Tag: review

Aberrations in the Cross-Talks Among Redox, Nuclear Factor-κB, and Wnt/β-Catenin Pathway Signaling Underpin Myalgic Encephalomyelitis and Chronic Fatigue Syndrome

Abstract:

There is evidence that chronic fatigue spectrum disorders (CFAS-D) including Myalgic Encephalomyelitis (ME), chronic fatigue syndrome (CFS) and chronic fatigue with physiosomatic symptoms including when due to comorbid medical disease are characterized by neuroimmune and neuro-oxidative biomarkers.

The present study was performed to delineate the protein-protein interaction (PPI) network of CFAS-D and to discover the pathways, molecular patterns and domains enriched in their PPI network.

We performed network, enrichment and annotation analysis using differentially expressed proteins and metabolics, which were established in CFAS-D patients.

PPI network analysis revealed that the backbone of the highly connective CFAS-D network comprises NFKB1, CTNNB1, ALB, peroxides, NOS2, TNF, and IL6, and that the network comprises interconnected immune-oxidative-nitrosative and Wnt/catenin subnetworks.

MultiOmics enrichment analysis shows that the CFAS-D network is highly significantly associated with cellular (antioxidant) detoxification, hydrogen peroxide metabolic process, peroxidase and oxidoreductase activity, IL10 anti-inflammatory signaling, and neurodegenerative, canonical Wnt, the catenin complex, cadherin domains, cell-cell junctions and TLR2/4 pathways; and the transcription factors NF-κB and RELA.

The top-10 DOID annotations of the CFAS-D network include four intestinal, three immune system disorders, cancer and infectious disease.

Custom GO term annotation analysis revealed that the CFAS-D network is associated with a response to a toxic substance, lipopolysaccharides, bacterium or virus.

In conclusion, CFAS-D may be triggered by a variety of stimuli and their effects are mediated by aberrations in the cross-talks between redox, NF-κB, and Wnt/catenin signaling pathways leading to dysfunctions in multicellular organismal homeostatic processes.

Source: Michael Maes, Marta Kubera and Magdalena Kotańska. Aberrations in the Cross-Talks Among Redox, Nuclear Factor-κB, and Wnt/β-Catenin Pathway Signaling Underpin Myalgic Encephalomyelitis and Chronic Fatigue Syndrome. Frontiers in Psychiatry 13: 822382. https://www.frontiersin.org/articles/10.3389/fpsyt.2022.822382/full  (Full text)

Long COVID-19: Psychological symptoms in COVID-19 and probiotics as an adjunct therapy

Abstract:

There is an increase in mental health sequelae following COVID-19 infection, with some studies showing a higher prevalence rate of psychiatric sequelae in post-COVID-19 survivors than in the general population. This review discusses the possible causes, prevalence, and risk factors of COVID-19 associated psychological manifestations, namely anxiety, depression, and post-traumatic stress disorder (PTSD).

Although the exact cause is yet to be determined, it is likely multifactorial involving environmental, biological, and psychological factors due to the pandemic. Variation exists for risk factors and prevalence, but the female gender and psychiatric disorder history seem to be consistent risk factors across several studies. While conventional psychotropic medications are the common therapeutic intervention, probiotics could be a potential adjunct treatment to prevent and treat COVID-19 and its associated psychological manifestations. Their anti-inflammatory effects have been seen directly via reducing plasma concentration of proinflammatory cytokines or indirectly via the suppression within the kynurenine pathway and restoration of gut permeability.

Additionally, short-chain fatty acids (SCFAs) are crucial gut microbial metabolites with essential roles, including signaling along the microbiota-gut-brain (MGB) axis, maintaining blood-brain barrier’s (BBB) integrity, neuronal functions, neurotransmitters, and neurotrophic factors modulation.

Source: Angel Yun, Kuan Thye, Loh Teng, Hern Tan, Jodi Woan, Fei Law, Priyia Pusparajah, Vengadesh Letchumanan. Long COVID-19: Psychological symptoms in COVID-19 and probiotics as an adjunct therapy. Progress in Microbes and Molecular Biology. April 20, 2022. https://journals.hh-publisher.com/index.php/pmmb/article/view/616/340 (Full text)

Molecular Hydrogen as a Medical Gas for the Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Possible Efficacy Based on a Literature Review

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disorder that is characterized by fatigue that persists for more than 6 months, weakness, sleep disturbances, and cognitive dysfunction.

There are multiple possible etiologies for ME/CFS, among which mitochondrial dysfunction plays a major role in abnormal energy metabolism.

The potential of many substances for the treatment of ME/CFS has been examined; however, satisfactory outcomes have not yet been achieved. The development of new substances for curative, not symptomatic, treatments is desired.

Molecular hydrogen (H2) ameliorates mitochondrial dysfunction by scavenging hydroxyl radicals, the most potent oxidant among reactive oxygen species.

Animal experiments and clinical trials reported that H2 exerted ameliorative effects on acute and chronic fatigue. Therefore, we conducted a literature review on the mechanism by which H2 improves acute and chronic fatigue in animals and healthy people and showed that the attenuation of mitochondrial dysfunction by H2 may be involved in the ameliorative effects.

Although further clinical trials are needed to determine the efficacy and mechanism of H2 gas in ME/CFS, our literature review suggested that H2 gas may be an effective medical gas for the treatment of ME/CFS.

Source: Shin-ichi Hirano, Yusuke Ichikawa, Bunpei Sato, Yoshiyasu Takefuji and Fumitake Satoh. Molecular Hydrogen as a Medical Gas for the Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Possible Efficacy Based on a Literature Review. Front. Neurol., 11 April 2022  https://doi.org/10.3389/fneur.2022.841310 (Full text)

The underlying sex differences in neuroendocrine adaptations relevant to Myalgic Encephalomyelitis Chronic Fatigue Syndrome

Abstract:

Introduction: Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome (ME/CFS) is a complex multisystem disease characterised by severe and disabling new-onset symptoms of post-exertional malaise (PEM), fatigue, brain fog, and sleep dysfunction that lasts for at least six months. Accumulating evidence suggests that sex and endocrine events have a significant influence on symptom onset and moderation of ME/CFS, with female sex being one of the most consistent and credible predictive risk factors associated with diagnosis. Such sex differences suggest sex chromosomes and sex steroids may play a part in the development of the condition or moderation of symptoms, although this has yet to be explored in detail.

Methods/aims: This narrative review outlines sex differences in ME/CFS in terms of vulnerability factors and clinical phenotype and explores the known sex differences in neuroendocrine systems affected in ME/CFS and how this may relate to disease risk, onset, pathophysiology, and potential treatment avenues.

Conclusions: There is clear evidence of a sex dimorphism with regards to prevalence (3:1 female preponderance), clinical phenotypes, and aetiological triggers prior to symptom onset of ME/CFS. Endocrinological events, particularly those throughout the female lifespan, are associated with ME/CFS and include reproductive menstrual cycle fluctuations, pregnancy, post-partum and perimenopause. Further, there is evidence for gonadal sex, adrenal stress and renal neuroendocrine systems as implicated in ME/CFS, including changes in estrogen, progesterone compounds, aldosterone, and cortisol levels, of which there are established sex differences. The broad effects of steroid hormones on the physiological systems may also speak to the diversity of ME/CFS symptomatology observed in patients. Further attention must be paid to sex, age, and steroid biology in ME/CFS.

Source: Thomas N, Gurvich C, Huang K, Gooley PR, Armstrong CW. The underlying sex differences in neuroendocrine adaptations relevant to Myalgic Encephalomyelitis Chronic Fatigue Syndrome. Front Neuroendocrinol. 2022 Apr 11:100995. doi: 10.1016/j.yfrne.2022.100995. Epub ahead of print. PMID: 35421511. https://www.sciencedirect.com/science/article/abs/pii/S0091302222000188?via%3Dihub  (Full text)

Dietary Recommendations for Post-COVID-19 Syndrome

Abstract:

At the beginning of the coronavirus disease (COVID-19) pandemic, global efforts focused on containing the spread of the virus and avoiding contagion. Currently, it is evident that health professionals should deal with the overall health status of COVID-19 survivors. Indeed, novel findings have identified post-COVID-19 syndrome, which is characterized by malnutrition, loss of fat-free mass, and low-grade inflammation. In addition, the recovery might be complicated by persistent functional impairment (i.e., fatigue and muscle weakness, dysphagia, appetite loss, and taste/smell alterations) as well as psychological distress.

Therefore, the appropriate evaluation of nutritional status (assessment of dietary intake, anthropometrics, and body composition) is one of the pillars in the management of these patients. On the other hand, personalized dietary recommendations represent the best strategy to ensure recovery. Therefore, this review aimed to collect available evidence on the role of nutrients and their supplementation in post-COVID-19 syndrome to provide a practical guideline to nutritionists to tailor dietary interventions for patients recovering from COVID-19 infections.

Source: Barrea L, Grant WB, Frias-Toral E, Vetrani C, Verde L, de Alteriis G, Docimo A, Savastano S, Colao A, Muscogiuri G. Dietary Recommendations for Post-COVID-19 Syndrome. Nutrients. 2022 Mar 20;14(6):1305. doi: 10.3390/nu14061305. PMID: 35334962; PMCID: PMC8954128. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8954128/(Full text)

Magnetic Resonance Imaging Confirmed Olfactory Bulb Reduction in Long COVID-19: Literature Review and Case Series

Abstract:

An altered sense of smell and taste was recognized as one of the most characteristic symptoms of coronavirus infection disease (COVID-19). Despite most patients experiencing a complete functional resolution, there is a 21.3% prevalence of persistent alteration at 12 months after infection. To date, magnetic resonance imaging (MRI) findings in these patients have been variable and not clearly defined. We aimed to clarify radiological alterations of olfactory pathways in patients with long COVID-19 characterized by olfactory dysfunction.
A comprehensive review of the English literature was performed by analyzing relevant papers about this topic. A case series was presented: all patients underwent complete otorhinolaryngology evaluation including the Sniffin’ Sticks battery test. A previous diagnosis of SARS-CoV-2 infection was confirmed by positive swabs. The MRIs were acquired using a 3.0T MR scanner with a standardized protocol for olfactory tract analysis. Images were first analysed by a dedicated neuroradiologist and subsequently reviewed and compared with the previous available MRIs.
The review of the literature retrieved 25 studies; most cases of olfactory dysfunction more than 3 months after SARS-CoV-2 infection showed olfactory bulb (OB) reduction. Patients in the personal case series had asymmetry and a reduction in the volume of the OB. This evidence was strengthened by the comparison with a previous MRI, where the OBs were normal. The results preliminarily confirmed OB reduction in cases of long COVID-19 with an altered sense of smell. Further studies are needed to clarify the epidemiology, pathophysiology and prognosis.
Source: Frosolini A, Parrino D, Fabbris C, Fantin F, Inches I, Invitto S, Spinato G, Filippis CD. Magnetic Resonance Imaging Confirmed Olfactory Bulb Reduction in Long COVID-19: Literature Review and Case Series. Brain Sciences. 2022; 12(4):430. https://doi.org/10.3390/brainsci12040430 (Full text)

Registered clinical trials investigating treatment of long COVID: a scoping review and recommendations for research

Abstract:

Background: A considerable proportion of individuals report persistent, debilitating and disparate symptoms despite resolution of acute COVID-19 infection (i.e. long COVID). Numerous registered clinical trials investigating treatment of long COVID are expected to be completed in 2021–2022. The aim of this review is to provide a scope of the candidate treatments for long COVID. A synthesis of ongoing long COVID clinical trials can inform methodologic approaches for future studies and identify key research vistas.

Methods: Scoping searches were conducted on multiple national and international clinical trial registries. Interventional trials testing treatments for long COVID were selected. The search timeline was from database inception to 28 July 2021.

Results: This scoping review included 59 clinical trial registration records from 22 countries with a total projected enrolment of 6718. Considerable heterogeneity was exhibited amongst component records with respect to the characterization of long COVID (i.e. name, symptoms- including frequency, intensity, trajectory and duration- mode of ascertainment, and definition of acute phase). In addition, the majority of proposed interventions were non-pharmacological and either targeted multiple long COVID symptoms simultaneously, or focussed on treatment of respiratory/pulmonary sequelae. Multiple interventions targeted inflammation, as well as tissue oxygenation and cellular recovery, and several interventions were repurposed from analogous conditions.

Conclusions: The results of this scoping review investigating ongoing clinical trials testing candidate treatments for long COVID suggest that a greater degree of definitional stringency and homogeneity is needed insofar as the characterization of long COVID and inclusion/exclusion criteria.

Source: Ceban F, Leber A, Jawad MY, Yu M, Lui LMW, Subramaniapillai M, Di Vincenzo JD, Gill H, Rodrigues NB, Cao B, Lee Y, Lin K, Mansur RB, Ho R, Burke MJ, Rosenblat JD, McIntyre RS. Registered clinical trials investigating treatment of long COVID: a scoping review and recommendations for research. Infect Dis (Lond). 2022 Mar 14:1-11. doi: 10.1080/23744235.2022.2043560. Epub ahead of print. PMID: 35282780; PMCID: PMC8935463. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8935463/ (Full text)

The Role of Nutrients in Prevention, Treatment and Post-Coronavirus Disease-2019 (COVID-19)

Abstract:

SARS-CoV-2 virus, infecting human cells via its spike protein, causes Coronavirus disease 2019 (COVID-19). COVID-19 is characterized by shortness of breath, fever, and pneumonia and is sometimes fatal. Unfortunately, to date, there is still no definite therapy to treat COVID-19. Therefore, the World Health Organization (WHO) approved only supportive care. During the COVID-19 pandemic, the need to maintain a correct intake of nutrients to support very weakened patients in overcoming disease arose. The literature available on nutrient intake for COVID-19 is mainly focused on prevention. However, the safe intake of micro- and/or macro-nutrients can be useful either for preventing infection and supporting the immune response during COVID-19, as well as in the post-acute phase, i.e., “long COVID”, that is sometimes characterized by the onset of various long lasting and disabling symptoms. The aim of this review is to focus on the role of nutrient intake during all the different phases of the disease, including prevention, the acute phase, and finally long COVID.

Source: Motti ML, Tafuri D, Donini L, Masucci MT, De Falco V, Mazzeo F. The Role of Nutrients in Prevention, Treatment and Post-Coronavirus Disease-2019 (COVID-19). Nutrients. 2022 Feb 26;14(5):1000. doi: 10.3390/nu14051000. PMID: 35267974; PMCID: PMC8912782. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8912782/ (Full text)

The effectiveness of pulmonary rehabilitation for Post-COVID symptoms: A rapid review of the literature

Abstract:

Background: Multi-disciplinary rehabilitation is recommended for individuals with post-acute sequelae of COVID-19 infection (i.e., symptoms 3-4 weeks after acute infection). There are emerging reports of use of pulmonary rehabilitation (PR) in the post-acute stages of COVID-19, however the appropriateness of PR for managing post-COVID symptoms remains unclear. To offer practical guidance with regards to post-COVID PR, a greater understanding of the clinical effectiveness literature is required.

Methods: A rapid review of the published literature was completed. An electronic database search of the literature published between July 1, 2020 and June 1, 2021 was performed in MEDLINE, Pubmed, and EMBASE. Primary studies evaluating the clinical effectiveness of PR for individuals with post-COVID symptoms were included.

Results: Nine studies evaluating the effectiveness of PR were identified; most were small, experimental or quasi-experimental studies, including 1 RCT, and were primarily of low quality. After attending PR, all studies reported improvements in exercise capacity, pulmonary function, and/or quality of life for individuals with post-COVID symptoms who had been hospitalized for their acute COVID-19 infection. Few studies evaluated changes in post-COVID symptom severity or frequency and, of these, improvements in dyspnea, fatigue, anxiety and depression were observed following PR. Further, no studies evaluated non-hospitalized patients or long-term outcomes beyond 3 months after initiating PR.

Conclusions: With limited high-quality evidence, any recommendations or practical guidance for PR programmes for those with post-COVID symptoms should consider factors such as feasibility, current PR capacity, and resource constraints.

Source: Soril LJJ, Damant RW, Lam GY, Smith MP, Weatherald J, Bourbeau J, Hernandez P, Stickland MK. The effectiveness of pulmonary rehabilitation for Post-COVID symptoms: A rapid review of the literature. Respir Med. 2022 Mar 2;195:106782. doi: 10.1016/j.rmed.2022.106782. Epub ahead of print. PMID: 35272262; PMCID: PMC8887973. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8887973/ (Full text)

Enhancing the management of long COVID in general practice: a scoping review

Abstract:

Background: Long COVID is a multifaceted condition, and it has impacted a considerable proportion of those with acute-COVID-19. Affected patients often have complex care needs requiring holistic and multidisciplinary care, the kind routinely provided in general practice. However, there is limited evidence regarding GP interventions.

Aim: This study aimed to address this issue by conducting a scoping review of literature on GP management of Long COVID.

Design & setting: Arksey and O’Malley’s six-stage scoping review framework with recommendations by Levac et al. was used.

Method: PubMed, Google Scholar, the Cochrane Library, SCOPUS, and Google searches were conducted to identify relevant peer-reviewed/grey literature, and study selection process was conducted according to the PRISMA Extension for Scoping Reviews guidelines. Braun and Clarke’s ‘Thematic Analysis’ approach was used to interpret data.

Results: Nineteen of 972 identified papers were selected for review. These included peer-reviewed articles and grey literature spanning a wide range of countries. Six themes were identified regarding GP management of Long COVID, these being: (i) GP uncertainty, (ii) Listening and empathy, (iii) Assessment and monitoring of symptoms, (iv) Coordinating access to appropriate services, (v) Facilitating provision of continual and integrated multi-disciplinary care and (vi) Need to facilitate psychological support.

Conclusion: The findings show that GPs can and have played a key role in the management of Long COVID, and that patient care can be improved through better understanding of patient experiences, standardised approaches for symptom identification/treatment, and facilitation of access to multidisciplinary specialist services when needed. Future research evaluating focused GP interventions is needed.

Source: Brennan A, Broughan JM, McCombe G, Brennan J, Collins C, Fawsitt R, Gallagher J, Guérandel A, O’Kelly B, Quinlan D, Lambert JS, Cullen W. Enhancing the management of long COVID in general practice: a scoping review. BJGP Open. 2022 Mar 7:BJGPO.2021.0178. doi: 10.3399/BJGPO.2021.0178. Epub ahead of print. PMID: 35256357.  https://bjgpopen.org/content/early/2022/03/06/BJGPO.2021.0178 (Full text available as PDF file)