In a recent study published in JAMA Network Open, researchers analyzed the incidence and risk of autoinflammatory and autoimmune disorders following coronavirus disease 2019 (COVID-19).

Study: Autoimmune and Autoinflammatory Connective Tissue Disorders Following COVID-19. Image Credit: Kateryna Kon / Shutterstock.com

COVID-19 and autoimmunity

The causal agent of COVID-19, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), may elicit autoimmune reactions and, as a result, contribute to autoimmunity. In fact, several studies have described the development of vitiligo, alopecia areata, vasculitis, and systemic lupus erythematosus (SLE) after recovery from COVID-19.

Respiratory and cardiovascular outcomes after COVID-19 have been extensively evaluated due to the potential role of SARS-CoV-2 in cardiopulmonary failure. Likewise, similarities between autoimmune diseases and COVID-19 have been reported; however, autoimmune diseases have not been comprehensively investigated as post-acute sequelae of COVID-19.

About the study

In the present study, researchers evaluate the risk and incidence of several autoinflammatory and autoimmune connective tissue disorders following recovery from COVID-19. To this end, Korean COVID-19 National Health Insurance Service (NHIS) Registry data were extracted for people with a COVID-19 diagnosis and general health evaluation from October 8, 2020, to December 31, 2021.

Individuals with general health examinations who were not diagnosed with COVID-19 were identified as controls. All study participants were followed up until outcome diagnosis, death, emigration, or the study end date. The risk and incidence of autoinflammatory and autoimmune disorders were estimated in study participants without these disorders before COVID-19.

The occurrence of these disorders was defined as having three or more medical visits with corresponding clinical diagnosis codes. Cardiovascular outcomes reported to be associated with COVID-19 were positive control outcomes, whereas outcomes less likely to be COVID-19-associated were negative control outcomes.

Demographic data, lifestyle factors, socioeconomic status, and comorbidity data were obtained from the NHIS database. Propensity scores and inverse probability weights were also estimated.

The risk of outcomes was assessed for COVID-19 and control cohorts. Multivariable Cox proportional hazard analysis was performed, with adjustments for covariates. Sub-group analyses were performed by sex, age, COVID-19 severity, and vaccination status.

Study findings

The study included 354,527 and 6.13 million individuals with and without COVID-19, respectively, with well-balanced covariates. The average follow-up duration was 119.7 days for the COVID-19 cohort and 121.4 days for controls.

The COVID-19 cohort had a significantly higher risk of Crohn's disease, sarcoidosis, alopecia areata, alopecia totalis, and anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, whereas the risk of SLE was lower.

Over-detection bias was minimal in the COVID-19 cohort. Females in the COVID-19 cohort were at a greater risk of subsequently developing vitiligo, Crohn's disease, sarcoidosis, alopecia totalis, alopecia areata, and ANCA-associated vasculitis.

Comparatively, males in the COVID-19 cohort were at a greater risk of developing ankylosing spondylitis, systemic sclerosis, adult-onset Still disease, Crohn's disease, psoriasis, and alopecia totalis. The risks of ANCA-associated vasculitis and alopecia totalis were much higher in those 40 or older.

The risks of sarcoidosis, adult-onset Still disease, rheumatoid arthritis, and Crohn's disease were also higher in people under 40. The overall risk of incident outcomes increased with COVID-19 severity.

Non-vaccinated individuals were at a greater risk of developing Crohn's disease, alopecia totalis, alopecia areata, and positive control outcomes. This excess risk of positive control outcomes and autoimmune disorders was not identified in vaccinated individuals.

In sensitivity analyses, the researchers compared demographic and clinical data between individuals with a general health examination and those without. The examined group primarily consisted of adults, given that health examination is aimed at employed individuals and householders. Both groups exhibited similar COVID-19 positivity rates; however, more examined people were vaccinated than non-examined individuals.

Conclusions

The current study compared the risks of autoinflammatory and autoimmune disorders in individuals with a history of COVID-19 as compared to non-COVID-19 controls. These risk estimates in the predominantly Asian sample were likely lower than in other ethnic groups, which may be due to delayed disease development/progression.

Some limitations of the current study include the primarily adult population and that the sample entirely comprised Asians, thereby limiting the generalizability of these findings to other ethnic groups and adolescents/children. Moreover, the researchers could not determine whether some individuals were more susceptible to autoimmunity than others.

Overall, the study findings suggest that SARS-CoV-2 infection might be associated with autoimmune disorders. Thus, long-term COVID-19 patient management should encompass autoimmunity assessments.

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