
  • Trouble breathing
  • Pain in the chest that does not go away
  • Severe abdominal pain
  • Gray, pale or blue lips, face or nails, depending on skin

Symptoms may present alongside COVID-19 or may develop a few weeks after an initial COVID-19 (SARS-CoV-2) infection, hence the name ‘temporally associated with SARS-CoV-2 (TS)”. For a diagnosis to be made, evidence of COVID-19 by PCR/antigen test is made. In some cases, there may not be any positive tests for SARS-CoV-2, but it may be associated with close contact with COVID-19 patients.

The clinical & pathological features of MIS-C/PIMS-TS can include:

  • Elevates serum markers of inflammation e.g. CRP, ESR
  • High levels of fibrinogen, D-dimers (coagulopathy), troponin and ferritin
  • No underlying microbial cause of inflammation e.g. bacterial sepsis
  • Cytokine storm with high serum IL-6 levels
  • Multisystem involvement (>2 organs) e.g. cardiac, renal, respiratory, hematological, gastrointestinal, dermatological or neurological
  • Cardiac involvement with features of macrophage activation syndrome – abnormal ECG and CT scans (coronary artery dilatation)
  • Leukopenia – reduced number of leukocytes (white blood cells)

A study published in February 2021, aimed at defining the differences between COVID-19 and MIS-C, found distinct patterns of clinical presentation and organ involvement including extreme inflammation and cardiovascular problems in MIS-C patients.

In some affected children, recovery is spontaneous if the condition is not too severe. However, if the condition is moderate-severe and includes features of toxic shock syndrome, severe hypotension, and coronary arterial aneurysm development, then emergency admission to a pediatric intensive care unit is urgently required.

Furthermore, the highest prevalence of MIS-C/PIMS-TS seems to be in those with Afro-Caribbean descent, as well as those with African American, Caribbean, and Hispanic ancestry. Data on a wider population is needed to contextualize these trends. Limited cases have been reported in many Asian countries which have experienced a COVID-19 epidemic.

However, Kawasaki disease is more prevalent in Asian countries such as Japan and South Korea. Socioeconomic and environmental factors and the way countries have dealt with COVID-19 also need to be considered to evaluate prevalence amongst certain demographics.

What causes MIS-C?

MIS-C/PIMS-TS was first reported in the UK, Italy, and France, and cases were reported during a high prevalence of the COVID-19 epidemic. Thus, scientists and clinicians initially thought it was associated with the presence of SARS-CoV-2. MIS-C/PIMS-TS is associated with a recent or current positive SARS-CoV-2 (COVID-19) infection.

Much like Kawasaki disease, the exact cause of the disease is still unknown – though it is thought to be an autoimmune/autoinflammatory response to SARS-CoV-2 infection. Most affected children will have IgG antibodies against SARS-CoV-2 (~90% in one study) or have had a positive PCR test. The risk to children overall is very low, even with a positive COVID-19 result.

Some scientists have suggested that a cytokine storm may be critical in the development of MIS-C/PIMS-TS. Coronaviruses are known to inhibit type I and III interferons – thus suggesting why MIS-C/PIMS-TS develops in a delayed manner post-SARS-CoV-2 infection.

Those with an abnormally high initial viral load may be more susceptible to developing a cytokine storm. Furthermore, SARS-CoV-2 also infects gastrointestinal epithelia, and the condition may be due to mesenteric lymph node inflammation.

In most cases, MIS-C/PIMS-TS occurs weeks after a SARS-CoV-2 infection (COVID-19) and is thought to be a delayed post-viral immunological reaction in those with a potential genetic predisposition to such.

A diagnosis will usually be made by taking blood tests to look at serum levels of inflammatory markers, as well as cardiac ultrasounds (ECHO), chest X-rays, and testing for a positive SARS-CoV-2 infection.

Although most cases have a recent or current positive SARS-CoV-2 IgG test or positive PCR test associated, there may be some rare cases not associated with any positive SARS-CoV-2 result. In such cases where clinical symptoms appear, all other forms of microbial infection must be excluded.

It is important to note that we are still learning about MIS-C/PIMS-TS and how COVID-19 leads to the condition, and the exact cause of the condition is still unknown. Over time with more cases and research, the exact biological mechanisms may become more apparent and pave way for more robust therapeutic options.

COVID-19Image Credit: Kjpargeter/

How is MIS-C Treated?

Treatment strategies currently depend on the clinical presentation and severity of the disease; however, many will undergo intravenous immunoglobulin therapy and/or the administration of corticosteroids. Doing so resulted in a clinically favorable outcome in all patients in one French study (published in the British Medical Journal).

Many children will need to be admitted to a pediatric intensive care unit to undergo stronger therapy; however, discharge rates are very high. Those that also develop shock syndrome may need fluid resuscitation and vasoactive agents due to sustained hypotensive shock.

For those with cardiac dysfunction (myocarditis), inotropic agents may be given. Individuals with the most severe respiratory symptoms may need mechanical ventilation or oxygen therapy and tend to have higher systemic inflammation markers than those not needing ventilation.


In summary, MIS-C (PIMS-TS) is a rare multisystem inflammatory condition that affects children and adolescents aged 0 to 21 years who have tested positive for COVID-19 (SARS-CoV-2 infection).

Clinical features are similar to Kawasaki disease, but children also exhibit other symptoms related to other pediatric inflammatory syndromes. In some cases, spontaneous recovery can be made, but in others with more severe symptoms, hospital admission is required to combat the inflammation and cardiac complications that may occur.

Much about MIS-C is still unknown, and many organizations and government bodies are undertaking research into the disease to improve information and communication about dealing with it.  

PICU COVID-19 International Collaborative - Epidemiology and Treatment of MIS-C by M. Levin et al.


Further Reading

Last Updated: Mar 29, 2023

Dr. Osman Shabir

Written by

Dr. Osman Shabir

Osman is a Postdoctoral Research Associate at the University of Sheffield studying the impact of cardiovascular disease (atherosclerosis) on neurovascular function in vascular dementia and Alzheimer's disease using pre-clinical models and neuroimaging techniques. He is based in the Department of Infection, Immunity & Cardiovascular Disease in the Faculty of Medicine at Sheffield.


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