Tag: review

Pathophysiology and mechanism of long COVID: a comprehensive review

Abstract:

Background: After almost 2 years of fighting against SARS-CoV-2 pandemic, the number of patients enduring persistent symptoms long after acute infection is a matter of concern. This set of symptoms was referred to as “long COVID”, and it was defined more recently as “Post COVID-19 condition” by the World health Organization (WHO). Although studies have revealed that long COVID can manifest whatever the severity of inaugural illness, the underlying pathophysiology is still enigmatic.

Aim: To conduct a comprehensive review to address the putative pathophysiology underlying the persisting symptoms of long COVID.

Method: We searched 11 bibliographic databases (Cochrane Library, JBI EBP Database, Medline, Embase, PsycInfo, CINHAL, Ovid Nursing Database, Journals@Ovid, SciLit, EuropePMC, and CoronaCentral). We selected studies that put forward hypotheses on the pathophysiology, as well as those that encompassed long COVID patients in their research investigation.

Results: A total of 98 articles were included in the systematic review, 54 of which exclusively addressed hypotheses on pathophysiology, while 44 involved COVID patients. Studies that included patients displayed heterogeneity with respect to the severity of initial illness, timing of analysis, or presence of a control group. Although long COVID likely results from long-term organ damage due to acute-phase infection, specific mechanisms following the initial illness could contribute to the later symptoms possibly affecting many organs. As such, autonomic nervous system damage could account for many symptoms without clear evidence of organ damage. Immune dysregulation, auto-immunity, endothelial dysfunction, occult viral persistence, as well as coagulation activation are the main underlying pathophysiological mechanisms so far.

Conclusion: Evidence on why persistent symptoms occur is still limited, and available studies are heterogeneous. Apart from long-term organ damage, many hints suggest that specific mechanisms following acute illness could be involved in long COVID symptoms.

KEY MESSAGES:

  • Long-COVID is a multisystem disease that develops regardless of the initial disease severity. Its clinical spectrum comprises a wide range of symptoms.
  • The mechanisms underlying its pathophysiology are still unclear. Although organ damage from the acute infection phase likely accounts for symptoms, specific long-lasting inflammatory mechanisms have been proposed, as well.
  • Existing studies involving Long-COVID patients are highly heterogeneous, as they include patients with various COVID-19 severity levels and different time frame analysis, as well.

Source: Castanares-Zapatero D, Chalon P, Kohn L, Dauvrin M, Detollenaere J, Maertens de Noordhout C, Primus-de Jong C, Cleemput I, Van den Heede K. Pathophysiology and mechanism of long COVID: a comprehensive review. Ann Med. 2022 Dec;54(1):1473-1487. doi: 10.1080/07853890.2022.2076901. PMID: 35594336; PMCID: PMC9132392. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9132392/ (Full text)

Pharmacological significance of MitoQ in ameliorating mitochondria-related diseases

Abstract:

The Mitochondria is a critical sub-cellular organelle that plays an integral part in a normal cellular process. Besides ATP production, the mitochondria participate in various key cellular processes such as cell signaling, epigenetic regulation leading to cell proliferation, migration, apoptosis, differentiation, and autophagy – highlighting their importance to cellular health. However, mitochondrial dysfunction has serious organismal consequences, playing critical roles in the pathophysiology of many diseases, including neurodegenerative disorders, cardiovascular diseases, cancer, pulmonary and liver diseases. In recent years, mitochondrial dysfunction has spurred a surge of interest in developing mitochondria-targeted therapies.

MitoQ is a selective antioxidant that concentrates in the mitochondria and prevents oxidative damage to the mitochondria. The therapeutic relevance of MitoQ has been studied in various diseased conditions to determine its efficacy in either slowing disease progression or alleviating symptoms. In this review, we discussed mitochondrial dysfunction in selected diseases and the therapeutic benefit of MitoQ in numerous studies.

Source: Lateef Adegboyega Sulaimon, Lukman Olalekan Afolabi, Rahmat Adetutu Adisa, Akinrinade George Ayankojo, Mariam Olanrewaju Afolabi, Abiodun Mohammed Adewolu, Xiaochun Wan. Pharmacological significance of MitoQ in ameliorating mitochondria-related diseases. Advances in Redox Research, 2022 [In Press, Journal pre-proof]  https://www.sciencedirect.com/science/article/pii/S2667137922000091 (Full text)

The Pathobiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: The Case for Neuroglial Failure

Abstract:

Although myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) has a specific and distinctive profile of clinical features, the disease remains an enigma because causal explanation of the pathobiological matrix is lacking. Several potential disease mechanisms have been identified, including immune abnormalities, inflammatory activation, mitochondrial alterations, endothelial and muscular disturbances, cardiovascular anomalies, and dysfunction of the peripheral and central nervous systems. Yet, it remains unclear whether and how these pathways may be related and orchestrated.

Here we explore the hypothesis that a common denominator of the pathobiological processes in ME/CFS may be central nervous system dysfunction due to impaired or pathologically reactive neuroglia (astrocytes, microglia and oligodendrocytes). We will test this hypothesis by reviewing, in reference to the current literature, the two most salient and widely accepted features of ME/CFS, and by investigating how these might be linked to dysfunctional neuroglia.

From this review we conclude that the multifaceted pathobiology of ME/CFS may be attributable in a unifying manner to neuroglial dysfunction. Because the two key features – post exertional malaise and decreased cerebral blood flow – are also recognized in a subset of patients with post-acute sequelae COVID, we suggest that our findings may also be pertinent to this entity.

Source: Renz-Polster H, Tremblay ME, Bienzle D, Fischer JE. The Pathobiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: The Case for Neuroglial Failure. Front Cell Neurosci. 2022 May 9;16:888232. doi: 10.3389/fncel.2022.888232. PMID: 35614970; PMCID: PMC9124899. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9124899/ (Full text)

Neurological and Psychiatric Symptoms of COVID-19: A Narrative Review

Abstract:

Recently dubbed Long COVID or Long-Haul COVID, those recovering from the initial COVID-19 infection may maintain clinical signs for longer than two or more weeks following the initial onset of the infection. The virus can gain entry into the CNS through axonal transport mediated through the olfactory nerve or hematogenous spread and can also cross the blood–brain barrier to access the temporal lobe and the brainstem. The neurologic and neuropsychiatric symptoms associated with COVID-19 patients are becoming a highly studied area due to the increased frequency of reported cases.
Multiple hospital case series and observational studies have found a headache to be a common symptom among patients who are symptomatic with the SARS-CoV-2 virus. The headache described by many of these patients is similar to new daily persistent headache (NDPH). NDPH potentially develops in response to pro-inflammatory cytokines during a persistent systemic or CNS inflammation, mostly due to the initial infection. The treatments investigated were high-dose steroids, tetracycline derivatives, onabotulinum toxin type A, and long-term multidrug regimens. Among the identified symptoms of post-COVID-19 viral illness, fatigue appears to be the most ubiquitous. High-dose vitamin C is currently a suggested therapy proposed for its antioxidant, anti-inflammatory, and immunomodulatory properties.
The mental health consequences of this diagnosis are being identified among large portions of COVID-19 survivors. Among these consequences, cases of major depressive disorder (MDD) and anxiety are being reported and closely examined. The aim of this narrative review is to highlight the neurological and psychiatric symptoms that have been associated with Long-Haul COVID and their possible treatments.
Source: Edinoff AN, Chappidi M, Alpaugh ES, Turbeville BC, Falgoust EP, Cornett EM, Murnane KS, Kaye AM, Kaye AD. Neurological and Psychiatric Symptoms of COVID-19: A Narrative Review. Psychiatry International. 2022; 3(2):158-168. https://doi.org/10.3390/psychiatryint3020013 https://www.mdpi.com/2673-5318/3/2/13/htm (Full text)

Intimate partner violence and women living with episodic disabilities: a scoping review protocol

Abstract:

Background: Violence towards women with disabilities is most commonly perpetrated by current or former intimate partners and more than half of disabled women experience intimate partner violence in their lifetime. Disabilities differ by presence, type, and complexity, yet are commonly researched collectively. A more nuanced understanding of the relationship between intimate partner violence and episodic disability is required to better support women living with these concurrent challenges. The objective of this scoping review is to investigate and synthesize the literature reporting on intimate partner violence for women living with an episodic disability to identify key concepts and knowledge gaps on this topic. Ultimately, this review aims to improve health services for this stigmatized group of women with episodic disabilities.

Methods: This scoping review will consider all studies that focus on women (18 years of age or older) who have experienced intimate partner violence and have an episodic disability. Episodic disabilities will include multiple sclerosis, chronic fatigue syndrome, fibromyalgia, lupus, or rheumatoid arthritis. The broad review question is what is known about intimate partner violence within the context of women living with an episodic disability? Databases to be searched include MEDLINE (OVID), CINAHL, Embase, PsychInfo, and Scopus with no limits on language or time frame. Joanna Briggs Institute methodology will guide this scoping review to address the review questions outlined in the protocol. For papers that meet the inclusion criteria, data will be extracted, and findings will be presented in tables and narrative form. A PRISMA table will be included to enhance the transparency of the process. A descriptive qualitative approach to analysis will be conducted following Braun and Clarke’s reflexive thematic analysis. The findings of the scoping review will be presented through a thematic narrative.

Discussion: Findings from this review will be used to identify important priorities for future research based on knowledge gaps and inform both health care practices and health and social interventions for women living with intimate partner violence and episodic disabilities.

Source: Campbell KA, Ford-Gilboe M, Stanley M, MacKinnon K. Intimate partner violence and women living with episodic disabilities: a scoping review protocol. Syst Rev. 2022 May 18;11(1):97. doi: 10.1186/s13643-022-01972-x. PMID: 35585642. https://systematicreviewsjournal.biomedcentral.com/articles/10.1186/s13643-022-01972-x  (Full text)

Unexplained post-acute infection syndromes

Abstract:

SARS-CoV-2 is not unique in its ability to cause post-acute sequelae; certain acute infections have long been associated with an unexplained chronic disability in a minority of patients. These post-acute infection syndromes (PAISs) represent a substantial healthcare burden, but there is a lack of understanding of the underlying mechanisms, representing a significant blind spot in the field of medicine.

The relatively similar symptom profiles of individual PAISs, irrespective of the infectious agent, as well as the overlap of clinical features with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), suggest the potential involvement of a common etiopathogenesis.

In this Review, we summarize what is known about unexplained PAISs, provide context for post-acute sequelae of SARS-CoV-2 infection (PASC), and delineate the need for basic biomedical research into the underlying mechanisms behind this group of enigmatic chronic illnesses.

Source: Choutka J, Jansari V, Hornig M, Iwasaki A. Unexplained post-acute infection syndromes. Nat Med. 2022 May;28(5):911-923. doi: 10.1038/s41591-022-01810-6. Epub 2022 May 18. PMID: 35585196. https://www.nature.com/articles/s41591-022-01810-6 (Full text)

Long COVID and neuropsychiatric manifestations (Review)

Abstract:

There is accumulating evidence in the literature indicating that a number of patients with coronavirus disease 2019 (COVID-19) may experience a range of neuropsychiatric symptoms, persisting or even presenting following the resolution of acute COVID-19. Among the neuropsychiatric manifestations more frequently associated with ‘long COVID’ are depression, anxiety, post-traumatic stress disorder, sleep disturbances, fatigue and cognitive deficits, that can potentially be debilitating and negatively affect patients’ wellbeing, albeit in the majority of cases symptoms tend to improve over time.

Despite variations in results obtained from studies using different methodological approaches to define ‘long COVID’ syndrome, the most widely accepted factors associated with a higher risk of developing neuropsychiatric manifestations include the severity of foregoing COVID-19, the female sex, the presence of comorbidities, a history of mental health disease and an elevation in the levels of inflammatory markers, albeit further research is required to establish causal associations. To date, the pathophysiological mechanisms implicated in neuropsychiatric manifestations of ‘long COVID’ remain only partially elucidated, while the role of the indirect effects of the COVID-19 pandemic, such as social isolation and uncertainty concerning social, financial and health recovery post-COVID, have also been highlighted.

Given the alarming effects of ‘long-COVID’, interdisciplinary cooperation for the early identification of patients who are at a high risk of persistent neuropsychiatric presentations, beyond COVID-19 recovery, is crucial to ensure that appropriate integrated physical and mental health support is provided, with the aim of mitigating the risks of long-term disability at a societal and individual level.

Source: Efstathiou V, Stefanou MI, Demetriou M, Siafakas N, Makris M, Tsivgoulis G, Zoumpourlis V, Kympouropoulos SP, Tsoporis JN, Spandidos DA, Smyrnis N, Rizos E. Long COVID and neuropsychiatric manifestations (Review). Exp Ther Med. 2022 May;23(5):363. doi: 10.3892/etm.2022.11290. Epub 2022 Apr 1. PMID: 35493431; PMCID: PMC9019760. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9019760/ (Full text)

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)