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.
Highlights
Coronavirus disease (COVID-19) has become one of the greatest global public health concerns of our century
We measured the degree of immune reactivity of human monoclonal antibody made against SARS-CoV-2 spike protein and nucleoprotein and rabbit polyclonal antibody made against SARS-CoV-2 envelope and membrane proteins with 55 different tissue proteins and peptides
These SARSCoV-2 antibodies reacted from low to very high with 28 out of 55 tissue antigens. These 28 antigens were a diverse collection of tissue groups that included gut and barrier proteins, gastrointestinal system cells, thyroid, nervous system, heart, joint, skin, muscle, mitochondria and liver tissues, and antigens used for the screening of autoimmune diseases
Summary
Coronavirus disease (COVID-19) has become one of the greatest global public health concerns of our century. The COVID-19 pandemic has placed an immediate call to action for medical researchers to investigate how SARS-CoV-2 can impact the worldwide human population. The search for a successful vaccine and efficient treatment protocols are paramount, immunologists who focus on autoimmunity have been concerned whether the infection or even a newly developed vaccine itself can trigger autoimmunity via cross-reactivity. Cross-reactivity occurs when amino acid sequence homology exists between a pathogen and self-tissue proteins [1]. In this mechanism, antibodies formed against SARS-CoV-2 would bind to human tissue proteins leading to autoimmune reactivity. An insufficiently vetted vaccine might mean trading freedom from COVID-19 to an autoimmune assault in the future
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