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Monday, December 5, 2022

What Causes Rare Inflammatory Disease in Children Post COVID?

Researchers have discovered a key clue to an uncommon but significant COVID-19 side effect known as a multisystem inflammatory syndrome in children, or MIS-C, in children under the age of 12.

Fever, discomfort, and inflammation of various organs, including the heart, lungs, kidneys, skin, eyes, and gastrointestinal tract, are all symptoms of MIS-C.

RNA sequencing of blood samples led to the discovery that specific infection-fighting cells of the immune system are downregulated in children with MIS-C and that this is associated with a sustained inflammatory response — a hallmark of infection with SARS-CoV-2, the virus that causes COVID-19, according to researchers from Mount Sinai Hospital in New York, US.

The findings were reported in the journal Nature Communications. The researchers looked at MIS-C and COVID-19 cases in children and discovered novel exploratory paths involving complex networks and subnetworks of genes.

The suppression of two types of immune cells, natural killer (NK) cells and CD8+ T cells were one of the more prominent of these gene networks.

Previous research has demonstrated that when CD8+ T cells are exposed to infections for an extended period of time, they become “exhausted,” losing their efficiency and ability to multiply.

The CD8+ T cells in the latest study were particularly mentioned as being tired, which could potentially impair the inflammatory immune response. Exhausted CD8+ T cells are linked to an increase in NK cells.

“One of the potential drivers of this disease in MIS-C patients is T cell exhaustion,” said Noam Beckmann, assistant professor of genetics and genomic sciences at Mount Sinai’s Icahn School of Medicine. “Increasing both NK cells and circulating exhausted CD8+ T cells may improve inflammatory disease symptoms.”

“We also discovered nine important regulators of this network that have been linked to NK cell and fatigued CD8+ T cell function,” Beckmann added.

One of these regulators, TBX21, is a prospective therapeutic target, according to Beckmann, because it acts as a master coordinator in the shift of CD8+ T cells from active to tired.

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