COVID-19 increases the risk of autoimmune diseases

From a recent study published in JAMA network openedresearchers analyzed the incidence and risk of autoinflammatory and autoimmune diseases following the coronavirus disease 2019 (COVID-19).

Study: Autoimmune and autoinflammatory connective tissue disorders after COVID-19. Image credits: Kateryna Kon / Shutterstock.com

COVID-19 and autoimmunity

The causative agent of COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can trigger 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 heart failure. Similarly, similarities have been reported between autoimmune diseases and COVID-19; However, autoimmune diseases have not been extensively investigated as post-acute consequences of COVID-19.

About the study

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

Individuals who underwent a general health examination and were not diagnosed with COVID-19 were identified as a control group. All study participants were followed until outcome diagnosis, death, emigration, or study end date. The risk and incidence of autoinflammatory and autoimmune diseases were estimated in study participants without these conditions before COVID-19.

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

Demographics, lifestyle factors, socio-economic status and comorbidity data were obtained from the NHIS database. Propensity scores and inverse probability weights were also estimated.

Risk of outcomes was assessed for COVID-19 and control cohorts. A multivariable Cox proportional hazards analysis was performed, with adjustments for covariates. Subgroup analyzes were conducted based on gender, age, COVID-19 severity, and vaccination status.

Findings of the study

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

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, while the risk of SLE was lower.

The overdetection bias was minimal in the COVID-19 cohort. Women in the COVID-19 cohort were at greater risk of subsequently developing vitiligo, Crohn’s disease, sarcoidosis, alopecia totalis, alopecia areata, and ANCA-associated vasculitis.

By comparison, men in the COVID-19 cohort were at greater risk of developing ankylosing spondylitis, systemic sclerosis, adult-onset Still’s disease, Crohn’s disease, psoriasis and alopecia totalis. The risks of ANCA-associated vasculitis and alopecia totalis were much higher in those aged 40 years or older.

The risks of sarcoidosis, adult-onset Still’s disease, rheumatoid arthritis and Crohn’s disease were also higher in people under 40. The overall risk of incidents increased as the severity of COVID-19 increases.

Unvaccinated individuals were at greater risk of developing Crohn’s disease, alopecia totalis, alopecia areata, and positive control results. This additional risk of positive control results and autoimmune diseases 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 group studied consisted mainly of adults, as the health research focuses on workers and households. Both groups showed similar COVID-19 positivity rates; however, more examined individuals were vaccinated than unexamined individuals.

Conclusions

The current study compared the risks of autoinflammatory and autoimmune diseases in individuals with a history of COVID-19 versus 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 the fact that the sample consisted entirely of Asians, limiting the generalizability of these findings to other ethnic groups and adolescents/children. In addition, the researchers were unable to determine whether some individuals were more susceptible to autoimmunity than others.

Overall, the study’s findings suggest that SARS-CoV-2 infection may be associated with autoimmune diseases. Thus, long-term management of COVID-19 patients should also include autoimmunity assessments.