Persistent Risk of Developing Autoimmune Diseases Associated With COVID-19

Abstract

Objective This study aimed to investigate the risk of developing autoimmune diseases associated with coronavirus disease 2019 (COVID-19) in Japan, including long-term risks and risks specific to different variants of concern. Methods This observational study used an electronic medical record database in Japan. The COVID-19 group is composed of patients diagnosed with COVID-19, whereas the non–COVID-19 group had data sampled from the database. The outcomes of interest encompassed several autoimmune diseases, including rheumatoid arthritis, systemic sclerosis, and immunoglobulin G4–related disease, as well as a composite of these diseases (any autoimmune disease). We examined the relative risk of autoimmune diseases using standardized mortality ratio weighting and the Cox proportional hazards model. Subgroup analyses based on epidemic variants were performed. In addition, short- and long-term risks were investigated using piecewise constant hazard models. Results A total of 90,855 COVID-19 and 459,827 non–COVID-19 patients were included between January 16, 2020, and December 31, 2022. The relative risk of any autoimmune disease was 2.32 (95% confidence interval, 2.08–2.60). All the investigated outcomes showed a significant risk associated with COVID-19. Several autoimmune diseases exhibit a risk associated with COVID-19 in the short to long term, and the long-term risk is substantial for systemic sclerosis and immunoglobulin G4–related disease. The variant-specific risk varied across outcomes. Conclusions COVID-19 is associated with an increased risk of developing autoimmune diseases in the Japanese population, and this effect persists for a long time. This study provides insights into the association between viral infections and autoimmunity.