COVID-19 Linked to Increased Risk of Rheumatic Disease

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After propensity score matching, patients with COVID-19 were at an increased risk for AIRD when compared with both uninfected controls and influenza-infected patients.

A SARS-CoV-2 infection was linked to an increased risk for incident autoimmune inflammatory rheumatic disease (AIRD) when compared with patients with influenza infection or those without SARS-CoV-2 infection, according to a study published in Annals of Internal Medicine.1 The risk of AIRD was higher in patients with greater COVID-19 severity.

“Emerging data suggest a higher risk for AIRDs among patients with a history of COVID-19,” wrote a team of investigators led by Min Seo Kim, MD, associated with the Medical and Population Genetics and Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, Massachusetts. “However, these findings are based entirely on comparisons between groups infected with SARS-CoV-2 and those that are not, which might be biased by differences in health-seeking behavior and inherent risk factors within the groups. In addition, studies have not explored the effect of vaccination and other modifiable factors on prevention of long-term COVID-19 complications.”

Although the clinical definition of long COVID, the term commonly used for patients who experience long-term sequelae, is still evolving, it is generally defined as new or persistent symptoms lasting for > 4 weeks post-diagnosis which cannot be attributed to another cause. Common symptoms can range from fatigue, depression, and dyspnea to diabetes, neurologic disease, and cardiovascular disease.2

To evaluate the effect of COVID-19 infection on the long-term risk for incident AIRD, investigators used data from nationwide claims-based databases in South Korea (K-COV-N) and Japan (JMDC). The binational, longitudinal, propensity-matched cohort study included 10,027,506 Korean and 12,218,680 Japanese patients aged ≥ 20 years, including those with a COVID-19 diagnosis, between January 1, 2020 and December 31, 2021 and matched them to patients with either influenza infection or uninfected controls.

As both cohorts were from countries with universal health insurance, data included information on when patients visited multiple facilities, switched hospitals, or died outside of the health care systems. The definitions of exposure and outcomes, general health examinations, and diagnoses codes were the same among Korean and Japanese groups.

The primary endpoint was the onset of AIRD at 1, 6, and, 12 months after COVID-19 or influenza infection or a matched index date of uninfected controls.

The mean age of Korean patients was 48.4 years and 50.1% were male. Among this cohort, 3.9% (n = 394,274) experienced a COVID-19 infection and .98 (n = 98,596) had influenza. Among the Japanese cohort, 8.2% (n = 1,002,525) were diagnosed with COVID-19 and .99 (n = 121,543) were diagnosed with influenza during the study period.

After matching, 225,313 were included in the comparison cohort between those with COVID-19 infection (n = 115,003) and those with influenza (n = 110,310). The median follow-up for comparison between patients with COVID-19 and influenza was 11.3 and 12.1 months, respectively, while the median follow-up for comparison between patients with COVID-19 and the general population was 11.2 months in both groups.

After propensity score matching, patients with COVID-19 were at a significantly increased risk for all-cause AIRD, untreated AIRD, treated AIRD, and connective tissue disease when compared with uninfected controls (adjusted hazard ratio [aHR], 1.25 [95% confidence interval (CI), 1.18 to 1.31]) and influenza-infected controls (aHR, 1.30 [CI, 1.02 to 1.59]). This risk was higher among patients with more severe acute COVID-19 infection.

Investigators noted limitations including residual confounding and a potential referral bias due to the pandemic. Additionally, results may not be generalizable as the sample population was comprised of all Asian patients diagnosed prior to the Omicron variant.

“This population-based cohort study shows that the increased risk for incident AIRD extends up to 12 months after SARS-CoV-2 infection,” investigators concluded. “Care strategies for patients who survive COVID-19 should pay close attention to manifestations of AIRD, particularly after severe COVID-19.”


  1. Kim MS, Lee H, Lee SW, et al. Long-Term Autoimmune Inflammatory Rheumatic Outcomes of COVID-19 : A Binational Cohort Study. Ann Intern Med. Published online March 5, 2024. doi:10.7326/M23-1831
  2. Xie Y, Al-Aly Z. Risks and burdens of incident diabetes in long COVID: a cohort study. Lancet Diabetes Endocrinol. 2022;10:311-321. [PMID: 35325624] doi:10.1016/S2213-8587(22)00044-4