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Multisystem Inflammatory Syndrome in Children (MIS-C)

  • A rare but serious condition that can occur in children diagnosed with COVID-19
  • Symptoms include a high fever for at least 24 hours and low blood pressure
  • Treatments include intravenous fluids and antibiotics
  • Involves Critical Care Medicine, General Pediatrics, Infectious Diseases


Early in 2020, as people across the world became aware of and took precautions against COVID-19, the serious—sometimes fatal—disease associated with the SARS-CoV-2 coronavirus, many took a small measure of comfort in believing that children infected with the disease were left relatively unharmed.

But in late April of that year, physicians in Europe and the United States began to report a small but growing number of cases of children afflicted with a new multisystem inflammatory syndrome that appears to be associated with COVID-19. Doctors began to report seeing very sick children, many of whom tested positive for COVID-19, with some combination of fever, red eyes, swollen hands and feet, rash, and gastrointestinal problems, all of which are symptoms related to inflammation.

At first, doctors noted similarities between these symptoms and those associated with other inflammatory syndromes, such as Kawasaki disease and toxic shock syndrome. But as they began to see more of these children, they started to suspect they were seeing something different. The condition was first called PMIS (pediatric multisystem inflammatory syndrome) but is now officially known as multisystem inflammatory syndrome in children, or MIS-C.  

Because MIS-C has only recently been identified, the medical community is still trying to understand what causes it, as well as why it appears to affect only children. And while there is mounting evidence that it is linked to COVID-19, the relationship between the two is not yet known. What is clear is that MIS-C is a serious health issue that requires prompt medical attention. Fortunately, it is also rare, and the vast majority of children affected by it survive.

“This new entity seen in children is a severe post-infectious manifestation of the virus,” says Marietta Vázquez, MD, a Yale Medicine pediatric infectious disease specialist. “It calls for us to be vigilant to its presentation without panic, as it remains rare.” 

What is MIS-C?

MIS-C is a serious though rare condition in children in which the body’s own immune system overreacts to a stimulus, resulting in inflammation of multiple organ systems throughout the body. It can affect the heart, blood vessels, gastrointestinal organs, lungs and other respiratory organs, kidneys, skin, eyes, and nervous system, and it can lead to impaired organ function and even organ failure. In most cases, though, children experience inflammation in only a few of these organs.

MIS-C shows similarities to other known inflammatory disorders, including Kawasaki disease and toxic shock syndrome.

  • Kawasaki disease is an inflammatory syndrome of unknown cause that mostly affects children, and is characterized by vasculitis, or inflammation of the blood vessels. It can cause fever, rash, red eyes, swollen hands and feet, swollen lymph nodes in the neck, and dry and red lips and tongue.
  • Toxic shock syndrome is an inflammatory condition caused by a bacterial infection that, like MIS-C, can result in low blood pressure, fever, and rash. 

At this point, MIS-C has been diagnosed only in children and adolescents under 21, and most cases have occurred in Europe and the United States. It is not known why the syndrome affects people in this age group or why it has appeared in these regions. Nor have researchers uncovered information regarding risk factors or preventive measures for MIS-C. 

What causes MIS-C?

The cause of MIS-C is not yet known, though it seems to be linked to COVID-19. Most children who have been treated for it have either tested positive for a current COVID-19 infection or have antibodies to it, meaning they’ve been exposed. 

Clinicians and researchers are working to determine the precise cause of MIS-C, whether it is connected to COVID-19, and why it appears to affect only children. 

What are the symptoms of MIS-C?

In nearly all known cases, children with MIS-C have had a fever of 100.4°F or higher for at least 24 hours, and most also have low blood pressure. Other symptoms associated with MIS-C may include but are not limited to:

  • Diarrhea, vomiting, or stomach pain
  • Skin rash
  • Myocarditis (inflammation of the heart)
  • Conjunctivitis (red eyes)
  • Swollen hands or feet
  • Swollen lymph nodes in the neck
  • Respiratory problems
  • Red, cracked lips
  • Swollen red tongue with bumps that resembles a strawberry (known as “strawberry tongue”)
  • Fainting
  • Confusion
  • Cough
  • Sore throat

How is MIS-C diagnosed?

There is no diagnostic test for MIS-C. Doctors instead diagnose the condition by assessing the child’s history, conducting a physical examination, and evaluating a series of lab tests.

The Centers for Disease Control and Prevention (CDC) has established the following set of criteria, all of which should be met for a diagnosis of MIS-C:

  • The patient is 21 years of age or younger and has had a fever of 100.4°F (38°C) for at least 24 hours (or if the patient’s temperature has not been measured, he or she has felt feverish for at least 24 hours).
  • Blood work shows indications of inflammation.
  • The patient requires treatment at a hospital (often in the intensive care unit) due to severe illness that includes dysfunction of two or more organs, in particular of the heart, blood vessels, gastrointestinal organs, lungs and other respiratory organs, kidneys, skin, eyes, or nervous system.
  • Absence of other diagnoses that explain inflammatory symptoms such as a bacterial infection
  • A positive test for current or past infection by SARS-CoV-2, the virus that causes COVID-19, or failing a positive test, evidence of exposure to someone with the virus within four weeks of the onset of symptoms of MIS-C  

In practice, this means that both symptoms and the possibility of exposure to COVID-19 will be taken into consideration. If the child has not undergone prior COVID-19 testing, the doctor will order a test. 

The doctor will also order blood tests to check markers of inflammation and organ function, as well as for a possible bacterial infection. Because MIS-C can affect the heart, the doctor may recommend an electrocardiogram (sometimes called ECG or EKG), a painless test that measures heart function. Finally, if there are respiratory symptoms, the child may need a chest X-ray or CT scan so that the doctor can examine the lungs for signs of inflammation or infection. 

How is MIS-C treated and what is the prognosis for children affected by it?

Many children with MIS-C will need to be cared for in the intensive care unit, where medical providers can treat and closely monitor their condition. Depending on the severity of the illness and the particular organs involved, the child may also need to be under the care of other specialists, such as a cardiologist, rheumatologist, infectious disease specialist, or critical care physician.

The hallmark of MIS-C is widespread inflammation across multiple organ systems. Left untreated, this inflammation can cause long-term organ damage. That’s why it is critical that children with MIS-C receive prompt medical treatment.

Treatment typically includes supportive care, which means that the focus is on relieving symptoms and preventing complications while the patient recovers. This usually involves the delivery of intravenous fluids and medications including antibiotics, with the goal of reducing fever, keeping blood pressure up, and eliminating any underlying bacterial infections.

Given that the symptoms of MIS-C are caused by the body’s own exaggerated immune response, doctors may also administer medications to temporarily suppress the body’s immune system. Immune suppression gives the patient’s body time to heal, helping to avert long-term organ damage.

Drugs commonly used to suppress immune response in children with MIS-C include steroids and certain biologic drugs that are typically used in people with autoimmune disorders and rheumatoid arthritis. Patients may also receive intravenous immunoglobulin, a medication containing antibodies (proteins that help fight off viral and other infections). 

Though MIS-C is a serious condition that usually requires hospitalization, with prompt medical attention, the vast majority of children with it recover fully.