Tag: 2022

Rationale for Nicotinamide Adenine Dinucleotide (NAD+) Metabolome Disruption as a Pathogenic Mechanism of Post-Acute COVID-19 Syndrome

Abstract:

Many acute COVID-19 convalescents experience a persistent sequelae of infection, called post-acute COVID-19 syndrome (PACS). With incidence ranging between 31% and 69%, PACS is becoming increasingly acknowledged as a new disease state in the context of SARS-CoV-2 infection. As SARS-CoV-2 infection can affect several organ systems to varying degrees and durations, the cellular and molecular abnormalities contributing to PACS pathogenesis remain unclear.

Despite our limited understanding of how SARS-CoV-2 infection promotes this persistent disease state, mitochondrial dysfunction has been increasingly recognized as a contributing factor to acute SARS-CoV-2 infection and, more recently, to PACS pathogenesis. The biological mechanisms contributing to this phenomena have not been well established in previous literature; however, in this review, we summarize the evidence that NAD+ metabolome disruption and subsequent mitochondrial dysfunction following SARS-CoV-2 genome integration may contribute to PACS biological pathogenesis.

We also briefly examine the coordinated and complex relationship between increased oxidative stress, inflammation, and mitochondrial dysfunction and speculate as to how SARS-CoV-2-mediated NAD+ depletion may be causing these abnormalities in PACS. As such, we present evidence supporting the therapeutic potential of intravenous administration of NAD+ as a novel treatment intervention for PACS symptom management.

Source: Block T, Kuo J. Rationale for Nicotinamide Adenine Dinucleotide (NAD+) Metabolome Disruption as a Pathogenic Mechanism of Post-Acute COVID-19 Syndrome. Clin Pathol. 2022 Jun 24;15:2632010X221106986. doi: 10.1177/2632010X221106986. PMID: 35769168; PMCID: PMC9234841. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9234841/ (Full text)

Evidence of previous SARS-CoV-2 infection in seronegative patients with long COVID

Abstract:

Background: There is currently no consensus on the diagnosis, definition, symptoms, or duration of COVID-19 illness. The diagnostic complexity of Long COVID is compounded in many patients who were or might have been infected with SARS-CoV-2 but not tested during the acute illness and/or are SARS-CoV-2 antibody negative.

Methods: Given the diagnostic conundrum of Long COVID, we set out to investigate SARS-CoV-2-specific T cell responses in patients with confirmed SARS-CoV-2 infection and/or Long COVID from a cohort of mostly non-hospitalised patients.

Findings: We discovered that IL-2 release (but not IFN-γ release) from T cells in response to SARS-CoV-2 peptides is both sensitive (75% +/-13%) and specific (88%+/-7%) for previous SARS-CoV-2 infection >6 months after a positive PCR test. We identified that 42-53% of patients with Long COVID, but without detectable SARS-CoV-2 antibodies, nonetheless have detectable SARS-CoV-2 specific T cell responses.

Interpretation: Our study reveals evidence (detectable T cell mediated IL-2 release) of previous SARS-CoV-2 infection in seronegative patients with Long COVID.

Funding: This work was funded by the Addenbrooke’s Charitable Trust (900276 to NS), NIHR award (G112259 to NS) and supported by the NIHR Cambridge Biomedical Research Centre. NJM is supported by the MRC (TSF MR/T032413/1) and NHSBT (WPA15-02). PJL is supported by the Wellcome Trust (PRF 210688/Z/18/Z, 084957/Z/08/Z), a Medical Research Council research grant MR/V011561/1 and the United Kingdom Research and a Innovation COVID Immunology Consortium grant (MR/V028448/1).

Source: Krishna BA, Lim EY, Mactavous L; NIHR BioResource Team, Lyons PA, Doffinger R, Bradley JR, Smith KGC, Sinclair J, Matheson NJ, Lehner PJ, Wills MR, Sithole N. Evidence of previous SARS-CoV-2 infection in seronegative patients with long COVID. EBioMedicine. 2022 Jul;81:104129. doi: 10.1016/j.ebiom.2022.104129. Epub 2022 Jun 27. PMID: 35772216; PMCID: PMC9235296. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9235296/ (Full text)

Disorders of gut-brain interaction in post-acute COVID-19 syndrome

Abstract:

The novel coronavirus SARS-CoV-2 is responsible for the devastating pandemic which has caused more than 5 million deaths across the world until today. Apart from causing acute respiratory illness and multiorgan dysfunction, there can be long-term multiorgan sequalae after recovery, which is termed ‘long COVID-19’ or ‘post-acute COVID-19 syndrome’. Little is known about long-term gastrointestinal (GI) consequences, occurrence of post-infection functional gastrointestinal disorders and impact the virus may have on overall intestinal health.

In this review, we put forth the various mechanisms which may lead to this entity and possible ways to diagnose and manage this disorder. Hence, making physicians aware of this spectrum of disease is of utmost importance in the present pandemic and this review will help clinicians understand and suspect the occurrence of functional GI disease post recovery from COVID-19 and manage it accordingly, avoiding unnecessary misconceptions and delay in treatment.

Source: Golla R, Vuyyuru SK, Kante B, Kedia S, Ahuja V. Disorders of gut-brain interaction in post-acute COVID-19 syndrome. Postgrad Med J. 2022 Jul 1:postgradmedj-2022-141749. doi: 10.1136/pmj-2022-141749. Epub ahead of print. PMID: 35777934. https://pmj.bmj.com/content/early/2022/07/01/pmj-2022-141749 (Full text)

Orthostatic Challenge Causes Distinctive Symptomatic, Hemodynamic and Cognitive Responses in Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Background: Some patients with acute COVID-19 are left with persistent, debilitating fatigue, cognitive impairment (“brain fog”), orthostatic intolerance (OI) and other symptoms (“Long COVID”). Many of the symptoms are like those of other post-infectious fatigue syndromes and may meet criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Common diagnostic laboratory tests are often unrevealing.

Methods: We evaluated whether a simple, standardized, office-based test of OI, the 10-min NASA Lean Test (NLT), would aggravate symptoms and produce objective hemodynamic and cognitive abnormalities, the latter being evaluated by a simple smart phone-based app.

Participants: People with Long COVID (N = 42), ME/CFS (N = 26) and healthy control subjects (N = 20) were studied just before, during, immediately after, 2 and 7 days following completion of the NLT.

Results: The NLT provoked a worsening of symptoms in the two patient groups but not in healthy control subjects, and the severity of all symptoms was similar and significantly worse in the two patient groups than in the control subjects (p < 0.001). In the two patient groups, particularly those with Long COVID, the NLT provoked a marked and progressive narrowing in the pulse pressure. All three cognitive measures of reaction time worsened in the two patient groups immediately following the NLT, compared to the healthy control subjects, particularly in the Procedural Reaction Time (p < 0.01).

Conclusions: A test of orthostatic stress easily performed in an office setting reveals different symptomatic, hemodynamic and cognitive abnormalities in people with Long COVID and ME/CFS, compared to healthy control subjects. Thus, an orthostatic challenge easily performed in an office setting, and the use of a smart phone app to assess cognition, can provide objective confirmation of the orthostatic intolerance and brain fog reported by patients with Long COVID and ME/CFS.

Source: Vernon SD, Funk S, Bateman L, Stoddard GJ, Hammer S, Sullivan K, Bell J, Abbaszadeh S, Lipkin WI, Komaroff AL. Orthostatic Challenge Causes Distinctive Symptomatic, Hemodynamic and Cognitive Responses in Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Front Med (Lausanne). 2022 Jun 23;9:917019. doi: 10.3389/fmed.2022.917019. PMID: 35847821; PMCID: PMC9285104. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9285104/ (Full text)

The Qigong of Prolong Life With Nine Turn Method Relieve Fatigue, Sleep, Anxiety and Depression in Patients With Chronic Fatigue Syndrome: A Randomized Controlled Clinical Study

Abstract

Background: Chronic fatigue syndrome (CFS) is a complex disease of unknown etiology and mechanism. The purpose of this study was to investigate the effect of Prolong Life with Nine Turn Method (PLWNT) Qigong exercise on CFS focusing on fatigue, sleep quality, depression, and anxiety.

Methods: A total of 90 participants diagnosed with CFS were randomly assigned into two parallel groups: PLWNT and cognitive behavioral therapy (CBT). The participants in the PLWNT or CBT group participated in qigong exercise or cognitive behavior education program, respectively, once a week in-person and were supervised online during the remaining 6 days at home, over 12 consecutive weeks. The primary outcome was fatigue (Multi-dimensional Fatigue Inventory 20 [MFI-20]), and secondary outcomes were sleep quality (Pittsburgh Sleep Quality Index [PSQI]), anxiety, depression (Hospital Anxiety and Depression Scale [HADS]), and changes in the Neuropeptide Y (NPY) of peripheral blood.

Results: The within-group comparisons of the PLWNT and CBT groups revealed significant improvement in both groups in MFI-20, PSQI, and HADS scores (P < 0.05). No significant difference were found between the PLWNT and CBT groups, even though the effective rate of the PLWNT group was 62.22%, which is slightly than 50.00% of the CBT group. The fatigue scores in the PLWNT group were positively correlated with sleep degree (r = 0.315) and anxiety degree (r = 0.333), only anxiety degree (r = 0.332) was found to be positively correlated with fatigue in the CBT group. The analysis of peripheral blood showed that NPY decreased after PLWNT intervention but increased significantly in the CBT.

Conclusion: The PLWNT qigong exercise has potential to be an effective rehabilitation method for CFS symptoms including fatigue, sleep disturbance, anxiety, and depression. Future studies should expand study sample size for in-depth investigation to determine the optimal frequency and intensity of PLWNT qigong intervention in CFS patients. The study was registered in the ClinicalTrials.gov database on April 12, 2018, with registration number NCT03496961.

Source: Xie F, You Y, Guan C, Xu J, Yao F. The Qigong of Prolong Life With Nine Turn Method Relieve Fatigue, Sleep, Anxiety and Depression in Patients With Chronic Fatigue Syndrome: A Randomized Controlled Clinical Study. Front Med (Lausanne). 2022 Jun 30;9:828414. doi: 10.3389/fmed.2022.828414. PMID: 35847786; PMCID: PMC9280429. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9280429/ (Full text)

Memory impairments in chronic fatigue syndrome patients

Abstract:

Background: Chronic Fatigue Syndrome (CFS) patients often report memory problems. Prior research has produced conflicting results on this topic. Episodic memory impairments appear to be robust, but tasks assessing other aspects of memory (e.g., working and semantic memory) show slower speed but no decrease in accuracy. This study examined whether the memory problems of CFS patients reflect slower responses. Methods: CFS patients were recruited from a specialist clinic. Sixty-seven patients carried out tasks measuring immediate recall, delayed recognition memory, logical reasoning and semantic processing. The control group were 126 healthy volunteers recruited from the general population.

Results: The CFS patients recalled fewer words and had poorer delayed recognition. The other tasks showed slower speed but no effect on accuracy.

Conclusions: CFS patients have poorer immediate recall and delayed recognition memory. The delayed recognition memory probably reflected the poorer immediate recall. Slower responding was present in three of the tasks, and it is possible that this also accounted for the reduced immediate recall.

Source:  Smith, Andrew. Memory impairments in chronic fatigue syndrome patients. wjpmr, 2022, 8(6), 50-54. ISSN 2455-3301 https://orca.cardiff.ac.uk/id/eprint/150176/1/article_1654063780_pub.pdf (Full text)

Dietary supplements, daily nutrient intake, and health-related quality of life among people with myalgic encephalomyelitis/chronic fatigue syndrome

There remains ambiguity surrounding the role of dietary supplementation and nutrient intake on the health status of myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) patients, yet supplement use and dietary modification appear to be common among people with the condition. This pilot cross-sectional study aimed to investigate if supplement use or nutrient intake was associated with self-reported health-related quality of life (HRQoL) scores among Australians with ME/CFS.

The eligibility criteria for this study included being a resident of Australia, being aged between 18 and 65 years, and having received a formal diagnosis of ME/CFS from a physician. Participants completed a series of self-administered questionnaires querying sociodemographic information, symptom presentation, HRQoL, routine supplement use, and nutrient intake. The 36-item Short-Form Health Survey version 2 (SF-36) was employed to assess participants’ HRQoL. Daily nutrient intake was estimated from participants’ responses to the Dietary Questionnaire for Epidemiological Studies (Cancer Council Victoria, Australia). Multiple linear regression analysis was performed for each of the eight SF-36 domains. Age, gender, body mass index, employment, education were controlled variables in each model, with supplement and nutrient variables entered in a stepwise manner.

Twenty-four Australians with ME/CFS, 54.2% of which met the International Consensus Criteria case definition for ME/CFS, participated in the study. Three of the eight regression models were statistically significant, being the ‘role limitations due to physical health problems’ (adjusted R 2 = 0.733, P < 0.001), ‘bodily pain’ (adjusted R 2 = 0.544, P = 0.004), and ‘general health perceptions’ (adjusted R 2 = 0.743, P < 0.001) SF-36 domains. Positive associations were observed between HRQoL and the routine use of vitamin C (ß = 0.300, P = 0.042) and herbal supplements (ß = 0.618, P < 0.001), as well as daily saturated fat (ß = 0.860, P < 0.001), total folate (ß = 0.710, P < 0.001), and calcium intake (ß = 0.897, P = 0.003). However, the routine use of evening primrose oil supplements (ß = -0.385, P = 0.006) and daily intakes of alpha-linolenic acid (ß = −0.543, P = 0.001), long chain omega-3 fatty acids (ß = −0.431, P = 0.017), and iodine (ß = −0.602, P = 0.034) were negatively associated with HRQoL scores. None of the supplements or nutrients studied had consistent associations with HRQoL across the three significant regression models.

The findings of this pilot study suggest that there may be links between dietary supplementation and nutrient intake with HRQoL among people with ME/CFS. Future studies should investigate supplement use, daily nutrient intake, and their relationships with HRQoL and symptom presentation among people with ME/CFS longitudinally and compared with healthy controls to further elucidate the role of supplements and nutrient intake in the management of ME/CFS.

Read the full study HERE.

Source: Weigel, B., Eaton-Fitch, N., Passmore, R., Cabanas, H., Staines, D., & Marshall-Gradisnik, S. (2022). Dietary supplements, daily nutrient intake, and health-related quality of life among people with myalgic encephalomyelitis/chronic fatigue syndrome. Proceedings of the Nutrition Society, 81(OCE3), E80. doi:10.1017/S0029665122001057 https://www.cambridge.org/core/journals/proceedings-of-the-nutrition-society/article/dietary-supplements-daily-nutrient-intake-and-healthrelated-quality-of-life-among-people-with-myalgic-encephalomyelitischronic-fatigue-syndrome/F837EC4FE783FFAEB44F66F7748C11F6 (Full text)

Semen raphani weakened the action of ginseng under chronic fatigue condition

Abstract:

Ethnopharmacological relevance: Fatigue is a kind of subhealth status and people paid much more attention on it. Ginseng is used to treating fatigue as a kind of qi -tonifying drug in Chinese medicine. In the traditional applications, there is a viewpoint that ginseng could not be used with semen raphani and supposed that semen raphani is a kind of qi regulating drug, which will reduce the qi invigorating effect of ginseng. However, the underlying combination mechanism of the two drugs remained unclear.

Aim of the study: The aim of this study is to explore whether ginseng can be used with semen raphani or not to remedy acute and chronic fatigue conditions.

Methods: We used normal and weight-bearing swimming method combined with appetite control animals. The biochemical indexes in energy metabolism, antioxidant, regulating endocrine system and immunity capacities were performed to explore the antagonism effect of semen raphani on ginseng under acute and chronic fatigue conditions. The serum and urine metabolomics were investigated using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF/MS). Fecal flora was analyzed via 16S rRNA amplicon sequencing.

Results: The combination of ginseng with semen raphani have no influence on acute fatigue effect compared with ginseng alone. Both can improve the exhausted swimming time, the activity of GSH-Px, LDH and Na+-K+-ATPase. Furthermore, the combination of ginseng with semen raphani can increase the urine volume of rats and down-regulate the content of AQP-3, which can alleviate the “fireness” side-effect of ginseng. But the abundance and diversity of bacterial are decreased under acute fatigue experiment. Both the combination of ginseng with semen raphani and ginseng alone can remedy chronic-fatigue. They can also regulate the endocrine system, immune system, citric acid cycle metabolism, tryptophan metabolism, fatty acid metabolism, glycolysis/gluconeogenesis, etc. Furthermore, they can promote substance metabolism and energy metabolism in qi deficiency rats, and increase the abundance and diversities of the flora. While with the increased content of semen raphani, the combination of ginseng and semen raphani weaken the capacity of antioxidant, lactic acid metabolism, energy metabolism, flora diversity and regulation of endocrine system.

Conclusion: Compared with ginseng alone, the combination of ginseng with semen raphani can weaken the qi invigorating ability under chronic fatigue condition. The more ratios of semen raphani is in the combination of the two drugs, the less the power of treating chronic fatigue is. Compared with ginseng alone, the combination of ginseng with semen raphani have no influence on the qi invigorating ability under actue fatigue experiment. But the combination of ginseng with semen raphani will benefit for the “fireness” side-effect of ginseng.

Source: Wang Y, Ma C, Dou D. Semen raphani weakened the action of ginseng under chronic fatigue condition. J Ethnopharmacol. 2022 Sep 15;295:115352. doi: 10.1016/j.jep.2022.115352. Epub 2022 May 19. PMID: 35598795. https://pubmed.ncbi.nlm.nih.gov/35598795/

The higher resting heart rate in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients compared to healthy controls: relation with stroke volumes

Abstract:

Introduction: In patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) a higher-than-normal resting heart rate has been reported in a number of studies. As heart rate is linked to stroke volume, the present study explored the relationship between the supine heart rate and stroke volume index in healthy controls and in ME/CFS patients. Moreover, as patients with a postural orthostatic tachycardia syndrome (POTS) during tilt testing, have a higher supine heart rate than patients with a normal heart rate and blood pressure response during tilting, these two patient groups were also compared.

Methods and results: From a database of individuals who had undergone tilt-testing, including supine Doppler measurements for stroke volume index calculation, we selected ME/CFS patients and healthy controls without evidence of hypotension or syncope. 474 ME/CFS patients were analyzed, 314 with a normal heart rate and blood pressure response and 160 with POTS during tilt-testing, and 56 healthy controls. Resting stroke volume indices were similar between the 3 groups. All 3 groups had an inverse relation between the resting stroke volume index and resting heart rate (all p<0.0001). The slope of the relation was not significantly different between the 3 groups. Using the upper limit of the 95% prediction interval for the heart rate of healthy controls, 46 (15%) of patients with a normal heart rate and blood pressure response had a resting heart rate above the upper limit, 248 (85%) a heart rate between the upper and lower limit. In 47 (29%) patients developing POTS the resting heart rate was above the upper limit, and in 113 (71%) patients within the upper limit and lower limit. This distribution was significantly different between the two patient groups (p=0.0001).

Conclusion: Patients and healthy controls showed a significant and inverse relation between the SVI and heart rate at rest. Already at rest heart rate in patients developing POTS during tilt-testing were higher compared to the patients with a normal heart rate and blood pressure response per unit of SVI, but the heart rate of the majority of all patients fell within the limits of normal of healthy controls. The difference of patients with heart rate above the upper limit versus between the upper limit and lower limit deserves further investigation and may have therapeutic implications.

Source: VAN CAMPEN, C (Linda) M.C.; VISSER, Frans C.. The higher resting heart rate in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients compared to healthy controls: relation with stroke volumes.. Medical Research Archives, [S.l.], v. 10, n. 6, june 2022. ISSN 2375-1924. Available at: https://esmed.org/MRA/mra/article/view/2891. Date accessed: 17 july 2022. doi: https://doi.org/10.18103/mra.v10i6.2891.

Comparison of the Degree of Deconditioning in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Patients with and without Orthostatic Intolerance

Abstract:

Background: Orthostatic intolerance (OI) is a core finding in individuals with myalgic encephalomyelitis /chronic fatigue syndrome (ME/CFS). Deconditioning is often proposed as an important determinant for OI. Deconditioning can be objectively classified using the predicted peak oxygen consumption (%VO2 peak) values as derived from cardiopulmonary exercise testing (CPET) and OI can be objectively quantified using cerebral blood flow (CBF) changes during tilt testing. Therefore, if deconditioning contributes to OI, a correlation between peak VO2 and the %CBF reduction is expected.

Methods and results: 18 healthy controls (HC) and 122 ME/CFS patients without hypotension or tachycardia on tilt testing were studied. Deconditioning was classified as follows: %VO2 peak ≥85%= no deconditioning, %VO2 peak 65-85%= mild deconditioning, %VO2 peak<65%= severe deconditioning. HC had higher %VO2 peak compared to ME/CFS patients (p<0.0001). ME/CFS patients had significantly larger CBF reduction than HC (p<0.0001). No relation between the degree of deconditioning by the %VO2 peak and the %CBF reduction in ME/CFS patients was found. Moreover, we separately analyzed ME/CFS patients without an abnormal CBF reduction. Despite equal CBF reductions compared to HC and large differences between these patients and the patients with an abnormal CBF reduction, cardiac index (CI) changes (measured by suprasternal Doppler) were significantly less compared to ME/CFS patients with an abnormal CBF reduction (p<0.0001) but larger than in HC (p=0.004). Despite these different hemodynamic findings, %VO2 values were not different between the two patient groups, argumenting again against the causative role of hemodynamic abnormalities in deconditioning.

Conclusion: In ME/CFS patients without hypotension or tachycardia there is no relation between the %VO2 peak during CPET and the %CBF and %CI reduction during tilt testing, whether or not patients have an abnormal CBF reduction during tilt testing. It suggests again that deconditioning does not play an important role in OI.

Source: VAN CAMPEN, C (Linda) M.C.; VISSER, Frans C.. Comparison of the Degree of Deconditioning in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Patients with and without Orthostatic Intolerance. Medical Research Archives, [S.l.], v. 10, n. 6, june 2022. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/2858>. Date accessed: 17 july 2022. doi: https://doi.org/10.18103/mra.v10i6.2858.