Hyperbaric Oxygen Therapy Counters Oxidative Stress/Inflammation-Driven Symptoms in Long COVID-19 Patients: Preliminary Outcomes

Abstract:

Long COVID-19 patients show systemic inflammation and persistent symptoms such as fatigue and malaise, profoundly affecting their quality of life. Since improving oxygenation can oppose inflammation at multiple tissue levels, we hypothesized that hyperbaric oxygen therapy (HBOT) could arrest inflammation progression and thus relieve symptoms of COVID-19.
We evaluated oxy-inflammation biomarkers in long COVID-19 subjects treated with HBOT and monitored with non-invasive methods. Five subjects (two athletes and three patients with other comorbidities) were assigned to receive HBOT: 100% inspired O2 at 2.4 ATA in a multiplace hyperbaric chamber for 90 min (three athletes: 15 HBOT × 5 days/wk for 3 weeks; two patients affected by Idiopathic Sudden Sensorineural Hearing Loss: 30 HBOT × 5 days/wk for 6 weeks; and one patient with osteomyelitis: 30 HBOT × 5 days/wk for week for 6 weeks and, after a 30-day break, followed by a second cycle of 20 HBOT).
Using saliva and/or urine samples, reactive oxygen species (ROS), antioxidant capacity, cytokines, lipids peroxidation, DNA damage, and renal status were assessed at T1_pre (basal level) and at T2_pre (basal level after treatment), and the results showed attenuated ROS production, lipid peroxidation, DNA damage, NO metabolites, and inflammation biomarker levels, especially in the athletes post-treatment. Thus, HBOT may represent an alternative non-invasive method for treating long COVID-19-induced long-lasting manifestations of oxy-inflammation.
Source: Mrakic-Sposta S, Vezzoli A, Garetto G, Paganini M, Camporesi E, Giacon TA, Dellanoce C, Agrimi J, Bosco G. Hyperbaric Oxygen Therapy Counters Oxidative Stress/Inflammation-Driven Symptoms in Long COVID-19 Patients: Preliminary Outcomes. Metabolites. 2023; 13(10):1032. https://doi.org/10.3390/metabo13101032 https://www.mdpi.com/2218-1989/13/10/1032 (Full text)

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)

Cognitive dysfunction in post-COVID-19 condition: Mechanisms, management, and rehabilitation

Abstract:

The long-term effects of COVID-19 on cognitive function have become an area of increasing concern. This paper provides an overview of characteristics, risk factors, possible mechanisms, and management strategies for cognitive dysfunction in post-COVID-19 condition (PCC).

Prolonged cognitive dysfunction is one of the most common impairments in PCC, affecting between 17% and 28% of the individuals more than 12 weeks after the infection and persisting in some cases for several years. Cognitive dysfunctions can be manifested as a wide range of symptoms including memory impairment, attention deficit, executive dysfunction, and reduced processing speed. Risk factors for developing PCC, with or without cognitive impairments, include advanced age, preexisting medical conditions, and the severity of acute illness. The underlying mechanisms remain unclear, but proposed contributors include neuroinflammation, hypoxia, vascular damage, and latent virus reactivation not excluding the possibility of direct viral invasion of the central nervous system, illustrating complex viral pathology.

As the individual variation of the cognitive impairments is large, a neuropsychological examination and a person-centered multidimensional approach are required. According to the World Health Organization, limited evidence on COVID-19-related cognitive impairments necessitates implementing rehabilitation interventions from established practices of similar conditions. Psychoeducation and compensatory skills training are recommended. Assistive products and environmental modifications adapted to individual needs might be helpful. In specific attention- and working memory dysfunctions, cognitive training—carefully monitored for intensity—might be effective for people who do not suffer from post-exertional malaise. Further research is crucial for evidence-based interventions specific to COVID-19-related cognitive impairments.

Source: Möller M, Borg K, Janson C, Lerm M, Normark J, Niward K. Cognitive dysfunction in post-COVID-19 condition: Mechanisms, management, and rehabilitation. J Intern Med. 2023 Sep 27. doi: 10.1111/joim.13720. Epub ahead of print. PMID: 37766515. https://onlinelibrary.wiley.com/doi/10.1111/joim.13720 (Full text)

Re-visiting professional ethics in psychotherapy: Reflections on the use of talking therapies as a supportive adjunct for myalgic encephalomyelitis / chronic fatigue syndrome and ‘medically unexplained symptoms’

Abstract:

Following years of debate over the effectiveness of cognitive behavioural therapy for myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS), public health bodies in the UK and beyond have determined that no psychotherapy is clinically proven for this patient group.

In the field of ME/CFS and the wider arena of ‘medically unexplained symptoms’ (MUS), patient survey data and qualitative research capturing patient experiences and psychotherapist attitudes suggest that therapeutic practice may sometimes fall short of required ethical standards. This raises questions about how psychotherapists can safely support, as opposed to treat, people with these debilitating conditions.

We consider four ethical principles that feature throughout psychotherapists’ codes of practice, those of respect, competence, responsibility, and integrity, and discuss examples of good and poor practice in this arena as evinced by recent empirical literature.

Following this, we offer a variety of suggestions to help strengthen ethical psychotherapy practice among patients with ME/CFS and other MUS. In terms of practitioner education, we recommend greater emphasis on humility and reflexive practice, exploration of personal as well professional ethics, and integration of patient expertise-by-experience, accompanied with latest evidence, into foundational and on-going training.

In terms of practice, we suggest consideration of formalized patient-focused feedback systems and greater transparency visà-vis patient access to clinical notes. Finally, we underline the importance of elevating patients from mere subjects to co-producers of psychotherapy research.

Source: Joanne Hunt, Charlotte Blease. Re-visiting professional ethics in psychotherapy: Reflections on the use of talking therapies as a supportive adjunct for myalgic encephalomyelitis / chronic fatigue syndrome and ‘medically unexplained symptoms.’ OSF preprints. https://osf.io/2m9eb/ (Full text)

Assessing Functional Capacity in ME/CFS: A Patient Informed Questionnaire

Abstract:

Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS) is an acquired disease with significant morbidity that affects both children and adults. Effective tools to assess functional capacity (FC) are severely lacking which has significant consequences for timely diagnosis, assessments for patient disability benefits and assessing the impact and effectiveness of interventions.

In interventional research the inability to assess FC can result in an incomplete assessment of the potential effect of the intervention. Specifically of concern is that if an intervention is effective in reducing symptom load, patients may increase their activity level to reach a pre-intervention symptom load. Thus, if FC is not accurately assessed, beneficial treatment outcomes may be missed.

To address this issue, using extensive, repeated patient feedback we have developed a new questionnaire, FUNCAP, to achieve optimal FC assessment in ME/CFS patients.

The questionnaire covers eight domains and activity types: A. Personal hygiene / basic functions, B. Walking / movement, C. Being upright, D. Activities in the home, E. Communication, F. Activities outside the home, G. Reactions to light and sound, and H. Concentration.

Through five rounds of anonymous web-based surveys and a further test – retest validation round, two versions of the questionnaire were developed; a longer version comprising 55 questions (FUNCAP55) to improve diagnostic and disability benefit/ insurance FC assessments and a shorter version (FUNCAP27) for interventional research and less extensive FC assessments. FUNCAP may also be useful in other conditions where fatigue and PEM is present, such as Long Covid.

Source: Sommerfelt, K.; Schei, T.; Seton, K.A.; Carding, S.R. Assessing Functional Capacity in ME/CFS: A Patient Informed Questionnaire. Preprints 2023, 2023092091 https://www.preprints.org/manuscript/202309.2091/v1 (Full text available as PDF file) Final version https://www.mdpi.com/2077-0383/13/12/3486 (Full text)

Is there a role for traditional and complementary medicines in managing chronic fatigue? A systematic review of randomized controlled trials

Abstract:

Introduction: Chronic fatigue syndrome (CFS) is an increasingly common condition that is challenging to treat due to unclear etiology and a lack of consensus on clinical diagnosis and treatment guidance. Many affected people resorted to using traditional and complementary medicines (T&CMs). However, the evidence for T&CMs for CF has been inconclusive and continues to evolve. The study aims to identify, summarize and assess the most recent evidence on the efficacy and safety of T&CMs for CFS.

Methods: Randomized controlled trials (RCTs) investigating T&CMs for CFS published in English of Chinese between 1 January 2013 and 31 December 2022 were searched from 7 databases. RCTs comparing T&CMs with no treatment, placebo, or pharmacological medicine were included, irrespective of language or blinding.

The Consolidated Standards of Reporting Trials Statement extensions for Chinese herbal medicine Formulas (CONSORT-CHM) and the Cochrane Collaboration’s Risk of Bias tool were used to evaluate the quality and risk of bias of included studies.

Results: A total of 62 RCTs investigating 43 types of T&CMs and involving 5,231 participants with CFS were included in this review. The primary outcome measures mainly included the scoring of fatigue symptoms using the validated tool Fatigue Scale-14 (FS-14) or the TCM syndrome score.

The main interventions showing overall efficacy were Chaihu Guizhi Decoction and Buzhong Yiqi combined with Xiao Chaihu Decoction, and 148 ingredients were identified, including Astragali Radix, Glycyrrhizae Radix et Rhizoma, Atractylodis Macrocephalae Rhizoma, and Bupleuri Radix.

The most significant effect was the improvement of fatigue, followed by TCM-diagnosed symptoms and other psychological conditions. No serious adverse effect had been reported. However, the quality of the RCTs included RCTs were found to be suboptimal, and the risk of bias remained uncertain.

Conclusions: Some evidence from RCTs supported the efficacy and safety of T&CM in CFS. However, given the methodological and quality heterogenicity of the included studies, the recommendations of T&CMs in treating CFS remain inconclusive. To develop better quality evidence about T&CMs for CFS, future studies should employ more objective diagnosis standards and outcome measurements, larger sample size, and better bias control, and ensure the compliance with the corresponding reporting guidelines.

Source: Yuxiao Li, Jingya Yang, Chi Ian Chau, Junnan Shi, Xianwen Chen, Hao Hu, Carolina Oi Lam Ung. Is there a role for traditional and complementary medicines in managing chronic fatigue? A systematic review of randomized controlled trials. Frontiers in Pharmacology, Volume 14, 2023. https://www.frontiersin.org/articles/10.3389/fphar.2023.1266803/abstract

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)

Unsupervised cluster analysis reveals distinct subtypes of ME/CFS patients based on peak oxygen consumption and SF-36 scores

Abstract:

Purpose: Myalgic encephalomyelitis, commonly referred to as chronic fatigue syndrome (ME/CFS), is a severe, disabling chronic disease and an objective assessment of prognosis is crucial to evaluate the efficacy of future drugs. Attempts are ongoing to find a biomarker to objectively assess the health status of (ME/CFS), patients. This study therefore aims to demonstrate that oxygen consumption is a biomarker of ME/CFS provides a method to classify patients diagnosed with ME/CFS based on their responses to the Short Form-36 (SF-36) questionnaire, which can predict oxygen consumption using cardiopulmonary exercise testing (CPET).

Methods: Two datasets were used in the study. The first contained SF-36 responses from 2,347 validated records of ME/CFS diagnosed participants, and an unsupervised machine learning model was developed to cluster the data. The second dataset was used as a validation set and included the cardiopulmonary exercise test (CPET) results of 239 participants diagnosed with ME/CFS. Participants from this dataset were grouped by peak oxygen consumption according to Weber’s classification. The SF-36 questionnaire was correctly completed by only 92 patients, who were clustered using the machine learning model. Two categorical variables were then entered into a contingency table: the cluster with values {0,1} and Weber classification {A, B, C, D} were assigned. Finally, the Chi-square test of independence was used to assess the statistical significance of the relationship between the two parameters.

Findings: The results indicate that the Weber classification is directly linked to the score on the SF-36 questionnaire. Furthermore, the 36-response matrix in the machine learning model was shown to give more reliable results than the subscale matrix (p – value < 0.05) for classifying patients with ME/CFS.

Implications: Low oxygen consumption on CPET can be considered a biomarker in patients with ME/CFS. Our analysis showed a close relationship between the cluster based on their SF-36 questionnaire score and the Weber classification, which was based on peak oxygen consumption during CPET. The dataset for the training model comprised raw responses from the SF-36 questionnaire, which is proven to better preserve the original information, thus improving the quality of the model.

Source: Lacasa M, Launois P, Prados F, Alegre J, Casas-Roma J. Unsupervised cluster analysis reveals distinct subtypes of ME/CFS patients based on peak oxygen consumption and SF-36 scores. Clin Ther. 2023 Oct 4:S0149-2918(23)00352-1. doi: 10.1016/j.clinthera.2023.09.007. Epub ahead of print. PMID: 37802746. https://www.clinicaltherapeutics.com/article/S0149-2918(23)00352-1/fulltext (Full text)

HERV activation segregates ME/CFS from fibromyalgia and defines a novel nosological entity for patients fulfilling both clinical criteria

Abstract:

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and fibromyalgia (FM) are chronic diseases with poorly understood pathophysiology and diagnosis based on clinical assessment of unspecific symptoms. The recent post-COVID-19 condition, which shares similarities with ME/CFS and FM, has raised concerns about viral-induced transcriptome changes in post-viral syndromes. Viral infections, and other types of stress, are known to unleash human endogenous retroviruses (HERV) repression that if maintained could lead to symptom chronicity. This study evaluated this possibility for ME/CFS and FM on a selected cohort of female patients complying with diagnosis criteria for ME/CFS, FM, or both, and matched healthy controls (n=43).

The results show specific HERV fingerprints for each disease, confirming biological differences between ME/CFS and FM. Unexpectedly, HERV profiles segregated patients that met both ME/CFS and FM clinical criteria from patients complying only with ME or FM criteria, while clearly differentiating patients from healthy subjects, supporting that the highly prevalent comorbidity condition must constitute a different nosological entity.

Moreover, HERV profiles exposed significant quantitative differences within the ME/CFS group that correlated with differences in immune gene expression and patient symptomatology, supporting ME/CFS patient subtyping and confirming immunological disturbances in this disease. Pending issues include validation of HERV profiles as disease biomarkers of post-viral syndromes and understanding the role of HERV during infection and beyond.

Source: Karen Gimenez-Orenga, Eva Martin-Martinez, Lubov Nathanson, Elisa Oltra. HERV activation segregates ME/CFS from fibromyalgia and defines a novel nosological entity for patients fulfilling both clinical criteria. bioRxiv 2023.10.05.561025; doi: https://doi.org/10.1101/2023.10.05.561025 https://www.biorxiv.org/content/10.1101/2023.10.05.561025v1 (Full text available as PDF file)

 

Identifying, synthesising and appraising existing evidence relating to myalgic encephalomyelitis/chronic fatigue syndrome and pregnancy: a mixed-methods systematic review

Abstract

Objectives: To identify, synthesise and appraise evidence relating to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and pregnancy.

Design: Mixed-methods systematic review, using convergent segregated design.

Data sources: MEDLINE, EMBASE, Scopus, PsycINFO, CINAHL, MedRxiv, PROSPERO and grey literature sources through 6 August 2023.

Eligibility criteria: We included original research studies, expert opinion and grey literature reporting on ME/CFS and pregnancy/post partum (up to 2 years), risk of pregnancy outcomes with ME/CFS or experiences during pregnancy for mother, partner or health and social care professionals following ME/CFS during pregnancy, all where the evidence was relevant to a confirmed ME/CFS diagnosis prior to pregnancy.

Data extraction and synthesis: Three independent reviewers completed all screening, data extraction and quality assessment. Risk of bias was assessed using the mixed-methods appraisal tool V.2018. Qualitative and quantitative literature was analysed separately using thematic and descriptive syntheses. Findings were integrated through configuration.

Results: Searches identified 3675 articles, 16 met the inclusion criteria: 4 quantitative (1 grey), 11 qualitative (9 grey) and 1 grey mixed-methods study. Of the four quantitative studies that reported on ME/CFS severity during pregnancy, two suggested pregnancy negatively impacted on ME/CFS, one found most women had no change in ME/CFS symptoms and one found ME/CFS improved; this difference in symptom severity across studies was supported by the qualitative evidence. The qualitative literature also highlighted the importance of individualised care throughout pregnancy and birth, and the need for additional support during family planning, pregnancy and with childcare. Only one quantitative study reported on pregnancy outcomes, finding decreased vaginal births and higher rates of spontaneous abortions and developmental and learning delays associated with pregnancies in those with ME/CFS.

Conclusions: Current evidence on ME/CFS in pregnancy is limited and findings inconclusive. More high-quality research is urgently needed to support the development of evidence-based guidelines on ME/CFS and pregnancy.

Source: Slack E, Pears KA, Rankin J, Newton JL, Pearce M. Identifying, synthesising and appraising existing evidence relating to myalgic encephalomyelitis/chronic fatigue syndrome and pregnancy: a mixed-methods systematic review. BMJ Open. 2023 Oct 5;13(10):e070366. doi: 10.1136/bmjopen-2022-070366. PMID: 37798026. https://bmjopen.bmj.com/content/13/10/e070366 (Full text)