A new study published by the researchers of Mount Sinai has revealed an important clue to a rare but serious side effects of Coronavirus in children, known as a multisystem inflammatory syndrome in children or MIS-C.
According to the researchers, RNA sequencing of blood samples from the Mount Sinai COVID-19 Biobank revealed that in children with MIS-C, specific infection-fighting immune cells are downregulated, and that this is linked to a sustained inflammatory response, which is a hallmark of infection with SARS-CoV-2, the virus that causes COVID-19.
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On August 11, the study was published in Nature Communications.
Fever, pain, and inflammation of multiple organs such as the heart, lungs, kidneys, skin, eyes, and gastrointestinal tract are all symptoms of MIS-C. Since the COVID-19 pandemic began, over 2,600 cases of MIS-C have been reported in the United States.
While an autoimmune disorder has been proposed as the underlying cause, the specific genes, pathways, and cell types involved remain unknown.
The Mount Sinai researchers have made a significant contribution to the field by developing new exploratory pathways using complex networks and subnetworks of genes derived from paediatric cases of MIS-C and COVID-19 from the Mount Sinai COVID-19 Biobank.
Several of these gene networks were associated with the suppression of two distinct types of immune cells: natural killer (NK) cells and CD8+ T cells.
Previous research has demonstrated that when CD8+ T cells are exposed to pathogens repeatedly, they enter a state of “exhaustion,” resulting in a loss of effectiveness and proliferation.
The new study’s authors specifically mentioned CD8+ T cells being exhausted, potentially weakening the inflammatory immune response. Additionally, an increase in NK cells is associated with depleted 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,” says lead co-author Noam Beckmann.
“Additionally, we found nine key regulators of this network known to have associations with NK cell and exhausted CD8+ T cell functionality.”
According to Dr Beckmann, one of these regulators, TBX21, is a promising therapeutic target because it acts as a master coordinator of the transition of CD8+ T cells from effective to exhausted.
Mount Sinai’s work on MIS-C is the first gene-expression study conducted using the hospital’s COVID-19 Biobank. The repository, which was established through the efforts of a volunteer team of over 100 nurses, doctors, and researchers, serves as the backbone of Mount Sinai’s rapidly expanding COVID-19 research.
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The team collected blood samples from several hundred COVID-19 patients admitted to Mount Sinai hospitals (including “longitudinal” or multiple samples from the same person), which resulted in a diverse set of molecular data that provided invaluable insights into the disease’s better understanding and development of new therapeutic approaches.