Generic Variations Linked to Severe COVID-19 Cases

Non-classical monocytes, a type of innate immune cell that signals molecule to alert other immune cells to threats, could be potential target for COVID-19 therapies.

Genetic variations linked to severe cases of COVID-19 affect our immune cells, results of a study lead by the La Jolla Institute (LJI) for Immunology showed.

Genetic variants called polymorphisms are associated with gene expression and appear to influence case severity, according to a press release.

"There are many different immune cell types, and they all contribute small functions to the global picture,” Benjamin Schmiedel, PhD, an instructor at LJI, said in a statement. "We have to look at every immune cell type separately to figure out how the immune system is able to respond to COVID."

Investigators report that a gene in a cell type called non-classical monocytes, a type of innate immune cell that signals molecule to alert other immune cells to threats, could be a potential target for COVID-19 therapies.

They identified several important associations of genetic variants, and among them was a risk variant that affected 12 of the 13 cell types studied. The severe COVID-19 risk variants in chromosome 21 were associated with reduced expression of a receptor on IFNAR2 cells.

The receptor is part of a signaling pathway that alerts the immune system to infection and could explain why some individuals fail to illicit a strong immune response to COVID-19.

A risk variant on chromosome 12 had the strongest effect in non-classical monocytes where it reduced the expression of the OAS1 gene. This could reduce the body’s defenses when the expression of a family of proteins activates the immune system’s antiviral responses.

The study used genetic data from the COVID-19 Host Genetic Initiative and LJI’s open-access Database of Immune Cell Epigenomes to define the genes and susceptible cell types affected by these risk variants.

Investigators looked at 13 subtypes of the body’s key protective and virus-fighting cells including T cells, B cells, NK cells, and monocytes.

The results could guide the development of new COVID-19 therapies to boost cell immunity.

The study was published in Nature Communications.

Reference

COVID-19 case severity: How genetic differences leave immune cells at a disadvantage. EurekAlert. News release. November 19, 2021. Accessed November 19, 2021. https://www.eurekalert.org/news-releases/935466