What causes rare inflammatory disease in kids post Covid

New York

MIS-C is characterised by fever, pain, and inflammation of multiple organs including the heart, lungs, kidneys, skin, eyes, or gastrointestinal tract.

The researchers from Mount Sinai Hospital in New York, US, reported that 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.

The study was published in Nature Communications.

The team analysed pediatric cases of MIS-C and Covid-19 and found new exploratory pathways involving complex networks and subnetworks of genes.

One of the more significant of these gene networks involved the suppression of two types of immune cells: natural killer (NK) cells and CD8+ T cells.

Previous research has shown that when CD8+ T cells are persistently exposed to pathogens, they enter a state of "exhaustion," resulting in a loss of their effectiveness and ability to proliferate.

The researchers in the new study specifically pointed to the CD8+ T cells being in this exhausted state, thus potentially weakening the inflammatory immune response. An increase in NK cells is also associated with exhausted CD8+ T cells.

"Our study implicated T cell exhaustion in MIS-C patients as one of the potential drivers of this disease, suggesting that an increase in both NK cells and circulating exhausted CD8+ T cells may improve inflammatory disease symptoms," said Noam Beckmann, Assistant Professor of Genetics and Genomic Sciences at the Icahn School of Medicine at Mount Sinai.

"Additionally, we found nine key regulators of this network known to have associations with NK cell and exhausted CD8+ T cell functionality," Beckmann said.

Beckmann added that one of those regulators, TBX21, is a promising therapeutic target because it serves as a master coordinator of the transition of CD8+ T cells from effective to exhausted.