children diagnosed with COVID have developed MIS-C.Throughout the pandemic, MIS-C has followed a predictable pattern, sending waves of children to the hospital about a month after a COVID surge.
At the Medical University of South Carolina Shawn Jenkins Children's Hospital, for example, doctors in September treated 37 children with COVID and nine with MIS-C — the highest monthly totals since the pandemic began.Although most children who develop MIS-C were previously healthy, 80% develop heart complications.Doctors have gotten better at diagnosing and treating MIS-C; the mortality rate has fallen from 2.4% to 0.7% since the beginning of the pandemic. Adults also can develop a post-COVID inflammatory syndrome, called MIS-A; it's even rarer than MIS-C, with a mortality rate seven times as high as that seen in children.Although MIS-C is new, doctors can treat it with decades-old therapies used for Kawasaki disease, a pediatric syndrome that also causes systemic inflammation.
Significantly, the genes are all involved in "removing the brakes" from the immune system, which could contribute to the hyperinflammation seen in MIS-C, said Dr.
And it raises new questions: If these children are genetically susceptible to immune problems, why didn't they become seriously ill from earlier childhood infections.Most children with MIS-C test negative for COVID, suggesting that the body has already cleared the novel coronavirus from the nose and upper airways.
Lael Yonker noticed that children with MIS-C are far more likely to develop gastrointestinal symptoms — such as stomach pain, diarrhea and vomiting — than the breathing problems often seen in acute COVID.Yonker, a pediatric pulmonologist at Boston's MassGeneral Hospital for Children, recently found evidence that the source of those symptoms could be the coronavirus, which can survive in the gut for weeks after it disappears from the nasal passages, Yonker said.In a May study in The Journal of Clinical Investigation, Yonker and her colleagues showed that more than half of patients with MIS-C had genetic material — called RNA — from the coronavirus in their stool.The body breaks down viral RNA very quickly, Chou said, so it's unlikely that genetic material from a COVID infection would still be found in a child's stool one month later.In some children, the virus irritates the intestinal lining, creating microscopic gaps that allow viral particles to escape into the bloodstream, Yonker said.Blood tests in children with MIS-C found that they had a high level of the coronavirus spike antigen — an important protein that allows the virus to enter human cells.Viral particles in the blood could cause problems far beyond upset stomachs, Yonker said.Although the first doctors to treat MIS-C compared it to Kawasaki disease — which also causes red eyes, rashes and high fevers — Arditi notes that MIS-C more closely resembles toxic shock syndrome, a life-threatening condition caused by particular types of strep or staph bacteria releasing toxins into the blood.Toxins released by these bacteria can trigger a massive overreaction from key immune system fighters called T cells, which coordinate the immune system's response, said Arditi, director of the pediatric infectious diseases division at Cedars-Sinai Medical Center.In a typical response to a foreign substance — known as an antigen — the immune system activates only about 0.01% of all T cells, Arditi said.Although multiple studies have found that children with MIS-C have fewer total T cells than normal, Arditi's team has found an explosive increase in a subtype of T cells capable of interacting with a superantigen.
Carrie Lucas, an assistant professor of immunobiology at Yale, whose team has identified changes in immune cells and proteins in the blood of children with MIS-C.
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