Fatigue in post COVID-19 patients: the P4O2 COVID-19 study

Abstract:

Background: Some patients do not fully recover after COVID-19 and have symptoms occurring 3 months after acute illness, lasting for >2 months, defined as post COVID-19. Fatigue seems most present in post COVID-19 and part of the patients might develop symptoms similar to chronic fatigue syndrome.

Aim: To determine the occurrence of fatigue and other symptoms in post COVID-19 patients.

Methods: In the prospective P4O2 COVID-19 cohort, post COVID-19 patients aged 40-65 years were recruited from outpatient post-COVID clinics in 5 Dutch hospitals between May 2021-September 2022. At 3-6 months post-COVID, patients completed the Fatigue Severity Scale (FSS). If the FSS score was ≥4 (the cut-off for severe fatigue), patients also completed the DePaul Symptom Questionnaire version 2 (DSQ-2). The FSS ranges from 1-7 and a higher score means more fatigued. The DSQ-2 rates frequency and severity of 79 symptoms on a 5-point Likert scale. Binary thresholds (if scored ≥2 on both severity and frequency, the threshold is met and the symptom is present) were calculated.

Results: The mean age of the 78 included patients was 53.9±6.2 and 51.7% were male. Median (IQR) FSS score was 5.6 (4.2-6.3) and 66 patients (84.6%) had a score ≥4. According to the DSQ-2 (n=61), patients reported a median (IQR) of 16 (8-23) symptoms. The majority of the patients experienced fatigue (85%). Furthermore, post-exertional malaise (PEM) (40%), sleep-related problems (37%), pain (21%) and neurocognitive problems (23%) were frequently reported.

Conclusion: The occurrence of severe fatigue 3-6 months after COVID-19 was 84.6% in our cohort. Patients with severe fatigue also frequently reported PEM, sleep related problems, pain and neurocognitive problems.

Source: Merel E.B. Cornelissen, Lizan D. Bloemsma, Nadia Baalbaki, Somayeh Bazdar, Jelle M. Blankestijn, Inés Beekers, Rosanne J.H.C.G. Beijers, Joop P. Van Den Bergh, Debbie Gach, J.J. Miranda Geelhoed, Sebastiaan Holverda, Laura Houweling, John J. Jacobs, Renée Jonker, Ivo Van Der Lee, Paulien M.A. Linders, Lieke C.E. Noij, Esther J. Nossent, Marianne A. Van De Pol, Daphne W. Schaminee, Annemie M.W.J. Schols, Lisanne T. Schuurman, Brigitte Sondermeijer, Anouk W. Vaes, Els J.M. Weersink, Yolanda De Wit-Van Wijck, Martijn A. Spruit, Anke H. Maitland-Van Der Zee. Fatigue in post COVID-19 patients: the P4O2 COVID-19 study.

Interdisciplinary multimodal pain therapy in postviral syndromes and ME/CFS : Features, pitfalls and model concept

Abstract:

Background: Multimodal pain therapy usually take place in the context of group therapy lasting several weeks and is based on a generally activating approach. Due to the specificity of stress intolerance with postexertional malaise (PEM) in patients with postviral syndromes, physical as well as psychological overload must be urgently avoided in these cases; however, these aspects can only be insufficiently considered in current medical pain therapy concepts.

Methods: Summary of the current literature and presentation of clinical characteristics as well as presentation of a model project for a multimodal pain therapy in postviral syndromes with PEM.

Model concept: The presented model project describes a day clinic treatment setting for interdisciplinary multimodal pain therapy adapted to the individual resilience with minimization of the risk of strain-induced deterioration of the condition.

Source: Luchting B, Behrends U, Eigner B, Stojanov S, Warlitz C, Haegele M, Neuwirth E, Mihatsch L, Richter HP. Interdisziplinäre multimodale Schmerztherapie bei postviralen Syndromen und ME/CFS : Besonderheiten, Fallstricke und Modellkonzept [Interdisciplinary multimodal pain therapy in postviral syndromes and ME/CFS : Features, pitfalls and model concept]. Schmerz. 2023 Oct 20. German. doi: 10.1007/s00482-023-00761-2. Epub ahead of print. PMID: 37 https://pubmed.ncbi.nlm.nih.gov/37864020/864020.

Predicting Myalgic Encephalomyelitis/Chronic Fatigue Syndrome from Early Symptoms of COVID-19 Infection

Abstract:

It is still unclear why certain individuals after viral infections continue to have severe symptoms. We investigated if predicting myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) development after contracting COVID-19 is possible by analyzing symptoms from the first two weeks of COVID-19 infection.
Using participant responses to the 54-item DePaul Symptom Questionnaire, we built predictive models based on a random forest algorithm using the participants’ symptoms from the initial weeks of COVID-19 infection to predict if the participants would go on to meet the criteria for ME/CFS approximately 6 months later.
Early symptoms, particularly those assessing post-exertional malaise, did predict the development of ME/CFS, reaching an accuracy of 94.6%. We then investigated a minimal set of eight symptom features that could accurately predict ME/CFS. The feature reduced models reached an accuracy of 93.5%. Our findings indicated that several IOM diagnostic criteria for ME/CFS occurring during the initial weeks after COVID-19 infection predicted Long COVID and the diagnosis of ME/CFS after 6 months.
Source: Hua C, Schwabe J, Jason LA, Furst J, Raicu D. Predicting Myalgic Encephalomyelitis/Chronic Fatigue Syndrome from Early Symptoms of COVID-19 Infection. Psych. 2023; 5(4):1101-1108. https://doi.org/10.3390/psych5040073 https://www.mdpi.com/2624-8611/5/4/73

A Scoping Review of ‘Pacing’ for Management of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Lessons Learned for the Long COVID Pandemic

Abstract:

Background Controversy over treatment for people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a barrier to appropriate treatment. Energy management or pacing is a prominent coping strategy for people with ME/CFS that involves regulating activity to avoid post exertional malaise (PEM), the worsening of symptoms after an activity. Until now, characteristics of pacing, and the effects on patients’ symptoms had not been systematically reviewed. This is problematic as the most common approach to pacing, pacing prescription, and the pooled efficacy of pacing was unknown. Collating evidence may help advise those suffering with similar symptoms, including long COVID, as practitioners would be better informed on methodological approaches to adopt, pacing implementation, and expected outcomes.

Objectives In this scoping review of the literature, we aggregated type of, and outcomes of, pacing in people with ME/CFS.

Eligibility criteria Original investigations concerning pacing were considered in participants with ME/CFS.

Sources of evidence Six electronic databases (PubMed, Scholar, ScienceDirect, Scopus, Web of Science and the Cochrane Central Register of Controlled Trials [CENTRAL]) were searched; and websites MEPedia, Action for ME, and ME Action were also searched for grey literature.

Methods A scoping review was conducted. Review selection and characterisation was performed by two independent reviewers using pretested forms.

Results Authors reviewed 177 titles and abstracts, resulting in included 17 studies: three randomised control trials (RCTs); one uncontrolled trial; one interventional case series; one retrospective observational study; two prospective observational studies; four cross-sectional observational studies; and five cross-sectional analytical studies. Studies included variable designs, durations, and outcome measures. In terms of pacing administration, studies used educational sessions and diaries for activity monitoring. Eleven studies reported benefits of pacing, four studies reported no effect, and two studies reported a detrimental effect in comparison to the control group.

Conclusions Highly variable study designs and outcome measures, allied to poor to fair methodological quality resulted in heterogenous findings and highlights the requirement for more research examining pacing. Looking to the long COVID pandemic, future studies should be RCTs utilising objectively quantified digitised pacing, over a longer duration of examination, using the core outcome set for patient reported outcome measures.

Source: Nilihan E.M. Sanal-Hayes, Marie Mclaughlin, Lawrence D. Hayes, Jacqueline L. Mair, Jane Ormerod, David Carless, Natalie Hilliard, Rachel Meach, Joanne Ingram, Nicholas F. Sculthorpe. A Scoping Review of ‘Pacing’ for Management of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Lessons Learned for the Long COVID Pandemic. medRxiv 2023.08.10.23293935; doi: https://doi.org/10.1101/2023.08.10.23293935 https://www.medrxiv.org/content/10.1101/2023.08.10.23293935v1.full-text (Full text)

The importance of estimating prevalence of ME/CFS in future epidemiological studies of long COVID

Abstract:

The resolution of the COVID-19 pandemic is giving rise to another public health challenge due to the explosion of long COVID (LC) cases. In many cases, LC results in persistent fatigue, post-exertional malaise (PEM), and other debilitating symptoms that resemble the clinical manifestation of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). The similarity of these two diseases suggests that future epidemiological studies of LC could take the opportunity to also estimate the prevalence of ME/CFS at a minimal cost.

With this opportunity in mind, we revisited the most consensual case definitions of ME/CFS for research purposes. We then compared the symptoms assessed at the participants’ enrollment in the UK ME/CFS Biobank with those documented in three systematic reviews encompassing hundreds of LC epidemiological studies. We found that published epidemiological studies of LC did not consistently assess or report the prevalence of PEM, which is a compulsory symptom for ME/CFS diagnosis. However, these studies assessed many neuro-cognitive, immunologic, and autonomic symptoms.

In this scenario, we recommend that the estimation of ME/CFS prevalence in the context of LC epidemiology is easily achievable by deploying tested and validated diagnosis tools used in ME/CFS. The knowledge of ME/CFS prevalence within the LC population is of cardinal importance to optimal allocation of resources and better design of healthcare interventions to manage and treat patients with this devastating disease.

Source: Anna D. Grabowska, Francisco Westermeier, Luís Nacul, Eliana Lacerda, Nuno Sepúlveda. The importance of estimating prevalence of ME/CFS in future epidemiological studies of long COVID. DOI:10.13140/RG.2.2.20997.52967 https://www.researchgate.net/publication/373043778_The_importance_of_estimating_prevalence_of_MECFS_in_future_epidemiological_studies_of_long_COVID (Full text)

Consequences of sarcolemma fatigue on maximal muscle strength production in patients with myalgic encephalomyelitis/chronic fatigue syndrome

Highlights:

  • Does force failure result from sarcolemma fatigue in Myalgic Encephalomyelitis patients?
  • Two groups of Myalgic Encephalomyelitis patients with or not M wave alterations were compared.
  • Maximal handgrip strength and M wave in forearm muscle were simultaneously measured.
  • Post-exercise changes in Maximal handgrip strength and M wave were positively correlated.
  • The post exercise sarcolemma fatigue measured could be the cause of muscle failure in these patients.

Background: Myalgic encephalomyelitis is an invalidating chronic disease often associated with exercise-induced alterations of muscle membrane excitability (M wave). No simultaneous measurements of maximal isometric force production and sarcolemma fatigue in the same muscle group have been previously reported. We hypothesized that M wave alterations could be partly responsible for the reduced muscle force present in this invalidating disease.

Methods: This retrospective study compared two groups of patients who presented (n = 30) or not (n = 28) alterations of M waves evoked by direct muscle stimulation during and after a cycling exercise bout. The maximal handgrip strength was measured before and after exercise, concomitantly with electromyogram recordings from flexor digitorum longus muscle. The patients also answered a questionnaire to identify eventual exacerbation of their clinical symptoms following the exercise test.

Findings: The M wave amplitude significantly decreased in muscles and the M wave duration significantly increased in the group of patients with M wave alterations after exercise. Resting values of handgrip were significantly lower in patients with exercise-induced M-wave alterations than in patients without M-wave abnormalities. In patients with exercise-induced M-wave alterations, handgrip significantly decreased after exercise and the changes in handgrip and M wave were positively correlated. The frequency of post-exertion malaise, increased fatigue, myalgia, headache and cognitive dysfunction was significantly higher in patients with M-wave alterations and variations in handgrip after exercise.

Interpretation: These data suggest that post-exercise sarcolemma fatigue often measured in patients with myalgic encephalomyelitis could be the cause of muscle failure.

Source: Frédérique Retornaz, Chloé Stavris, Yves Jammes. Consequences of sarcolemma fatigue on maximal muscle strength production in patients with myalgic encephalomyelitis/chronic fatigue syndrome. Clinical Biomechanics, Volume 108, August 2023, 106055. https://www.sciencedirect.com/science/article/pii/S0268003323001869 (Full text)

Long-term symptom severity and clinical biomarkers in post-COVID-19/chronic fatigue syndrome: results from a prospective observational cohort

Summary:

Background: Post-COVID-19 syndrome (PCS) is characterised by a wide range of symptoms, primarily fatigue and exertion intolerance. While disease courses in the early months post-infection have been well-described, the long-term health consequences for patients with PCS with disabling fatigue remain unclear.

Methods: In this prospective observational cohort study, we evaluated symptom severity and various biomarkers, including hand grip strength (HGS), cardiovascular function, and laboratory parameters, in 106 patients with PCS with moderate to severe fatigue and exertion intolerance at three time points after infection (3–8, 9–16, and 17–20 months). The study was conducted at the Charité’s Fatigue Centre and the Charité’s outpatient clinic for neuroimmunology at Berlin, Germany from July 16, 2020, to February 18, 2022. A subset of patients (PCS-ME/CFS) met the diagnostic criteria for myalgic encephalomyelitis/chronic fatigue syndrome according to the Canadian Consensus Criteria (CCC). The aim was to determine differences in the disease course between the two patient groups (i.e., PCS vs PCS-ME/CFS) and identify correlating biomarkers.

Findings: Patients with PCS-ME/CFS reported persistently high severity of most symptoms up to 20 months after infection, while patients with PCS showed overall health improvement. Although fatigue and post-exertional malaise (PEM), hallmarks of post-infectious fatigue syndromes, were still evident in both groups, they remained more pronounced in PCS-ME/CFS. Inflammatory biomarkers decreased in both groups, but not antinuclear antibodies. Lower HGS at onset correlated with symptom persistence, particularly in patients with PCS-ME/CFS.

Interpretation: Our findings suggest that PCS can persist beyond 20 months post-infection and encompass the full scope of post-infectious ME/CFS as defined by the CCC. Sub-classifying patients with PCS based on the CCC can assist in the management and monitoring of patients with PCS-ME/CFS due to their persistently higher symptom severity.

Source: Franziska Legler, Lil Meyer-Arndt, Lukas Mödl, Claudia Kedor, Helma Freitag, Elisa Stein, Uta Hoppmann, Rebekka Rust, Kirsten Wittke, Nadja Siebert, Janina Behrens, Andreas Thiel, Frank Konietschke, Friedemann Paul, Carmen Scheibenbogen, Judith Bellmann-Strobl,
Long-term symptom severity and clinical biomarkers in post-COVID-19/chronic fatigue syndrome: results from a prospective observational cohort, eClinicalMedicine, Volume 63, 2023, 102146, ISSN 2589-5370, https://doi.org/10.1016/j.eclinm.2023.102146. https://www.sciencedirect.com/science/article/pii/S2589537023003231 (Full text)

Home-based testing protocol to measure physiological responses to everyday activities in ME: a feasibility study

Abstract:

Background and objectives: Individuals with Myalgic Encephalomyelitis (ME) have shown altered physiological responses during maximum cardiopulmonary exercise testing. However, maximal testing is not representative of the everyday activities reported to cause or increase symptoms in ME, and is not accessible for those with severe or very severe illness. The aim of this study was to assess the feasibility and acceptability of a home-based testing protocol to measure physiological responses in ME to everyday activity.

Methods: Researchers attended participants’ homes to collect data and provide equipment for independent testing. Adults with ME who met the International Consensus Criteria wore a portable metabolic assessment system and a physiological stress monitor. Blood pressure, heart rate, oxygen saturation and lactic acid were assessed during a range of everyday positions and activities in their own homes.

Results: Online recruitment yielded 70 volunteers in 24 h. 17 eligible individuals reflecting a range of illness severities were enrolled. All participants found the procedures acceptable with 12 (70%) subjects completing every listed activity. Apparent physiological abnormalities were identified in all participants.

Conclusion: Physiological measurement during everyday activities was feasible for our participants who represented a range of ME severities. Activities must be adapted for different levels of severity to avoid significant symptom exacerbation. Further research is needed to develop home-based assessment protocols to advance the biobehavioral understanding of ME.

Trial registration number: ISRCTN78379409

Source: Nicola Clague-Baker, Sarah Tyson, Karen Leslie, Helen Dawes, Michelle Bull & Natalie Hilliard (2023) Home-based testing protocol to measure physiological responses to everyday activities in ME: a feasibility study, Fatigue: Biomedicine, Health & Behavior, DOI: 10.1080/21641846.2023.2245584 https://www.tandfonline.com/doi/full/10.1080/21641846.2023.2245584 (Full text)

Characterizing Sjögren-Associated Fatigue: A Distinct Phenotype from ME/CFS

Abstract:

Fatigue is the most commonly reported and debilitating extraglandular symptom of primary Sjögren′s syndrome (pSS). Fatigue and exertional intolerance are hallmark symptoms of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). We aimed to characterize fatigue and further symptoms among pSS patients and to determine whether there is a symptom overlap in pSS and ME/CFS.
In 19 patients with pSS, we assessed pSS symptom severity and disease activity via questionnaires as well as the Canadian Consensus Criteria (CCC) for ME/CFS. Hand grip strength (HGS) and levels of α1-, α2-, β1-, β2-, M3- and M4-receptor-autoantibodies were measured. A subgroup of pSS patients exhibited severe fatigue and had higher severity of pain (p = 0.045), depression (p = 0.021) and sleep disturbances (p = 0.020) compared to those with less fatigue.
Four of eighteen pSS patients fulfilled the CCC. HGS parameters strongly correlated with fatigue severity (p < 0.05), but strength fully recovered one hour after exertion in contrast to ME/CFS. Levels of β1-, β2- and M4-receptor-autoantibodies were elevated and correlated significantly with disease activity assessed by the ESSDAI (p < 0.05), but not fatigue severity.
Only a minor subgroup of pSS patients fulfills the CCC, and post exertional malaise (PEM) is atypical, as it is primarily triggered by mental/emotional but not physical exertion. HGS assessment is an objective measure to assess overall fatigue severity.
Source: Kim L, Kedor C, Buttgereit F, Heidecke H, Schaumburg D, Scheibenbogen C. Characterizing Sjögren-Associated Fatigue: A Distinct Phenotype from ME/CFS. Journal of Clinical Medicine. 2023; 12(15):4994. https://doi.org/10.3390/jcm12154994 https://www.mdpi.com/2077-0383/12/15/4994 (Full text)

Fatigue in Post-Acute Sequelae of Coronavirus Disease 2019

Abstract:

Fatigue from post-acute sequelae of coronavirus disease 2019 is a complex constellation of symptoms that could be driven by a wide spectrum of underlying etiologies. Despite this, there seems to be hope for treatment plans that focus on addressing possible etiologies and creating a path to improving quality of life and a paced return to activity.

Source: Abbott Z, Summers W, Niehaus W. Fatigue in Post-Acute Sequelae of Coronavirus Disease 2019. Phys Med Rehabil Clin N Am. 2023 Aug;34(3):607-621. doi: 10.1016/j.pmr.2023.04.006. Epub 2023 Apr 24. PMID: 37419535; PMCID: PMC10123359. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10123359/ (Full text)