Study Finds Infection-Fighting Immune Cells Are Downregulated in Children With COVID-19-Related Multisystem Inflammatory Syndrome

By sequencing blood samples from children with multi system inflammatory syndrome (MIS-C) following COVID-19 infection, researchers have found that specific infection-fighting cells of the immune system are downregulated, offering a potential clue to the cause of the prolonged illness.

According to a press release from Mount Sinai Hospital, this downregulation is associated with a sustained inflammatory response and is a key marker of SARS-CoV-2 infections. MIS-C is characterized by this prolonged infection, as well as fever, pain, and inflammation of multiple organs.

More than 2600 cases of MIS-C have been reported in the United States since the COVID-19 pandemic began, although its exact causes are still unknown. Some experts have suggested an autoimmune condition as an underlying cause, but specific genes, pathways, and cell types have not yet been identified; however, the new research may provide a clue.

The suppression of natural killer cells and CD8+ T cells was implicated by one significant gene network, according to the study. Earlier research found that when CD8+ T cells are persistently exposed to pathogens, they can lose effectiveness and the ability to proliferate due to a state of “exhaustion.”

In the current study, the researchers found that CD8+ T cells were in this exhausted state in MIS-C patients, potentially weakening the inflammatory immune response. An increase in natural killer cells was also noted, which is associated with this exhaustion, according to the study.

“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 [natural killer] cells and circulating exhausted CD8+ T cells may improve inflammatory disease symptoms,” said lead co-author Noam Beckmann, PhD, an assistant professor of genetics and genomic sciences at the Icahn School of Medicine at Mount Sinai, in the press release. “Additionally, we found 9 key regulators of this network known to have associations with [natural killer] cell and exhausted CD8+ T cell functionality.”

The study authors noted that one of those key regulators is TBX21, which may be a promising therapeutic target because it coordinates the transition of CD8+ T cells from their effective to exhausted states.

REFERENCE

Mount Sinai researchers find important clue to rare inflammatory disease in children following COVID-19 infection. News release. EurekAlert; August 11, 2021. Accessed August 11, 2021. https://www.eurekalert.org/news-releases/924971