The molecular mimicry and COVID-19

Abstract

A significant part of the complications of COVID-19 and manifestations of post-COVID syndrome is associated with autoimmune reactions caused by SARS-CoV-2. The key mechanism for enabling autoimmunity in COVID-19 results from molecular mimicry, which is involved in developing cytokine storm, systemic multiorgan hyperinflammation, endothelial dysfunction, also being a trigger for arising post-COVID-19 autoimmune diseases (autoimmune thrombocytopenia, autoimmune vasculitis, Guillain–Barrésyndrome, Miller–Fisher syndrome, autoimmune neuropathy, autoimmune thyroiditis, rheumatoid arthritis, etc.). Overall, there have been identified 59 common immune determinants in 80 epitopes of the SARS-CoV-2 spike protein and 53 anti-inflammatory proteins, receptors regulating cell proliferation, differentiation and apoptosis as well as immune response. It was found that among the 37 viral proteins, only 8 of them bear no immunogenic regions identical to human proteins. Cross-reactivity results in emergence of more than 15 distinct types of autoantibodies including antiphospholipid antibodies against cardiolipin and beta-2-glycoprotein I, antibodies specific to transmembrane adenosine receptor A2b, adiponectin, phosphatidylserine-prothrombin, antinuclear antigens, mitochondrial M2, type I interferons, and other cytokines, chemokines, complement components and cell membrane proteins. Autoantibodies formed during COVID-19 react to antigens of cells located in the thyroid gland, cardiac and skeletal muscles, lung, joints, liver, kidneys, brain and bone marrow, peripheral nervous system, skin and adipose tissue, gastrointestinal tract, testicles, eyes as well as mitochondrial antigens, mediating development of severe disease-related complications and post-COVID syndrome. The presence of 24 homologous pentapeptides with those found inB. pertussis, C. diphtheriae,C. tetani,H. influenzaeandN. meningitidisposes a risk of developing ineffective vaccination immune response paralleled with higher risk of autoimmune complications. It is imperative to take into account the phenomenon of molecular mimicry while proposing new approaches for rehabilitation and treatment of COVID-19 as well as in development and testing of vaccines against SARS-CoV-2.