Exposure to SARS-CoV-2 and Infantile Diseases.

Background and Aim Immune response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in newborns and children after prophylactic immunization is currently a relevant research topic. The present study analyzes the issue by examining the possibility that the anti-SARS-CoV-2 immune responses are not uniquely directed against the virus but can-via molecular mimicry and the consequent cross-reactivity-also hit human proteins involved in infantile diseases. Methods Human proteins that-if altered-associate with infantile disorders were searched for minimal immune pentapeptide determinants shared with SARS-CoV-2 spike glycoprotein (gp). Then, the shared pentapeptides were analyzed for immunologic potential and immunologic imprinting phenomena. Results Comparative sequence analysis shows that: (1) numerous pentapeptides (namely, 54) are common to SARS-CoV-2 spike gp and human proteins that, when altered, are linked to infantile diseases; (2) all the shared peptides have an immunologic potential since they are present in experimentally validated SARS-CoV-2 spike gp-derived epitopes; and (3) many of the shared peptides are also hosted in infectious pathogens to which children can have already been exposed, thus making immunologic imprint phenomena feasible. Conclusion Molecular mimicry and the consequent cross-reactivity can represent the mechanism that connects exposure to SARS-CoV-2 and various pediatric diseases, with a fundamental role of the immunologic memory and the history of the child's infections in determining and specifying the immune response and the pathologic autoimmune sequela.

From Anti-SARS-CoV-2 Immune Response to the Cytokine Storm via Molecular Mimicry.

The aim of this study was to investigate the role of molecular mimicry in the cytokine storms associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Human proteins endowed with anti-inflammatory activity were assembled and analyzed for peptide sharing with the SARS-CoV-2 spike glycoprotein (gp) using public databases. It was found that the SARS-CoV-2 spike gp shares numerous pentapeptides with anti-inflammatory proteins that, when altered, can lead to cytokine storms characterized by diverse disorders such as systemic multiorgan hyperinflammation, macrophage activation syndrome, ferritinemia, endothelial dysfunction, and acute respiratory syndrome. Immunologically, many shared peptides are part of experimentally validated epitopes and are also present in pathogens to which individuals may have been exposed following infections or vaccinal routes and of which the immune system has stored memory. Such an immunologic imprint might trigger powerful anamnestic secondary cross-reactive responses, thus explaining the raging of the cytokine storm that can occur following exposure to SARS-CoV-2. In conclusion, the results support molecular mimicry and the consequent cross-reactivity as a potential mechanism in SARS-CoV-2-induced cytokine storms, and highlight the role of immunological imprinting in determining high-affinity, high-avidity, autoimmune cross-reactions as a pathogenic sequela associated with anti-SARS-CoV-2 vaccines.