May 14, 2020 -- As COVID-19 continues to spread, there is growing evidence that children may be vulnerable to a rare but serious complication triggered by the infection.
So far, studies have shown that children appear to be less vulnerable to this new coronavirus than adults. Kids under the age of 18 represent just 1%-2% of reported COVID-19 cases.
But new reports, from the U.S. and several European countries, suggest that in rare cases, children can have a collection of symptoms -- including lengthy fevers, low blood pressure, rashes, red eyes, stomach upset, and inflammation of the heart and its arteries -- that share features of toxic shock syndrome and Kawasaki disease.
There’s even a debate about what to call it. A group of pediatricians studying these cases around the world has named the new condition pediatric multisystem inflammatory syndrome, or PMIS. Some believe it is a more severe form of Kawasaki disease. The CDC told doctors to watch for and report cases of multisystem inflammatory syndrome - children, or MISC, to their local health departments.
In New York, 102 cases of the rare condition have been diagnosed, and three children, ages 5, 7, and 18, have died. New York City, the epicenter of the outbreak, has more than 50 cases.
“This is a truly disturbing situation, and I know parents around the state and around the country are very concerned about this, and they should be. If we have this issue in New York, it’s probably in other states,” New York Gov. Andrew Cuomo said at a recent news briefing.
Reports of the syndrome are coming just as day cares and schools in many states are thinking through when and how they can safely reopen.
On that front, experts say parents and school administrators should stay alert but not be overly alarmed.
“This is still very, very rare,” says Alan Schroeder, MD, the associate chief of research in the division of pediatric hospital medicine at Lucile Packard Children’s Hospital at Stanford University. “This is a very uncommon complication of this infection.”
Doing a very back-of-the-envelope calculation, Schroeder says that if recent antibody studies done in New York City are correct, about 20% of people there have had COVID-19 infections. If that applies to kids, maybe 400,000 or so have had this infection at some point. So far, just over 50 have been diagnosed with the new syndrome.
“Even with this new information about this possible association, the overall risk to children is still far below what we’ve seen in adults,” he says.
So far, 15 states and a handful of European countries, including Italy, Spain, France, and the U.K., have reported cases of the syndrome, which shares many features of Kawasaki disease.
New Complication Comes to Light
Kawasaki disease was first described in Japan about 50 years ago. Doctors aren’t sure what causes it. It tends to strike kids soon after they fight off an infection, leading doctors to believe that an autoimmune attack on the body’s own organs and tissues sets it off.
Most kids who get this disease recover completely, but in very rare cases, it can cause permanent heart damage.
Cases of Kawasaki disease tend to cluster in the winter and spring. So many of these patients are being reported exactly when doctors would expect to see an uptick in their numbers.
But experts say the increase this year has topped the charts, and it seems to be more severe than the kind of Kawasaki disease they are used to treating.
“In the U.K., in Spain, and France, about a month into the pandemic, they suddenly had this cluster of kids who were coming in with fairly striking pictures of shock -- so low blood pressure -- and some of these needed ECMO, and you just don’t see this,” says Mary Beth Son, MD, a pediatrician. She directs the rheumatology program at Boston Children’s Hospital, one of the many specialty hospitals around the U.S. that have reported cases of the syndrome.
ECMO stands for extracorporeal membrane oxygenation. It’s a machine that takes over for the heart and lungs when the body isn’t getting enough oxygen.
After reports of the new inflammatory syndrome came to light, Children’s Hospital Los Angeles reviewed its patient files. The hospital says that since April 1, it’s treated 16 children who had symptoms consistent with Kawasaki disease, an increase compared to the previous 2 years. None of the children had active COVID-19 infections. The hospital did additional blood testing on 14 of those children. Antibody testing, to look for evidence of past infections, found that four of the children had antibodies to the new coronavirus. The other 10, so far, are negative. The hospital says it will now follow up with all patients who were diagnosed with Kawasaki disease since January 1 to look for evidence of COVID-19 infections.
In a study published on Wednesday in The Lancet, doctors in Bergamo, Italy, one of the earliest COVID-19 hot spots outside of China, report treating a series of 10 children with features of severe Kawasaki-like disease from late February to late April of this year. They’ve now treated 20 such patients -- more than 30 times the number they would typically see.
“Around March 15, we had 2-3 patients come to the ER with Kawasaki-like disease. We were just surprised, because we said ‘Whoa, just one after the other. Unusual,’” says study author Lorenzo D’Antiga, MD, who works in the department of pediatric hepatology, gastroenterology, and transplantation at Hospital Papa Giovanni XXIII in Bergamo.
D’Antiga says his team was cautious about drawing conclusions since they tend to see more Kawasaki disease in the spring.
Then, he says, in the following 10 days, his team treated another seven patients, so one every 2 to 3 days. “So there were 10 patients altogether within 15 days. We were really surprised.”
They tested the kids for SARS-CoV-2, the virus that causes COVID-19. Eight of the children had antibodies against the virus, suggesting that they’d recently fought off an infection. Two of the initial 10 had no signs of the virus in blood tests. That could mean their immune systems hadn’t yet produced enough antibodies to show up on the tests, or that their cases were triggered by something else, D’Antiga says.
“Usually, an immune response to any infectious agent takes about 15 days, more or less, to show antibodies,” he says.
Strikingly, none of the children treated in Bergamo had symptoms of a COVID-19 infection.
A Different Type of Disease?
It’s not surprising that a Kawasaki-like disease would show up after COVID-19, D’Antiga says. Previous studies have implicated other kinds of coronaviruses in Kawasaki patients.
He says Kawasaki disease exists on a spectrum. His patients met the criteria for it, but they seemed to be on the more severe end of the spectrum, with more heart trouble linked to it. He says there is a form of Kawasaki disease that includes features of shock called Kawasaki disease shock syndrome, or KDSS. He’s not sure he sees the need for a new name.
“It is rare, but in these patients, it’s actually very common. The spectrum is wide, but I think it actually is the same disease,” he says.
But other doctors are standing firm. They say the patients they are seeing don’t exactly fit the Kawasaki mold.
The American Academy of Pediatrics, for example, says that while PMIS may have features of both Kawasaki disease and toxic shock syndrome, “at this time, it is thought to be a separate condition.”
Kawasaki disease tends to strike children under 5 years old. But the syndrome linked to COVID-19 seems to affect older children, too. In New York, most of the cases have been in kids ages 5 to 14.
In very severe cases, blood pressure plummets because the heart can’t pump enough blood, or blood vessels aren’t constricting properly, causing shock. Some children have a headache, dizziness, or other nervous system complaints. Other symptoms are in the digestive system -- severe stomach pain, diarrhea, or vomiting.
“A lot of them have been misdiagnosed initially with appendicitis,” says Deepika Thacker, MD, medical director of the cardiac inpatient unit at Nemours Hospital for Children in Wilmington, DE. “I heard from Europe, they actually ended up opening the belly surgically to look for a cause on a couple of these kids and found nothing there to operate on.”
“These kids have a multi-organ involvement,” she says.
That makes sense, Thacker says, because this syndrome sets in after the body has fought off the infection.
“It’s not really a direct attack by the virus on the different organs in the body,” she says. “It’s the child’s own immune system that’s kind of activated out of control.”
As doctors begin to see new cases of the new syndrome, they’ve noted that strangely, there haven’t been any reports of it out of China, where the virus was first identified, or Japan, where Kawasaki disease tends to be more common.
D’Antiga thinks that’s because the disease is difficult to diagnose and rare. He says cases just haven’t been recognized in those countries yet.
Thacker wonders if it might be because a different strain of the virus was more prevalent in Asia. She says certain populations may also be more likely to get it because of their genes.
What to Look For
She says that even though the syndrome is serious, parents should be reassured.
First, Thacker says, “It’s not common.” Second, “It’s not contagious.” Once kids have this, they’ve already fought off the virus. Finally, in most cases, kids will make a full recovery.
“Most of these patients are responding well to treatment,” she says.
The New York State Department of Health has recommended that parents seek care for their child right away if they have the following symptoms:
- A fever that lasts more than 5 days
- Severe belly pain, diarrhea, or vomiting
- Bloodshot eyes
- A skin rash
- Change in skin color -- becoming pale, patchy, and/or blue
- A hard time feeding in babies, or a child too sick to drink fluids
- Trouble breathing or breathing very quickly
- Racing heart or chest pain
- Tiredness, crankiness, or confusion