Reaction of Human Monoclonal Antibodies to SARS-CoV-2 Proteins With Tissue Antigens: Implications for Autoimmune Diseases

Abstract

We sought to determine whether immune reactivity occurs between anti-SARS-CoV-2 protein antibodies and human tissue antigens, and whether molecular mimicry between COVID-19 viral proteins and human tissues could be the cause. We applied both human monoclonal anti-SARS-Cov-2 antibodies (spike protein, nucleoprotein) and rabbit polyclonal anti-SARS-Cov-2 antibodies (envelope protein, membrane protein) to 55 different tissue antigens. We found that SARS-CoV-2 antibodies had reactions with 28 out of 55 tissue antigens, representing a diversity of tissue groups that included barrier proteins, gastrointestinal, thyroid and neural tissues, and more. We also did selective epitope mapping using BLAST and showed similarities and homology between spike, nucleoprotein, and many other SARS-CoV-2 proteins with the human tissue antigens mitochondria M2, F-actin and TPO. This extensive immune cross-reactivity between SARS-CoV-2 antibodies and different antigen groups may play a role in the multi-system disease process of COVID-19, influence the severity of the disease, precipitate the onset of autoimmunity in susceptible subgroups, and potentially exacerbate autoimmunity in subjects that have pre-existing autoimmune diseases. Very recently, human monoclonal antibodies were approved for use on patients with COVID-19. The human monoclonal antibodies used in this study are almost identical with these approved antibodies. Thus, our results can establish the potential risk for autoimmunity and multi-system disorders with COVID-19 that may come from cross-reactivity between our own human tissues and this dreaded virus, and thus ensure that the badly-needed vaccines and treatments being developed for it are truly safe to use against this disease.

The Association of Thyroid Hormone Changes with Inflammatory Status and Prognosis in COVID-19

“…Thus, it is obvious that there is a link between the pathogenesis of COVID-19 and autoimmune thyroid disease. In one study, SARS-CoV-2 monoclonal antibodies were applied to different tissues and the thyroid gland was reactive, which has proved that COVID-19 might lead to thyroiditis [ 23 ]. However, clinical studies showed contradictory results.…”

A Review of the Global Impact of the COVID-19 Pandemic on Public Mental Health, with a Comparison Between the USA, Australia, and Poland with Taiwan and Thailand

“…Patients with COVID-19 infection should routinely be screened for major psychiatric symptoms; they should be prospectively followed because many of these patients will develop a post-COVID syndrome and chronic fatigue, and depression, which are cognitive impairments that are major features of this syndrome. The neuro-immune approach is warranted because: (a) the psychiatric symptoms during infection are associated with inflammation, immune disorders, and oxidative stress, and (b) increased autoimmunity is one of the features of COVID-19 infection [ 56 ], which is probably associated with the post-COVID-19 syndrome.…”

Novel human neutralizing mAbs specific for Spike-RBD of SARS-CoV-2

“…Recently, novel human antibodies raised against SARS-CoV-2 spike protein S1 and S2 domains or against SARS-CoV-2 nucleoprotein were obtained and generated as fully human IgG1 antibodies 28 – 30 . Cross-reactive patterns between SARS-CoV-2 proteins and autoimmune target proteins were found to play a role in the systemic inflammatory response in patients affected by Covid-19 leading to the development of autoimmune diseases post-infection in susceptible subgroups of patients 31 .…”