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

Overview

All SARS-CoV-2 immunogenic epitopes have similarity to human proteins except one. • Roughly one-third of the potentially targeted human proteins (putative autoantigens) are key players in the adaptive immune system. • The list of viral/human protein matches provides clues on which epitopes or parts of epitopes might be involved in the immunopathogenesis of COVID-19 disease from SARS-CoV-2 infection. • It also indicates which epitopes might be responsible for autoimmunological pathogenic priming due to prior infection or following exposure to SARS-CoV-2 or relatives following vaccination. • These epitopes should be excluded from vaccines under development to minimize autoimmunity due to risk of pathogenic priming.

Summary

Past coronavirus vaccines failed due to pathogenic priming leading to disease enhancement. Molecular similarities between human proteins and SARS-CoV-2 proteins are expected to induce autoimmunity to myriad tissues. The prolonged infection period of SARS-CoV-2 may explain why pathogenic priming can occur.

Author Comments

Dr. jameslyonsweiler, PhD
Dr. jameslyonsweiler, PhD
The Institute for Pure and Applied Knowledge
CEO/Director
ALLISON PARK, PA | United States
Translational impact: We must not rush to human viral challenge studies when animal studies designed to detect disease enhancement from pathogenic priming can be conducted more quickly. Dr. jameslyonsweiler, PhD

Resources

IPAK COVID-19 Research
http://ipaknowledge.org/covid-19-and-sars-cov-2-research.php
Pubmed Link
https://www.ncbi.nlm.nih.gov/pubmed/32292901
PMC Full Text
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7142689/

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

Journal of Translational Autoimmunity

J Trans Autoimm 3, 2020, 100051

Highlights

All SARS-CoV-2 immunogenic epitopes have similarity to human proteins except one.

Roughly one-third of the potentially targeted human proteins (putative autoantigens) are key players in the adaptive immune system.

The list of viral/human protein matches provides clues on which epitopes or parts of epitopes might be involved in the immunopathogenesis of COVID-19 disease from SARS-CoV-2 infection.

It also indicates which epitopes might be responsible for autoimmunological pathogenic priming due to prior infection or following exposure to SARS-CoV-2 or relatives following vaccination.

These epitopes should be excluded from vaccines under development to minimize autoimmunity due to risk of pathogenic priming.

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.

April 2020
64 Reads

Similar Publications