Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): An Overview

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic systemic disease that manifests via various symptoms such as chronic fatigue, post-exertional malaise, and cognitive impairment described as “brain fog”. These symptoms often prevent patients from keeping up their pre-disease onset lifestyle, as extended periods of physical or mental activity become almost impossible. However, the disease presents heterogeneously with varying severity across patients. Therefore, consensus criteria have been designed to provide a diagnosis based on symptoms. To date, no biomarker-based tests or diagnoses are available, since the molecular changes observed also largely differ from patient to patient.

In this review, we discuss the infectious, genetic, and hormonal components that may be involved in CFS pathogenesis, we scrutinize the role of gut microbiota in disease progression, we highlight the potential of non-coding RNA (ncRNA) for the development of diagnostic tools and briefly mention the possibility of SARS-CoV-2 infection causing CFS.

Source: Deumer US, Varesi A, Floris V, Savioli G, Mantovani E, López-Carrasco P, Rosati GM, Prasad S, Ricevuti G. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): An Overview. J Clin Med. 2021 Oct 19;10(20):4786. doi: 10.3390/jcm10204786. PMID: 34682909; PMCID: PMC8538807. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8538807/ (Full text)

The 1918 Influenza Pandemic: Back to the Future?

Abstract:

Background: It is just over a century since the 1918 flu pandemic, sometimes referred to as the “mother” of pandemics. This brief retrospective of the 1918 pandemic is taken from the viewpoint of the current SARS-CoV-2/COVID-19 pandemic and is based on a short lecture given during the 2021 Virtual Congress of the ERA-EDTA.

Summary: This review summarizes and highlights some of the earlier pandemic’s salient features, some parallels with today, and some potential learnings, bearing in mind that the flu pandemic occurred over 100 years ago at a time of major turmoil during the climax to WWl, and with limited medical expertise and knowledge, research facilities, or well-structured and resourced healthcare services. While there is little or no information on renal complications at the time, or an effective treatment, some observations in relation to COVID-19 and vaccination are included.

Key Messages: Lessons are difficult to draw from 1918 other than the importance and value of non-pharmaceutical measures to limit viral transmission. While the economic impact of the 1918 pandemic was significant, as it is now with COVID-19, subsequent economic analysis has shown that protecting public health and preserving economic activity are not mutually exclusive. Both H1N1 and SARS-CoV-2 viruses are neurotropic and may cause chronically debilitating neurological diseases, including conditions such as encephalitis lethargica (still debated) and myalgic encephalomyelitis (chronic fatigue syndrome), respectively. Although coronavirus and influenza viral infections have some similarities, they are certainly not the same, as we are realising, and future infectious pandemics may still surprise us, but being “forewarned is forearmed.”

Source: Unwin RJ. The 1918 Influenza Pandemic: Back to the Future? Kidney Blood Press Res. 2021 Oct 18:1-8. doi: 10.1159/000519288. Epub ahead of print. PMID: 34662882. https://pubmed.ncbi.nlm.nih.gov/34662882/ 

Fatigue in post-acute sequelae of SARS-CoV2 (PASC) treated with oxygen-ozone autohemotherapy – preliminary results on 100 patients

Abstract:

Objective: Post-acute sequelae of SARS-CoV2 infection (PASC) are a novel terminology used to describe post-COVID persistent symptoms, mimicking somehow the previously described chronic fatigue syndrome (CFS). In this manuscript, we evaluated a therapeutical approach to address PASC-derived fatigue in a cohort of past-COVID-19 positive patients.

Patients and methods: A number of 100 patients, previously diagnosed as COVID-19 positive subjects and meeting our eligibility criteria, was diagnosed having PASC-related fatigue. They were recruited in the study and treated with oxygen-ozone autohemotherapy (O2-O3-AHT), according to the SIOOT protocol. Patients’ response to O2-O3-AHT and changes in fatigue were measured with the 7-scoring Fatigue Severity Scale (FSS), according to previously published protocols.

Results: Statistics assessed that the effects of O2-O3-AHT on fatigue reduced PASC symptoms by 67%, as a mean, in all the investigated cohort of patients (H = 148.4786 p < 0.0001) (Figure 1). Patients following O2-O3-AHT therapy, quite completely recovered for PASC-associated fatigue, a quote amounting to about two fifths (around 40%) of the whole cohort undergoing ozone treatment and despite most of patients were female subjects, the effect was not influenced by sex distribution (H = 0.7353, p = 0.39117).

Conclusions: Ozone therapy is able to recover normal functionality and to relief pain and discomfort in the form of PASC-associated fatigue in at least 67% of patients suffering from post-COVID sequelae, aside from sex and age distribution.

Source: Tirelli U, Franzini M, Valdenassi L, Pisconti S, Taibi R, Torrisi C, Pandolfi S, Chirumbolo S. Fatigue in post-acute sequelae of SARS-CoV2 (PASC) treated with oxygen-ozone autohemotherapy – preliminary results on 100 patients. Eur Rev Med Pharmacol Sci. 2021 Sep;25(18):5871-5875. doi: 10.26355/eurrev_202109_26809. PMID: 34604980. https://pubmed.ncbi.nlm.nih.gov/34604980/

Evolving phenotypes of non-hospitalized patients that indicate long COVID

Abstract:

Background: For some SARS-CoV-2 survivors, recovery from the acute phase of the infection has been grueling with lingering effects. Many of the symptoms characterized as the post-acute sequelae of COVID-19 (PASC) could have multiple causes or are similarly seen in non-COVID patients. Accurate identification of PASC phenotypes will be important to guide future research and help the healthcare system focus its efforts and resources on adequately controlled age- and gender-specific sequelae of a COVID-19 infection.

Methods: In this retrospective electronic health record (EHR) cohort study, we applied a computational framework for knowledge discovery from clinical data, MLHO, to identify phenotypes that positively associate with a past positive reverse transcription-polymerase chain reaction (RT-PCR) test for COVID-19. We evaluated the post-test phenotypes in two temporal windows at 3-6 and 6-9 months after the test and by age and gender. Data from longitudinal diagnosis records stored in EHRs from Mass General Brigham in the Boston Metropolitan Area was used for the analyses. Statistical analyses were performed on data from March 2020 to June 2021. Study participants included over 96 thousand patients who had tested positive or negative for COVID-19 and were not hospitalized.

Results: We identified 33 phenotypes among different age/gender cohorts or time windows that were positively associated with past SARS-CoV-2 infection. All identified phenotypes were newly recorded in patients’ medical records 2 months or longer after a COVID-19 RT-PCR test in non-hospitalized patients regardless of the test result. Among these phenotypes, a new diagnosis record for anosmia and dysgeusia (OR 2.60, 95% CI [1.94-3.46]), alopecia (OR 3.09, 95% CI [2.53-3.76]), chest pain (OR 1.27, 95% CI [1.09-1.48]), chronic fatigue syndrome (OR 2.60, 95% CI [1.22-2.10]), shortness of breath (OR 1.41, 95% CI [1.22-1.64]), pneumonia (OR 1.66, 95% CI [1.28-2.16]), and type 2 diabetes mellitus (OR 1.41, 95% CI [1.22-1.64]) is one of the most significant indicators of a past COVID-19 infection. Additionally, more new phenotypes were found with increased confidence among the cohorts who were younger than 65.

Conclusions: The findings of this study confirm many of the post-COVID-19 symptoms and suggest that a variety of new diagnoses, including new diabetes mellitus and neurological disorder diagnoses, are more common among those with a history of COVID-19 than those without the infection. Additionally, more than 63% of PASC phenotypes were observed in patients under 65 years of age, pointing out the importance of vaccination to minimize the risk of debilitating post-acute sequelae of COVID-19 among younger adults.

Source: Estiri H, Strasser ZH, Brat GA, Semenov YR; Consortium for Characterization of COVID-19 by EHR (4CE), Patel CJ, Murphy SN. Evolving phenotypes of non-hospitalized patients that indicate long COVID. BMC Med. 2021 Sep 27;19(1):249. doi: 10.1186/s12916-021-02115-0. PMID: 34565368. https://pubmed.ncbi.nlm.nih.gov/34565368/

Long COVID and Chronic Fatigue Syndrome: A survey of elderly female survivors in Egypt

Abstract:

Objectives: This study aimed to investigate post COVID 19 symptoms amongst elderly females and whether they could be a risk factor for developing Chronic Fatigue Syndrome (CFS) later on.

Methods: This was a retrospective cross-sectional study, in the form of an online survey. A total of 115 responses were finally included.

Results: The mean age was 73.18±6.42. Eighty-nine reported symptoms in the post recovery period; of these 54 had no symptoms of CFS, 60 were possible, and only 1 was probable. Fatigue was reported by 66, musculoskeletal symptoms by 56, and sleep problems by 73. Twenty-nine patients visited a doctor’s office as a result. Post recovery symptoms were significantly related to stress, sadness and sleep disturbances. Also, stress, sadness, sleep disturbances, fatigue, cognitive impairment, and recurrent falls were all significantly associated with CFS like symptoms.

Conclusions: From our findings the presence of fatigue, cognitive impairment, stress, sadness, sleep disturbances, and recurrent falls in the post-recovery period were all significantly associated with CFS like symptoms. To conclude it would be reasonable to screen for Long COVID and consider the potential for developing CFS later on. Whether it can be a risk factor for developing CFS like other viral infections will need more larger scale studies to confirm this.

Source: Aly MA, Saber HG. Long COVID and Chronic Fatigue Syndrome: A survey of elderly female survivors in Egypt. Int J Clin Pract. 2021 Sep 19:e14886. doi: 10.1111/ijcp.14886. Epub ahead of print. PMID: 34537995. https://pubmed.ncbi.nlm.nih.gov/34537995/

Long COVID: Is it really myalgic encephalomyelitis? Bibliographic review and considerations

Abstract:

Clinical sequelae of a disease as widespread as COVID-19 can be of great importance for primary care due to their prevalence and the morbidity they entail. The definition of long COVID and the establishment of its temporality are various, but some authors consider possible that this syndrome is actually myalgic encephalomyelitis.

Similarities are observed when comparing the International Consensus Criteria for the diagnosis of myalgic encephalomyelitis with the symptoms described for long COVID. Blood tests, pulse oximetry, chest radiography, and thoracic ultrasound are recommended in patients with persistent symptoms after acute infection. Management in both conditions consists of treating the main symptoms. The possibility that COVID-19 can lead to a chronic condition such as myalgic encephalomyelitis makes long-term follow-up of patients who have suffered from this infection essential.

Source: Espinosa Rodríguez, P et al. “COVID persistente: ¿es en realidad una encefalomielitis miálgica? Revisión bibliográfica y consideraciones” [Long COVID: Is it really myalgic encephalomyelitis? Bibliographic review and considerations]. Semergen, S1138-3593(21)00091-5. 13 Sep. 2021, doi:10.1016/j.semerg.2021.03.006 [Abstract in English, Spanish] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8437705/  (Full text)

Research Summary – Are people with ME/CFS at higher risk of complications from COVID infection?

From the ME Association

Are people with ME/CFS at higher risk of complications from COVID infection? A recent publication by Malato et al. carried out using ME/CFS patients from Germany has shown that this could be the case.

This paper looked at two enzymes called ACE and ACE2 (human angiotensin-converting enzymes). The enzyme ACE2 is of significant importance due to it being found to be the main receptor used by the virus COVID-19 (SARS-CoV2) to enter human cells.

Patients with ME/CFS are often found to have an unbalanced immune system. Previous studies have suggested that the ACE enzyme could provide a potential biomarker with the ACE enzyme being elevated in 80% of patients (Lieberman and Bell, 1993). This study looked at increasing our knowledge of the role of the ACE2 enzyme as little is known about its role in ME/CFS to date.

Read the rest of this article HERE.

Fatigue and post-exertional symptom exacerbation in Covid

Long Covid rehabilitation should include educating people about resuming everyday activities conservatively: WHO

By SHAHISTHA HAQUE

Fatigue is a feeling of extreme exhaustion. One feels over tired, low level of energy and extreme urge to sleep. It is the most common symptom of long Covid. It is easily relieved by rest or sleep. It is not the result of usually difficult activity. It can limit functioning in day to day activities. It negatively impacts the quality of life.

Now talking about post-exertional symptom exacerbation (PESE), it is a disabling and often delayed exhaustion disproportionate to the effort made. It is something described as crash.
The activity that can trigger this worsening of symptoms can be something that was easily tolerated before such as a daily activity e.g., a shower, a social activity, walking, reading, writing or working at a desk, an emotionally charged conversation, being in a sensory environment e.g., loud music or flashing lights.
Many of the symptoms experienced by those living with long Covid are very similar to those of myalgic encephalomyelitis (ME) or chronic fatigue syndrome (CFS).
According to WHO, long Covid rehabilitation should include educating people about resuming everyday activities conservatively, at an appropriate pace that is safe and manageable for energy levels within the limit of current symptoms and exertion should not be pushed to the point of fatigue or symptom exacerbation.
Read the rest of this article HERE.

Redox imbalance links COVID-19 and myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

Although most patients recover from acute COVID-19, some experience postacute sequelae of severe acute respiratory syndrome coronavirus 2 infection (PASC). One subgroup of PASC is a syndrome called “long COVID-19,” reminiscent of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). ME/CFS is a debilitating condition, often triggered by viral and bacterial infections, leading to years-long debilitating symptoms including profound fatigue, postexertional malaise, unrefreshing sleep, cognitive deficits, and orthostatic intolerance. Some are skeptical that either ME/CFS or long COVID-19 involves underlying biological abnormalities. However, in this review, we summarize the evidence that people with acute COVID-19 and with ME/CFS have biological abnormalities including redox imbalance, systemic inflammation and neuroinflammation, an impaired ability to generate adenosine triphosphate, and a general hypometabolic state.

These phenomena have not yet been well studied in people with long COVID-19, and each of them has been reported in other diseases as well, particularly neurological diseases. We also examine the bidirectional relationship between redox imbalance, inflammation, energy metabolic deficits, and a hypometabolic state. We speculate as to what may be causing these abnormalities. Thus, understanding the molecular underpinnings of both PASC and ME/CFS may lead to the development of novel therapeutics.

Source: Paul BD, Lemle MD, Komaroff AL, Snyder SH. Redox imbalance links COVID-19 and myalgic encephalomyelitis/chronic fatigue syndrome. Proc Natl Acad Sci U S A. 2021 Aug 24;118(34):e2024358118. doi: 10.1073/pnas.2024358118. PMID: 34400495. https://pubmed.ncbi.nlm.nih.gov/34400495/

Chronic fatigue syndrome: an emerging sequela in COVID-19 survivors?

Abstract:

SARS-CoV-2 survivors may report persistent symptoms that resemble myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). We explored (a) ME/CFS-like symptom prevalence and (b) whether axonal, inflammatory, and/or lung changes may contribute to ME/CFS-like symptoms in SARS-CoV-2 survivors through clinical, neuropsychiatric, neuropsychological, lung function assessment, and serum neurofilament light chain, an axonal damage biomarker. ME/CFS-like features were found in 27% of our sample. ME/CFS-like group showed worse sleep quality, fatigue, pain, depressive symptoms, subjective cognitive complaints, Borg baseline dyspnea of the 6-min walking test vs. those without ME/CFS-like symptoms. These preliminary findings raise concern on a possible future ME/CFS-like pandemic in SARS-CoV-2 survivors.

Source: Mantovani E, Mariotto S, Gabbiani D, Dorelli G, Bozzetti S, Federico A, Zanzoni S, Girelli D, Crisafulli E, Ferrari S, Tamburin S. Chronic fatigue syndrome: an emerging sequela in COVID-19 survivors? J Neurovirol. 2021 Aug 2:1–7. doi: 10.1007/s13365-021-01002-x. Epub ahead of print. PMID: 34341960; PMCID: PMC8328351. https://pubmed.ncbi.nlm.nih.gov/34341960/