"It's still very rare, but there's been a wave of cases. Physicians and scientists are working hard to understanding the mechanisms at play, and why only some children are so severely affected," Newburger says.
Some symptoms can resemble features of Kawasaki Disease Shock Syndrome. Kawasaki disease is an acute illness in children involving fever with symptoms including rash; conjunctivitis; redness in the lips, tongue and mucous membranes of the mouth and throat; swollen hands and/or feet; and sometimes an enlarged group of lymph nodes on one side of the neck, says Newburger. Some children with the condition develop enlargement of the coronary arteries and aneurysms in those blood vessels.
A small percentage of Kawasaki cases go on to develop symptoms of shock, which can include a steep drop in systolic blood pressure and difficulty with sufficient blood supply to the body's organs. Kawasaki disease and KDSS more often affect young children, although they can sometimes affect teens, Newburger says.
Some cases of the new inflammatory syndrome have features that overlap with KD or with KDSS — including rash, conjunctivitis, and swollen hands or feet. The new inflammatory syndrome can affect not only young children but also older children and teens.
But patients with the new syndrome have lab results that look very different, in particular, "cardiac inflammation to a greater degree than we typically see in Kawasaki shock syndrome," which is usually very rare, O'Leary says. In New York City and London, which have seen large numbers of COVID-19 cases, "those types of patients are being seen with greater frequency."
Some patients "come in very, very sick," with low blood pressure and high fever, O'Leary says. Some children have had coronary artery aneurysms, though most have not, he adds.
Other patients exhibit symptoms more similar to toxic shock syndrome, with abdominal pain, vomiting and diarrhea, and high levels of inflammation in the body, including the heart, O'Leary says. Most cases are treated in the intensive care unit, he says. Treatment includes intravenous immunoglobulin, which can "calm the immune system," says Newburger, as well as steroids and cytokine blockers.
The evidence so far from Europe, where reports of the syndrome first emerged, suggests most children will recover with proper supportive care, says O'Leary, though one adolescent, a 14-year-old boy in London, has died, according to a report published Wednesday in The Lancet.
Most children with the syndrome, O'Leary and Newburger note, have either tested positive for a current infection with the coronavirus, or for antibodies to the virus, which would suggest they were infected earlier and recovered.
And, according to case reports, some of the kids with the inflammatory syndrome who tested negative on coronavirus tests had been exposed at some point to someone known to have COVID-19. The inflammatory syndrome can appear days to weeks after COVID-19 illness, doctors say, suggesting the syndrome arises out of the immune system's response to the virus.
"One theory is that as one begins to make antibodies to SARS-COV-2, the antibody itself may be provoking an immune response," says Newburger. "This is only happening in susceptible individuals whose immune systems are built in a particular way. It doesn't happen in everybody. It's still a really uncommon event in children."
In late April, the U.K.'s National Health Service issued an alert to pediatricians about the syndrome. Reports have also surfaced in France, Spain and Italy, and probably number in the dozens globally, Newburger and O'Leary say, though doctors still don't have hard numbers. Newburger says there needs to be a registry where doctors can report cases "so we can begin to generate some statistics."
"Doctors across countries are talking to each other, but we need for there to be some structure and some science so that everybody can interpret," she says.
Dr. Deepika Thacker, a cardiologist with Nemours Children's Health System, in Wilmington, Del., says she's seen three cases in children that fit the profile for the new syndrome. The first case was back in mid-April.
"When we first saw that kid, we didn't know what it was," she says. But a couple of days later, a pediatrician friend from the U.K. sent her a WhatsApp message about the emerging syndrome. "In retrospect, that's what it was," Thacker says now.
"He responded beautifully to treatment, so he was already out of the hospital by the time I got bad reports from Europe," she says. Since then, doctors have gone back to that first patient and tested the boy for antibodies to the coronavirus; they're still awaiting the results.
Earlier this week, the New York City Health Department issued an alert saying 15 children ranging in age from 2 to 15 had been hospitalized with the syndrome. Dr. Purvi Parikh, a pediatric immunologist at NYU Langone Health, says she's seen three patients with the syndrome in the past week, all of whom are doing well with treatment.
"They all present in varying ways," says Parikh, who is also a spokesperson for Physicians for Patient Protection. "But the common theme was fever and rash. One had very, very swollen lymph nodes and lymph glands. And then, aside from that, they had markers of inflammation elevated in their blood."
"Up until now, we were mostly seeing these markers of inflammation in adults that were presenting with COVID-19," Parikh says. "But now we're also seeing a similar syndrome in children."
A spokesperson for Children's Healthcare of Atlanta says infectious disease specialists there are evaluating several cases of children who have exhibited Kawasaki-like symptoms and inflammation — to determine if those patients may also have had COVID-19 and to investigate if any association between the two conditions might exist.
Newburger says that she's been contacted about cases in New Jersey and Philadelphia, as well.
While the syndrome's precise connection to the coronavirus isn't yet clear, O'Leary says the fact that the children in most of these cases are testing positive for exposure to the virus, one way or another, provides one point of evidence. The sheer number of cases — small in absolute terms, but still "much higher than we would expect normally for things like severe Kawasaki or toxic shock syndrome" — provides another, he says.
And then there's the fact that most reports of the syndrome have come out of the U.K. and New York City, places that have been hit with large numbers of COVID-19 cases.