COVID-19 Linked to Long-Term Risk of Autoimmune Inflammatory Rheumatic Diseases

Individuals with a history of COVID-19 infection had an increased risk for incident autoimmune inflammatory rheumatic disease (AIRD) compared with those without prior COVID-19 infection or with influenza infection, according to one study.

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Findings from this binational, population-based study from South Korea and Japan were published in Annals of Internal Medicine.

“We found increased risk for incident AIRD up to 12 months after COVID-19 diagnosis compared with influenza-infected and uninfected control patients,” wrote the researchers of the study. “Greater severity of acute COVID-19 was associated with higher risk for incident AIRD. Among modifiable factors, SARS-CoV-2–infected patients who had prior vaccination against COVID-19 did not show increased risk for AIRD, with the exception of patients with severe COVID-19.”

In this study, the researchers aimed to investigate the long-term risk for incident AIRD after COVID-19 infection over various follow-up periods. The researchers based their findings from 2 national, large-scale, population-based cohort studies from Korea (n = 10,027,506) and Japan (n = 12,218,680). Both studies included patients 20 years and older who had COVID-19 between January 1, 2020, and December 31, 2021.

Additionally, the researchers randomly selected uninfected individuals or patients with influenza, which has been associated with increased risk for autoimmunity and inflammation, between 2020 and 2021.

Patients with missing data on socioeconomic status, coinfection or reinfection with COVID-19 and influenza, or a history of AIRD were excluded from the study.

The primary outcome was AIRD, identified by at least 2 claims beyond the first 30 days after infection, at 1, 6, and 12 months after COVID-19 or influenza. Secondary outcomes included incident inflammatory arthritis, connective tissue disease, untreated AIRD, and treated AIRD after 30 days of COVID-19 or influenza infection.

The study revealed that between 2020 and 2021, 394,274 (3.9%) and 98,596 (0.98%) of South Koreans had a history of COVID-19 or influenza, respectively. The mean (SD) age of these individuals was 48.4 (13.4) years, and 50.1% were male. Among the Japanese participants, 1,002,525 (8.2%) and 121,543 (0.99%) had COVID-19 or influenza, respectively. They had a

Propensity score matching showed that beyond the first 30 days after infection, South Korean individuals with COVID-19 were at increased risk of AIRD compared with uninfected patients (adjusted HR, 1.25; 95% CI, 1.18-1.31) and influenza-infected patients (adjusted HR, 1.30; 95% CI, 1.02-1.59). Among individuals with moderate to severe COVID-19 events (n = 375), the risk was increased (HR, 1.42; 95% CI, 1.27-1.59).

Additionally, sex, age group, income level, history of respiratory infections, Charlson Comorbidity Index score, body mass index, smoking status, alcohol consumption, and aerobic physical activity also showed consistent results for the association between AIRD and Covid infection. Similar findings were observed for both the South Korea and Japan cohorts.

However, the researchers acknowledged some limitations to the study. Since the results were derived from an Asian population during the period before the arrival of the Omicron variant, the findings may not be generalizable to more recent variants or among different ethnic groups. Additionally, some AIRD outcomes were uncommon and may have led to imprecise estimates. Lastly, the researchers noted that scrutiny of patients with COVID-19 may have resulted in increased referrals and detection rates for AIRD compared with uninfected patients.

Despite these limitations, the researchers believe the study showed an increased risk for incident AIRD up to 12 months after infection.

“Care strategies for patients who survive COVID-19 should pay close attention to manifestations of AIRD, particularly after severe COVID-19,” wrote the researchers. “COVID-19 vaccination was associated with reduced risk for incident AIRD after SARS-CoV-2 infection, except among those who had severe COVID-19 despite vaccination.”

Reference

Kim MS, Lee H, Lee SW, et al. Long-term autoimmune inflammatory rheumatic outcomes of COVID-19. Ann Intern Med. 2024;177(3):291-302. doi:10.7326/m23-1831