From Anti-SARS-CoV-2 Immune Responses to COVID-19 via Molecular Mimicry

Abstract

Aim: To define the autoimmune potential of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. Methods: Experimentally validated epitopes cataloged at the Immune Epitope DataBase (IEDB) and present in SARS-CoV-2 were analyzed for peptide sharing with the human proteome. Results: Immunoreactive epitopes present in SARS-CoV-2 were mostly composed of peptide sequences present in human proteins that—when altered, mutated, deficient or, however, improperly functioning—may associate with a wide range of disorders, from respiratory distress to multiple organ failure. Conclusions: This study represents a starting point or hint for future scientific–clinical investigations and suggests a range of possible protein targets of autoimmunity in SARS-CoV-2 infection. From an experimental perspective, the results warrant the testing of patients’ sera for autoantibodies against these protein targets. Clinically, the results warrant a stringent surveillance on the future pathologic sequelae of the current SARS-CoV-2 pandemic.

Molecular mimicry between SARS-CoV-2 spike glycoprotein and mammalian proteomes: implications for the vaccine

“…Accordingly, lungs and airways dysfunctions associated with SARS-CoV-2 infection might be explained by the sharing of peptides between SARS-CoV-2 spike glycoprotein and alveolar lung surfactant proteins [ 2 ]. In support of this thesis, additional reports [ 5 – 8 ] highlight molecular mimicry and cross-reactivity as capable of explaining the SARS-CoV diseases. Of special interest, cross-reactive T cell recognition between circulating “common cold” coronaviruses and SARS-CoV-2 has been also suggested [ 9 ].…”

“…Instead, no or a lowest number of common peptides are present in mammals that have no major pathologic sequelae once infected by SARS-CoV-2 [ 10 – 12 ]. Hence, the data appear to be an indisputable proof in favor of molecular mimicry as a potential mechanism that can contribute to or cause the SARS-CoV-2 associated diseases [ 8 ].…”

Vaccine- and natural infection-induced mechanisms that could modulate vaccine safety

“…The above analyzed COVID-19 vaccine safety considerations become even more cogent in light of the fact that cross-reactivity might represent the mechanism underlying the immunopathology and the disease multitude associated with the coronavirus infection [ 145 ]. The rationale is that the sharing of peptides between SARS-CoV-2 and human proteins might trigger immune responses hitting not only the virus but also the human proteins, with consequent autoimmune pathologies in the human host [ 146 ].…”

Coronavirus-associated molecular mimicry through homology to a SARS-CoV-2 peptide could be leading to susceptibility in patients with HLA-A*02:01 and HLA-A*24:02 serotypes

“…More than 1/3 of peptides that are immunogenic were found to be homologous to the proteins that are significant in the adaptive immune system. Kanduc [50] suggested that there is an extensive range of health disorders, related to probable autoimmunity reactions against peptides of the human proteome, which have homology with the immunogenic peptides of SARS-CoV-2. Also, it was indicated in another study [51] that cerebrospinal fluids from the patients of COVID-19 were suggestive of autoimmunity.…”