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UVa research: COVID-related inflammation syndrome should be red flag for vaccine developers

An inflammation syndrome in some children exposed to COVID-19 may serve as a warning to researchers working on a virus vaccine to keep safety in mind, a University of Virginia researcher and his colleagues say.

New findings in the study of multisystem inflammatory syndrome in children, known as MIS-C, show that children with the condition have elevated levels of antibodies that their bodies created to fight the proteins the COVID-causing virus uses to infect a body.

The exact cause of MIS-C and whether the increased antibodies are a cause or an effect of the condition is not known. However, the researchers say it’s important that the findings be considered as labs everywhere race to bring a vaccine to market.

“The great thing about vaccines is, when they work well, they teach the immune system to fight off the pathogen for the future. If you had a measles vaccine as a child and are exposed to measles as an adult, your body knows how to defend itself,” said Dr. Steven Zeichner, of the UVa Children’s Hospital. “But it’s because of the long-term impacts that there needs to be a higher standard for a vaccine.”

Zeichner and Dr. Andrea Cruz, of Baylor College of Medicine in Houston, wrote commentaries for the journal Pediatrics pointing out that MIS-C could be a harbinger of potential dangers of a vaccine or COVID-19 treatment if research is not thorough.

Zeichner and Cruz are both editors of the publication.

MIS-C can result in inflammation of the heart, lungs, kidneys, brain, skin, eyes, or gastrointestinal organs. It can result in abdominal pain, vomiting, diarrhea, neck pain, rash, bloodshot eyes, exhaustion and, in the most severe cases, death.

An estimated 98% of MIS-C cases were in children diagnosed as having COVID-19 and developed between two and four weeks after infection. The other 2% were in children who had been exposed to people with COVID-19, according to research.

MIS-C is caused by a massive activation of pro-inflammatory cells called cytokines, referred to as a cytokine storm. Researchers believe similar cytokine storms may cause some of the severe responses to COVID-19 seen in adults.

Multiple studies of deaths related to COVID-19 and patients who recovered from the disease indicate that the virus causes inflammatory responses throughout the body. Many studies suggested treating COVID-19 as “an acute inflammatory disease” and indicated the more someone’s immune response is compromised, the more serious the disease will be for that person.

Zeichner and Cruz’s commentary accompanies an article written by Christina A. Rostad and colleagues from Emory University and the University of Texas Medical Branch, Galveston. They discovered that children with MIS-C had high levels of antibodies against the virus’ spike proteins, or receptor binding domain, that hook the virus into host cells in the body.

The discovery could prove helpful in diagnosing MIS-C, but should throw up red flags for the binding cell antibody treatments and antibody-based vaccines currently under development.

Researchers currently are studying the effectiveness of treating severely ill COVID patients with plasma from people who have recovered from COVID-19. The idea is that the plasma already contains antibodies to the SARS-CoV-2 virus that causes the disease.

Many of the 200 or so vaccines being studied also rely on antibodies to the binding domain proteins.

“We don’t know if antibodies against [binding domain cells] are associated with the development of MIS-C or if they could somehow help to cause MIS-C or other inflammatory processes,” Zeichner said. “If they do contribute to inflammation, it might have an impact on convalescent plasma treatments or a vaccine.”

In their commentary, Zeichner and Cruz note that researchers studying treatments or working on vaccines should carefully evaluate those participating in the program while being treated and, in the case of a vaccine, for a period of time afterward.

“Safety, especially in a vaccine, is important. A vaccine teaches the body to respond in a certain way and, if there’s a chance that response could make things worse, we need to know,” Zeichner said. “We do not want to have a situation where patients do not have confidence that a vaccine is safe or that is prematurely approved and later has significant safety concerns.”

Zeichner said COVID is a “huge challenge” for society but it’s important not to cut corners while making haste.

“We need to remember the vaccines would be given to healthy people to prevent the disease,” he said. “Vaccines work well by teaching the immune system how to fight off a pathogen. But we need to know if that response that the body learns can make the disease worse. The MIS-C finding should be considered a warning to keep safety in mind.”


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