Tag: long covid vs ME/CFS

Accelerating discovery: A novel flow cytometric method for detecting fibrin(ogen) amyloid microclots using long COVID as a model

Abstract:

Long COVID has become a significant global health and economic burden, yet there are currently no established methods or diagnostic tools to identify which patients might benefit from specific treatments. One of the major pathophysiological factors contributing to Long COVID is the presence of hypercoagulability; this results in insoluble amyloid microclots that are resistant to fibrinolysis. Our previous research using fluorescence microscopy has demonstrated a significant amyloid microclot load in Long COVID patients. However, this approach lacked the elements of statistical robustness, objectivity, and rapid throughput.

In the current study, we have used imaging flow cytometry for the first time to show a significantly increased concentration and size of these microclots. We identified notable variations in size and fluorescence between microclots in Long COVID and those of controls even using a 20× objective. By combining cell imaging and the high-event-rate and full-sample analysis nature of a conventional flow cytometer, imaging flow cytometry can eliminate erroneous results and increase accuracy in gating and analysis beyond what pure quantitative measurements from conventional flow cytometry can provide.

Although imaging flow cytometry was used in our study, our results suggest that the signals indicating the presence of microclots should be easily detectable using a conventional flow cytometer. Flow cytometry is a more widely available technique than fluorescence microscopy and has been used in pathology laboratories for decades, rendering it a potentially more suitable and accessible method for detecting microclots in individuals suffering from Long COVID or conditions with similar pathology, such as myalgic encephalomyelitis.

Source: Turner S, Laubscher GJ, Khan MA, Kell DB, Pretorius E. Accelerating discovery: A novel flow cytometric method for detecting fibrin(ogen) amyloid microclots using long COVID as a model. Heliyon. 2023 Aug 29;9(9):e19605. doi: 10.1016/j.heliyon.2023.e19605. PMID: 37809592; PMCID: PMC10558872. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10558872/ (Full text)

People With Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Exhibit Similarly Impaired Vascular Function

Abstract:

Background: This study aimed to compare flow-mediated dilation values between individuals with Long COVID, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), and healthy age-matched controls to assess the potential implications for clinical management and long-term health outcomes.

Methods: A case-case-control approach was employed, and flow-mediated dilation measurements were obtained from 51 participants (17 Long COVID patients, 17 ME/CFS patients, and 17 healthy age-matched controls). Flow-mediated dilation values were analysed using one-way ANOVA for between-group comparisons.

Results: Results revealed significantly impaired endothelial function in both Long COVID and ME/CFS groups compared to healthy age-matched controls as determined by maximum % brachial artery diameter post-occlusion compared to pre-occlusion resting diameter (6.99 ± 4.33% and 6.60 ± 3.48% vs. 11.30 ± 4.44%, respectively, both p < 0.05). Notably, there was no difference in flow-mediated dilation between Long COVID and ME/CFS groups (p = 0.949), despite significantly longer illness duration in the ME/CFS group (ME/CFS: 16 ± 11.15 years vs. Long COVID: 1.36 ± 0.51 years, p < 0.0001).

Conclusion: The study demonstrates that both Long COVID and ME/CFS patients exhibit similarly impaired endothelial function, indicating potential vascular involvement in the pathogenesis of these post-viral illnesses. The significant reduction in flow-mediated dilation values suggests an increased cardiovascular risk in these populations, warranting careful monitoring and the development of targeted interventions to improve endothelial function and mitigate long-term health implications.

Source: Marie Mclaughlin Ph.D , Nilihan E.M. Sanal-Hayes Ph.D ,Lawrence D. Hayes Ph.D , Ethan C. Berry BSc , Nicholas F. Sculthorpe Ph.D , People WithLong COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Exhibit Similarly Impaired Vascular Function, The American Journal of Medicine (2023). https://www.amjmed.com/article/S0002-9343(23)00609-5/fulltext (Full text)

Dysautonomia and small fiber neuropathy in post-COVID condition and Chronic Fatigue Syndrome

Abstract:

Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and post-COVID condition can present similarities such as fatigue, brain fog, autonomic and neuropathic symptoms.

Methods: The study included 87 patients with post-COVID condition, 50 patients with ME/CFS, and 50 HC. The hemodynamic autonomic function was evaluated using the deep breathing technique, Valsalva maneuver, and Tilt test. The presence of autonomic and sensory small fiber neuropathy (SFN) was assessed with the Sudoscan and with heat and cold evoked potentials, respectively. Finally, a complete neuropsychological evaluation was performed. The objective of this study was to analyze and compare the autonomic and neuropathic symptoms in post-COVID condition with ME/CFS, and healthy controls (HC), as well as, analyze the relationship of these symptoms with cognition and fatigue.

Results: Statistically significant differences were found between groups in heart rate, with ME/CFS group presenting the highest (H = 18.3; p ≤ .001). The Postural Orthostatic Tachycardia Syndrome (POTS), and pathological values in palms on the Sudoscan were found in 31% and 34% of ME/CFS, and 13.8% and 19.5% of post-COVID patients, respectively. Concerning evoked potentials, statistically significant differences were found in response latency to heat stimuli between groups (H = 23.6; p ≤ .01). Latency was highest in ME/CFS, and lowest in HC. Regarding cognition, lower parasympathetic activation was associated with worse cognitive performance.

Conclusions: Both syndromes were characterized by inappropriate tachycardia at rest, with a high percentage of patients with POTS. The prolonged latencies for heat stimuli suggested damage to unmyelinated fibers. The higher proportion of patients with pathological results for upper extremities on the Sudoscan suggested a non-length-dependent SFN.

Source: Naiara Azcue, Rocio Del Pino, Marian Acera et al. Dysautonomia and small fiber neuropathy in post-COVID condition and Chronic Fatigue Syndrome, 06 October 2023, PREPRINT (Version 1) available at Research Square [https://doi.org/10.21203/rs.3.rs-3388628/v1] https://www.researchsquare.com/article/rs-3388628/v1 (Full text)

THU581 Possible Markers For Myalgic Encephalomyelitis / Chronic Fatigue Syndrome Developed In Long Covid: Utility Of Serum Ferritin And Insulin-like Growth Factor-I

Abstract:

Almost three years have passed since coronavirus disease 2019 (COVID-19) pandemic broke out, and along with the number of acute COVID-19 patients, the number of patients suffering from chronic prolonged symptoms after COVID-19, long COVID, or post COVID-19 condition, has also increased.

We established an outpatient clinic specialized for COVID-19 after care (CAC) in Okayama University Hospital in Japan in February 2021. Our recent study has revealed that the most common symptom is “fatigue”, a part of which potentially may develop into myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). However, the pathogenesis and specific prognosticator have yet to be elucidated. The aim of this study was to elucidate the clinical characteristics of patients who developed ME/CFS after COVID-19.

This retrospective observational study investigated the patients who visited our CAC outpatient clinic between February 2021 and March 2022. Of the 234 patients, 139 (59.4%) had fatigue symptoms, of whom 50 (21.4%) met the criteria for ME/CFS (ME/CFS group), while other 89 did not (non-ME/CFS group); 95 patients had no fatigue complaints (no-fatigue group). Although the patients’ backgrounds were not significantly different among the three groups, the ME/CFS group presented the highest scores on the self-rating symptom scales, including the Fatigue Assessment Scale (FAS), EuroQol, and Self-Rating Depression Scale (SDS).

Of note, serum ferritin levels, which were correlated to FAS and SDS scores, were significantly higher in the ME/CFS group (193.0 μg/mL; interquartile range (IQR), 58.8-353.8) than those of non-ME/CFS (98.2 μg/mL; 40.4-251.5) and no-fatigue (86.7 μg/mL; 37.5-209.0) groups, and this trend was prominent in the female patients. Endocrine workup further showed that the ME/CFS group had higher thyrotropin levels but lower growth hormone levels in the serum, and that insulin-like growth factor (IGF)-I levels were inversely correlated with ferritin levels (R = -0.328, p < 0.05).

Collectively, we revealed that serum ferritin levels could be a possible predictor for developing ME/CFS related to long COVID, especially in female patients. Earlier studies have suggested that hyperferritinemia is a clinical feature in the patients of long COVID, in which hepcidin-like effects could also be involved. Our present study also uncovered a relationship between hyperferrinemia and endocrine disorders among patients developing ME/CFS after COVID-19, although further investigations are necessary to understand the characteristics of ferritin metabolism.

Presentation: Thursday, June 15, 2023

Source: Yukichika Yamamoto, Yuki Otsuka, Kazuki Tokumasu, Naruhiko Sunada, Yasuhiro Nakano, Hiroyuki Honda, Yasue Sakurada, Toru Hasegawa, Hideharu Hagiya, Fumio Otsuka, THU581 Possible Markers For Myalgic Encephalomyelitis / Chronic Fatigue Syndrome Developed In Long Covid: Utility Of Serum Ferritin And Insulin-like Growth Factor-I, Journal of the Endocrine Society, Volume 7, Issue Supplement_1, October-November 2023, bvad114.1370, https://doi.org/10.1210/jendso/bvad114.1370 (Full text available as PDF file)

Atopy and Elevation of IgE, IgG3, and IgG4 May Be Risk Factors for Post COVID-19 Condition in Children and Adolescents

Abstract:

SARS-CoV-2 infection causes transient cardiorespiratory and neurological disorders, and severe acute illness is rare among children. Post COVID-19 condition (PCC) may cause profound, persistent phenotypes with increasing prevalence. Its manifestation and risk factors remain elusive. In this monocentric study, we hypothesized that atopy, the tendency to produce an exaggerated immunoglobulin E (IgE) immune response, is a risk factor for the manifestation of pediatric PCC.
We present a patient cohort (n = 28) from an early pandemic period (2021–2022) with comprehensive evaluations of phenotypes, pulmonary function, and molecular investigations. PCC predominantly affected adolescents and presented with fatigue, dyspnea, and post-exertional malaise. Sensitizations to aeroallergens were found in 93% of cases.
We observed elevated IgE levels (mean 174.2 kU/L, reference < 100 kU/L) regardless of disease severity. Concurrent Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) was found in 29% of patients that also faced challenges in school attendance. ME/CFS manifestation was significantly associated with elevated immunoglobulin G subclasses IgG3 (p < 0.05) and IgG4 (p < 0.05). A total of 57% of patients showed self-limiting disease courses with mean recovery at 12.7 months (range 5–25 months), 29% at 19.2 months (range 12–30 months), and the rest demonstrated overall improvement. These findings offer additional insights into immune dysregulation as a risk factor for pediatric PCC.
Source: Körner RW, Bansemir OY, Franke R, Sturm J, Dafsari HS. Atopy and Elevation of IgE, IgG3, and IgG4 May Be Risk Factors for Post COVID-19 Condition in Children and Adolescents. Children. 2023; 10(10):1598. https://doi.org/10.3390/children10101598 https://www.mdpi.com/2227-9067/10/10/1598 (Full text)

Investigating the Effect of COVID-19 Infection on Professional Athletes’ Post-infection With a Focus on Fatigue and Chronic Fatigue Syndrome

Abstract:

Introduction and objectives: COVID-19 has been reported to cause long-term sequela including persistent fatigue and Chronic Fatigue Syndrome (CFS) in the general population. However, it remains to be seen if similar effects are observed in an athlete population. The aetiology and pathophysiology are poorly understood but is thought to be multi-factorial. Patient reported outcome measures are commonly used to improve patient-centred outcomes (PROMs). They are essential to assess patient quality of life post-COVID infection. This paper aims to assess the effect of COVID-19 on athletes’ long-term fatigue and CFS and identify the PROMs used to characterise this.

Methodology: Articles were selected for extraction based on the eligibility criteria and PRISMA guidelines. The inclusion criteria required papers to assess competitive athletes over eighteen years of age who were clinically diagnosed with COVID-19. Articles were extracted to assess different variables including type of sport, type of athlete and ethnicity. Key terms were obtained using MeSH trees and utilised with Web of Science and NCBI Pubmed. Papers were graded by quality using the Hawker quality assessment tool.

Results and discussion: Forty articles (N=40) were identified for full-text screening (N=8). Eight were selected for extraction based on the eligibility criteria. Data was obtained on athlete characteristics, sport characteristics, properties of PROM measurement techniques and fatigue presentation. Male athletes were found to be 10-50% more likely than female athletes to suffer from persistent fatigue symptoms (N=2). Persistent fatigue was present in 9-10% Athletes from mixed backgrounds and genders (N=2). Initial fatigue was documented to be between 47-56% (N=2). A heterogenous range of PROMs were utilised to assess symptoms including fatigue and excluded emotional or mental fatigue.

Conclusion: COVID-19 is associated with signs of persisting fatigue and potentially CFS in athlete populations. More work needs to be done to develop standardised and validated PROMs specific to CFS.

Source: Sarwary, Reza and Tareen, Manahil and Hocaoglu, Mevhibe, Investigating the Effect of COVID-19 Infection on Professional Athletes’ Post-infection With a Focus on Fatigue and Chronic Fatigue Syndrome (January 16, 2023). Available at SSRN: https://ssrn.com/abstract=4573649 or http://dx.doi.org/10.2139/ssrn.4573649 (Full text available as PDF file)

Diagnosis and Management of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic neurologic disease often preceded by infection. There has been increased interest in ME/CFS recently because of its significant overlap with the post-COVID syndrome (long COVID or post-acute sequelae of COVID), with several studies estimating that half of patients with post-COVID syndrome fulfill ME/CFS criteria. Our concise review describes a generalist approach to ME/CFS, including diagnosis, evaluation, and management strategies.

Source: Grach SL, Seltzer J, Chon TY, Ganesh R. Diagnosis and Management of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Mayo Clin Proc. 2023 Oct;98(10):1544-1551. doi: 10.1016/j.mayocp.2023.07.032. PMID: 37793728. https://www.mayoclinicproceedings.org/article/S0025-6196(23)00402-0/fulltext (Full text)

Immune cell proteomes of Long COVID patients have functional changes similar to those in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Of those infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), ~ 10% develop the chronic post-viral debilitating condition, Long COVID (LC). Although LC is a heterogeneous condition, about half of cases have a typical post-viral fatigue condition with onset and symptoms that are very similar to Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). A key question is whether these conditions are closely related.

ME/CFS is a post-stressor fatigue condition that arises from multiple triggers. To investigate the pathophysiology of LC, a pilot study of patients and healthy controls has used quantitative proteomics to discover changes in peripheral blood mononuclear cell (PBMC) proteins. A principal component analysis separated all Long COVID patients from healthy controls.

Analysis of 3131 proteins identified 162 proteins differentially regulated, of which 37 were related to immune functions, and 21 to mitochondrial functions. Markov cluster analysis identified clusters involved in immune system processes, and two aspects of gene expression-spliceosome and transcription. These results were compared with an earlier dataset of 346 differentially regulated proteins in PBMC’s from ME/CFS patients analysed by the same methodology.

There were overlapping protein clusters and enriched molecular pathways particularly in immune functions, suggesting the two conditions have similar immune pathophysiology as a prominent feature, and mitochondrial functions involved in energy production were affected in both conditions.

Source: Katie Peppercorn, Christina D. Edgar, Torsten Kleffmann, Warren. P Tate. Immune cell proteomes of Long COVID patients have functional changes similar to those in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Research Square preprint https://doi.org/10.21203/rs.3.rs-3335919/v1 https://www.researchsquare.com/article/rs-3335919/v1 (Full text) https://www.nature.com/articles/s41598-023-49402-9 (Final full text)

What Long COVID investigators can learn from four decades of ME/CFS research

Abstract:

Four decades of research in the field of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) have yielded lessons that may be instructive for those devising criteria to better comprehend Post-Acute Sequelae of SARS CoV-2 Infection (PASC) and Long COVID.

For instance, substantial effort has been devoted to defining classification systems, operationalizing methods, and developing instruments with adequate reliability and validity in the ME/CFS field.

The current article provides guidelines for developing a case definition for Long COVID and discusses the significance of psychometric issues and criterion variance, including how to specify symptoms, develop thresholds, subtypes, and exclusionary conditions. ME/CFS research could enhance our knowledge of Long COVID pathophysiology, early diagnosis, prognosis, and the identification of effective treatments.

Source: Leonard A. Jason, Benjamin H. Natelson, Hector Bonilla, Zaki A. Sherif, Suzanne D. Vernon, Monica Verduzco Gutierrez, Lisa O’Brien, Emily Taylor. What Long COVID investigators can learn from four decades of ME/CFS research. Brain Behavior and Immunity Integrative, Volume 4, 2023, 100022. https://www.sciencedirect.com/science/article/pii/S2949834123000211 (Full text)

Epstein-Barr virus-acquired immunodeficiency in myalgic encephalomyelitis-Is it present in long COVID?

Abstract:

Both myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS) and long COVID (LC) are characterized by similar immunological alterations, persistence of chronic viral infection, autoimmunity, chronic inflammatory state, viral reactivation, hypocortisolism, and microclot formation. They also present with similar symptoms such as asthenia, exercise intolerance, sleep disorders, cognitive dysfunction, and neurological and gastrointestinal complaints. In addition, both pathologies present Epstein-Barr virus (EBV) reactivation, indicating the possibility of this virus being the link between both pathologies.

Therefore, we propose that latency and recurrent EBV reactivation could generate an acquired immunodeficiency syndrome in three steps: first, an acquired EBV immunodeficiency develops in individuals with “weak” EBV HLA-II haplotypes, which prevents the control of latency I cells. Second, ectopic lymphoid structures with EBV latency form in different tissues (including the CNS), promoting inflammatory responses and further impairment of cell-mediated immunity.

Finally, immune exhaustion occurs due to chronic exposure to viral antigens, with consolidation of the disease. In the case of LC, prior to the first step, there is the possibility of previous SARS-CoV-2 infection in individuals with “weak” HLA-II haplotypes against this virus and/or EBV.

Source: Ruiz-Pablos M, Paiva B, Zabaleta A. Epstein-Barr virus-acquired immunodeficiency in myalgic encephalomyelitis-Is it present in long COVID? J Transl Med. 2023 Sep 17;21(1):633. doi: 10.1186/s12967-023-04515-7. PMID: 37718435. https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-04515-7 (Full text)