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Many children and teenagers who developed the mysterious inflammatory syndrome that can emerge several weeks after contracting the coronavirus never had classic COVID-19 symptoms at the time of their infection, according to the largest study so far of cases in the United States.

The study, led by researchers from the Centers for Disease Control and Prevention, found that in over 1,000 cases in which information about whether they got sick from their

initial COVID-19 illness was available, 75% of the patients did not experience such symptoms. But two to five weeks later, they became sick enough to

be hospitalized for the condition, called multisystem inflammatory syndrome in children (MIS-C), which can affect multiple organs, especially the heart.

Published Tuesday in JAMA Pediatrics, the study said that "most MIS-C illnesses are believed to result from asymptomatic or mild COVID-19" followed by a hyper-inflammatory response that appears to occur when the patients' bodies have produced their maximum level of antibodies

to the virus. Experts do not yet

know why some young people, and a smaller number of adults, respond this way.

"It means primary-care pediatricians need to have a high index of suspicion for this because COVID is so prevalent in the society and children often

have asymptomatic disease as their initial COVID infection," said Dr. Jennifer Blumenthal, a pediatric intensivist

and pediatric infectious disease

specialist at Boston Children's Hospital, who was not involved in the study.

The researchers evaluated 1,733

of the 2,090 cases of the syndrome in people age 20 and younger that had been reported to the CDC as of January.

The findings show that although the syndrome is rare, it can be serious. The CDC's data only included patients who were hospitalized. Over 90% of those young people experienced symptoms involving at least four organ systems and 58% needed treatment in intensive care units.

Many experienced significant heart issues: over half developed low blood pressure, 37% developed cardiogenic shock and 31% experienced

cardiac dysfunction involving their heart's inability to pump adequately. The study said that a significantly higher percentage of patients who

had not had COVID-19 symptoms experienced those heart problems, compared with those who

had initial coronavirus symptoms. A greater percentage of initially asymptomatic patients also ended up in intensive care.

"Even the kids with severe MIS-C, who were in the ICU — the vast majority of them did not have a preceding illness that they recognized," said Dr. Roberta DeBiasi, chief of infectious diseases at Children's National Hospital in Washington, D.C., who was not involved in the research.

The vast majority of patients (nearly 86%) were younger than 15. The study found that those younger than 5 had the lowest risk of serious heart complications and were less likely to need intensive care. Patients 10 and older were significantly more likely to develop issues like shock, low blood pressure and myocarditis (inflammation of the heart muscle).

"I think that's similar to what we saw with COVID, that the older kids seemed to have more severe disease," DeBiasi said. "And that's because what makes people really sick from the COVID is the inflammatory aspect of it, so maybe these older kids, for whatever reasons, make more inflammation, whether that's in primary COVID or MIS-C."

Still, significant numbers of the youngest patients developed heart problems. In the newborn-to-4 age group, 36% had low blood pressure, 25% had shock and 44% were treated in the ICU.

Patients of all ages in the study had about the same occurrence of some of the less-common heart issues linked to the syndrome, including coronary aneurysms and fluid buildup. Children 14 and younger were more likely to have rash and red eyes, while those older than 14 were more likely to have chest pain, shortness of breath and cough. Abdominal pain and vomiting afflicted about two-thirds of all patients.

There were 24 deaths recorded, spread across all age groups. There was no information in the study about whether patients had underlying medical conditions, but doctors and researchers have reported that young people with MIS-C were often previously healthy and significantly more likely to be healthy than the relatively small number of young people who become seriously ill from initial COVID infections.

Of the 1,075 patients for whom information about initial COVID illness was available, only 265 had symptoms at that time. They were more likely to be older — their median age was 11, while the median age of those with asymptomatic COVID infections was 8. But that could be because "younger children can't express their

concerns as well," said Blumenthal, who co-wrote an editorial about the study.

"We don't necessarily know if there's actually less symptomatology in the very young population, " she said.

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