Early intervention key to curb COVID-related inflammatory disease among children
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Clinicians and researchers continue to debate the etiology and treatment paradigms for the severe inflammatory syndrome that impacts some children with COVID-19, according to a speaker at the ACR State-of-the-Art Clinical Symposium.
“We got good news early” in the pandemic, with most data showing that children were largely spared the most severe forms of COVID-19, Karen Onel, MD, of the departments of pediatrics and rheumatology at the Hospital for Special Surgery, said in her presentation. “Most children and young adults were doing very well. Everyone was feeling really good that magically the children were going to be able to skate through this pandemic, doing relatively well by comparison. And then everything changed.”
That change was a data set from April 2020 showing a reported rise in incidence of COVID-associated multi-inflammatory syndrome in children (MIS-C).
The condition is marked by hyper-inflammatory shock, unrelenting fever, rash, conjunctivitis, gastrointestinal symptoms, renal involvement, respiratory symptoms, peripheral edema and generalized extremity pain, among other symptoms. MIS-C may also involve the neurological system, there may be dermatologic or hematologic involvement. It is defined by occurrence in individuals aged 21 years or younger, and it can be fatal.
What concerned clinicians is that this condition resembled Kawasaki disease, which Onel described as vasculitis that impacts small or medium-sized vessels. “It is the second most common childhood vasculitis,” she said. “People started to panic about mortality from a serious Kawasaki-like phenomenon.”
It was then that she raised one important clinical consideration. “Are the Kawasaki-like phenomenon and MIS-C the same thing?” she said. “We realized early on that it is probably not Kawasaki disease.”
Alternately, Onel offered another diagnostic consideration. “Sometimes, maybe it is just bad COVID,” she said.
It is important, then, to understand who may be impacted by this MIS-C. Children aged 6 to 12 years are more likely than their younger counterparts than to develop this complication, as are children with cardiorespiratory or cardiovascular without respiratory involvement, those mucocutaneous infection, neutrophil or lymphocyte ratios greater than five and low platelet counts. It is most likely to occur in non-Hispanic Black children.
Regarding the immune system involvement in MIS-C, interleukin (IL)-6, IL-17a and IL-18 may be implicated, along with CCL4, CCL20, CCL28, CDCP1 and ICCL3. Onel described this group as “non-classical” monocytes, natural killer cells and T lymphocytes. “Getting these specimens early, before symptoms develop, can be quite challenging,” she said.
As for treatment, early research conducted by Onel’s group showed that intravenous immunoglobulin (IVIG), along with aspirin, administered before day 10 of infection, could be most effective. “That is not to say it would not be effective on day 11,” she said. “That was just what we studied.”
The ACR supports IVIG as first-line treatment for children who have shock or organ-threatening disease that may or may not be MIS-C. The College stipulates that IVIG may be administered with steroids for severe disease and without steroids for non-severe disease.
The key point, for Onel, is to intervene as early as possible. However, she acknowledged that this can often prove challenging, given that COVID-19 can be asymptomatic for a prolonged duration after infection.
“For most children, including those under immunosuppressive medications, COVID-19 infections are mild and self-limiting,” she said. “A group of approximately 2500 in the United States have developed severe inflammatory disorder that must be treated aggressively.”
Onel closed her presentation with some information on vaccines that may provide hope. She noted that the Pfizer product has been granted emergency use authorization for individuals aged 16 years and older. Both Pfizer and Moderna are conducting trials in younger individuals, with Pfizer finishing a trial in those aged 12 to 15 years and Moderna studying its product in children aged 6 months to 11 years and in those aged 12 to 17 years.
“The plan is to get all the high schoolers done by the end of this year,” she said, and added that middle-school children may be eligible by next year.
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Onel K. COVID Update: For Adults and Children. Presented at: American College of Rheumatology State-of-the-Art Clinical Symposium. April 9-11, 2021 (virtual meeting).
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