Tag: molecular mimicry

Biological mechanisms underpinning the development of Long COVID

Abstract:

As COVID-19 evolves from a pandemic to an endemic disease, the already staggering number of people that have been or will be infected with SARS-COV-2 is only destined to increase, and the majority of humanity will be infected. It is well understood that COVID-19, like many other viral infections, leaves a significant fraction of the infected with prolonged consequences.

Continued high number of SARS-CoV-2 infections, viral evolution with escape from post-infection and vaccinal immunity, and reinfections heighten the potential impact of Long COVID. Hence, the impact of COVID-19 on human health will be seen for years to come until more effective vaccines and pharmaceutical treatments become available.

To that effect, it is imperative that the mechanisms underlying the clinical manifestations of Long COVID be elucidated. In this article, we provide an in-depth analysis of the evidence on several potential mechanisms of Long COVID and discuss their relevance to its pathogenesis.

Source: Perumal R, Shunmugam L, Naidoo K, Wilkins D, Garzino-Demo A, Brechot C, Vahlne A, Nikolich J. Biological mechanisms underpinning the development of Long COVID. iScience. 2023 May 18:106935. doi: 10.1016/j.isci.2023.106935. Epub ahead of print. PMCID: PMC10193768. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10193768/ https://www.cell.com/iscience/pdf/S2589-0042(23)01012-X.pdf?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS258900422301012X%3Fshowall%3Dtrue (Full text)

Post COVID and Apheresis – Where are we Standing?

Abstract:

A continual increase in cases of Long/Post COVID constitutes a medical and socioeconomic challenge to health systems around the globe. While the true extent of this problem cannot yet be fully evaluated, recent data suggest that up to 20% of people with confirmed SARS-CoV-2 suffer from clinically relevant symptoms of Long/Post COVID several weeks to months after the acute phase. The clinical presentation is highly variable with the main symptoms being chronic fatigue, dyspnea, and cognitive symptoms. Extracorporeal apheresis has been suggested to alleviate symptoms of Post/COVID. Thus, numerous patients are currently treated with apheresis.

However, at present there is no data from randomized controlled trials available to confirm the efficacy. Therefore, physicians rely on the experience of practitioners and centers performing this treatment. Here, we summarize clinical experience on extracorporeal apheresis in patients with Post/COVID from centers across Germany.

Source: Steenblock C, Walther R, Tselmin S, Jarzebska N, Voit-Bak K, Toepfner N, Siepmann T, Passauer J, Hugo C, Wintermann G, Julius U, Barbir M, Khan TZ, Puhan MA, Straube R, Hohenstein B, Bornstein SR, Rodionov RN. Post COVID and Apheresis – Where are we Standing? Horm Metab Res. 2022 Nov;54(11):715-720. doi: 10.1055/a-1945-9694. Epub 2022 Sep 16. PMID: 36113501. https://www.thieme-connect.de/products/ejournals/html/10.1055/a-1945-9694 (Full text)

Molecular Mimicry between SARS-CoV-2 and Human Endocrinocytes: A Prerequisite of Post-COVID-19 Endocrine Autoimmunity?

Abstract:

Molecular mimicry between human and microbial/viral/parasite peptides is common and has long been associated with the etiology of autoimmune disorders provoked by exogenous pathogens. A growing body of evidence accumulated in recent years suggests a strong correlation between SARS-CoV-2 infection and autoimmunity. The article analyzes the immunogenic potential of the peptides shared between the SARS-CoV-2 spike glycoprotein (S-protein) and antigens of human endocrinocytes involved in most common autoimmune endocrinopathies.

A total of 14 pentapeptides shared by the SARS-CoV-2 S-protein, thyroid, pituitary, adrenal cortex autoantigens and beta-cells of the islets of Langerhans were identified, all of them belong to the immunoreactive epitopes of SARS-CoV-2. The discussion of the findings relates the results to the clinical correlates of COVID-19-associated autoimmune endocrinopathies. The most common of these illnesses is an autoimmune thyroid disease, so the majority of shared pentapeptides belong to the marker autoantigens of this disease.

The most important in pathogenesis of severe COVID-19, according to the authors, may be autoimmunity against adrenals because their adequate response prevents excessive systemic action of the inflammatory mediators causing cytokine storm and hemodynamic shock. A critique of the antigenic mimicry concept is given with an assertion that peptide sharing is not a guarantee but only a prerequisite for provoking autoimmunity based on the molecular mimicry. The latter event occurs in carriers of certain HLA haplotypes and when a shared peptide is only used in antigen processing.

Source: Churilov LP, Normatov MG, Utekhin VJ. Molecular Mimicry between SARS-CoV-2 and Human Endocrinocytes: A Prerequisite of Post-COVID-19 Endocrine Autoimmunity? Pathophysiology. 2022 Aug 25;29(3):486-494. doi: 10.3390/pathophysiology29030039. PMID: 36136066; PMCID: PMC9504401. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9504401/ (Full text)

Long COVID from rheumatology perspective: a simple mimicker or promoter of autoimmunity?

Dear editor,

We have read with great interest the review article by Sapkota et al. which has been recently published in the Clinical Rheumatology journal dealing with long COVID []. In this paper, the authors reported the symptoms and immunological findings of patients who were infected from severe acute respiratory syndrome coronovirus-2 (SARS-CoV-2). These symptoms and laboratory features share similarities with those of patients suffering from autoimmune rheumatic diseases (ARDs). They concluded that long COVID is a mimicker of ARDs and needs to be excluded to ensure a correct diagnosis [].

Recently, we reported a patient who contracted SARS-CoV-2 infection and developed an erosive seronegative arthritis six months after infection []. Musculoskeletal, cutaneous, and other systemic manifestations, along with the presence of autoantibodies, are frequently observed in these patients. On the other hand, SARS-CoV-2 may trigger autoimmune responses and the development of de-novo manifestations of ARDs, as in our patient []. The pathogenesis of these phenomena is not well defined. One hypothesis implies the presence of autoantibodies against interferon (IFN) type-I, or inborn errors in the type-I IFN immunity [, ]. Another hypothesis is that SARS-CoV-2 might trigger autoimmune responses through molecular mimicry []. Several viruses have been implicated as possible etiological factors for the development of ARDs, mostly systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and others. Between viruses Epstein-Barr virus (EBV) is implicated in the pathogenesis of the above disorders [, ]. Indeed, EBV can trigger immune responses through molecular mimicry and is a polyclonal activator of B-cells and increases the production of rheumatoid factor (RF). Several studies suggested that molecular mimicry is a possible mechanism responsible for the development of ARDs in SARS-CoV-2 infection [, ]. Thus, SARS-CoV-2 may trigger autoimmunity and the possible development of the de novo manifestations of ARDs.

Read the full article HERE.

Source: Drosos AA, Pelechas E, Voulgari PV. Long COVID from rheumatology perspective: a simple mimicker or promoter of autoimmunity? Clin Rheumatol. 2022 Feb 11:1–2. doi: 10.1007/s10067-022-06092-4. Epub ahead of print. PMID: 35147823; PMCID: PMC8831874. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8831874/ (Full text)

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in the Era of the Human Microbiome: Persistent Pathogens Drive Chronic Symptoms by Interfering With Host Metabolism, Gene Expression, and Immunity

Abstract:

The illness ME/CFS has been repeatedly tied to infectious agents such as Epstein Barr Virus. Expanding research on the human microbiome now allows ME/CFS-associated pathogens to be studied as interacting members of human microbiome communities. Humans harbor these vast ecosystems of bacteria, viruses and fungi in nearly all tissue and blood. Most well-studied inflammatory conditions are tied to dysbiosis or imbalance of the human microbiome. While gut microbiome dysbiosis has been identified in ME/CFS, microbes and viruses outside the gut can also contribute to the illness.

Pathobionts, and their associated proteins/metabolites, often control human metabolism and gene expression in a manner that pushes the body toward a state of illness. Intracellular pathogens, including many associated with ME/CFS, drive microbiome dysbiosis by directly interfering with human transcription, translation, and DNA repair processes. Molecular mimicry between host and pathogen proteins/metabolites further complicates this interference. Other human pathogens disable mitochondria or dysregulate host nervous system signaling. Antibodies and/or clonal T cells identified in patients with ME/CFS are likely activated in response to these persistent microbiome pathogens.

Different human pathogens have evolved similar survival mechanisms to disable the host immune response and host metabolic pathways. The metabolic dysfunction driven by these organisms can result in similar clusters of inflammatory symptoms. ME/CFS may be driven by this pathogen-induced dysfunction, with the nature of dysbiosis and symptom presentation varying based on a patient’s unique infectious and environmental history. Under such conditions, patients would benefit from treatments that support the human immune system in an effort to reverse the infectious disease process.

Source: Proal A, Marshall T. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in the Era of the Human Microbiome: Persistent Pathogens Drive Chronic Symptoms by Interfering With Host Metabolism, Gene Expression, and Immunity. Front Pediatr. 2018 Dec 4;6:373. doi: 10.3389/fped.2018.00373. eCollection 2018. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6288442/ (Full article)

Is chronic fatigue syndrome an autoimmune disorder of endogenous neuropeptides, exogenous infection and molecular mimicry?

Abstract:

Chronic fatigue syndrome is a disorder characterised by prolonged fatigue and debility and is mostly associated with post-infection sequelae although ongoing infection is unproven. Immunological aberration is likely and this may prove to be associated with an expanding group of vasoactive neuropeptides in the context of molecular mimicry and inappropriate immunological memory.

Vasoactive neuropeptides including vasoactive intestinal peptide (VIP) and pituitary adenylate activating polypeptide (PACAP) belong to the secretin/glucagon superfamily and act as hormones, neurotransmitters, immune modulators and neurotrophes. They are readily catalysed to smaller peptide fragments by antibody hydrolysis. They and their binding sites are immunogenic and are known to be associated with a range of autoimmune conditions. Vasoactive neuropeptides are widely distributed in the body particularly in the central, autonomic and peripheral nervous systems and have been identified in the gut, adrenal gland, reproductive organs, vasculature, blood cells and other tissues. They have a vital role in maintaining vascular flow in organs, and in thermoregulation, memory and concentration. They are co-transmitters for acetylcholine, nitric oxide, endogenous opioids and insulin, are potent immune regulators with primarily anti-inflammatory activity, and have a significant role in protection of the nervous system to toxic assault, promotion of neural development and the maintenance of homeostasis.

This paper describes a biologically plausible mechanism for the development of CFS based on loss of immunological tolerance to the vasoactive neuropeptides following infection, significant physical exercise or de novo. It is proposed that release of these substances is accompanied by a loss of tolerance either to them or their receptor binding sites in CFS. Such an occurrence would have predictably serious consequences resulting from compromised function of the key roles these substances perform. All documented symptoms of CFS are explained by vasoactive neuropeptide compromise, namely fatigue and nervous system dysfunction through impaired acetylcholine activity, myalgia through nitric oxide and endogenous opioid dysfunction, chemical sensitivity through peroxynitrite and adenosine dysfunction, and immunological disturbance through changes in immune modulation. Perverse immunological memory established against these substances or their receptors may be the reason for the protracted nature of this condition.

The novel status of these substances together with their extremely small concentrations in blood and tissues means that clinical research into them is still in its infancy. A biologically plausible theory of CFS causation associated with vasoactive neuropeptide dysfunction would promote a coherent and systematic approach to research into this and other possibly associated disabling conditions.

 

Source: Staines DR. Is chronic fatigue syndrome an autoimmune disorder of endogenous neuropeptides, exogenous infection and molecular mimicry? Med Hypotheses. 2004;62(5):646-52. http://www.ncbi.nlm.nih.gov/pubmed/15082083