Persistent Inflammation May Link Long COVID to Autoimmune Disease

A paper recently published in Autoimmunity Reviews examines evidence suggesting that persistent inflammation following SARS-CoV-2 infection may link Long COVID to the development and exacerbation of autoimmune diseases. While the exact mechanisms driving Long COVID have not been fully established, the authors emphasize that a sustained inflammatory response after infection can lead to widespread immune dysregulation, even after the acute virus has resolved.

Long COVID is described as a multi-system condition with symptoms that may persist for months or years, affecting neurological, immune, respiratory, and other organ systems. The review highlights how continued activation of the innate and adaptive immune systems may trigger a cascade of inflammatory signaling. When immune pathways remain activated, cytokines can become persistently elevated, contributing to chronic inflammation. The authors discuss the role of pro-inflammatory cytokines such as interleukins and tumor necrosis factors, which can disrupt immune balance, alter T cell regulation, and impair immune tolerance over time.

Several biological mechanisms are explored as contributors to this sustained immune activation, including mast cell activation, inflammasome signaling, coagulation abnormalities, cytokine storms and prolonged pro-inflammatory responses, and changes in the gut microbiota. The authors note that lingering viral components may continue to stimulate immune responses through ACE2-related pathways, maintaining inflammation even in the absence of active infection.

The review also connects these inflammatory processes to autoimmune diseases observed following COVID-19. Systemic lupus erythematosus (SLE) is discussed in the context of immune dysregulation and chronic inflammation that may promote autoantibody production. Guillain-Barré syndrome (GBS) is highlighted as a post-infectious autoimmune neurological condition, with molecular mimicry and immune cross-reactivity proposed as potential mechanisms. Rheumatoid arthritis (RA) is also included, reflecting how persistent inflammatory signaling may unmask or exacerbate joint-targeted autoimmunity.

Citation

Chen, K., Wang, Z., Li, J., Xu, Y., Gu, S., Li, H., Li, J., Zhang, Y., & Mao, N. (2025). Chronic inflammation in Long COVID relationship to autoimmune diseases. Autoimmunity Reviews, 24(10), 103882. https://doi.org/10.1016/j.autrev.2025.103882