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/

The Presentation of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Is Not Influenced by the Presence or Absence of Joint Hypermobility

Abstract:

Objective: To examine demographic and clinical characteristics of individuals with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) with and without joint hypermobility We hypothesized that JH+ patients would have an earlier onset of ME/CFS symptoms as well as increased severity, greater number of co-morbid conditions, and lower health related quality of life.

Study design: From an observational cohort study of 55 individuals meeting the Fukuda criteria for ME/CFS, we compared groups using a Beighton score cut-off of 4 or higher to indicate JH. Chart data were collected to examine the age and type of onset of ME/CFS, and the presence of comorbid conditions. The impact on quality of life was assessed through questionnaires that included the Peds QL, Functional Disability Inventory, Peds QL Multidimensional Fatigue Scale, and Anxiety Subscale of the Symptom Checklist 90.

Results: There was no significant difference between groups in mean (SD) age at onset of ME/CFS (13.3 [3.3] years vs 13.3 [2.3] years; P = .92), sex, frequency, and severity of ME/CFS symptoms, orthostatic intolerance symptoms, or comorbid conditions. There was no significant difference between groups in measures of health-related quality of life using a Beighton score cut-off of 4 or a cut-off of 5 to define joint hypermobility.

Conclusions: Despite being a risk factor for the development of ME/CFS, JH as defined in this study was not associated with other clinical characteristics of the illness.

Source: Vogel SK, Primavera IR, Marden CL, Jasion SE, Cranston EM, Flaherty MAK, Violand RL, Rowe PC. The Presentation of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Is Not Influenced by the Presence or Absence of Joint Hypermobility. J Pediatr. 2021 Sep 16:S0022-3476(21)00887-8. doi: 10.1016/j.jpeds.2021.09.014. Epub ahead of print. PMID: 34537220. https://pubmed.ncbi.nlm.nih.gov/34537220/

Human herpesvirus 6 infection and risk of Chronic fatigue syndrome: a systematic review and meta-analysis

Abstract:

Introduction: Chronic fatigue syndrome (CFS) is a neurological disease that is accompanied by excessive fatigue or tiredness. There are several reports confirming the association between human herpesvirus 6 (HHV-6) infection and CFS illness. This systematic review and meta-analysis was performed to integrate the information of published studies with regard to this association until May 2021.

Methods: The literature search was based on keywords including “chronic fatigue syndrome and HHV 6,” “chronic fatigue syndrome and HHV-6,” “chronic fatigue syndrome and HHV6,” “chronic fatigue syndrome and Herpes virus 6,” and “chronic fatigue syndrome and Herpesvirus6” in MEDLINE (PubMed), Web of Science, and EMBASE.

Results: The literature search identified 17 studies to be included in the systematic review and 11 studies in meta-analysis. The symmetry funnel plot and Egger’s test (p value = 0.2) identified no publication bias among studies. Moreover, the low level of I2 revealed homogeneity across studies.

Discussion: In conclusion, the association between the HHV-6 infection and CFS incidence was substantiated. However, the results of this study also suggest that further comprehensive studies are needed to solidify the association between HHV-6 and CFS. Future studies should consider additional factors that may have affected the significance of such a correlation.

Source: Sayed-Hamidreza Mozhgani, Farid Rajabi, Mohsen Qurbani, Yousef Erfani, Somayeh Yaslianifard, Azam Moosavi, Kiomars Pourrostami, Ali Baradaran Bagheri, Alireza Soleimani, Farida Behzadian, Mahshid Safavi, Farhad Rezaei. Human herpesvirus 6 infection and risk of Chronic fatigue syndrome: a systematic review and meta-analysis. Intervirology (IF1.763), Pub Date : 2021-06-23, DOI: 10.1159/000517930 https://www.karger.com/Article/Abstract/517930 (Full text as PDF file)

The SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: a meta-analysis of public DNA methylation and gene expression data

Abstract:

People with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) often report a high frequency of viral infections and flu-like symptoms during their disease course. Since this reporting is in line with different immunological abnormalities and altered gene expression profiles observed in the disease, we aimed to explore whether the expression of the human angiotensin-converting enzyme-2 (ACE2), the major cell entry receptor for SARS-CoV-2, is also altered in this neglected clinical population. In particular, a low expression of ACE2 is usually indicative of a high risk of developing COVID-19.

We then performed a meta-analysis of public data on CpG DNA methylation and gene expression of this enzyme and its homologous ACE protein in peripheral blood mononuclear cells and related subsets. We found that patients with ME/CFS have decreased methylation levels of four CpG probes in the ACE locus (cg09920557, cg19802564, cg21094739, and cg10468385) and of another probe in the promoter region of the ACE2 gene (cg08559914). We also found a decreased expression of ACE2 but not of ACE in patients with ME/CFS when compared to healthy controls.

Accordingly, in newly collected data, we found evidence for a higher proportion of samples with an ACE2 expression below the limit of detection in patients with ME/CFS than in healthy controls. Altogether, patients with ME/CFS could be at a higher COVID-19 risk when infected by SARS-CoV-2. To further support this conclusion, similar research should be conducted for other human cell entry receptors and other cell types, namely, those mainly targeted by the virus.

Source: Malato J, Sotzny F, Bauer S, Freitag H, Fonseca A, Grabowska AD, Graça L, Cordeiro C, Nacul L, Lacerda EM, Castro-Marrero J, Scheibenbogen C, Westermeier F, Sepúlveda N. The SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: a meta-analysis of public DNA methylation and gene expression data. Heliyon. 2021 Jul 29;7(8):e07665. doi: 10.1016/j.heliyon.2021.e07665. Epub ahead of print. PMID: 34341773; PMCID: PMC8320404. https://pubmed.ncbi.nlm.nih.gov/34341773/

Identifying and managing suicidality in Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome

Adult patients affected by myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are at an increased risk of death by suicide. Based on the scientific literature and our clinical/research experiences, we identify risk and protective factors and provide a guide to assessing and managing suicidality in an outpatient medical setting. A clinical case is used to illustrate how information from this article can be applied.
Characteristics of ME/CFS that make addressing suicidality challenging include absence of any disease-modifying treatments, severe functional limitations, and symptoms which limit therapies. Decades-long misattribution of ME/CFS to physical deconditioning or psychiatric disorders have resulted in undereducated healthcare professionals, public stigma, and unsupportive social interactions. Consequently, some patients may be reluctant to engage with mental health care. Outpatient medical professionals play a vital role in mitigating these effects.
By combining evidence-based interventions aimed at all suicidal patients with those adapted to individual patients’ circumstances, suffering and suicidality can be alleviated in ME/CFS. Increased access to newer virtual or asynchronous modalities of psychiatric/psychological care, especially for severely ill patients, may be a silver lining of the COVID-19 pandemic.
Source: Chu L, Elliott M, Stein E, Jason LA. Identifying and Managing Suicidality in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Healthcare. 2021; 9(6):629. https://doi.org/10.3390/healthcare9060629 https://www.mdpi.com/2227-9032/9/6/629/htm (Full text)

Long COVID or post-COVID-19 syndrome: putative pathophysiology, risk factors, and treatments

Abstract:

Long COVID or post-COVID-19 syndrome first gained widespread recognition among social support groups and later in scientific and medical communities. This illness is poorly understood as it affects COVID-19 survivors at all levels of disease severity, even younger adults, children, and those not hospitalized. While the precise definition of long COVID may be lacking, the most common symptoms reported in many studies are fatigue and dyspnoea that last for months after acute COVID-19. Other persistent symptoms may include cognitive and mental impairments, chest and joint pains, palpitations, myalgia, smell and taste dysfunctions, cough, headache, and gastrointestinal and cardiac issues. Presently, there is limited literature discussing the possible pathophysiology, risk factors, and treatments in long COVID, which the current review aims to address.

In brief, long COVID may be driven by long-term tissue damage (e.g. lung, brain, and heart) and pathological inflammation (e.g. from viral persistence, immune dysregulation, and autoimmunity). The associated risk factors may include female sex, more than five early symptoms, early dyspnoea, prior psychiatric disorders, and specific biomarkers (e.g. D-dimer, CRP, and lymphocyte count), although more research is required to substantiate such risk factors. While preliminary evidence suggests that personalized rehabilitation training may help certain long COVID cases, therapeutic drugs repurposed from other similar conditions, such as myalgic encephalomyelitis or chronic fatigue syndrome, postural orthostatic tachycardia syndrome, and mast cell activation syndrome, also hold potential. In sum, this review hopes to provide the current understanding of what is known about long COVID.

Source: Yong SJ. Long COVID or post-COVID-19 syndrome: putative pathophysiology, risk factors, and treatments. Infect Dis (Lond). 2021 May 22:1-18. doi: 10.1080/23744235.2021.1924397. Epub ahead of print. PMID: 34024217. https://pubmed.ncbi.nlm.nih.gov/34024217/

The Role of Prevention in Reducing the Economic Impact of ME/CFS in Europe: A Report from the Socioeconomics Working Group of the European Network on ME/CFS (EUROMENE)

Abstract:

This report addresses the extent to which there may be scope for preventive programmes for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), and, if so, what economic benefits may accrue from the implementation of such programmes. We consider the economic case for prevention programmes, whether there is scope for preventive programmes for ME/CFS, and what are the health and economic benefits to be derived from the implementation of such programmes.

We conclude that there is little scope for primary prevention programmes, given that ME/CFS is attributable to a combination of host and environmental risk factors, with host factors appearing to be most prominent, and that there are few identified modifiable risk factors that could be the focus of such programmes. The exception is in the use of agricultural chemicals, particularly organophosphates, where there is scope for intervention, and where Europe-wide programmes of health education to encourage safe use would be beneficial. There is a need for more research on risk factors for ME/CFS to establish a basis for the development of primary prevention programmes, particularly in respect of occupational risk factors. Secondary prevention offers the greatest scope for intervention, to minimise diagnostic delays associated with prolonged illness, increased severity, and increased costs.

Source: Pheby DFH, Araja D, Berkis U, Brenna E, Cullinan J, de Korwin JD, Gitto L, Hughes DA, Hunter RM, Trepel D, Wang-Steverding X. The Role of Prevention in Reducing the Economic Impact of ME/CFS in Europe: A Report from the Socioeconomics Working Group of the European Network on ME/CFS (EUROMENE). Medicina (Kaunas). 2021 Apr 16;57(4):388. doi: 10.3390/medicina57040388. PMID: 33923830; PMCID: PMC8073750.  https://pubmed.ncbi.nlm.nih.gov/33923830/ (Full text)

Suicidal ideation in non-depressed individuals: The effects of a chronic, misunderstood illness

Abstract:

Chronic illness is a risk factor for suicide but is often explained with depression. Research has shown an increased suicide rate in patients with myalgic encephalomyelitis and chronic fatigue syndrome, but specific risk factors have been unexplored. We qualitatively analyzed responses from 29 patients who endorsed suicidal ideation but did not meet depression criteria. Two themes were developed: (1) feeling trapped and (2) loss of self, loss of others, stigma and conflict. Myalgic encephalomyelitis and chronic fatigue syndrome caused patients severe disability, restructured their lives, and inflicted serious pain. Participants emphasized that they were not depressed, but felt trapped by the lack of treatments available.

Source: Devendorf AR, McManimen SL, Jason LA. Suicidal ideation in non-depressed individuals: The effects of a chronic, misunderstood illness. J Health Psychol. 2020 Nov-Dec;25(13-14):2106-2117. doi: 10.1177/1359105318785450. Epub 2018 Jul 11. PMID: 29992837. https://pubmed.ncbi.nlm.nih.gov/29992837/

How peptic ulcer disease could potentially lead to the lifelong, debilitating effects of chronic fatigue syndrome: an insight

Abstract:

Chronic Fatigue Syndrome (CFS) has been defined as unexplained relapsing or persistent fatigue for at least 6 consecutive months. Immuno-inflammatory pathway, bacterial infection, and other causes play essential roles in CFS. Helicobacter pylori infection is one of the most common causes of foregut inflammation, leading to peptic ulcer disease (PUD). This study aimed to analyze the risk of CFS development between patients with and without PUD. Other related factors were also analyzed. We performed a retrospective, nationwide cohort study identifying patients with or without PUD respectively by analyzing the Longitudinal Health Insurance Database 2000 (LHID2000), Taiwan. The overall incidence of CFS was higher in the PUD cohort than in the non- PUD cohort (HR = 2.01, 95% CI = 1.75-2.30), with the same adjusted HR (aHR) when adjusting for age, sex, and comorbidities. The sex-specific PUD cohort to the non-PUD cohort relative risk of CFS was significant in both genders. The age-specific incidence of CFS showed incidence density increasing with age in both cohorts. There is an increased risk of developing CFS following PUD, especially in females and the aging population. Hopefully, these findings can prevent common infections from progressing to debilitating, chronic conditions such as CFS.

Source: Kuo CF, Shi L, Lin CL, Yao WC, Chen HT, Lio CF, Wang YT, Su CH, Hsu NW, Tsai SY. How peptic ulcer disease could potentially lead to the lifelong, debilitating effects of chronic fatigue syndrome: an insight. Sci Rep. 2021 Apr 6;11(1):7520. doi: 10.1038/s41598-021-87018-z. PMID: 33824394. https://pubmed.ncbi.nlm.nih.gov/33824394/

Chronic COVID-19 Syndrome and Chronic Fatigue Syndrome (ME/CFS) following the first pandemic wave in Germany: a first analysis of a prospective observational study

Abstract:

Objective: Characterization of the clinical features of patients with persistent symptoms after mild to moderate COVID-19 infection and exploration of factors associated with the development of Chronic COVID-19 Syndrome (CCS). Methods: Setting: Charite Fatigue Center with clinical immunologists and rheumatologist, neurologists and cardiologists at Charite University hospital.

Participants: 42 patients who presented with persistent moderate to severe fatigue six months following a mostly mild SARS-CoV-2 infection at the Charite Fatigue Center from July to November 2020.

Main outcome measures: The primary outcomes were clinical and paraclinical data and meeting diagnostic criteria for Chronic Fatigue Syndrome (ME/CFS). Relevant neurological and cardiopulmonary morbidity was excluded.

Results: The median age was 36.5, range 22-62, 29 patients were female and 13 male. At six months post acute COVID-19 all patients had fatigue (Chalder Fatigue Score median 25 of 33, range 14-32), the most frequent other symptoms were post exertional malaise (n=41), cognitive symptoms (n=40), headache (n=38), and muscle pain (n=35). Most patients were moderately to severely impaired in daily live with a median Bell disability score of 50 (range 15-90) of 100 (healthy) and Short Form 36 (SF36) physical function score of 63 (range 15-80) of 100. 19 of 42 patients fulfilled the 2003 Canadian Consensus Criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). These patients reported more fatigue in the Chalder Fatigue Score (p=0.006), more stress intolerance (p=0.042) and more frequent and longer post exertional malaise (PEM) (p= 0.003), and hypersensitivity to noise (p=0.029), light (p=0.0143) and temperature (0.024) compared to patients not meeting ME/CFS criteria. Handgrip force was diminished in most patients compared to healthy control values, and lower in CCS/CFS compared to non-CFS CCS (Fmax1 p=0.085, Fmax2, p=0.050, Fmean1 p=0.043, Fmean2 p=0.034, mean of 10 repeat handgrips, 29 female patients). Mannose-binding lectin (MBL) deficiency was observed frequently (22% of all patients) and elevated IL-8 levels were found in 43% of patients.

Conclusions: Chronic COVID-19 Syndrome at months 6 is a multisymptomatic frequently debilitating disease fulfilling diagnostic criteria of ME/CFS in about half of the patients in our study. Research in mechanisms and clinical trials are urgently needed.

Source: Claudia Kedor, Helma Freitag, Lil-Antonia Meyer-Arndt, Kirsten Wittke, thomas Zoller, Fridolin Steinbeis, Milan Haffke, Rudolf Gordon, Bettina Heidecker, Hans Dieter Volk, Carsten Skurk, Friedemann Paul, Judith Bellmann-Strobl, Carmen Scheibenbogen. Chronic COVID-19 Syndrome and Chronic Fatigue Syndrome (ME/CFS) following the first pandemic wave in Germany: a first analysis of a prospective observational study. medRxiv 2021.02.06.21249256; doi: https://doi.org/10.1101/2021.02.06.21249256 https://www.medrxiv.org/content/10.1101/2021.02.06.21249256v1