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. 2020 Apr 9:3:100051.
doi: 10.1016/j.jtauto.2020.100051. eCollection 2020.

Pathogenic priming likely contributes to serious and critical illness and mortality in COVID-19 via autoimmunity

Affiliations

Pathogenic priming likely contributes to serious and critical illness and mortality in COVID-19 via autoimmunity

James Lyons-Weiler. J Transl Autoimmun. .

Abstract

Homology between human and viral proteins is an established factor in viral- or vaccine-induced autoimmunity. Failure of SARS and MERS vaccines in animal trials involved pathogenesis consistent with an immunological priming that could involve autoimmunity in lung tissues due to previous exposure to the SARS and MERS spike protein. Exposure pathogenesis to SARS-CoV-2 in COVID-19 likely will lead to similar outcomes. Immunogenic peptides in viruses or bacteria that match human proteins are good candidates for pathogenic priming peptides (similar to the more diffuse idea of "immune enhancement"). Here I provide an assessment of potential for human pathogenesis via autoimmunity via exposure, via infection or injection. SAR-CoV-2 spike proteins, and all other SARS-CoV-2 proteins, immunogenic epitopes in each SARS-CoV-2 protein were compared to human proteins in search of high local homologous matching. Only one immunogenic epitope in a SARS-CoV-2 had no homology to human proteins. If all of the parts of the epitopes that are homologous to human proteins are excluded from consideration due to risk of pathogenic priming, the remaining immunogenic parts of the epitopes may be still immunogenic and remain as potentially viable candidates for vaccine development. Mapping of the genes encoding human protein matches to pathways point to targets that could explain the observed presentation of symptoms in COVID-19 disease. It also strongly points to a large number of opportunities for expected disturbances in the immune system itself, targeting elements of MHC Class I and Class II antigen presentation, PD-1 signaling, cross-presentation of soluble exogenous antigens and the ER-Phagosome pathway. Translational consequences of these findings are explored.

Keywords: Autoimmunity; COVID-19; Immune Enhancement; Pathogenic priming; SARS-CoV-2.

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Conflict of interest statement

Dr. Lyons-Weiler has, in the past, served as expert witness in the National Vaccine Injury Compensation Program.

References

    1. Shi H. Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study. Lancet. 2020 doi: 10.1016/S1473-3099(20)30086-4. - DOI - PMC - PubMed
    1. Deming D., Sheahan T., Heise M. Vaccine efficacy in senescent mice challenged with recombinant SARS-CoV bearing epidemic and zoonotic spike variants. PLoS Med. 2006;3(12):e525. 2006 Dec. - PMC - PubMed
    1. Weingartl H., Czub M., Czub S. Immunization with modified vaccinia virus Ankara-based recombinant vaccine against severe acute respiratory syndrome is associated with enhanced hepatitis in ferrets. J. Virol. 2004 Nov;78(22):12672–12676. - PMC - PubMed
    1. Yao B., Zhang L., Liang S., SVMTriP C. Zhang. A method to predict antigenic epitopes using support vector machine to integrate tri-peptide similarity and propensity. PloS One. 2012;7(9) - PMC - PubMed
    1. Ahmed S.S., Volkmuth W., Duca J. Antibodies to influenza nucleoprotein cross-react with human hypocretin receptor 2. Sci. Transl. Med. 2015 Jul 1;7(294) doi: 10.1126/scitranslmed.aab2354. 294ra105. - DOI - PubMed