Autoimmune and Autoinflammatory Connective Tissue Disorders Following COVID-19

Abstract

Importance: Multiple cases of autoimmune and autoinflammatory diseases after COVID-19 have been reported. However, their incidences and risks have rarely been quantified.

Objective: To investigate the incidences and risks of autoimmune and autoinflammatory connective tissue disorders after COVID-19.

Design, setting, and participants: This was a retrospective population-based study conducted between October 8, 2020, and December 31, 2021, that used nationwide data from the Korea Disease Control and Prevention Agency COVID-19 National Health Insurance Service cohort and included individuals who received a diagnosis of COVID-19 via polymerase chain reaction testing and a control group with no evidence of COVID-19 identified from National Health Insurance Service of Korea cohort. Data analysis was conducted from September 2022 to August 2023.

Exposures: Receipt of diagnosis of COVID-19.

Main outcomes and measures: The primary outcomes were the incidence and risk of autoimmune and autoinflammatory connective tissue disorders following COVID-19. A total of 32 covariates, including demographics, socioeconomic statuses, lifestyle factors, and comorbidity profiles, were balanced through inverse probability weighting. The incidences and risks of autoimmune and autoinflammatory connective tissue disorders were compared between the groups using multivariable Cox proportional hazard analyses.

Results: A total of 354 527 individuals with COVID-19 (mean [SD] age, 52.24 [15.55] years; 179 041 women [50.50%]) and 6 134 940 controls (mean [SD] age, 52.05 [15.63] years; 3 074 573 women [50.12%]) were included. The risks of alopecia areata (adjusted hazard ratio [aHR], 1.12; 95% CI, 1.05-1.19), alopecia totalis (aHR, 1.74; 95% CI, 1.39-2.17), antineutrophil cytoplasmic antibody-associated vasculitis (aHR, 2.76; 95% CI, 1.64-4.65), Crohn disease (aHR, 1.68; 95% CI, 1.31-2.15), and sarcoidosis (aHR, 1.59; 95% CI, 1.00-2.52) were higher in the COVID-19 group. The risks of alopecia totalis, psoriasis, vitiligo, vasculitis, Crohn disease, ulcerative colitis, rheumatoid arthritis, adult-onset Still disease, Sjögren syndrome, ankylosing spondylitis, and sarcoidosis were associated with the severity of COVID-19.

Conclusions and relevance: In this retrospective cohort study, COVID-19 was associated with a substantial risk for autoimmune and autoinflammatory connective tissue disorders, indicating that long-term management of patients with COVID-19 should include evaluation for such disorders.

Figure 1.. Flowchart of Study Population Selection

A total of 354 527 individuals with COVID-19 and 6 134 940 individuals without COVID-19 (as controls) were selected from the Korean Disease Control and Prevention Agency (KDCA) COVID-19 National Health Insurance Service (NHIS) cohort. PCR indicates polymerase chain reaction.

Figure 2.. Risks of Incident Autoimmune and Autoinflammatory Disease Outcomes in the COVID-19 Cohort Compared With the Control Cohort

The forest plot depicts adjusted hazard ratios (aHRs) and 95% CIs of individuals with COVID-19 compared with control participants. The hazard estimates were adjusted for all 32 covariates used for the inverse probability of treatment weighting. ANCA indicates antineutrophilic cytoplasmic antibody.

Figure 3.. Subgroup Analyses of the Risks of Incident Autoimmune and Autoinflammatory Disease Outcomes Stratified by Age and Sex

The forest plot depicts adjusted hazard ratios (aHRs) and 95% CIs of individuals with COVID-19 compared with control participants. The hazard estimates were adjusted for all 32 covariates used for the inverse probability of treatment weighting. ANCA indicates antineutrophilic cytoplasmic antibody; and NA, not available.

Figure 4.. Subgroup Analysis of the Risks of Incident Autoimmune and Autoinflammatory Disease Outcomes in the COVID-19 Cohort Stratified by COVID-19 Severity and COVID-19 Vaccination Status

The forest plot depicts adjusted hazard ratios (aHRs) and 95% CIs of individuals with COVID-19 compared with control participants. Subgroup analyses stratified by severity of COVID-19 (intensive care unit [ICU] vs non-ICU) and vaccination status are shown. Vaccination completion was assessed according to the schedules recommended for each vaccine. The hazard estimates were adjusted for 32 covariates used for the inverse probability of treatment weighting. ANCA indicates antineutrophilic cytoplasmic antibody; and NA, not available.