Many children with serious inflammatory illness did not display any symptoms of COVID-19 disease and those who did show only mild symptoms, according to a new US study.

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According to the results published in the JAMA Pediatrics on 6th March, of the largest US study of the cases of the multisystem inflammatory syndrome (MIS-C) in children, which can strike young people weeks after they were infected with COVID-19. 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, says the study.

According to the New York Times, 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 per cent of the patients did not experience such symptoms. However, 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.

The study said "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. However, experts were not able to file any concrete findings on the reason behind such a high rate of an inflammatory syndrome in younger children. "It means primary-care paediatricians need to have a high index of suspicion for this because COVID is so prevalent in the society and children often have an 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 per cent of those young people experienced symptoms involving at least four organ systems and 58 per cent needed treatment in intensive care units. Many experienced significant heart issues: over half developed low blood pressure, 37 per cent developed cardiogenic shock and 31 per cent experienced cardiac dysfunction involving their heart's inability to pump adequately. The study further 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, reported the New York Times. "Even the kids with severe MIS-C, who was in the I.C.U. 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 study provided the most detailed demographic and geographic picture of the syndrome to date. About 34 per cent of the patients were Black and 37 per cent were Hispanic, reflecting the way that the coronavirus has disproportionately affected members of those communities. As the pandemic went on, the authors wrote, the proportion of patients who were white increased, comprising 20 per cent of all cases. People of Asian heritage comprised just over 1 per cent of patients.

Overall, nearly 58 per cent of the patients were male, but the proportion was not the same across all ages. The youngest group newborn to age 4 had roughly equal numbers of boys and girls, and the male-to-female ratio increased in the older groups until it was more than two-to-one male to female in the 18-to-20 group. The vast majority of patients (nearly 86 per cent) were younger than 15. The study found that those under 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 a more severe disease", Dr 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".
Children aged 14 and under were more likely to have a 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.

Similarly unclear are the reasons behind the study's finding that in the first wave of MIS-C, from March 1 to July 1, 2020, young people were more prone to a few of the most serious heart complications. Dr DeBiasi said that did not match the experience of her hospital, where "the kids were sicker in the second wave".

The study documented two waves of MIS-C cases that followed surges in overall coronavirus cases by about a month or more. "The most recent third peak of the COVID-19 pandemic appears to be leading to another MIS-C peak perhaps involving urban and rural communities", the authors wrote. Dr Blumenthal said, "right now, we don't know anything about how the variants necessarily affect children".