The Long Covid-19 Syndrome the Spike Protein and Stem Cells, the Underrated Role of Retrotransposons, a Working Hypothesis

Abstract

Coronavirus disease-2019 (COVID-19) was seen as a respiratory disease, however, an increasing number of reports indicated that the spike protein could also be the cause of the long-term post-infectious conditions known as Long-COVID characterized by a group of unresponsive idiopathic severe neuro, cardio-vascular disorders, including strokes, cardiopathies, neuralgias, fibromyalgia, and Parkinson’s like-disease. Different lines of pieces of evidence confirmed that the spike protein that can be found on the surface of the SARS-CoV-2 virus latches onto angiotensin-converting enzyme 2 (ACE2) receptors located on target cells.
The RNA genome of coronaviruses, which, has a median length of 29 kb and is the longest among all RNA viruses, is comprised of six to ten open reading frames (ORFs) that are responsible for encoding both the replicase and structural proteins for the virus. Each of the components of the viral genome is packaged into a helical nucleocapsid that is surrounded by a lipid bilayer. The viral envelope of coronaviruses is typically made up of three proteins that include the membrane protein (M), the envelope protein (E), and the spike protein (S). The spike protein not only facilitates the virus entry into healthy cells, which is the first step in infection but also promote profound damage to different organs and tissues leading to severe impairments and long-term disabilities.
Here, we discussed the pervasive mechanism that spikes mRNA adopted to alter multipotent and pluripotent stem cell (SCs) genomes and the acquired disability of generating an infinite number of affected clonal cells. This stance is based on the molecular and evolutionary aspects obtained from retrotransposons-retrotransposition in mammalians and humans that documented the frequent integration of mRNA molecules into genomes and thus into DNA. Retrotransposition is the molecular process in which transcribed and spliced mRNAs are accidentally reverse-transcribed and inserted into new genomic positions to form a retrogene.
Sequence-specific traits of mRNA clearly showed long interspersed element-1 (LINE-1 or L1) to confirm the retrotransposition, considered the most abundant autonomously active retrotransposons in the human genome. In mammals, L1 retrotransposons drive retrotransposition and are composed of long terminal repeats (LTRs) and non-LTR retrotransposons (mainly long interspersed nuclear elements or LINEs); specifically, the LTR-mediated retrocopies are immediately cotranscribed with their flanking LTR retrotransposons.
In response to retrotransposons transposition, stem cells (SCs) employ a number of silencing mechanisms, such as DNA methylation and histone modification. This manuscript theorizes the expression patterns, functions, and regulation of mRNA Spike protein imprinted by SCs retrotransposons which generate unlimited lines of affected cell progenies and tissues as the main condition of untreatable Spike-related inflammatory conditions.
Source: Balzanelli, M.G.; Distratis, P.; Lazzaro, R.; Dipalma, G.; Inchingolo, F.; Del Prete, R.; Hung Pham, V.; Aityan, S.K.; Nguyen, K.C.; Isacco Gargiulo, C. The Long Covid-19 Syndrome the Spike Protein and Stem Cells, the Underrated Role of Retrotransposons, a Working Hypothesis. Preprints 2023, 2023081130. https://doi.org/10.20944/preprints202308.1130.v1 https://www.preprints.org/manuscript/202308.1130/v1 (Full text available as PDF file)

Post-COVID-19 Symptoms in Adults with Asthma—Systematic Review

Abstract:

Background: Research on the longer-term sequelae of COVID-19 in patients with asthma is limited. Objective: To assess the frequency and severity of long-term symptoms of COVID-19 in the population of asthma patients.
Methods: A systematic review of the published literature was conducted in accordance with the recommendations of the PRISMA statement. EMBASE, MEDLINE/PubMed, Web of Science, CINAHL, and Scopus Scholar were searched for terms related to asthma and post or long COVID-19, and for systematic reviews related to specific questions within our review, up to June 2022.
Results: Data from 9 references publications included in the review were extracted. A total of 1466 adult asthmatic patients with COVID-19 infection were described in all the publications mentioned above. Of the long-term symptoms reported after COVID-19, patients indicated: lower respiratory symptoms, fatigue, cognitive symptoms, psychological problems, and other such as skin rashes, gastrointestinal disorders, tachycardia, palpitations, ocular disorders, ageusia/hypogeusia, anosmia/hyposmia, and poor sleep quality. These symptoms in similar intensity were observed in the comparison groups without a diagnosis of asthma.
Conclusions: The published data neither confirm nor deny that long-term COVID-19 symptoms in patients with asthma diagnosis are different in strength and frequency from patients without asthma diagnosis. To indicate associations between asthma and COVID-19 infection and severity, as well as the frequency of long-term symptoms of COVID-19, more longitudinal research is needed in chronic asthma patients with different phenotypes, intensity of treatment, and degree of asthma control.
Source: Kaszuba M, Madej N, Pilinski R, Sliwka A. Post-COVID-19 Symptoms in Adults with Asthma—Systematic Review. Biomedicines. 2023; 11(8):2268. https://doi.org/10.3390/biomedicines11082268 https://www.mdpi.com/2227-9059/11/8/2268 (Full text)

Long Covid requires a global response centred on equity and dialogue

Abstract:

Long Covid, or Post-Covid Conditions, is a global health problem. Yet we know strikingly little about the different experiences of Long Covid patients cross-nationally. To address this shortcoming, we conducted an online survey of Long Covid patients active on social media in the U.S. (n = 334, October to December 2021) and Brazil (n = 144, January to April 2022). Our analysis of short answer responses indicates patient dissatisfaction with medical care provided for Long Covid in both the U.S. and Brazil. For Long Covid patients in Brazil, there were additional concerns raised about the lack of local expertise about their condition.

Based on these results, we urge policymakers to expand the education of medical professionals in order to raise awareness of Long Covid. Experts in the Global North should also be encouraged to engage in dialogue with patient groups and experts in the Global South, in order to better understand how local contexts shape the experience of Long Covid.

Source: Au L, Capotescu C, Curi A, Gonçalves Leonel da Silva R, Eyal G. Long Covid requires a global response centred on equity and dialogue. Glob Health Action. 2023 Dec 31;16(1):2244757. doi: 10.1080/16549716.2023.2244757. PMID: 37581581; PMCID: PMC10431739. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10431739/ (Full text)

Cocreation of Assistive Technologies for Patients With Long COVID: Qualitative Analysis of a Literature Review on the Challenges of Patient Involvement in Health and Nursing Sciences

Abstract:

Background: Digital assistive technologies have the potential to address the pressing need for adequate therapy options for patients with long COVID (also known as post-COVID-19 condition) by enabling the implementation of individual and independent rehabilitation programs. However, the involvement of the target patient group is necessary to develop digital devices that are closely aligned to the needs of this particular patient group.

Objective: Participatory design approaches, such as cocreation, may be a solution for achieving usability and user acceptance. However, there are currently no set methods for implementing cocreative development processes incorporating patients. This study addresses the following research questions: what are the tasks and challenges associated with the involvement of patient groups? What lessons can be learned regarding the adequate involvement of patients with long COVID?

Methods: First, a literature review based on a 3-stage snowball process was conducted to identify the tasks and challenges emerging in the context of the cocreation of digital assistive devices and services with patient groups. Second, a qualitative analysis was conducted in an attempt to extract relevant findings and criteria from the identified studies. Third, using the method of theory adaptation, this paper presents recommendations for the further development of the existing concepts of cocreation in relation to patients with long COVID.

Results: The challenges of an active involvement of patients in cocreative development in health care include hierarchical barriers and differences in the levels of specific knowledge between professionals and patients. In the case of long COVID, patients themselves are still inexperienced in dealing with their symptoms and are hardly organized into established groups. This amplifies general hurdles and leads to questions of group identity, power structure, and knowledge creation, which are not sufficiently addressed by the current methods of cocreation.

Conclusions: The adaptation of transdisciplinary methods to cocreative development approaches focusing on collaborative and inclusive communication can address the recurring challenges of actively integrating patients with long COVID into development processes.

Source: Dalko K, Kraft B, Jahn P, Schildmann J, Hofstetter S. Cocreation of Assistive Technologies for Patients With Long COVID: Qualitative Analysis of a Literature Review on the Challenges of Patient Involvement in Health and Nursing Sciences. J Med Internet Res. 2023 Aug 15;25:e46297. doi: 10.2196/46297. PMID: 37581906. https://www.jmir.org/2023/1/e46297 (Full text)

Post-COVID-19 syndrome management: Utilizing the potential of dietary polysaccharides

Abstract:

The COVID-19 pandemic has caused significant global impact, resulting in long-term health effects for many individuals. As more patients recover, there is a growing need to identify effective management strategies for ongoing health concerns, such as post-COVID-19 syndrome, characterized by persistent symptoms or complications beyond several weeks or months from the onset of symptoms. In this review, we explore the potential of dietary polysaccharides as a promising approach to managing post-COVID-19 syndrome.

We summarize the immunomodulatory, antioxidant, antiviral, and prebiotic activities of dietary polysaccharides for the management of post-COVID-19 syndrome. Furthermore, the review investigates the role of polysaccharides in enhancing immune response, regulating immune function, improving oxidative stress, inhibiting virus binding to ACE2, balancing gut microbiota, and increasing functional metabolites. These properties of dietary polysaccharides may help alleviate COVID-19 symptoms, providing a promising avenue for effective treatment strategies.

Source: Cheong KL, Yu B, Teng B, Veeraperumal S, Xu B, Zhong S, Tan K. Post-COVID-19 syndrome management: Utilizing the potential of dietary polysaccharides. Biomed Pharmacother. 2023 Aug 16;166:115320. doi: 10.1016/j.biopha.2023.115320. Epub ahead of print. PMID: 37595427. https://www.sciencedirect.com/science/article/pii/S0753332223011113 (Full text)

Evaluation of Post–COVID-19 Cognitive Dysfunction: Recommendations for Researchers

Opinion:

SARS-CoV-2 infection is associated with increased rates of postillness cognitive dysfunction, colloquially referred to as “brain fog,”1 that may portend significant consequences for patient functioning and quality of life. Post–COVID-19 cognitive dysfunction is 1 of approximately 200 symptoms of post–COVID-19 condition (PCC), defined by the World Health Organization as developing within 3 months of an initial SARS-CoV-2 infection, lasting at least 2 months, and cannot be explained by an alternative diagnosis. A pooled analysis of 54 studies and 1.2 million individuals found that 3.2% of patients’ self-reported cognitive problems 3 months after symptomatic infection,1 while other studies have shown objective evidence of cognitive dysfunction in approximately 24% of patients nearly 1 year later.2 Accumulating evidence also supports the hypothesis that COVID-19 may increase risk for later neurodegeneration3 and exacerbate preexisting cognitive dysfunction.4 As one of the most common symptoms of PCC and one for which affected individuals may seek accommodations and disability benefits in accordance with the Americans With Disabilities Act, it is imperative that we use more rigorous studies of cognitive outcomes. Accordingly, the following recommendations have been generated by members of the NeuroCOVID International Neuropsychology Taskforce based on initial guidelines.5

Source: Jaqueline H. Becker, PhD; Tracy D. Vannorsdall, PhD; Sara L. Weisenbach, PhD. JAMA Psychiatry. Published online August 16, 2023. doi:10.1001/jamapsychiatry.2023.2820 https://jamanetwork.com/journals/jamapsychiatry/article-abstract/2808155

Increased gut permeability and bacterial translocation are associated with fibromyalgia and myalgic encephalomyelitis/chronic fatigue syndrome: implications for disease-related biomarker discovery

Abstract:

Background: There is growing evidence of the significance of gastrointestinal complaints in the impairment of the intestinal mucosal barrier function and inflammation in fibromyalgia and myalgic encephalomyelitis/chronic fatigue syndrome. However, data on intestinal permeability and gut barrier dysfunction in FM and ME/CFS are still limited with conflicting results. This study aimed to assess circulating biomarkers potentially related to intestinal barrier dysfunction and bacterial translocation and their association with self-reported symptoms in these conditions.

Methods: A pilot multicentre, cross-sectional cohort study with consecutive enrolment of 22 patients with FM, 30 with ME/CFS, and 26 matched healthy controls. Plasma levels of anti-beta-lactoglobulin antibodies (IgG anti-beta-LGB), zonulin-1 (ZO-1), LPS, sCD14, and IL-1β) were assayed using ELISA. Demographic and clinical characteristics of the participants were recorded using validated self-reported outcome measures. The diagnostic accuracy of each biomarker was assessed using the ROC curve analysis.

Results: FM patients had significantly higher levels of anti-β-LGB, ZO-1, LPS, and sCD14 than healthy controls (all P < 0.0001). In ME/CFS patients, levels of anti-β-LGB, ZO-1, LPS, and sCD14 were significantly higher than controls, but lower than in FM (all P < 0.01), while there was no significant difference in IL-1β level. In the FM and ME/CFS cohorts, both anti-β-LGB and ZO-1 correlated significantly with LPS and sCD14 (P < 0.001 for both). In the FM group, both anti-beta-LGB and ZO-1 were correlated significantly with physical and mental health components on the SF-36 scale (P < 0.05); whereas IL-1beta negatively correlated with the COMPASS-31 score (P < 0.05). In the ME/CFS cohort, ZO-1 was positively correlated with the COMPASS-31 score (P < 0.05). The ROC curve analysis indicated a strong ability of anti-β-LGB, ZO-1, LPS, and sCD14 to predictively distinguish between FM and ME/CFS from healthy controls (P < 0.0001).

Conclusions: Biomarkers of intestinal barrier function and inflammation were associated with autonomic dysfunction assessed by COMPASS-31 scores in FM and ME/CFS respectively. Anti-β-LGB antibodies, ZO-1, LPS, and sCD14 may be putative predictors of intestinal barrier dysfunction in these cohorts. Further studies are needed to assess whether these findings are causal and can therefore be applied in clinical practice.

Source: Franz Martin, Manuel Blanco Suárez2 Paola Zambrano, Óscar Cáceres Calle, Miriam Almirall, Jose Alegre-Martín, Beatriz Lobo, Ana María Gonzalez-Castro, Javier Santos, Joan Carles Domingo, Joanna Jurek, Jesús Castro-Marrero. Increased gut permeability and bacterial translocation are associated with fibromyalgia and myalgic encephalomyelitis/chronic fatigue syndrome: implications for disease-related biomarker discovery. Front. Immunol., Sec. Mucosal Immunity, Volume 14 – 2023 | doi: 10.3389/fimmu.2023.1253121 https://www.frontiersin.org/articles/10.3389/fimmu.2023.1253121/abstract

A Scoping Review of ‘Pacing’ for Management of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Lessons Learned for the Long COVID Pandemic

Abstract:

Background Controversy over treatment for people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a barrier to appropriate treatment. Energy management or pacing is a prominent coping strategy for people with ME/CFS that involves regulating activity to avoid post exertional malaise (PEM), the worsening of symptoms after an activity. Until now, characteristics of pacing, and the effects on patients’ symptoms had not been systematically reviewed. This is problematic as the most common approach to pacing, pacing prescription, and the pooled efficacy of pacing was unknown. Collating evidence may help advise those suffering with similar symptoms, including long COVID, as practitioners would be better informed on methodological approaches to adopt, pacing implementation, and expected outcomes.

Objectives In this scoping review of the literature, we aggregated type of, and outcomes of, pacing in people with ME/CFS.

Eligibility criteria Original investigations concerning pacing were considered in participants with ME/CFS.

Sources of evidence Six electronic databases (PubMed, Scholar, ScienceDirect, Scopus, Web of Science and the Cochrane Central Register of Controlled Trials [CENTRAL]) were searched; and websites MEPedia, Action for ME, and ME Action were also searched for grey literature.

Methods A scoping review was conducted. Review selection and characterisation was performed by two independent reviewers using pretested forms.

Results Authors reviewed 177 titles and abstracts, resulting in included 17 studies: three randomised control trials (RCTs); one uncontrolled trial; one interventional case series; one retrospective observational study; two prospective observational studies; four cross-sectional observational studies; and five cross-sectional analytical studies. Studies included variable designs, durations, and outcome measures. In terms of pacing administration, studies used educational sessions and diaries for activity monitoring. Eleven studies reported benefits of pacing, four studies reported no effect, and two studies reported a detrimental effect in comparison to the control group.

Conclusions Highly variable study designs and outcome measures, allied to poor to fair methodological quality resulted in heterogenous findings and highlights the requirement for more research examining pacing. Looking to the long COVID pandemic, future studies should be RCTs utilising objectively quantified digitised pacing, over a longer duration of examination, using the core outcome set for patient reported outcome measures.

Source: Nilihan E.M. Sanal-Hayes, Marie Mclaughlin, Lawrence D. Hayes, Jacqueline L. Mair, Jane Ormerod, David Carless, Natalie Hilliard, Rachel Meach, Joanne Ingram, Nicholas F. Sculthorpe. A Scoping Review of ‘Pacing’ for Management of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Lessons Learned for the Long COVID Pandemic. medRxiv 2023.08.10.23293935; doi: https://doi.org/10.1101/2023.08.10.23293935 https://www.medrxiv.org/content/10.1101/2023.08.10.23293935v1.full-text (Full text)

The importance of estimating prevalence of ME/CFS in future epidemiological studies of long COVID

Abstract:

The resolution of the COVID-19 pandemic is giving rise to another public health challenge due to the explosion of long COVID (LC) cases. In many cases, LC results in persistent fatigue, post-exertional malaise (PEM), and other debilitating symptoms that resemble the clinical manifestation of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). The similarity of these two diseases suggests that future epidemiological studies of LC could take the opportunity to also estimate the prevalence of ME/CFS at a minimal cost.

With this opportunity in mind, we revisited the most consensual case definitions of ME/CFS for research purposes. We then compared the symptoms assessed at the participants’ enrollment in the UK ME/CFS Biobank with those documented in three systematic reviews encompassing hundreds of LC epidemiological studies. We found that published epidemiological studies of LC did not consistently assess or report the prevalence of PEM, which is a compulsory symptom for ME/CFS diagnosis. However, these studies assessed many neuro-cognitive, immunologic, and autonomic symptoms.

In this scenario, we recommend that the estimation of ME/CFS prevalence in the context of LC epidemiology is easily achievable by deploying tested and validated diagnosis tools used in ME/CFS. The knowledge of ME/CFS prevalence within the LC population is of cardinal importance to optimal allocation of resources and better design of healthcare interventions to manage and treat patients with this devastating disease.

Source: Anna D. Grabowska, Francisco Westermeier, Luís Nacul, Eliana Lacerda, Nuno Sepúlveda. The importance of estimating prevalence of ME/CFS in future epidemiological studies of long COVID. DOI:10.13140/RG.2.2.20997.52967 https://www.researchgate.net/publication/373043778_The_importance_of_estimating_prevalence_of_MECFS_in_future_epidemiological_studies_of_long_COVID (Full text)

Contesting oppressive regimes of truth: A critical feminist re-examination of (bio)psychosocial hegemony in the field of myalgic encephalomyelitis / chronic fatigue syndrome

Abstract:

Myalgic encephalomyelitis / chronic fatigue syndrome, a disabling condition disproportionately affecting women, is predominantly clinically managed through a (bio)psychosocial lens with psychosocial-inspired therapies, criticised for facilitating social and epistemic injustice, psychological and physical harms. Whilst most literature contesting (bio)psychosocial practices espouses a mainstream scientific perspective, politics and power relations undergirding psychosocial hegemony are better explicated through a critical lens. This article re-examines the ascendancy of psychosocial therapies and related practices through a critical feminist psychology and Foucauldian lens, with a view to locating oppressive practices in their socio-political and cultural context and promoting dialogue on possibilities for positive social change.

Source: Hunt, J. E. (2023, August 10). Contesting oppressive regimes of truth: A critical feminist re-examination of (bio)psychosocial hegemony in the field of myalgic encephalomyelitis / chronic fatigue syndrome. https://doi.org/10.31235/osf.io/3g7kp https://osf.io/preprints/socarxiv/3g7kp/ (Full text)