Covid-19 increases risk of developing autoimmune disease, but vaccination helps, large study shows

Having Covid-19 increases a person’s risk of developing an autoimmune disease in the year after infection, a large study out of South Korea and Japan reports, but vaccination helps decrease that risk.

Researchers used the medical records of 10 million Korean and 12 million Japanese adults to see whether those who had Covid were more likely to be diagnosed with autoimmune inflammatory rheumatic diseases, or AIRDs, in the year following infection. AIRDs include rheumatoid arthritis, systemic lupus erythematosus, Sjögren syndrome, mixed connective tissue disease, vasculitis, and other conditions. The Covid group was compared with an uninfected control group and a group of patients who had influenza during the same period from 2020 to 2022.

In both the South Korean and Japanese cohorts, the researchers found a heightened risk of autoimmune disease up to one year after Covid infection. Compared to the general population, the Covid group had about a 25% higher risk of AIRD. When compared to the group with influenza, the risk was about 30% higher in those who’d had Covid. And the more severe a person’s bout of Covid, the higher their risk of developing a new autoimmune disease, according to findings published in the Annals of Internal Medicine on Monday, underscoring why preventing infection in the first place is important.

Researchers also found that vaccination against Covid, with either mRNA or viral vector shot, reduced the risk of developing a new autoimmune disease. They did not spell out in the study exactly how much vaccines reduced the risk of AIRDs. And after the year-mark, the Covid group’s risk of AIRD returned to normal. These numbers are on the population level, so an individual’s risk could be higher or lower depending on their susceptibility.

While other researchers have reported similar findings, the new study is one of the largest to explore post-Covid complications in Asian populations, adding valuable data on vaccination and autoimmune disease in understudied ethnic groups and showcasing what researchers can learn from South Korea and Japan’s detailed, integrated health datasets. The findings provide “rigorous evidence” to further our understanding of Covid’s long-term consequences, said Alison Cohen, a professor of epidemiology and biostatistics at the University of California, San Francisco who was not involved in the study. It also “adds to the evidence base that COVID-19 is worse than the flu,” she said in an email.

Lead author Min Seo Kim, a physician-scientist at the Broad Institute of Harvard and MIT and Massachusetts General Hospital, said the drop in AIRDs risk after one year might point to a decline in autoimmunity as time goes on post-Covid infection. In the first year following infection, if patients are “really well-managed during this period, they’ll be very less likely to suffer from this disease for their life,” he said.

The pandemic and emergence of long Covid has only made more urgent the need to understand — and find treatments for — rising rates of autoimmune disease around the world, including in the U.S. It’s estimated up to 50 million Americans live with an autoimmune condition.

Senior author Dong Keon Yon’s South Korean data came from the country’s national insurance system, which streamlines patient data so infections, vaccinations, and post-infection diagnoses are all linked. The Japanese data was provided by Seung Won Lee, one of the paper’s authors.

Only patients with AIRD recorded on two separate occasions were analyzed. The researchers also replicated the findings in patients who had undergone treatment for an autoimmune disease. This approach was meant to eliminate patients who might’ve been dealing with short-term complications of Covid, Kim said. “Steroids, immunotherapy, those are not easy to go through for patients so physicians do not really do that, put that on the table without confidence,” he said, adding that the researchers were quite confident they’d found actual AIRD cases.

The influenza control group was used to minimize referral bias — the likelihood that Covid patients were diagnosed with autoimmune diseases at higher rates just because they received more medical attention than the general, uninfected population during the pandemic.

Some outside researchers might not be convinced that the AIRDs cases reported in the paper represented true chronic disease. Amr Hakam Sawalha, chief of the division of pediatric rheumatology at the University of Pittsburgh Medical Center’s children’s hospital, suspects that a share of the AIRDs cases reported in the study might just be short-term immune system flares. Many of the diseases included in the analysis, like rheumatoid arthritis or ankylosing spondylitis, usually take longer than a few months to reach “full blown clinical presentation,” suss out and diagnose, he said. The fact that the study found a decreased risk of AIRDs at 12 months raised his eyebrows.

Sawalha also pointed out that the diagnostic codes used by the researchers to establish the presence of autoimmune diseases couldn’t be validated. These concerns could be addressed by another study with a longer follow-up window and confirmation of the findings in other populations, he said. “All that being said, the authors are to be complimented for this study,” he added.

Kim’s research analyzed data from the original SARS-CoV-2 strain and the Delta variant. Cohen noted that it will be worth replicating the research with people who got infected with Omicron strains, and with people who were re-infected with Covid.

But the fact that the study found increased risk of autoimmune disease with the first batch of variants lends credibility to the idea that earlier, more aggressive waves are more damaging to the body, said Falko Tesch, a research associate at the Center for Evidence-Based Healthcare in Dresden, Germany who has conducted his own research on increased autoimmunity after Covid.

In order for the virus to avoid dying out, it weakens over time, killing fewer people. So later variants might be more contagious, spreading far and wide more quickly, but cause less severe illness — and potentially less severe long-term consequences, Tesch said. That’s important information to have on hand for future pandemics, because public health officials could recommend more thorough screening of infected people to catch autoimmune disease early on, he said.

Even if variants grow weaker, “every year there’s a new proportion of people heading to the collective of people who are suffering from autoimmune conditions,” he said. “Every year.”

Kim, the lead author, suspects the reduced autoimmunity risk among those who’d been immunized might be because vaccination can reduce the severity of Covid. The one exception was in those patients who developed severe Covid and required hospitalization despite vaccination. That group maintained a higher risk of later autoimmune disease.

Lowering the threat of rheumatic disease, according to Abraham Edgar Gracia-Ramos, a researcher at La Raza National Medical Center in Mexico City who was not involved in the study, is “yet another reason to encourage people to get vaccinated.”