Medical questions are piling up as the COVID-19 pandemic wears on. At Le Bonheur Children’s Hospital, some of the most vexing are why the disease looks so different in children, including what can be a life-threatening illness weeks after the initial symptoms have passed.

Of the more than 350 children in Shelby County who have tested positive for COVID-19, a tiny handful have developed what appears to a form of Kawasaki disease, the autoimmune disease that causes blood vessels to inflame.

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“When blood vessels aren’t happy, bad things happen,” said Dr. Terri Finkel, the hospital’s new vice chair of clinical affairs and associate chair of pediatrics at University of Tennessee Health Science Center.

“Clotting happens. Aneurysms happen. ... The blood vessels’ thickness can cause strokes,” she said.

The blood clots can shut down the lungs. If the body can’t absorb oxygen, the kidneys stop.

The reaction can also look similar to toxic shock syndrome in children.

“The risk of shock appears to be much higher in this form of Kawasaki disease that’s associated with COVID-19 in children,” Finkel said.

Le Bonheur has seen two cases of apparent Kawasaki disease likely brought on by COVID-19 since pandemic arrived. One child tested positive; the other didn’t.

As testing begins to ramp up among people who do not have symptoms, Finkel expects the number of COVID-19 cases in children will rise.

Children get the disease as often as adults but they clear it briskly, often showing no symptoms. In early April, 1.7% of the 150,000 reported cases in the U.S. were children. By the end of May, the incidence had doubled to 3.8% of 1.3 million cases.

As cases rise, she and researchers at St. Jude Children’s Research Hospital want parents to know a child with a persistent high fever (103-104) may have a rare reaction to COVID-19. They need to seek medical attention immediately.

“The children will also have severe abdominal pain. They’ll have nausea; they’ll have vomiting, and that will go on for a few days and that’s unusual for Kawasaki disease,” Finkel said.

In children, the Kawasaki-looking disease can include puffy feet and hands, a “strawberry tongue,” which is redder than usual, and red eyes or conjunctivitis.

There are treatments for Kawasaki disease and children here have responded well.

Le Bonheur is using convalescent plasma, which includes the antibodies of COVID-19 patients who have recovered. It is also using steroids and anti-inflammatory drugs. Le Bonheur and UTHSC are also participating in clinical trials for the drug Baricitinib.

“I’m a rheumatologist and explain to my patients that flaring immune disease is like a runaway speeding train — we have to get in front of that train and stop it as safely as possible, and we can’t do it without medicines that have been shown in careful and safe clinical studies to apply the brakes. We know what medicines apply the brakes on most cases of Kawasaki disease,” Finkel said.

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In the growing research on this form of Kawasaki disease, the children often test negative “because they have cleared the virus. But they are antibody positive,” she said.

Some of the same symptoms are happening in adults, including the clotting, low oxygenation in the blood and eventual shutdown of the organs as the brain and heart take all the blood flow.

Those similarities have researchers thinking that COVID is causing the reaction in children, but because of the way their immune systems work, the reaction is delayed and can also include the plummeting blood pressure of shock syndrome.

A child’s healthy blood pressure is often lower than 120 over 80 that is normal for adults.

“But these children are getting down to 43 over 18. The heart cannot support that kind of low pressure, and all systems fail,” Finkel said.

The poor circulation causes the purplish COVID toes dermatologists around the nation have reported seeing, frequently in children.

“As if COVID in the adult population wasn’t enough, now we have to worry about our kids,” said Dr. Scott Strome, dean of the College of Medicine at UTHSC. “And I just think that the best way to combat this is with knowledge.

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“I think we have to be very, very humble in our understanding or what we claim is our understanding of this disease,” he said. “If we’ve learned anything from COVID-19, it is that we have to be cautious and then we have to be willing to accept that we’re continuing to learn.”

Finkel and others suggest the number of children testing positive was low because testing initially was for people with symptoms and secondary risk factors.

“Testing starts with adults,” she said. “And then, as we become familiar with processes and with the safety of whatever we’re testing, and the efficacy of what we’re testing, then we spread it to kids.”

Most kids didn’t meet the early criteria, she said.

“So, is the low frequency who we were testing or not testing? Or it is truly a correct observation? I know that question is being asked nationally and internationally.”