Long-Term Autoimmune Inflammatory Rheumatic Outcomes of COVID-19 : A Binational Cohort Study

Ann Intern Med. 2024 Mar;177(3):291-302. doi: 10.7326/M23-1831. Epub 2024 Mar 5.


Background: Some data suggest a higher incidence of diagnosis of autoimmune inflammatory rheumatic diseases (AIRDs) among patients with a history of COVID-19 compared with uninfected patients. However, these studies had methodological shortcomings.

Objective: To investigate the effect of COVID-19 on long-term risk for incident AIRD over various follow-up periods.

Design: Binational, longitudinal, propensity-matched cohort study.

Setting: Nationwide claims-based databases in South Korea (K-COV-N cohort) and Japan (JMDC cohort).

Participants: 10 027 506 Korean and 12 218 680 Japanese patients aged 20 years or older, including those with COVID-19 between 1 January 2020 and 31 December 2021, matched to patients with influenza infection and to uninfected control patients.

Measurements: The primary outcome was onset of AIRD (per appropriate codes from the International Classification of Diseases, 10th Revision) 1, 6, and 12 months after COVID-19 or influenza infection or the respective matched index date of uninfected control patients.

Results: Between 2020 and 2021, among the 10 027 506 Korean participants (mean age, 48.4 years [SD, 13.4]; 50.1% men), 394 274 (3.9%) and 98 596 (0.98%) had a history of COVID-19 or influenza, respectively. After propensity score matching, beyond the first 30 days after infection, patients with COVID-19 were at increased risk for incident AIRD compared with uninfected patients (adjusted hazard ratio, 1.25 [95% CI, 1.18 to 1.31]) and influenza-infected control patients (adjusted hazard ratio, 1.30 [CI, 1.02 to 1.59]). The risk for incident AIRD was higher with more severe acute COVID-19. Similar patterns were observed in the Japanese cohort.

Limitations: Referral bias due to the pandemic; residual confounding.

Conclusion: SARS-CoV-2 infection was associated with increased risk for incident AIRD compared with matched patients without SARS-CoV-2 infection or with influenza infection. The risk for incident AIRD was higher with greater severity of acute COVID-19.

Primary funding source: National Research Foundation of Korea.

MeSH terms

  • COVID-19* / epidemiology
  • Cohort Studies
  • Female
  • Humans
  • Influenza, Human*
  • Longitudinal Studies
  • Male
  • Middle Aged
  • SARS-CoV-2