EBV infections may affect risk of developing scleroderma: Analysis

Findings may benefit prevention, diagnosis, and prognosis of disease by Marisa Wexler, MS | August 26, 2025

Infection with Epstein-Barr virus (EBV), the virus that causes mononucleosis, may increase the risk of developing systemic sclerosis (SSc), according to a new analysis of genetic data.

Findings also indicate that SSc is less likely to develop in people who’ve been infected with human immunodeficiency virus (HIV) or SARS-CoV-2, the virus that causes COVID-19.

“These findings may benefit the prevention, diagnosis, and prognosis of SSc,” the investigators wrote.
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The study, “Mendelian randomization unveils genetic causal relationships between viral infections and systemic sclerosis,” was published in Scientific Reports.

HIV, SARS-CoV-2 associated with a reduced risk of SSc, analysis finds
SSc is an autoimmune disease marked by the accumulation of scar tissue in various organs. The causes of SSc are incompletely understood.

An emerging body of evidence has begun linking some autoimmune diseases with certain viral infections — one prevailing theory is that when the immune system is activated to fight off the virus, it may accidentally start attacking healthy parts of the body as well. For example, recent data has shown that infection with EBV — which causes infectious mononucleosis, commonly called mono, as well as nonspecific childhood diseases — is a key risk factor for multiple sclerosis.

Scientists in China conducted an analysis to examine the possible link between SSc and various viruses, including EBV, HIV, SARS-CoV-2, varicella-zoster virus — which causes chicken pox and shingles — and some strains of herpes and influenza.

The researchers used an analysis technique called Mendelian randomization. This method draws on genetic data to determine if there is a causal link between an exposure — in this case, viral infections — and an outcome, which would be having SSc, in this instance. The basic idea is that, if infection-related genetic variants are more common among SSc patients than in the general population, then it follows that the virus itself might be associated with SSc risk.

Results indicated EBV infection was associated with a more than threefold increase in the risk of developing SSc. By contrast, HIV and SARS-CoV-2 were associated with a reduced risk of SSc, by about 21% and 66% respectively. Other viruses didn’t show statistically significant associations with SSc risk.

These data suggest there might be cause-and-effect relationships between SSc risk and these viruses, the researchers said, though they stressed that further work will be needed to confirm and expand upon these associations.
“Our [Mendelian randomization] study suggested a causal association of EBV infection on the elevated risk of SSc and the causal effects of HIV and SARS-CoV-2 on the decreased risk of SSc, providing valuable insights into the genetic underpinning of associations between virus infections and SSc,” the researchers concluded.