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 Research22(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)

Post-acute Sequelae of SARS Co-V2 and Chronic Fatigue/Myalgic Encephalitis Share Similar Pathophysiologic Mechanisms of Exercise Limitation

Abstract:

Abstract available online: https://www.atsjournals.org/doi/abs/10.1164/ajrccm-conference.2023.207.1_MeetingAbstracts.A6470

Source: S. Jothi, G. Claessen, M. Insel, S. Kubba, E. Howden, S.-R. Carmona, F.P. Rischard. Post-acute Sequelae of SARS Co-V2 and Chronic Fatigue/Myalgic Encephalitis Share Similar Pathophysiologic Mechanisms of Exercise Limitation. https://www.atsjournals.org/doi/abs/10.1164/ajrccm-conference.2023.207.1_MeetingAbstracts.A6470

COVID-19: Post-recovery Manifestations

Abstract:

Background Post-COVID-19 syndrome, also known as long COVID, is a disorder that has many characteristics, one of which is chronic fatigue following acute infection with the SARS-CoV-2 virus.

Methodology We distributed a web-based survey among patients diagnosed with COVID-19 across the world and collected 190 responses regarding their demographics, histories, COVID-19 infection courses, and common symptoms.

Results We found that about 85.3% of the patients experienced some form of symptom following recovery from the infection. Among the reported symptoms, 59% of patients experienced fatigue or lethargy, 48.9% reported decreased stamina, 32.6% reported shortness of breath, 16.8% had a persistent cough, and 23.7% experienced anxiety following recovery from COVID-19.

Conclusions Reported symptoms closely resembled myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS); however, a deeper biochemical understanding of ME/CFS is required to confirm causation.

Source: Shaikh S, Siddiqi Z, Ukachukwu C, Mehkari Z, Khan S, Pamurthy K, Jahan F, Brown A. COVID-19: Post-recovery Manifestations. Cureus. 2023 Mar 29;15(3):e36886. doi: 10.7759/cureus.36886. PMID: 37128534; PMCID: PMC10147564. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10147564/ (Full text)

Symptom presentation and quality of life are comparable in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and post COVID-19 condition

Abstract:
Background and Οbjective: Considerable overlap exists in the clinical presentation of Post COVID-19 Condition and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). The current study aimed to compare symptoms and patient-reported Quality of Life (QoL) among people with Post COVID-19 Condition and ME/CFS in Australia. Methods: QoL data was collected from n=61 ME/CFS patients, n=31 Post COVID-19 Condition patients, and n=54 Healthy Controls (HCs) via validated instruments. The ME/CFS and Post COVID-19 Condition participants also provided self-reported severity and frequency of symptoms derived from the Canadian and International Consensus Criteria for ME/CFS and the World Health Organization case definition for Post COVID-19 Condition. Study variables were compared with Chi-square, Fisher’s exact, Fisher-Freeman-Halton, Mann-Whitney U, and Kruskal-Wallis H tests using Statistical Package for the Social Sciences version 29. Symptom clusters among the two illness cohorts were identified with hierarchical cluster analysis.
Results: ME/CFS was associated with a higher prevalence of short-term memory loss (p=0.039), muscle weakness (p<0.001), lymphadenopathy (p=0.013), and nausea (p=0.003). People with ME/CFS also reported more severe light-headedness (p=0.011) and more frequent unrefreshed sleep (p=0.011), but less frequent heart palpitations (p=0.040). Symptom prevalence, severity, and frequency were otherwise comparable. Few differences existed in the QoL of the two illness cohorts, both of which returned significantly impaired QoL scores when compared with HCs (p<0.001). Cluster analysis of symptom prevalence revealed four clusters: 1) Low gastrointestinal, low neurosensory; 2) Moderate gastrointestinal, low orthostatic and memory loss; 3) Moderate gastrointestinal, high orthostatic and memory loss; and 4) High gastrointestinal, high pain, which did not differ in sociodemographic information, illness status, or diagnostic criteria met.
Conclusions: Post COVID-19 Condition and ME/CFS are remarkably similar in presentation and, like ME/CFS, Post COVID-19 Condition has a profound and negative impact on patient QoL. Gastrointestinal symptoms may have a role in determining ME/CFS and Post COVID-19 Condition subtypes.
Source: Weigel B, Eaton-Fitch N, Thapaliya K, Marshall-Gradisnik S. Symptom presentation and quality of life are comparable in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and post COVID-19 condition. Population Medicine. 2023;5(Supplement):A372. doi:10.18332/popmed/165669.  http://www.populationmedicine.eu/Symptom-presentation-and-quality-of-life-are-comparable-in-Myalgic-Encephalomyelitis,165669,0,2.html

Female reproductive health impacts of Long COVID and associated illnesses including ME/CFS, POTS, and connective tissue disorders: a literature review

Long COVID disproportionately affects premenopausal women, but relatively few studies have examined Long COVID’s impact on female reproductive health. We conduct a review of the literature documenting the female reproductive health impacts of Long COVID which may include disruptions to the menstrual cycle, gonadal function, ovarian sufficiency, menopause, and fertility, as well as symptom exacerbation around menstruation.

Given limited research, we also review the reproductive health impacts of overlapping and associated illnesses including myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), postural orthostatic tachycardia syndrome (POTS), connective tissue disorders like Ehlers-Danlos syndrome (EDS), and endometriosis, as these illnesses may help to elucidate reproductive health conditions in Long COVID.

These associated illnesses, whose patients are 70%–80% women, have increased rates of dysmenorrhea, amenorrhea, oligomenorrhea, dyspareunia, endometriosis, infertility, vulvodynia, intermenstrual bleeding, ovarian cysts, uterine fibroids and bleeding, pelvic congestion syndrome, gynecological surgeries, and adverse pregnancy complications such as preeclampsia, maternal mortality, and premature birth. Additionally, in Long COVID and associated illnesses, symptoms can be impacted by the menstrual cycle, pregnancy, and menopause.

We propose priorities for future research and reproductive healthcare in Long COVID based on a review of the literature. These include screening Long COVID patients for comorbid and associated conditions; studying the impacts of the menstrual cycle, pregnancy, and menopause on symptoms and illness progression; uncovering the role of sex differences and sex hormones in Long COVID and associated illnesses; and addressing historical research and healthcare inequities that have contributed to detrimental knowledge gaps for this patient population.

Source: Pollack Beth, von Saltza Emelia, McCorkell Lisa, Santos Lucia, Hultman Ashley, Cohen Alison K., Soares Letícia. Female reproductive health impacts of Long COVID and associated illnesses including ME/CFS, POTS, and connective tissue disorders: a literature review. Frontiers in Rehabilitation Sciences, Vol 4, 2023, ISSN=2673-6861. DOI: 10.3389/fresc.2023.1122673 https://www.frontiersin.org/articles/10.3389/fresc.2023.1122673 (Full text)

Symptom persistence and biomarkers in post-COVID-19/chronic fatigue syndrome – results from a prospective observational cohort

Abstract:

Introduction: Post-COVID-19 syndrome (PCS) is characterized by a wide range of symptoms, predominantly fatigue and exertional intolerance. While disease courses during the first year post infection have been repeatedly described, little is known about long-term health consequences.

Methods: We assessed symptom severity and various biomarkers at three time points post infection (3-8 months (mo), 9-16mo, 17-20mo) in 106 PCS patients with moderate to severe fatigue and exertional intolerance. A subset of patients fulfilled diagnostic criteria of myalgic encephalomyelitis/chronic fatigue syndrome (PCS-ME/CFS) based on the Canadian Consensus Criteria.

Results: While PCS-ME/CFS patients showed persisting symptom severity and disability up to 20mo post infection, PCS patients reported an overall health improvement. Inflammatory biomarkers equally decreased in both groups. Lower hand grip force at onset correlated with symptom persistence especially in PCS-ME/CFS.

Discussion: Debilitating PCS may persist beyond 20mo post infection, particularly in patients fulfilling diagnostic criteria for ME/CFS.

Source: Anna Franziska Legler, Lil Meyer-Arndt, Lukas Moedl, Claudia Kedor, Helma Freitag, Elena Steinle, Uta Hoppmann, Rebekka Rust, Frank Konietschke, Andreas Thiel, Friedemann Paul, Carmen Scheibenbogen, Judith Bellmann-Strobl. Symptom persistence and biomarkers in post-COVID-19/chronic fatigue syndrome – results from a prospective observational cohort.
medRxiv 2023.04.15.23288582; doi: https://doi.org/10.1101/2023.04.15.23288582 (Full text available as PDF file)

A review of cytokine-based pathophysiology of Long COVID symptoms

Abstract:

The Long COVID/Post Acute Sequelae of COVID-19 (PASC) group includes patients with initial mild-to-moderate symptoms during the acute phase of the illness, in whom recovery is prolonged, or new symptoms are developed over months. Here, we propose a description of the pathophysiology of the Long COVID presentation based on inflammatory cytokine cascades and the p38 MAP kinase signaling pathways that regulate cytokine production.

In this model, the SARS-CoV-2 viral infection is hypothesized to trigger a dysregulated peripheral immune system activation with subsequent cytokine release. Chronic low-grade inflammation leads to dysregulated brain microglia with an exaggerated release of central cytokines, producing neuroinflammation. Immunothrombosis linked to chronic inflammation with microclot formation leads to decreased tissue perfusion and ischemia. Intermittent fatigue, Post Exertional Malaise (PEM), CNS symptoms with “brain fog,” arthralgias, paresthesias, dysautonomia, and GI and ophthalmic problems can consequently arise as result of the elevated peripheral and central cytokines.

There are abundant similarities between symptoms in Long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). DNA polymorphisms and viral-induced epigenetic changes to cytokine gene expression may lead to chronic inflammation in Long COVID patients, predisposing some to develop autoimmunity, which may be the gateway to ME/CFS.

Source: Low RN, Low RJ, Akrami A. A review of cytokine-based pathophysiology of Long COVID symptoms. Front Med (Lausanne). 2023 Mar 31;10:1011936. doi: 10.3389/fmed.2023.1011936. PMID: 37064029; PMCID: PMC10103649. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10103649/ (Full text)