Post-COVID Endocrine Disorders: Putative Role of Molecular Mimicry and Some Pathomorphological Correlates

Abstract

In order to identify corresponding amino acid sequences (pentapeptides) between the SPs, MPs and NPs of human coronaviruses and human autoantigens targeted in autoimmune endocrinopathies, and for a comparative analysis of the various coronaviruses proteome and the proteome of human, the original computer program was used. Quantitatively, SP, MP and NP of the human coronaviruses were found to share totally 117 minimal immune pentapeptide epitopes: 79 in SP, 14 in MP and 24 in NP, – with 18 autoantigens expressed by human endocrinocytes. The shared pentapeptides belong to the proteins of human endocrine cells. Samples of the pituitary, adrenal and thyroid from patients who died from coronavirus infection (COVID-19) were studied morphologically using histochemical methods. A high incidence of SARS-CoV-2 infection of endocrine cells was showed. The high affinity of SARS-CoV-2 the cells of the adenohypophysis was revealed, but there was no expression of viral proteins by the cells of the neurohypophysis. The foci of lesions in endocrine organs contained abundant lymphocytic infiltrates which may indicate the impact of autoimmune processes. Autoimmune disorders have a multi-faceted etiology and depend on polygenic predispose and additive action of many epigenetic and environmental factors causing hyperstimulation of imperfectly functioning immune system. It means that the phenomenon of molecular mimicry cannot be blamed as their single prerequisite, but it is just a tile in mosaic of autoimmunity. The facts revealed emphasize the need of endocrinological diagnostic alertness of a physician while observing patients with post-vaccination and post-COVID-19 health disorders.

SARS-CoV-2 Gut-Targeted Epitopes: Sequence Similarity and Cross-Reactivity Join Together for Molecular Mimicry

“…Several pathways were suggested to operate in the SARS-CoV-2-AD cross-talks [1,11,12]. However, the most accepted and reported mechanism is molecular mimicry between the viral epitopes and human antigens [9,40,41,53,111]. Molecular mimicry is defined as the process where sequence similarities between foreign and self-peptides are sufficient to result in the cross-activation of B or autoreactive T cells, induced by pathogen-derived peptides [39,112].…”

“…Several mechanisms drive autoimmunity [1]: molecular mimicry [19,[39][40][41], epitope spreading [42,43], bystander activation [44,45] violation of biological barriers in immune-privileged organs [46], polyclonal activation of lymphocytes as a result of the action of superantigens [47], and finally, immune cross-reactivity between non-self-and self-antigens [48][49][50][51][52]. Several of those modes of action were even suggested to drive SARS-CoV-2-associated autoimmunity [1,11,12,40,[47][48][49][50]53]. A major under-studied aspect of the SARS-CoV-2-induced ADs is the molecular mimicry between the virus and the enteric epitopes.…”

In Silico and In Vitro Evaluation of the Molecular Mimicry of the SARS-CoV-2 Spike Protein by Common Short Constituent Sequences (cSCSs) in the Human Proteome: Toward Safer Epitope Design for Vaccine Development

“…In immunology, "molecular mimicry" has been used for identifying sequence similarities between pathogens and the host regardless of evolutionary cheating, suggesting that such similarities may induce autoantibodies leading to autoimmune diseases. Many studies have reported that COVID-19 is associated with autoimmune responses [47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64]. Indeed, many spike epitopes of antibodies from COVID-19 patients have been identified [65][66][67][68][69][70][71][72][73][74][75][76], but whether these anti-spike antibodies cross-react with human proteins is unknown.…”

Is Pulmonary Involvement a Distinct Phenotype of Post-COVID-19?

“…PCC is defined as the continuation or development of new symptoms after 3 months from infection, lasting for a minimum period of another 2 months [9]. Its manifestations derive from multiple mechanisms that the virus has the potential of inflicting [10]; SARS-CoV-2 interacts with the host microbiome/virome, paving the way for the reactivation of pathogens such as herpesviruses or fungi under the conditions of immune dysregulation [11][12][13][14][15]; it damages the vessel endothelium and provokes clotting issues [16,17]; it alters the brainstem and vagus nerve signaling because of its neuroinvasive capabilities [18][19][20]; finally, it provokes autoimmunity due to immune cells' overactivity and molecular mimicry between pathogens and the host proteins [21,22].…”