Genetic Susceptibility to SLE May Protect Against Severe COVID-19

A new genetic analysis of systemic lupus erythematosus (SLE) and COVID-19 suggests that the same genetic variants that can increase a person’s risk of autoimmune diseases may confer protection against severe illness due to coronavirus infection.

The study, published in PLOS Genetics, could help scientists better understand both diseases, as well as how genetic factors play a complex role in the risk of various diseases.

The COVID-19 pandemic coincided with a moment in scientific history where it was possible to do genome-wide association studies to better understand the genetic components of patients’ responses to infection, explained the study authors. Genome-wide association studies of severe COVID-19 have suggested that clinical outcomes might be affected by genetic factors, they said.

“Some of the genetic loci identified unsurprisingly point to pathways involved in the host immune response,” the authors noted.

They therefore decided to see what they could find by comparing the genetics of COVID-19 to the genetics of a major autoimmune disease. The authors said they chose SLE for 2 reasons: because some risk alleles for SLE augment interferon response and other lupus susceptibility genes are active in the intracellular viral sensing pathway.

The investigators used a variety of techniques to analyze the genetics of the 2 conditions. They then used biomedical databases to better understand the biology of their shared genetics.

The analysis led to the discovery that the gene TYK2 seems to play a key—but opposite—role in the 2 diseases. Specifically, the gene appears to provide protection against severe disease from viruses like SARS-CoV-2, but also is associated with an increased risk of autoimmune disease.

“The locus with the most evidence of shared association (TYK2) is involved in interferon production, a process that is important in response to viral infection and known to be dysregulated in SLE patients,” the authors said in a press release. “In seeking to uncover the mechanisms underlying these relationships it was apparent that the functional effects of the risk and protective genotypes are complex.”

The findings come with several caveats. Among them, the investigators noted that a disproportionate number of people in the data set used were of European ancestry, and thus the results may not be generalizable to other populations. Further studies will be required to fully verify and understand the apparent connection between COVID-19 severity and autoimmune diseases, they added.

However, they said the initial findings suggest an interesting interplay between genetic risk profiles that may help explain how genetics affect a person’s response to SARS-CoV-2 infection.

“This is an exciting result made possible by the large genetic studies in COVID-19 and lupus and opens the door to our understanding of how the biology of the immune system is calibrated to protect us against infection from viruses and other infectious agents, but at the risk of developing autoimmune disease,” the authors said.

Reference

Wang Y, Guga S, Wu K, Khaw Z, et al. COVID-19 and systemic lupus erythematosus genetics: a balance between autoimmune disease risk and protection against infection. PLoS Genet. Published online November 3, 2022. doi:10.1371/journal.pgen.1010253