SARS-CoV-2 triggering autoimmune diseases

Abstract

Autoimmunity, hyperstimulation of the immune system, can be caused by a variety of reasons. Viruses are thought to be important environmental elements that contribute to the development of autoimmune antibodies. It seems that viruses cause autoimmunity with mechanisms such as molecular mimicry, bystander activation of T cells, transient immunosuppression, and inflammation, which has also been seen in post-Covid-19 autoimmunity. Infection of respiratory epithelium by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) dysregulates the immune response, triggers both innate and acquired immunity that led to the immune system's hyperactivation, excessive cytokine secretion known as "cytokine storm," and finally acute respiratory distress syndrome (ARDS) associated with high mortality. Any factor in the body that triggers chronic inflammation can contribute to autoimmune disease, which has been documented during the Covid-19 pandemic. It has been observed that some patients produce autoantibody and autoreactive CD4⁺ and CD8⁺ T cells, leading to the loss of self-tolerance. However, there is a scarcity of evidence defining the precise molecular interaction between the virus and the immune system to elicit autoreactivity. Here, we present a review of the relevant immunological findings in Covid-19 and the current reports of autoimmune disease associated with the disease.

Keywords: Autoimmune disease; Autoimmunity; Covid-19; Cytokine; SARS-CoV-2.

Fig. 1

The SARS-CoV-2 proliferates by binding to ACE-2 receptor on the surface of host epithelial cell. Intracellular signaling pathways are activated and produce inflammatory cytokines such as TNF-α, IFN-β, IL-6, IL-1β, IL-17, and IL-18 that may cause autoimmunity via systemic inflammation. APCs process the antigens and present them to TCD4⁺ cells. Activated TCD4⁺ cells have a role in inflammatory cytokine secretion, MQ activation, and antibody formation. Antibody against the viral antigen can recognize host tissue antigens that cause autoimmunity. Also, TCD8⁺ cells can detect viral antigens via TCR-MHC I and cause apoptosis in virus-infected and uninfected cells mainly via perforin-granzyme and Fas and its ligand. This procedure is named bystander activation and causes autoimmunity. The apoptotic bodies which contain self-antigens are presented to autoreactive T cells and cause autoimmunity. Given that autoimmunity is driven by recognition of self-antigen and CD8 T-cell exhaustion dependent on chronic antigen stimulation, T-cell exhaustion could facilitate the retention of antigen-specific T cells in the repertoire under chronic stimulation. Also, the reduction of T-reg by the SARS-CoV-2 reduces self-tolerance and leads to autoimmunity.