Connection Between COVID-19 Severity and Immune Cell Gene Expression Identified

New research shows how genetic variations linked to severe cases of COVID-19 affect our immune cells. The study, led by scientists at La Jolla Institute for Immunology, took an in-depth look at the connections between COVID-19 severity and gene expression in many types of immune cells. Their findings were published in Nature Communications study

For the new study, the team combined patient genetic data from the COVID-19 Host Genetic Initiative and LJI's open-access Database of Immune Cell Epigenomes (DICE) to define the genes and susceptible cell types affected by these risk variants. The team looked at 13 subtypes of the body's key protective and virus-fighting cells: T cells, B cells, NK cells, and monocytes.

The researchers identified several important associations of genetic variants with disease severity. Among them was a risk variant that affected 12 of the 13 cell types studied. This severe COVID-19-risk variant in chromosome 21 was associated with reduced expression of a receptor on cells called IFNAR2. This receptor is part of a signaling pathway that alerts the immune system to infection. This new association may help explain why some people fail to mount a strong immune response to SARS-CoV-2.

Meanwhile, a risk variant on chromosome 12 displayed the strongest effect in non-classical monocytes, a type of innate immune cell that patrols the body and sends signaling molecules to alert other immune cells to threats. The risk variant led non-classical monocytes to reduce the expression of a gene called OAS1. A lack of OAS1 expression could hobble the body's defenses by reducing the expression of a family of proteins that normally degrades viral RNA and activates the immune system's antiviral responses.