Tag: 2022

Chronic fatigue syndrome and cognitive deficit are associated with acute-phase neuropsychiatric manifestations of COVID-19: A 9-month follow-up study

Abstract:

The prevalence of long-COVID symptoms is rising but it is not still possible to predict which patients will present them, and which types of symptoms they will present. We followed up 95 patients with confirmed COVID-19 for 9 months to identify and characterize long-COVID symptoms.

Easy fatigability was the most common symptom (51.04%), followed by anxiety (38.54%), dyspnea (38.54%), and new-onset headache (38.54%). There was no association between COVID-19 severity in the acute phase and the number of long-COVID symptoms (F(1,93) = 0.75, p = 0.45), and cognitive function (MoCA) scores (F(1,90) = 0.073, p = 0.787) at follow-up. Being female (F(1,92) = – 2.27, p = 0.02), having a higher number of symptoms (F(1,93) = 2.76, p = 0.0068), and experiencing constitutional neuropsychiatric symptoms (F(1,93) = 2.529, p = 0.01) in the acute phase were associated with having chronic fatigue syndrome at follow-up.

Moreover, constitutional neuropsychiatric symptoms in the acute phase were associated with a lower MoCA score (F(1,93) = 10.84, p = 0.001) at follow-up. Specific clinical presentations such as constitutional neuropsychiatric symptoms in the acute phase might be predictors of debilitating long-COVID symptoms such as chronic fatigue syndrome and cognitive deficits.

Source: Mirfazeli FS, Sarabi-Jamab A, Pereira-Sanchez V, Kordi A, Shariati B, Shariat SV, Bahrami S, Nohesara S, Almasi-Dooghaee M, Faiz SHR. Chronic fatigue syndrome and cognitive deficit are associated with acute-phase neuropsychiatric manifestations of COVID-19: A 9-month follow-up study. Neurol Sci. 2022 Jan 21. doi: 10.1007/s10072-021-05786-y. Epub ahead of print. PMID: 35059902. https://pubmed.ncbi.nlm.nih.gov/35059902/

Psychogenic Pseudosyncope: Real or Imaginary? Results from a Case-Control Study in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Patients

Abstract:

Background and objectives: Orthostatic intolerance (OI) is a clinical condition in which symptoms worsen upon assuming and maintaining upright posture and are ameliorated by recumbency. OI has a high prevalence in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Exact numbers on syncopal spells especially if they are on a weekly or even daily basis are not described. Although not a frequent phenomenon, this symptomatology is of very high burden to the patient if present. To explore whether patients with very frequent (pre)syncope spells diagnosed elsewhere with conversion or psychogenic pseudosyncope (PPS) might have another explanation of their fainting spells than behavioral psychiatric disorders, we performed a case-control study comparing ME/CFS patients with and without PPS spells.

Methods and results: We performed a case-control study in 30 ME/CFS patients diagnosed elsewhere with PPS and compared them with 30 control ME/CFS patients without syncopal spells. Cases were gender, age and ME/CFS disease duration matched. Each underwent a tilt test with extracranial Doppler measurements for cerebral blood flow (CBF). ME/CFS cases with PPS had a significant larger CBF reduction at end tilt than controls: 39 (6)% vs. 25 (4)%; (p < 0.0001). Cases had more severe disease compared with controls (chi-square p < 0.01 and had a p = 0.01) for more postural orthostatic tachycardia syndrome in cases compared with controls. PETCO2 end-tilt differed also, but the magnitude of difference was smaller than compared with the CBF reduction: there were no differences in heart rate and blood pressure at either end-tilt testing period. Compared with the test with the stockings off, the mean percentage reduction in cardiac output during the test with compression stockings on was lower, 25 (5) mmHg versus 29 (4) mmHg (p < 0.005).

Conclusions: This study demonstrates that in ME/CFS patients suspected of having PPS, or conversion, CBF measurements end-tilt show a large decline compared with a control group of ME/CFS patients. Therefore, hypoperfusion offers an explanation of the orthostatic intolerance and syncopal spells in these patients, where it is clear that origin might not be behavioral or psychogenic, but have a clear somatic pathophysiologic background.

Source: van Campen CLMC, Visser FC. Psychogenic Pseudosyncope: Real or Imaginary? Results from a Case-Control Study in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Patients. Medicina (Kaunas). 2022 Jan 9;58(1):98. doi: 10.3390/medicina58010098. PMID: 35056406. https://pubmed.ncbi.nlm.nih.gov/35056406/

Commonalities in the Features of Cancer and Chronic Fatigue Syndrome (CFS): Evidence for Stress-Induced Phenotype Instability?

Abstract:

Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) and Cancer-Related Fatigue (CRF) are syndromes with considerable overlap with respect to symptoms. There have been many studies that have compared the two conditions, and some of this research suggests that the etiologies of the conditions are linked in some cases. In this narrative review, CFS/ME and cancer are introduced, along with their known and putative mechanistic connections to multiple stressors including ionizing radiation.

Next, we summarize findings from the literature that suggest the involvement of HPA-axis dysfunction, the serotonergic system, cytokines and inflammation, metabolic insufficiency and mitochondrial dysfunction, and genetic changes in CRF and CFS/ME. We further suspect that the manifestation of fatigue in both diseases and its causes could indicate that CRF and CFS/ME lie on a continuum of potential biological effects which occur in response to stress. The response to this stress likely varies depending on predisposing factors such as genetic background.

Finally, future research ideas are suggested with a focus on determining if common biomarkers exist in CFS/ME patients and those afflicted with CRF. Both CFS/ME and CRF are relatively heterogenous syndromes, however, it is our hope that this review assists in future research attempting to elucidate the commonalities between CRF and CFS/ME.

Source: Rusin A, Seymour C, Cocchetto A, Mothersill C. Commonalities in the Features of Cancer and Chronic Fatigue Syndrome (CFS): Evidence for Stress-Induced Phenotype Instability? Int J Mol Sci. 2022 Jan 8;23(2):691. doi: 10.3390/ijms23020691. PMID: 35054876. https://pubmed.ncbi.nlm.nih.gov/35054876/

Differential Effects of Exercise on fMRI of the Midbrain Ascending Arousal Network Nuclei in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Gulf War Illness (GWI) in a Model of Postexertional Malaise (PEM)

Abstract:

Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), Gulf War Illness (GWI) and control subjects underwent fMRI during difficult cognitive tests performed before and after submaximal exercise provocation (Washington 2020). Exercise caused increased activation in ME/CFS but decreased activation for GWI in the dorsal midbrain, left Rolandic operculum and right middle insula. Midbrain and isthmus nuclei participate in threat assessment, attention, cognition, mood, pain, sleep, and autonomic dysfunction.

Methods: Activated midbrain nuclei were inferred by a re-analysis of data from 31 control, 36 ME/CFS and 78 GWI subjects using a seed region approach and the Harvard Ascending Arousal Network.

Results: Before exercise, control and GWI subjects showed greater activation during cognition than ME/CFS in the left pedunculotegmental nucleus. Post exercise, ME/CFS subjects showed greater activation than GWI ones for midline periaqueductal gray, dorsal and median raphe, and right midbrain reticular formation, parabrachial complex and locus coeruleus. The change between days (delta) was positive for ME/CFS but negative for GWI, indicating reciprocal patterns of activation. The controls had no changes.

Conclusions: Exercise caused the opposite effects with increased activation in ME/CFS but decreased activation in GWI, indicating different pathophysiological responses to exertion and mechanisms of disease. Midbrain and isthmus nuclei contribute to postexertional malaise in ME/CFS and GWI.

Source: Baraniuk JN, Amar A, Pepermitwala H, Washington SD. Differential Effects of Exercise on fMRI of the Midbrain Ascending Arousal Network Nuclei in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Gulf War Illness (GWI) in a Model of Postexertional Malaise (PEM). Brain Sci. 2022 Jan 5;12(1):78. doi: 10.3390/brainsci12010078. PMID: 35053821. https://pubmed.ncbi.nlm.nih.gov/35053821/

The Gut Microbiome in Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS)

Abstract:

Myalgic encephalomyelitis (ME) or Chronic Fatigue Syndrome (CFS) is a neglected, debilitating multi-systemic disease without diagnostic marker or therapy. Despite evidence for neurological, immunological, infectious, muscular and endocrine pathophysiological abnormalities, the etiology and a clear pathophysiology remains unclear. The gut microbiome gained much attention in the last decade with manifold implications in health and disease. Here we review the current state of knowledge on the interplay between ME/CFS and the microbiome, to identify potential diagnostic or interventional approaches, and propose areas where further research is needed.

We iteratively selected and elaborated on key theories about a correlation between microbiome state and ME/CFS pathology, developing further hypotheses. Based on the literature we hypothesize that antibiotic use throughout life favours an intestinal microbiota composition which might be a risk factor for ME/CFS. Main proposed pathomechanisms include gut dysbiosis, altered gut-brain axis activity, increased gut permeability with concomitant bacterial translocation and reduced levels of short-chain-fatty acids, D-lactic acidosis, an abnormal tryptophan metabolism and low activity of the kynurenine pathway. We review options for microbiome manipulation in ME/CFS patients including probiotic and dietary interventions as well as fecal microbiota transplantations. Beyond increasing gut permeability and bacterial translocation, specific dysbiosis may modify fermentation products, affecting peripheral mitochondria. Considering the gut-brain axis we strongly suspect that the microbiome may contribute to neurocognitive impairments of ME/CFS patients.

Further larger studies are needed, above all to clarify whether D-lactic acidosis and early-life antibiotic use may be part of ME/CFS etiology and what role changes in the tryptophan metabolism might play. An association between the gut microbiome and the disease ME/CFS is plausible. As causality remains unclear, we recommend longitudinal studies. Activity levels, bedridden hours and disease progression should be compared to antibiotic exposure, drug intakes and alterations in the composition of the microbiota. The therapeutic potential of fecal microbiota transfer and of targeted dietary interventions should be systematically evaluated.

Source: König RS, Albrich WC, Kahlert CR, Bahr LS, Löber U, Vernazza P, Scheibenbogen C, Forslund SK. The Gut Microbiome in Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS). Front Immunol. 2022 Jan 3;12:628741. doi: 10.3389/fimmu.2021.628741. PMID: 35046929; PMCID: PMC8761622. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8761622/ (Full text)

 

Evidence for Peroxisomal Dysfunction and Dysregulation of the CDP-Choline Pathway in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic and debilitating disease that is characterized by unexplained physical fatigue unrelieved by rest. Symptoms also include cognitive and sensory dysfunction, sleeping disturbances, orthostatic intolerance, and gastrointestinal problems. A syndrome clinically similar to ME/CFS has been reported following well-documented infections with the coronaviruses SARS-CoV and MERS-CoV. At least 10% of COVID-19 survivors develop post acute sequelae of SARS-CoV-2 infection (PASC). Although many individuals with PASC have evidence of structural organ damage, a subset have symptoms consistent with ME/CFS including fatigue, post exertional malaise, cognitive dysfunction, gastrointestinal disturbances, and postural orthostatic intolerance. These common features in ME/CFS and PASC suggest that insights into the pathogenesis of either may enrich our understanding of both syndromes, and could expedite the development of strategies for identifying those at risk and interventions that prevent or mitigate disease.

Methods: Using regression, Bayesian and enrichment analyses, we conducted targeted and untargeted metabolomic analysis of 888 metabolic analytes in plasma samples of 106 ME/CFS cases and 91 frequency-matched healthy controls.

Results: In ME/CFS cases, regression, Bayesian and enrichment analyses revealed evidence of peroxisomal dysfunction with decreased levels of plasmalogens. Other findings included decreased levels of several membrane lipids, including phosphatidylcholines and sphingomyelins, that may indicate dysregulation of the cytidine-5’-diphosphocholine pathway. Enrichment analyses revealed decreased levels of choline, ceramides and carnitines, and increased levels of long chain triglycerides (TG) and hydroxy-eicosapentaenoic acid. Elevated levels of dicarboxylic acids were consistent with abnormalities in the tricarboxylic acid cycle. Using machine learning algorithms with selected metabolites as predictors, we were able to differentiate female ME/CFS cases from female controls (highest AUC=0.794) and ME/CFS cases without self-reported irritable bowel syndrome (sr-IBS) from controls without sr-IBS (highest AUC=0.873).

Conclusion: Our findings are consistent with earlier ME/CFS work indicating compromised energy metabolism and redox imbalance, and highlight new abnormalities that may provide insights into the pathogenesis of ME/CFS.

One sentence summary: Plasma levels of plasmalogens are decreased in patients with myalgic encephalomyelitis/chronic fatigue syndrome suggesting peroxisome dysfunction.

Source: Che X, Brydges CR, Yu Y, Price A, Joshi S, Roy A, Lee B, Barupal DK, Cheng A, Palmer DM, Levine S, Peterson DL, Vernon SD, Bateman L, Hornig M, Montoya JG, Komaroff AL, Fiehn O, Lipkin WI. Evidence for Peroxisomal Dysfunction and Dysregulation of the CDP-Choline Pathway in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. medRxiv [Preprint]. 2022 Jan 11:2021.06.14.21258895. doi: 10.1101/2021.06.14.21258895. PMID: 35043127; PMCID: PMC8764736. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8764736/ (Full text)

Review of the Midbrain Ascending Arousal Network Nuclei and Implications for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), Gulf War Illness (GWI) and Postexertional Malaise (PEM)

Abstract:
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS and Gulf War Illness (GWI) share features of post-exertional malaise (PEM), exertional exhaustion, or postexertional symptom exacerbation. In a two-day model of PEM, submaximal exercise induced significant changes in activation of the dorsal midbrain during a high cognitive load working memory task (Washington 2020) (Baraniuk this issue). Controls had no net change. However, ME/CFS had increased activity after exercise, while GWI had significantly reduced activity indicating differential responses to exercise and pathological mechanisms.
These data plus findings of the midbrain and brainstem atrophy in GWI inspired a review of the anatomy and physiology of the dorsal midbrain and isthmus nuclei in order to infer dysfunctional mechanisms that may contribute to disease pathogenesis and postexertional malaise. The nuclei of the ascending arousal network were addressed. Midbrain and isthmus nuclei participate in threat assessment, awareness, attention, mood, cognition, pain, tenderness, sleep, thermoregulation, light and sound sensitivity, orthostatic symptoms, and autonomic dysfunction and are likely to contribute to the symptoms of postexertional malaise in ME/CFS and GWI.
Source: James N. Baraniuk. Review of the Midbrain Ascending Arousal Network Nuclei and Implications for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), Gulf War Illness (GWI) and Postexertional Malaise (PEM) Brain Sci. 2022, 12(2), 132; https://doi.org/10.3390/brainsci12020132 (registering DOI) https://www.mdpi.com/2076-3425/12/2/132/htm (Full text)

Prevalence, characteristics, and predictors of Long COVID among diagnosed cases of COVID-19

Abstract:

Background: Long COVID or long-term complication after COVID-19 has the ability to affect health and quality of life. Knowledge about the burden and predictors could aid in their prevention and management. Most of the studies are from high-income countries and focus on severe cases. We did this study to estimate the prevalence and identify the characteristics and predictors of Long COVID among our patients.

Methodology: We recruited adult (≥18 years) patients who were diagnosed as Reverse Transcription Polymerase Chain Reaction (RTPCR) confirmed SARS-COV-2 infection and were either hospitalized or tested on outpatient basis. Eligible participants were followed up telephonically after four weeks of diagnosis of SARS-COV-2 infection to collect data on sociodemographic, clinical history, vaccination history, Cycle threshold (Ct) values during diagnosis and other variables. Characteristics of Long COVID were elicited, and multivariable logistic regression was done to find the predictors of Long COVID.

Results: We have analyzed 487 individual data with a median follow-up of 44 days (Inter quartile range (IQR): 39,47). Overall, Long COVID was reported by 29.2% (95% Confidence interval (CI): 25.3%,33.4%) participants. Prevalence of Long COVID among patients with mild/moderate disease (n = 415) was 23.4% (95% CI: 19.5%,27.7%) as compared to 62.5% (95% CI: 50.7%,73%) in severe/critical cases(n=72). The most common Long COVID symptom was fatigue (64.8%) followed by cough (32.4%). Statistically significant predictors of Long COVID were – Pre-existing medical conditions (Adjusted Odds ratio (aOR)=2.00, 95% CI: 1.16,3.44), having a more significant number of symptoms during acute phase of COVID-19 disease (aOR=11.24, 95% CI: 4.00,31.51), two doses of COVID-19 vaccination (aOR=2.32, 95% CI: 1.17,4.58), the severity of illness (aOR=5.71, 95% CI: 3.00,10.89) and being admitted to hospital (Odds ratio (OR)=3.89, 95% CI: 2.49,6.08).

Conclusion: A considerable proportion of COVID-19 cases reported Long COVID symptoms. More research is needed in Long COVID to objectively assess the symptoms and find the biological and radiological markers.

Source: M. C. Arjun, Arvind Kumar Singh, Debkumar Pal, Kajal Das, Alekhya Gajjala, Mahalingam Venkateshan, Baijayantimala Mishra, Binod Kumar Patro, Prasanta Raghab Mohapatra, Sonu Hangma Subba. Prevalence, characteristics, and predictors of Long COVID among diagnosed cases of COVID-19. medRxiv 2022.01.04.21268536; doi: https://doi.org/10.1101/2022.01.04.21268536 https://www.medrxiv.org/content/10.1101/2022.01.04.21268536v1.full-text (Full text)

Symptoms Experienced at the Acute Phase of SARS-CoV-2 Infection as Risk Factor of Long-term Post-COVID Symptoms: The LONG-COVID-EXP-CM Multicenter Study

Abstract:

Objective: This multicenter study investigated clinical risk factors associated with the number of long-term post-COVID symptoms.

Methods: Clinical features, symptoms at hospital admission, hospitalization data, and the number of post-COVID symptoms was systematically assessed from patients recovered from COVID-19 at four hospitals in Madrid (Spain) from February 20 to May 31, 2020.

Results: Overall, 1,969 patients (46.5% women, age: 61, SD: 16 years) were randomly assessed at 8.4 months (SD 1.5) after hospital discharge. Female gender (OR1.82, 95%CI 1.57-2.10), number of morbidities (OR1.182, 95%CI 1.08-1.29), number of symptoms at hospital admission (OR1.309, 95%CI 1.15-1.49) and days at the hospital (OR1.01, 95%CI 1.007-1.017) were associated (all, P<0.001) with more long-term post-COVID symptoms. Further, vomiting (OR1.78, 95%CI 1.26-2.52), throat pain (OR1.36, 95%CI 1.02-1.81), diarrhoea (OR1.51, 95%CI 1.25-1.82), dyspnea (OR1.20, 95%CI 1.01-1.41), or headache (OR1.50, 95%CI 1.28-1.75) as symptoms at hospital admission were also associated (all, P<0.01) with a higher number of post-COVID symptoms.

Conclusion: This multicenter study found that a higher number of symptoms at hospital admission was the most relevant risk factor for developing more post-COVID symptoms, supporting the assumption that a higher symptom load at the acute phase is associated with a greater likelihood of long-term post-COVID symptoms.

Source: Fernández-de-Las-Peñas C, Pellicer-Valero OJ, Navarro-Pardo E, Palacios-Ceña D, Florencio LL, Guijarro C, Martín-Guerrero JD. Symptoms Experienced at the Acute Phase of SARS-CoV-2 Infection as Risk Factor of Long-term Post-COVID Symptoms: The LONG-COVID-EXP-CM Multicenter Study. Int J Infect Dis. 2022 Jan 8:S1201-9712(22)00007-8. doi: 10.1016/j.ijid.2022.01.007. Epub ahead of print. PMID: 35017102; PMCID: PMC8743274. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8743274/ (Full text)

Premorbid vulnerability and disease severity impact on Long-COVID cognitive impairment

Abstract:

Background: Cognitive deficits have been increasingly reported as possible long-term manifestations after SARS-CoV-2 infection.

Aims: In this study we aimed at evaluating the factors associated with cognitive deficits 6 months after hospitalization for Coronavirus Disease 2019 (COVID-19).

Methods: One hundred and six patients, discharged from a pneumology COVID-19 unit between March 1 and May 30 2020, accepted to be evaluated at 6 months according to an extensive neurological protocol, including the Montreal Cognitive Assessment (MoCA).

Results: Abnormal MoCA scores at 6 months follow-up were associated with higher pre-hospitalization National Health System (NHS) score (Duca et al. in Emerg Med Pract 22:1-2, 2020) (OR 1.27; 95% CI 1.05-1.6; p = 0.029) and more severe pulmonary disease expressed by the Brescia-COVID Respiratory Severity Scale (Duca et al. in Emerg Med Pract 22:1-2, 2020) (BCRSS > 1OR 4.73; 95% CI 1.53-14.63; p = 0.003) during the acute phase of the disease.

Discussion: This longitudinal study showed that the severity of COVID-19, indicated by BCRSS, and a complex score given by age and premorbid medical conditions, expressed by NHS, play a major role in modulating the long-term cognitive consequences of COVID-19 disease.

Conclusions: These findings indicate that the association of age and premorbid factors might identify people at risk for long-term neurological consequences of COVID-19 disease, thus deserving longer and proper follow-up.

Source: Cristillo V, Pilotto A, Cotti Piccinelli S, Bonzi G, Canale A, Gipponi S, Bezzi M, Leonardi M, Padovani A; Neuro Covid Next Study group. Premorbid vulnerability and disease severity impact on Long-COVID cognitive impairment. Aging Clin Exp Res. 2022 Jan 11:1–4. doi: 10.1007/s40520-021-02042-3. Epub ahead of print. PMID: 35014002; PMCID: PMC8747881. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8747881/ (Full text)