May 14, 2020 4:35 PM

Rare, COVID-Related Inflammatory Disease Affecting Children

The novel coronavirus still affects a very small number of children, but new reports describe serious symptoms in some pediatric cases in parts of the U.S. and Europe.

COVIDKIDS 3

Updated as of July 13, 2020.

Editor’s note: Information on the COVID-19 crisis is constantly changing. For the latest numbers and updates, keep checking the CDC’s website. For the most up-to-date information from Michigan Medicine, visit the hospital's Coronavirus (COVID-19) webpage

Children seem to have mostly been spared from serious COVID-19 complications. But now, new reports suggest that a rare and potentially fatal inflammatory disease linked to the novel coronavirus is afflicting a small number of kids.

Cases of what’s being called multi-system inflammatory syndrome (MIS-C), formerly referred to as pediatric multi-symptom inflammatory syndrome or PMIS, have been reported in parts of the U.S. and Europe. Some children have experienced organ failure and at least two deaths have been reported in New York.

Experts suspect that in children with multi-symptom inflammatory syndrome, the virus may trigger the immune system to overreact and cause widespread inflammation throughout the body.

Symptoms include a high fever that lasts four or more days, a rash, very red eyes, abdominal pain and skin peeling on hands or feet. The condition resembles a rare childhood illness called Kawasaki disease, which has similar signs and symptoms and can lead to enlargement of blood vessels that in severe forms may cause heart damage.

Pediatric health experts are closely monitoring new data, emphasizing that while parents should learn about the new condition and know the symptoms – they also shouldn’t panic.

“This condition is extremely rare,” says Elizabeth Lloyd, M.D., pediatric infectious diseases physician at Michigan Medicine C.S. Mott Children’s Hospital.

“COVID-19 is affecting a very small number of children to begin with, and even fewer are getting severely sick or experiencing this inflammatory syndrome. While we don’t want to cause alarm, we do want the community to be aware of signs to watch out for. Parents should take this seriously and seek care right away if their children show any of these symptoms.”

As of June 29, there were nearly 300 cases in at least 26 states.

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The disease has been described as “Kawasaki-like” for its likeness to the childhood disease that usually appears in children under age five.

But early treatment usually prevents severe heart problems, and most children don’t experience long term health issues from Kawasaki disease, says Mott pediatric cardiologist Gabe Owens, M.D., Ph.D.

“Most children who get Kawasaki disease and those who may experience symptoms of this new inflammatory disease should recover,” says Owens. “But we don’t want to miss opportunities to diagnose these kids. A later diagnosis can limit treatment options.”

Lloyd and Owens answer more questions about what is known about how the novel coronavirus SARS-CoV-2 affects children and the newly reported inflammatory condition linked to the virus.

How prevalent is COVID-19 in children?

In the U.S., just 2% of confirmed cases of COVID-19 are among people under the age of 18, according to the Centers for Disease Control and Prevention.

It’s unclear if the lower number is because children are more resistant to getting the virus, or they just aren’t getting as sick with it, Lloyd says. Without widespread testing, experts also can’t confirm how many more children may have been affected.

How does COVID-19 affect children?

New research continues to describe differences in how the virus behaves in children compared to older patients. When it comes to common respiratory viruses, like the flu, the very young (and the very old) tend to be more severely affected. But that’s not the case with SARS-CoV-2.

"This condition is extremely rare. While we don’t want to cause alarm, we do want the community to be aware of signs to watch out for. "
Elizabeth Lloyd, M.D.

Small studies so far indicate that roughly 90% of children experience mild to moderate symptoms or show no symptoms at all.

“In general, healthy children seem to do much better with this disease than adults,” Lloyd says.

SEE ALSO: Seeking Medical Care During COVID-19

While there is still little scientific evidence backing potential reasons for children’s apparent resilience, there are some theories, Lloyd says, including:

  • A developing immune system: The virus causes severe sickness when the immune system over-responds, causing inflammation in the lungs and throughout the body. Because children’s immune systems are still “learning,” they may be less likely to react aggressively to the virus.

  • Coronavirus exposure: Pre-COVID-19 coronaviruses have been around for years and often circulate among kids. Children who have recently been sick with another type of coronavirus may have antibodies that provide cross-protection. Repeated viral exposure may better prepare the child’s immune system to fight off the virus.

  • Angiotensin converting enzyme 2 (ACE2) receptor: Experts believe that the coronavirus may enter cells by binding to a key receptor called ACE2. Some studies have shown potentially less of this receptor in children.

  • General health: The most at-risk populations are older adults with other underlying health conditions. Kids are generally healthier.

How often are children hospitalized for COVID-19?

Small studies during the pandemic have found between 6-20% of pediatric COVID-19 cases requiring hospitalization and 1-2% needing ICU care.

Most of the children admitted to pediatric intensive care units had other health conditions, such as cancer, obesity or diabetes, according to currently available data.

What do we know about the newly reported multi-system inflammatory disease?

Starting in late April and early May, several U.S. states and parts of Europe began reporting a possible link between an inflammatory arterial disease and COVID-19 in children.

“We are seeing reports of a small number of children, many who seemed to be otherwise healthy, experiencing significant systemic inflammation through the body that appears to be linked to COVID-19,” Lloyd says. “A lot of these children had low blood pressures, persistent fevers, red eyes and rashes.”

“We’re still learning about this condition and trying to understand why it affects certain children. We suspect that something is triggering the immune system to overreact.”

The inflammatory response shares common features with other pediatric inflammatory conditions, including Kawasaki disease and toxic shock syndromes.

What is the connection between the inflammatory disease and COVID-19?

Some children who experience the inflammatory disease are testing positive for the novel coronavirus, SARS-CoV-2. Others are testing negative for the virus but positive for coronavirus antibodies, suggesting a possible post-infectious inflammatory response even weeks after exposure to the virus or being sick, Lloyd says.

“Many of these kids are testing negative for COVID-19, which indicates that the inflammatory condition is most likely caused by an immune response and not the virus itself,” says Lloyd. “There appears to be a temporal relationship with COVID-19, but we still don’t have enough data to understand the link.”

This new condition has been described as “Kawasaki-like.” What is Kawasaki disease?

Unlike congenital heart defects present at birth, Kawasaki disease is an acquired heart condition that appears in early childhood without any previous symptoms, Owens says. The disease is rare, affecting nine to 20 per 100,000 children under age five in the U.S. It’s more frequently diagnosed in Japan and among Asian-American populations.

It causes swelling in the walls of blood vessels throughout the body. The most serious risk involves an inflammation of coronary arteries, which supply the heart with blood and nutrients, and can lead to organ failure.

"Most children who get Kawasaki disease and those who may experience symptoms of this new inflammatory disease should recover. But we don’t want to miss opportunities to diagnose these kids."
Gabe Owens, M.D., Ph.D.

“Even outside of the context of COVID, there are many unknowns around Kawasaki disease,” Owens says. “The disease process for Kawasaki is not well understood but there are theories that it might be triggered by a virus or infection combined with genetic or environmental factors.”

What signs should parents and providers look for?

Symptoms include prolonged fever (four or more days), very red eyes, a rash spread across the body, reddening or peeling on palms and soles of feet, abdominal pain, vomiting or diarrhea.

SEE ALSO: Keeping Our Patients Safe During COVID-19

If children experience these symptoms, parents should call their provider to seek an evaluation immediately.

How is it treated?

The standard treatment for Kawasaki disease involves intravenous immunoglobulin, a mixture of antibodies from blood donors. Aspirin and blood thinners may also decrease the risk of coronary artery problems after the inflammatory process has occurred.

The same strategies are being used for children who experience similar symptoms from the new multi-system inflammatory disease associated with COVID-19, Owens says.

“With early and proper medical care, Kawasaki disease is treatable, and most children recover without serious problems,” Owens says. “But it is essential that we identify it early. We should consider the same approach for this new inflammatory condition related to COVID-19”.

Even under normal circumstances, it can be difficult to differentiate Kawasaki disease from other childhood diseases that cause similar symptoms, Owens says. There are no definitive blood tests but children whose symptoms match the description should be monitored for signs of inflammation in the body.

Are certain children, such as those with congenital heart disease, at higher risk?

Children with an underlying health condition or an immunodeficiency – such as those who have undergone chemotherapy – are generally at higher risk for serious illness from COVID-19.

But so far, there is little information about how or why the virus may trigger multi-symptom inflammatory syndrome in a small number of children who are seemingly healthy, experts say.

However, since the gravest risk is heart failure, Owens says families of children with congenital heart disease should be extra vigilant for concerning symptoms.

“The most severe complication of the condition appears to be cardiovascular collapse,” he says. “We don’t have enough evidence to know how this inflammatory disease specifically affects children with existing heart conditions, but it’s possible that they may have more vulnerability to complications if they get it.”

“Any pediatric patient with a chronic condition is at increased risk for any acquired infection,” Owens adds. “We need to be very diligent about evaluating kids with new symptoms and err on the side of caution by seeing them earlier to make sure we aren’t missing anything.”

What should parents and providers do to keep children healthy?

Lloyd says parents should follow all of the standard guidance on preventing transmission and spread of coronavirus, including proper handwashing (at least 20 seconds using warm water and soap), not touching your face, nose, eyes or mouth and following aggressive social distancing (not going out unless you absolutely have to and staying six feet apart from others.)

The CDC has also recommended that community members wear cloth masks if they have to go somewhere like the grocery store.

Additionally, families should make sure they are keeping up with regular pediatric care and immunizations as best they can and not wait to call their doctor if they notice any concerning symptoms.

“Routine pediatric health care has really been affected by COVID,” Lloyd says. “Parents should work with primary care providers to make sure their children are still getting important routine care and that health concerns are being addressed in a safe environment.”

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