COVID-19 and Autoimmunity: The Role of Autoantibodies

The research article “Autoantibodies in COVID-19: Implications for Disease Severity and Clinical Outcomes“ explores the complex relationship between COVID-19 and autoimmune disease. The study highlights how SARS-CoV-2 infection can lead to the production of autoantibodies, which may contribute to disease severity, long COVID, and the development of autoimmune conditions.

Autoantibodies, which mistakenly target the body’s own tissues, have been detected in patients with severe COVID-19 and long-COVID. These include anti-nuclear antibodies (ANA), anti-cytokine antibodies (ACA), and anti-ACE2 antibodies.

The presence of these autoantibodies suggests that COVID-19 could act as a trigger for autoimmune disorders, similar to other viral infections like Epstein-Barr virus.

The study outlines several mechanisms that may explain how COVID-19 induces autoimmunity, including molecular mimicry (where viral proteins resemble human proteins), bystander activation (where an overactive immune response inadvertently attacks the body), and epitope spreading (where an immune response broadens to attack self-antigens). The findings suggest that individuals with pre-existing autoantibodies may be at greater risk for severe COVID-19, while others may develop new autoimmune conditions post-infection.

Understanding the overlap between COVID-19 and autoimmunity is crucial for predicting long-term health outcomes and developing targeted treatments for those affected by persistent symptoms.

A second study, “Dysregulated Autoantibodies Targeting AGTR1 Are Associated with the Accumulation of COVID-19 Symptoms,“ expands on these findings by identifying specific autoantibodies that may contribute to prolonged and severe COVID-19 symptoms. The study focuses on anti-AGTR1 autoantibodies, which target the angiotensin II type 1 receptor (AGTR1), a key component of the renin-angiotensin system (RAS) that regulates blood pressure and inflammation. Researchers found that these autoantibodies were strongly linked to severe COVID-19 symptoms such as fever, muscle aches, anosmia (loss of smell), and dysgeusia (loss of taste).

One of the major implications of this study is the role of AGTR1 autoantibodies in vascular and immune system dysfunction. The research suggests that these autoantibodies contribute to endothelial damage, which can lead to blood vessel inflammation, microclots, and increased severity of COVID-19. Additionally, the degradation of the endothelial glycocalyx—a protective layer lining blood vessels—was observed in patients with high levels of anti-AGTR1 antibodies. This damage disrupts normal circulation and may play a role in long-COVID symptoms like persistent fatigue and cognitive issues.

The study also found that the severity of COVID-19 symptoms increased with the number of autoantibodies present.

Patients with multiple autoantibodies, including those targeting interferons and cytokines, had a higher risk of complications and prolonged illness. This aligns with previous research showing that autoantibodies can interfere with the immune system’s ability to clear the virus, leading to more severe disease and persistent symptoms.

Another key finding was that losartan, a commonly prescribed medication for high blood pressure that blocks AGTR1, was able to reverse some of the effects of anti-AGTR1 autoantibodies in lab tests. This suggests that RAS-targeting therapies might have potential as treatments for severe or long-COVID cases.

These studies provide strong evidence that COVID-19 is not just a respiratory illness but also an immune-disrupting disease with long-term consequences.

The identification of autoantibodies like anti-AGTR1 adds to growing concerns that COVID-19 could act as a trigger for autoimmune conditions, even in people who had no prior autoimmune disease. As researchers continue to study these immune system abnormalities, targeted therapies for post-COVID complications and long-COVID may become more available.

Citations

Galipeau, Y., Cooper, C., & Langlois, M. A. (2025). Autoantibodies in COVID-19: implications for disease severity and clinical outcomes. Frontiers in immunology, 15, 1509289. https://doi.org/10.3389/fimmu.2024.1509289

Fonseca, D.L.M., Jäpel, M., Gyamfi, M.A. et al. Dysregulated autoantibodies targeting AGTR1 are associated with the accumulation of COVID-19 symptoms. npj Syst Biol Appl 11, 7 (2025). https://doi.org/10.1038/s41540-025-00488-z