Why doctors keep monitoring kids who recover from mysterious COVID-linked illness

“Hold your horses, I think I know what I’m gonna make,” he said, holding up a finger in the middle of a conversation. “I’m gonna make something that lights up and attaches to things with glue, so if you don’t have a flashlight, you can just use it!”

In New York, at least 237 kids, including Israel, appear to have Multisystem Inflammatory Syndrome in Children, or MIS-C. And state officials continue to track the syndrome, but the Centers for Disease Control and Prevention did not respond to repeated requests for information on how many children nationwide have been diagnosed so far with MIS-C.

A study published June 29 in the New England Journal of Medicine reported on 186 patients in 26 states who had been diagnosed with MIS-C. A researcher writing in the same issue added reports from other countries, finding that about 1,000 children worldwide have been diagnosed with MIS-C.

Tracking the long-term health effects of MIS-C

Israel is friendly and energetic, but he’s also really good at sitting still. During a recent checkup at Children’s Hospital at Montefiore, in the Bronx, he had no complaints about all the stickers and wires a health aide attached to him for an EKG. And when Dr. Marc Foca, an infectious disease specialist, came by to listen to his heart and lungs, and prod his abdomen, Israel barely seemed to notice.

There were still some tests pending, but overall, Foca said, “Israel looks like a totally healthy 5-year-old.”

“Stay safe!” Israel called out, as Foca left. It’s his new signoff, instead of goodbye. His mother, Janelle Moholland, explained Israel came up with it himself.

And she’s also hoping that after a harrowing couple of weeks in early May, Israel himself will “stay safe.”

That’s why they’ve been returning to Montefiore for the periodic checkups, even though Israel seems to have recovered fully from both COVID-19 and MIS-C.

MIS-C is relatively rare, and it apparently responds well to treatment, but it is new enough — and mysterious enough — that doctors here want to make sure the children who recover don’t experience any related health complications in the future.

“We’ve seen these kids get really sick, and get better and recover and go home, yet we don’t know what the long-term outcomes are,” said Dr. Nadine Choueiter, a pediatric cardiologist at Montefiore. “So that’s why we will be seeing them.”

When Israel first got sick at the end of April, his illness didn’t exactly look like COVID-19. He had persistent high fevers, with his temperature reaching 104 degrees — but no problems breathing. He wasn’t eating. He was barely drinking. He wasn’t using the bathroom. He had abdominal pains. His eyes were red.

They went to the emergency room a couple of times and visited an urgent care center, but the doctors sent them home without testing him for the coronavirus. Moholland, 29, said she felt powerless.

“There was nothing I could do but make him comfortable,” she said. “I literally had to just trust in a higher power and just hope that He would come through for us. It taught me a lot about patience and faith.”

As Israel grew sicker, and they still had no answers, Moholland grew frustrated. “I wish his pediatrician and [the emergency room and urgent care staff] had done what they were supposed to do and given him a test” when Israel first got sick, Moholland said. “What harm would it have done? He suffered for about 10 or 11 days that could have been avoided.”

In a later interview, she talked with NPR about how COVID-19 has disproportionately affected the African American community, due to a combination of underlying health conditions and lack of access to good health care. She said she felt she, too, had fallen victim to those disparities.

“It affects me, personally, because I am African American, but you just never know,” she said. “It’s hard. We’re living in uncertain times — very uncertain times.”

Finally, Children’s Hospital at Montefiore admitted Israel — and the test she’d been trying to get for days confirmed he had the virus.

“I was literally in tears, like begging them not to discharge me because I knew he was not fine,” she recalled.

Israel was in shock, and by the time he got to the hospital, doctors were on the lookout for MIS-C, so they recognized his symptoms — which were distinct from most people with COVID-19.

Doctors gave Israel fluids and intravenous immune globulin, a substance obtained from donated human plasma, which is used to treat deficiencies in the immune system.

Immune globulin has been effective in children like Israel because MIS-C appears to be caused by an immune overreaction to the initial coronavirus infection, according to Choueiter, the Montefiore pediatric cardiologist.

“The immune system starts attacking the body itself, including the arteries of the heart,” she said.

In some MIS-C cases — though not Israel’s — the attack occurs in the coronary arteries, inflaming and dilating them. That also happens in a different syndrome affecting children, Kawasaki disease. About 5% of Kawasaki patients experience aneurysms — which can fatally rupture blood vessels — after the initial condition subsides.

Choueiter and her colleagues want to make sure MIS-C patients don’t face similar risks. So far, they’re cautiously optimistic.

“We have not seen any new decrease in heart function or any new coronary artery dilations,” she said. “When we check their blood, their inflammatory markers are back to normal. For the parents, the child is back to baseline, and it’s as if this illness is a nightmare that’s long gone.”

For a Pennsylvania teen, the MIS-C diagnosis came much later

Not every child who develops MIS-C tests positive for the coronavirus, though many will test positive for antibodies to the coronavirus, indicating they had been infected previously. That was the case with Andrew Lis, a boy from Pennsylvania who was the first MIS-C patient seen at the Nemours/Alfred I. duPont Hospital for Children in Wilmington, Delaware.

Andrew had been a healthy 14-year-old before he got sick. He and his twin brother love sports and video games. He said the first symptom was a bad headache. He developed a fever the next day, then constipation and intense stomach pain.

“It was terrible,” Andrew said. “It was unbearable. I couldn’t really move a lot.”

His mother, Ingrid Lis, said they were thinking appendicitis, not coronavirus, at first. In fact, she hesitated to take Andrew to the hospital, for fear of exposing him to the virus. But after Andrew stopped eating because of his headache and stomach discomfort, “I knew I couldn’t keep him home anymore,” Lis said.

Andrew was admitted to the hospital April 12, but that was before reports of the mysterious syndrome had started trickling out of Europe.

Over about five days in the pediatric intensive care unit, Andrew’s condition deteriorated rapidly, as doctors struggled to figure out what was wrong. Puzzled, they tried treatments for scarlet fever, strep throat and toxic shock syndrome. Andrew’s body broke out in rashes, then his heart began failing and he was put on a ventilator. Andrew’s father, Ed Lis, said doctors told the family to brace for the worst: “We’ve got a healthy kid who a few days ago was just having these sort of strange symptoms. And now they’re telling us that we could lose him.”

Though Andrew’s symptoms were atypical for Kawasaki disease, doctors decided to give him the standard treatment for that condition — administering intravenous immune globulin, the same treatment Israel Shippy received.

“Within the 24 hours of the infusion, he was a different person,” Ingrid Lis said. Andrew was removed from the ventilator, and his appetite eventually returned. “That’s when we knew that we had turned that corner.”

It wasn’t until after Andrew’s discharge that his doctors learned about MIS-C from colleagues in Europe. They recommended the whole family be tested for antibodies to the coronavirus. Although Andrew tested positive, the rest of the family — both parents, Andrew’s twin brother and two older siblings — all tested negative. Andrew’s mother is still not sure how he was exposed since the family had been observing a strict lockdown since mid-March. Both she and her husband were working remotely from home, and she says they all wore masks and were conscientious about hand-washing when they ventured out for groceries. She thinks Andrew must have been exposed at least a month before his illness began.

And she’s puzzled why the rest of her close-knit family wasn’t infected as well. “We are a Latino family,” Ingrid Lis said. “We are very used to being together, clustering in the same room.” Even when Andrew was sick, she says, all six of them huddled in his bedroom to comfort him.

Meanwhile, Andrew has made a quick recovery. Not long after his discharge in April, he turned 15 and resumed an exercise routine involving running, pushups and situps. A few weeks later, an echocardiogram showed Andrew’s heart was “perfect,” Ed Lis said. Still, doctors have asked Andrew to follow up with a cardiologist every three months.

An eye on the long-term effects

The medical team at Montefiore is tracking the 40 children they have already treated and discharged. With kids showing few symptoms in the immediate aftermath, Chouetier hopes the long-term trajectory after MIS-C will be similar to what happens after Kawasaki disease.

“Usually children who have had coronary artery dilations [from Kawasaki disease] that have resolved within the first six weeks of the illness do well long-term,” said Choueiter, who runs the Kawasaki disease program at Montefiore.

The Montefiore team is asking patients affected by MIS-C to return for a checkup one week after discharge, then after one month, three months, six months and a year. They will be evaluated by pediatric cardiologists, hematologists, rheumatologists and infectious disease specialists.

Montefiore and other children’s hospitals around the country are sharing information. Choueiter wants to establish an even longer-term monitoring program for MIS-C, comparable to registries that exist for other diseases.

Moholland is glad the hospital is being vigilant.

“The uncertainty of not knowing whether it could come back in his future is a little unsettling,” she said. “But I am hopeful.”

This story is part of a partnership that includes WNYC, NPR and Kaiser Health News.