The intersection of COVID-19 and autoimmunity: What is our current understanding?

Abstract

Viral infections have historically had a complex relationship with autoimmune diseases. For patients with preexisting autoimmune disorders, often complicated by immunosuppressive therapies, there are numerous potential effects of COVID-19, a disease of complex immunobiology, including the potential to alter the natural history when infected. In addition, individuals without recognized autoimmune disease may be vulnerable to virally induced autoimmunity in the forms of autoantibody formation, as well as the development of clinical immune mediated inflammatory diseases. Until quite recently in the pandemic this relationship between COVID-19 and autoimmune diseases has been relatively under- explored, yet such investigation offers potential insights into immunopathogenesis as well as for the development of new immune based therapeutics. This review examines this relationship through exploration of a series of questions with relevance to both immunopathogenic mechanisms as well as some clinical implications.

New Onset of Autoimmune Diseases Following COVID-19 Diagnosis

“…Historically, viral infections have had a complex relationship with a variety of autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Sjögren’s syndrome (SS), systemic vasculitis, celiac disease, and multiple sclerosis [ 1 , 2 ]. Examples of viruses that play a role in triggering autoimmune disease include hepatitis C virus, hepatitis B virus, Chikungunya virus, parvovirus B19, herpes viruses, and others [ 2 , 3 ].…”

“…Autoantibodies against those proteins were detected in typical autoimmune conditions [ 10 ]. Other hypothetical mechanisms include bystander activation triggered by a hyper-inflammatory state (often referred to as “cytokine storm” or “cytokine release syndrome”), viral persistence (polyclonal activation due to the constant presence of viral antigens driving immune-mediated injury) and the formation of neutrophil extracellular traps [ 1 , 11 , 12 ].…”

COVID-19 Immunobiology: Lessons Learned, New Questions Arise

“…COVID-19 in patients already suffering from an ADeither clinically or subclinicallymay be affected by this AD or the medications used for it and, to the contrary, may influence this AD. On the other hand, patients without any AD face the danger of developing a new AD as a result of COVID-19 (207). Theoretically, patients with autoimmune diseases are at increased risk for infections and thus increased risk for COVID-19, due to deregulated adaptive immunity (cellular and/or humoral) (208).…”

Rheumatology and COVID-19 at 1 year: facing the unknowns

“… 3 For patients with pre-existing clinical or subclinical autoimmune/autoinflammatory diseases, there is potential for their disease and/or therapies to have an effect on the clinical course of COVID-19 infection, as well as the potential for their disease to be influenced by the infection after recovery ( figure 1 ). For those without apparent autoimmune/autoinflammatory diseases, there is the potential for new-onset immune-mediated diseases which have been anecdotally reported 9 and await more critical appraisal. In terms of laboratory evidence of autoimmunity, it should not be surprising that numerous groups have documented the presence of autoantibodies including antinuclear antibodies 10 11 and antiphospholipid antibodies 12 in patients with COVID-19 as mechanistically viral infections have long been known to disturb immunological tolerance.…”