Children and COVID—What’s Known

In two new papers, pediatricians from Columbia University Irving Medical Center and NewYork-Presbyterian Morgan Stanley Children's Hospital describe two types of serious, but rare, COVID-19 disease that can occur in children.

New York City — the epicenter of pandemic in the United States — was the first U.S. city to encounter children who required hospitalization for COVID-19.

Reports describing COVID-19 infection in children have been relatively limited, and the new papers are among a few that characterize the disease in a significant number of children.

“Other parts of the country are on a different timeline with COVID-19  than New York City, so these reports provide important information for pediatricians who’ve seen relatively few cases,” says Eva Cheung, MD, assistant professor of pediatrics at Columbia University Vagelos College of Physicians and Surgeons and attending pediatric cardiologist and intensivist at NewYork-Presbyterian Morgan Stanley Children’s Hospital.

 

Initial cases were primarily respiratory illnesses

The first paper, published in JAMA Pediatrics, describes 50 children with COVID-19 who were admitted to the hospital during the first six weeks of the pandemic. These children — like adults who were also hospitalized at this time — presented mainly with respiratory symptoms and fever, though some cases involved only gastrointestinal or neurological issues.

“Even within young people, there is a spectrum of disease,” says the paper’s lead author Philip Zachariah, MD, assistant professor of pediatrics at Columbia University Vagelos College of Physicians and Surgeons and an infectious disease attending and hospital epidemiologist at NewYork-Presbyterian Morgan Stanley Children's Hospital.

“It’s not a homogeneous disease; there are varied presentations, just as seen in adults.”

Among the 50 children described in the paper, most had only experienced symptoms for a few days before they were hospitalized, and three-quarters of the children were discharged, on average, after three days.

“I do want to emphasize that severe disease seems relatively rare and most children and adolescents are going to be fine,” Zachariah says.

Similar to adults hospitalized for COVID-19, many children treated in the hospital had other medical comorbidities. 

“Obesity was common in this group, but this may just reflect our population, which has a high prevalence of obesity,” Zachariah says. “We cannot make any conclusions about causality at this point since there could be other associated variables at play.”

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Encouragingly, none of the 14 infants with COVID-19 had severe disease, in contrast to previous reports that suggest infants are more susceptible to COVID-19. Immune-compromised children also had better outcomes than expected.

“Some previous data suggested that infants were affected more severely by this virus,” Zachariah says, “but that has not been our experience here. Infants could be hospitalized more often for less severe disease out of an abundance of caution.”

“We also observed higher levels of inflammation with severe respiratory disease, which aligns with experience from adults.” 

Going forward, Zachariah says, pediatricians and academic medical centers across the country are collaborating on research to identify which children with COVID-19 are more likely to become severely ill.

 

Second Phase: Multisystem Inflammatory Syndrome in Children

In mid-April, cases of COVID-19 among children took a different turn. 

Instead of children with underlying medical problems presenting with respiratory issues, previously healthy children were coming in with signs of a severe inflammatory disease resembling Kawasaki disease (a rare vascular inflammatory disease in infants) or toxic shock syndrome.

“For parents, it’s hard to miss this syndrome. These kids have had many days of moderately high fever, many have severe GI symptoms — the abdominal pain and discomfort they complain about is not like a typical stomach ache — and the rashes are not subtle,” says Eva Cheung, MD, the lead author of a paper in JAMA that describes the first 17 children admitted to NewYork-Presbyterian Morgan Stanley Children’s Hospital.

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Similar cases of what is now called Multisystem Inflammatory Syndrome in Children (MIS-C) were first reported in the U.K. in early April.

“We believe this is an entirely different syndrome caused by the new coronavirus,” Cheung says. “The features we see in our patients overlap with, but are clearly distinct from, Kawasaki disease or toxic shock syndrome.”

Among the 17 children with MIS-C in the new report, all patients had prolonged, high fever, most had GI symptoms. Rash, pinkeye, and lip redness or swelling also were common. Children of all ages and ethnicities were affected. None of the patients died, and all were discharged from the hospital after a median of 7 days.

Effects on heart function were seen in many patients, but those improved over the course of their stay in the hospital. Cheung and her colleagues have some preliminary data that show that heart function continues to recover over time.

Since the report was drafted, the number of patients with MIS-C at NewYork-Presbyterian Morgan Stanley Children’s Hospital has more than doubled, but fewer of the recent cases have needed intensive care.

“I think public awareness of the disease was dramatically heightened in the time since we wrote the report,” Cheung says. “That may have prompted parents to bring in kids earlier, and we’re moving ahead with treatments earlier.”

“Kids are getting better, they are recovering,” she says.

 

Studies underway to find causes, treatments

Children with MIS-C at NewYork-Presbyterian Morgan Stanley Children’s Hospital are treated early with anti-inflammatory drugs such as steroids and intravenous immunoglobulin. 

“We can’t say our approach is better or worse than other centers,” Cheung adds, “but we’ll know more as we monitor the long-term outcomes.”

It’s still unknown if certain children are more susceptible to MIS-C than others. Researchers at Columbia University are actively working on what may be the cause of MIS-C, if there are any genetic factors that may increase risk of MIS-C, and how genetic factors will impact treatment and outcomes for children with MIS-C.

Severe inflammatory responses seem to be the underlying feature in both these presentations, and how to effectively prevent and target this will be the subject of much ongoing work, Cheung and Zachariah say.

References

More information

"Epidemiology, Clinical Features, and Disease Severity in Patients With Coronavirus Disease 2019 (COVID-19) in a Children's Hospital in New York City, New York," was published June 3 in JAMA Pediatrics.

Other authors: Candace L. Johnson, Katia C. Halabi, Danielle Ahn, Anita I. Sen, Avital Fischer, Sumeet L. Banker, Mirna Giordano, Christina S. Manice, Rebekah Diamond, Taylor B. Sewell, Adam J. Schweickert, John R. Babineau, R. Colin Carter, Daniel B. Fenster, Jordan S. Orange, Teresa A. McCann, Steven G. Kernie, and Lisa Saiman, for the Columbia Pediatric COVID-19 Management Group.

 

"Multisystem Inflammatory Syndrome Related to COVID-19 in Previously Healthy Children and Adolescents in New York City," was published June 8 in the Journal of the American Medical Association.

Other authors: Philip Zachariah, Mark Gorelik, Alexis Boneparth, Steven G. Kernie, Jordan S. Orange, and Joshua D. Milner (all from CUIMC).

 

"Gastrointestinal Symptoms as a Major Presentation Component of a Novel Multisystem Inflammatory Syndrome in Children (MIS-C) That Is Related to COVID-19: A Single Center Experience of 44 Cases," was published June 4 in Gastroenterology.

Other authors: Jonathan Miller, Amanda Cantor, Philip Zachariah, Danielle Ahn 3, and Mercedes Martinez.

 

J. Orange reported receiving personal fees from ADMA Biologics, CSL Bhering, Gigagen, Grifols, and Takeda. L.Saiman reported grants from Merck, the CF Foundation, the National Institute of Allergy and Infectious Diseases, and the Bill and Melinda Gates Foundation and serving on the scientific advisory boards of Merck and AstraZeneca outside the submitted work. No other disclosures were reported.