Tag: long covid vs ME/CFS

Increased circulating fibronectin, depletion of natural IgM and heightened EBV, HSV-1 reactivation in ME/CFS and long COVID

Abstract:

Myalgic Encephalomyelitis/ Chronic Fatigue syndrome (ME/CFS) is a complex, debilitating, long-term illness without a diagnostic biomarker. ME/CFS patients share overlapping symptoms with long COVID patients, an observation which has strengthened the infectious origin hypothesis of ME/CFS. However, the exact sequence of events leading to disease development is largely unknown for both clinical conditions.

Here we show antibody response to herpesvirus dUTPases, particularly to that of Epstein-Barr virus (EBV) and HSV-1, increased circulating fibronectin (FN1) levels in serum and depletion of natural IgM against fibronectin ((n)IgM-FN1) are common factors for both severe ME/CFS and long COVID. We provide evidence for herpesvirus dUTPases-mediated alterations in host cell cytoskeleton, mitochondrial dysfunction and OXPHOS.

Our data show altered active immune complexes, immunoglobulin-mediated mitochondrial fragmentation as well as adaptive IgM production in ME/CFS patients. Our findings provide mechanistic insight into both ME/CFS and long COVID development. Finding of increased circulating FN1 and depletion of (n)IgM-FN1 as a biomarker for the severity of both ME/CFS and long COVID has an immediate implication in diagnostics and development of treatment modalities.

Source: Zheng Liu, Claudia Hollmann, Sharada Kalanidhi, Arnhild Grothey, Samuel Keating, Irene Mena-Palomo, Stephanie Lamer, Andreas Schlosser, Agnes Kaiping, Carsten Scheller, Franziska Sotzny, Anna Horn, Carolin Nuernberger, Vladimir Cejka, Boshra Afshar, Thomas Bahmer, Stefan Schreiber, Joerg Janne Vehreschild, Olga Milljukov, Christian Schaefer, Luzie Kretzler, Thomas Keil, Jens-Peter Reese, Felizitas A Eichner, Lena Schmidbauer, Peter U Heuschmann, Stefan Stoerk, Caroline Morbach, Gabriela Riemekasten, Niklas Beyersdorf, Carmen Scheibenbogen, Robert K Naviaux, Marshall Williams, Maria E Ariza, Bhupesh Kumar Prusty. Increased circulating fibronectin, depletion of natural IgM and heightened EBV, HSV-1 reactivation in ME/CFS and long COVID. medRxiv 2023.06.23.23291827; doi: https://doi.org/10.1101/2023.06.23.23291827 https://www.medrxiv.org/content/10.1101/2023.06.23.23291827v1 (Full text available as PDF file)

Cognitive impairment in post-acute sequelae of COVID-19 and short duration myalgic encephalomyelitis patients is mediated by orthostatic hemodynamic changes

Introduction: Cognitive impairment is experienced by people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and post-acute sequelae of COVID-19 (PASC). Patients report difficulty remembering, concentrating, and making decisions. Our objective was to determine whether orthostatic hemodynamic changes were causally linked to cognitive impairment in these diseases.

Methods: This prospective, observational cohort study enrolled PASC, ME/CFS, and healthy controls. All participants underwent clinical evaluation and assessment that included brief cognitive testing before and after an orthostatic challenge. Cognitive testing measured cognitive efficiency which is defined as the speed and accuracy of subject’s total correct responses per minute. General linear mixed models were used to analyze hemodynamics and cognitive efficiency during the orthostatic challenge. Additionally, mediation analysis was used to determine if hemodynamic instability induced during the orthostatic challenge mediated the relationship between disease status and cognitive impairment.

Results: Of the 276 participants enrolled, 256 were included in this study (34 PASC, 71 < 4 year duration ME/CFS, 69 > 10 year ME/CFS duration, and 82 healthy controls). Compared to healthy controls, the disease cohorts had significantly lower cognitive efficiency scores immediately following the orthostatic challenge. Cognitive efficiency remained low for the >10 year ME/CFS 2 and 7 days after orthostatic challenge. Narrow pulse pressure less than 25% of systolic pressure occurred at 4 and 5 min into the orthostatic challenge for the PASC and ME/CFS cohorts, respectively. Abnormally narrow pulse pressure was associated with slowed information processing in PASC patients compared to healthy controls (−1.5, p = 0.04). Furthermore, increased heart rate during the orthostatic challenge was associated with a decreased procedural reaction time in PASC and < 4 year ME/CFS patients who were 40 to 65 years of age.

Discussion: For PASC patients, both their disease state and hemodynamic changes during orthostatic challenge were associated with slower reaction time and decreased response accuracy during cognitive testing. Reduced cognitive efficiency in <4 year ME/CFS patients was associated with higher heart rate in response to orthostatic stress. Hemodynamic changes did not correlate with cognitive impairment for >10 year ME/CFS patients, but cognitive impairment remained. These findings underscore the need for early diagnosis to mitigate direct hemodynamic and other physiological effects on symptoms of cognitive impairment.

Source: Day Heather, Yellman Brayden, Hammer Sarah, Rond Candace, Bell Jennifer, Abbaszadeh Saeed, Stoddard Greg, Unutmaz Derya, Bateman Lucinda, Vernon Suzanne D. Cognitive impairment in post-acute sequelae of COVID-19 and short duration myalgic encephalomyelitis patients is mediated by orthostatic hemodynamic changes. Frontiers in Neuroscience, VOLUME=17, 2023. DOI=10.3389/fnins.2023.1203514. ISSN=1662-453X. https://www.frontiersin.org/articles/10.3389/fnins.2023.1203514 (Full text)

Tryptophan catabolites, inflammation, and insulin resistance as determinants of chronic fatigue syndrome and affective symptoms in long COVID

Abstract:

Critical COVID-19 disease is accompanied by depletion of plasma tryptophan (TRY) and increases in indoleamine-dioxygenase (IDO)-stimulated production of neuroactive tryptophan catabolites (TRYCATs), including kynurenine (KYN). The TRYCAT pathway has not been studied extensively in association with the physiosomatic and affective symptoms of Long COVID.

In the present study, we measured serum TRY, TRYCATs, insulin resistance (using the Homeostatic Model Assessment Index 2-insulin resistance, HOMA2-IR), C-reactive protein (CRP), physiosomatic, depression, and anxiety symptoms in 90 Long COVID patients, 3–10 months after remission of acute infection.

We were able to construct an endophenotypic class of severe Long COVID (22% of the patients) with very low TRY and oxygen saturation (SpO2, during acute infection), increased kynurenine, KYN/TRY ratio, CRP, and very high ratings on all symptom domains. One factor could be extracted from physiosomatic symptoms (including chronic fatigue-fibromyalgia), depression, and anxiety symptoms, indicating that all domains are manifestations of the common physio-affective phenome.

Three Long COVID biomarkers (CRP, KYN/TRY, and IR) explained around 40% of the variance in the physio-affective phenome. The latter and the KYN/TRY ratio were significantly predicted by peak body temperature (PBT) and lowered SpO2 during acute infection. One validated latent vector could be extracted from the three symptom domains and a composite based on CRP, KYN/TRY, and IR (Long COVID), and PBT and SpO2 (acute COVID-19).

In conclusion, the physio-affective phenome of Long COVID is a manifestation of inflammatory responses during acute and Long COVID, and lowered plasma tryptophan and increased kynurenine may contribute to these effects.

Source: Al-Hakeim HK, Khairi Abed A, Rouf Moustafa S, Almulla AF, Maes M. Tryptophan catabolites, inflammation, and insulin resistance as determinants of chronic fatigue syndrome and affective symptoms in long COVID. Front Mol Neurosci. 2023 Jun 2;16:1194769. doi: 10.3389/fnmol.2023.1194769. PMID: 37333619; PMCID: PMC10272345. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10272345/ (Full text)

Clinical Features of Post-Covid Syndrome

Abstract:

There is no common understanding of the clinical picture of post-covid syndrome. The US regulator CDC proposes to highlight:

(A) persistent symptoms and conditions that begin during acute COVID-19 illness;

B) new onset late complications after asymptomatic disease or a period of acute symptomatic relief or remission;

(C) the evolution of symptoms and conditions that include some persistent symptoms (eg, shortness of breath) with the addition of new symptoms or conditions over time (eg, cognitive difficulties).

Some manifestations may resemble other postviral syndromes such as myalgic encephalomyelitis/chronic fatigue syndrome, dysautonomia (eg, postural orthostatic tachycardia syndrome), or mast cell activation syndrome.

Source: Sayfulloyevich, P. S. ., & Musayevich, U. R. . (2023). Clinical Features of Post-Covid Syndrome. EUROPEAN JOURNAL OF INNOVATION IN NONFORMAL EDUCATION, 3(6), 34–36. Retrieved from http://inovatus.es/index.php/ejine/article/view/1786 http://inovatus.es/index.php/ejine/article/view/1786/1794 (Full text)

Increasing serum soluble CD40 ligand (sCD40L) may be a biomarker of ME/CFS and chronic Long COVID progression

Abstract:

To date, no single blood lab test exists to diagnose or track ME/CFS or chronic Long COVID. Based on existing literature, this article brings together evidence that a molecule secreted by the immune system called sCD40L tends to become increasingly elevated in ME/CFS, Long COVID, and Multiple Sclerosis.

These studies, along with what’s known about the role of sCD40L in health and other diseases, suggest sCD40L may be useful to track over time in ME/CFS and Long COVID patients.

Source: Vijay Iyer. Increasing serum soluble CD40 ligand (sCD40L) may be a biomarker of ME/CFS and chronic Long COVID progression. Patient-Generated Hypotheses Journal | Issue 1, May 2023. https://patientresearchcovid19.com/storage/2023/05/Patient-Generated-Hypotheses-Issue-1-May-2023.pdf#page=42 (Full text)

The relevance of pacing strategies in managing symptoms of post-COVID-19 syndrome

Abstract:

Background: Post-COVID-19 syndrome (PCS) shares many features with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). PCS represents a major health issue worldwide because it severely impacts patients’ work activities and their quality of life. In the absence of treatment for both conditions and given the beneficial effect of pacing strategies in ME/CFS, we conducted this study to assess the effectiveness of pacing in PCS patients.

Methods: We retrospectively included patients meeting the World Health Organization definition of PCS who attended the Internal Medicine Department of Angers University Hospital, France between June 2020 and June 2022, and were followed up until December 2022. Pacing strategies were systematically proposed for all patients. Their medical records were reviewed and data related to baseline and follow-up assessments were collected. This included epidemiological characteristics, COVID-19 symptoms and associated conditions, fatigue features, perceived health status, employment activity, and the degree of pacing adherence assessed by the engagement in pacing subscale (EPS). Recovery was defined as the ability to return to work, and improvement was regarded as the reduction of the number and severity of symptoms.

Results: A total of 86 patients were included and followed-up for a median time of 10 [6-13] months. Recovery and improvement rates were 33.7% and 23.3%, respectively. The EPS score was the only variable significantly associated with recovery on multivariate analysis (OR 40.43 [95% CI 6.22-262.6], p < 0.001). Patients who better adhered to pacing (high EPS scores) experienced significantly higher recovery and improvement rates (60-33.3% respectively) than those with low (5.5-5.5% respectively), or moderate (4.3-17.4% respectively) scores.

Conclusion: Our findings demonstrated that pacing is effective in the management of patients with PCS, and that high levels of adherence to pacing are associated with better outcomes.

Source: Ghali A, Lacombe V, Ravaiau C, Delattre E, Ghali M, Urbanski G, Lavigne C. The relevance of pacing strategies in managing symptoms of post-COVID-19 syndrome. J Transl Med. 2023 Jun 8;21(1):375. doi: 10.1186/s12967-023-04229-w. PMID: 37291581; PMCID: PMC10248991. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10248991/ (Full text)

Long-COVID: A Chronic Fatigue Condition: Case Report

Abstract:

For the growing number of patients suffering from post-COVID-19 syndrome, there is little definitive guidance for treatment protocols or prognosis. Neurologic manifestations following acute COVID-19 infection are continually surfacing in the literature, with fatigue being the most common persistent symptom.

This case study follows a 44-year-old female experiencing debilitating fatigue and neurologic symptoms persisting after the resolution of an acute SARS-COV-2 infection. The complex medical history of this patient, including past Epstein-Barr Virus (EBV) infection and Myalgic Encephalomyelitis, commonly known as Chronic Fatigue Syndrome, suggests a potential predisposition for the development of neurologic long-COVID.

Through investigation of current research and treatment responses, this case report aims to gain an understanding of the complicated nature of this illness, and to propose treatments that address this specific subset of post-acute SARS-COV-2 sequelae.

Source: Lavelle , M., & Brusewitz , N. D. J. (2023). Long-COVID: A Chronic Fatigue Condition: Case Report. Journal of Complementary and Alternative Medical Research, 22(3), 1–7. https://doi.org/10.9734/jocamr/2023/v22i3457 http://stmlibrary.uk/id/eprint/2217/1/Lavelle2232023JOCAMR100443.pdf (Full text)

Fighting Post-COVID and ME/CFS – development of curative therapies

Abstract:

The sequela of COVID-19 include a broad spectrum of symptoms that fall under the umbrella term post-COVID-19 condition or syndrome (PCS). Immune dysregulation, autoimmunity, endothelial dysfunction, viral persistence, and viral reactivation have been identified as potential mechanisms.

However, there is heterogeneity in expression of biomarkers, and it is unknown yet whether these distinguish different clinical subgroups of PCS. There is an overlap of symptoms and pathomechanisms of PCS with postinfectious myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

No curative therapies are available for neither ME/CFS nor PCS. The mechanisms identified so far provide targets for therapeutic interventions.

To accelerate the development of therapies, we propose evaluating drugs targeting different mechanisms in clinical trial networks using harmonized diagnostic and outcome criteria and subgrouping patients based on a thorough clinical profiling including a comprehensive diagnostic and biomarker phenotyping.

Source: Carmen Scheibenbogen, Judith T. Bellmann-Strobl, Cornelia Heindrich, Kirsten Wittke, Elisa Stein, Christiana Franke, Harald Prüss, Hannah Preßler, Marie-Luise Machule, Heinrich Audebert, Carsten Finke, Hanna G. Zimmerman,  Birgit Sawitzki, Christian Meisel, Markus Tölle, Anne Krüger, Anna C. Aschenbrenner, Joachim L. Schultz, Marc D. Beyer, Markus Ralser, Michael Mülleder, Leif E. Sander, Frank Konietschke, Friedemann Paul, Silvia Stojanov, Lisa Bruckert, Dennis M. Hedderich, Franziska Knolle, Gabriela Riemekasten, Maria J. Vehreschild, Oliver A. Cornely, Uta Behrends and Susen Burock.  Fighting Post-COVID and ME/CFS – development of curative therapies. Frontiers in Medicine, Sec. Infectious Diseases: Pathogenesis and Therapy: Volume 10 – 2023. https://www.frontiersin.org/articles/10.3389/fmed.2023.1194754/abstract

 

ME/CFS and Long COVID share similar symptoms and biological abnormalities: road map to the literature

Summary:

Some patients remain unwell for months after “recovering” from acute COVID-19. They develop persistent fatigue, cognitive problems, headaches, disrupted sleep, myalgias and arthralgias, post-exertional malaise, orthostatic intolerance and other symptoms that greatly interfere with their ability to function and that can leave some people housebound and disabled. The illness (Long COVID) is similar to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) as well as to persisting illnesses that can follow a wide variety of other infectious agents and following major traumatic injury. Together, these illnesses are projected to cost the U.S. trillions of dollars.

In this review, we first compare the symptoms of ME/CFS and Long COVID, noting the considerable similarities and the few differences. We then compare in extensive detail the underlying pathophysiology of these two conditions, focusing on abnormalities of the central and autonomic nervous system, lungs, heart, vasculature, immune system, gut microbiome, energy metabolism and redox balance. This comparison highlights how strong the evidence is for each abnormality, in each illness, and helps to set priorities for future investigation. The review provides a current road map to the extensive literature on the underlying biology of both illnesses.

Source: Anthony L. Komaroff and W. Ian Lipkin. ME/CFS and Long COVID share similar symptoms and biological abnormalities: road map to the literature. Front. Med., 02 June 2023. Sec. Infectious Diseases: Pathogenesis and Therapy. Volume 10 – 2023 | https://doi.org/10.3389/fmed.2023.1187163 (Full text)

Could vascular damage caused by massive inflammatory events underlie a relapse/recovery phenotype of ME/CFS and Long COVID?

Abstract:

I hypothesize that there is a relapse/recovery type of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Long COVID in which a massive inflammatory event—like the inflammatory cascade prompted by the restoration of blood flow (reperfusion) to tissue that had been deprived of blood (ischemia) or an allergic or pseudoallergic reaction—causes substantial damage to blood vessels, launching a more severe phase of ME/CFS.
People with Ehlers-Danlos syndrome and other connective tissue disorders may be at particular risk of this phenotype due to having connective tissue (a key component of blood vessels) that is more easily and severely injured during inflammatory events and slower to heal, causing a much longer recovery.

Source: Tamara Carnac. Could vascular damage caused by massive inflammatory events underlie a relapse/recovery phenotype of ME/CFS and Long COVID? Patient-Generated Hypotheses Journal | Issue 1, May 2023. https://patientresearchcovid19.com/storage/2023/05/Patient-Generated-Hypotheses-Issue-1-May-2023.pdf#page=30 (Full text)