Risk of SSc Higher Following COVID-19, Study Finds

Finding reinforces research that viral infections increase likelihood of autoimmune disorders

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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People who were infected with SARS-CoV-2, the virus that causes COVID-19, are at greater risk for developing autoimmune diseases, including scleroderma (SSc), according to a large study.

The findings support recent evidence that viral infections may increase the likelihood of autoimmune conditions, although the mechanisms remain unknown.

“It is crucial for physicians to have relevant notions and to recognize these autoimmune manifestations in order to respond appropriately in the ongoing pandemic and long-term post-pandemic phase,” the researchers wrote.

The study, “Risk of autoimmune diseases in patients with COVID-19: A retrospective cohort study,” was published in the journal eClinical Medicine.

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Immune Genes May Be Biomarkers of SSc Diagnosis, Therapy Response

Viral infections, such as those triggered by SARS-CoV-2, are believed to serve as potential triggers of autoimmune disorders in people who have genetic predisposition for such conditions. In fact, a number of cases of autoimmune diseases — such as Guillain-Barré syndrome and systemic lupus erythematosus — after SARS-CoV-2 infection have been reported.

“However, obtaining conclusive evidence of a connection between viral infection and subsequent autoimmune diseases is challenging, not only because it is frequently impossible to extract the virus from diseased tissues, but also because the collection of sufficient amounts of epidemiological evidence is constrained by lengthy process and geographic distances,” the scientists wrote.

Since the COVID-19 pandemic began, millions of people experienced this acute infection around the same time, which enabled the collection of large amounts of data to better establish the link between SARS-CoV-2 and autoimmune diseases.

Researchers in Taiwan conducted a retrospective analysis of data from the U.S. Collaborative Network, from 48 global healthcare organizations part of the TriNetX Research Network. TriNetX holds the largest global COVID-19 dataset.

In total, the analysis included 3,814,479 participants from January 2020 to December 2021. They were divided into two groups after matching for age, sex, race, socioeconomic status, lifestyle-related variables, and coexisting diseases.

After matching, participants with a positive test for the SARS-CoV-2 virus were part of the COVID-19 group (mean age 45.2 years) and those with a negative test were included in the control group (45.1 years). Each group had 887,455 participants. Women represented 57.4% of the COVID-19 group, and the majority were White (64.4%).

Patients who had received COVID-19 vaccinations were excluded from the study.

6 months of follow-up

The researchers analyzed six months of follow-up data after a positive SARS-CoV-2 test to determine the risk for autoimmune diseases between both groups.

Results showed that participants in the COVID-19 group had a generally higher risk — from 1.78 to 3.21 times higher — for new-onset autoimmune diseases compared to controls. The risk of mortality also was higher.

The risk of scleroderma, or systemic sclerosis, was 2.58 times higher in those who had COVID-19.

Rheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematosus, Sjögren’s syndrome and inflammatory bowel disease were among other autoimmune diseases with a significantly higher prevalence among the COVID-19 group.

However, subgroup analyses based on sex, age and race, showed that the risk of scleroderma was increased significantly only in women who had COVID-19.

Overall, the risk autoimmune disease among COVID-19 patients was generally similar across age subgroups. In contrast, differences were found when analyzing race, as whites had a significantly higher risk of autoimmune conditions and mortality. Blacks showed a higher risk of ankylosing spondylitis and psoriasis, whereas Asians were more likely to have systemic lupus erythematosus.

Inpatients vs. outpatients

Finally, the researchers conducted separate analyses for patients who were admitted to the hospital within four weeks of a PCR test for COVID-19 (inpatient group) and those on outpatient care.

The findings showed that outpatients had higher risk for all autoimmune diseases and mortality. In contrast, the risks of scleroderma and inflammatory bowel disease were significantly lower in inpatients.

Overall, “our preliminary data suggest that COVID-19 is associated with a significantly different risk of various autoimmune diseases,” the researchers wrote.

“The impact of vaccination on the development of autoimmune diseases should also be studied in the future,” they highlighted.