Category: Overlapping Illnesses

COVID-19: A methyl-group assault?

Abstract:

The socio-economic implications of COVID-19 are devastating. Considerable morbidity is attributed to ‘long-COVID’ – an increasingly recognized complication of infection. Its diverse symptoms are reminiscent of vitamin B12 deficiency, a condition in which methylation status is compromised. We suggest why SARS-CoV-2 infection likely leads to increased methyl-group requirements and other disturbances of one-carbon metabolism. We propose these might explain the varied symptoms of long-COVID. Our suggested mechanism might also apply to similar conditions such as myalgic encephalomyelitis/chronic fatigue syndrome. The hypothesis is evaluable by detailed determination of vitamin B12 and folate status, including serum formate as well as homocysteine and methylmalonic acid, and correlation with viral and host RNA methylation and symptomatology. If confirmed, methyl-group support should prove beneficial in such individuals.

Source: McCaddon A, Regland B. COVID-19: A methyl-group assault? Med Hypotheses. 2021 Feb 18;149:110543. doi: 10.1016/j.mehy.2021.110543. Epub ahead of print. PMID: 33657459; PMCID: PMC7890339. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890339/ (Full text)

Our Evolving Understanding of ME/CFS

Abstract:

The potential benefits of the scientific insights gleaned from years of treating ME/CFS for the emerging symptoms of COVID-19, and in particular Longhaul- or Longhauler-COVID-19 are discussed in this opinion article. Longhaul COVID-19 is the current name being given to the long-term sequelae (symptoms lasting beyond 6 weeks) of SARS-CoV-2 infection. Multiple case definitions for ME/CFS exist, but post-exertional malaise (PEM) is currently emerging as the ‘hallmark’ symptom. The inability to identify a unique trigger of ME/CFS, as well as the inability to identify a specific, diagnostic laboratory test, led many physicians to conclude that the illness was psychosomatic or non-existent. However, recent research in the US and the UK, championed by patient organizations and their use of the internet and social media, suggest underlying pathophysiologies, e.g., oxidative stress and mitochondrial dysfunction. The similarity and overlap of ME/CFS and Longhaul COVID-19 symptoms suggest to us similar pathological processes.

We put forward a unifying hypothesis that explains the precipitating events such as viral triggers and other documented exposures: For their overlap in symptoms, ME/CFS and Longhaul COVID-19 should be described as Post Active Phase of Infection Syndromes (PAPIS). We further propose that the underlying biochemical pathways and pathophysiological processes of similar symptoms are similar regardless of the initiating trigger. Exploration of the biochemical pathways and pathophysiological processes should yield effective therapies for these conditions and others that may exhibit these symptoms. ME/CFS patients have suffered far too long. Longhaul COVD-19 patients should not be subject to a similar fate. We caution that failure to meet the now combined challenges of ME/CFS and Longhaul COVID-19 will impose serious socioeconomic as well as clinical consequences for patients, the families of patients, and society as a whole.

Source: Friedman KJ, Murovska M, Pheby DFH, Zalewski P. Our Evolving Understanding of ME/CFS. Medicina (Kaunas). 2021 Feb 26;57(3):200. doi: 10.3390/medicina57030200. PMID: 33652622. https://www.mdpi.com/1648-9144/57/3/200 (Full text)

Chronic fatigue syndrome (CFS)/Myalgic Encephalomyelitis (ME) and Fibromyalgia (FM): the foundation of a relationship

Abstract:

Introduction: Chronic fatigue syndrome (CFS)/Myalgic Encephalomyelitis (ME) and fibromyalgia (FM) are both debilitating syndromes with complex polysymptomatology. Early research infers that a relationship may exist even though the diagnosis provided may influence the management trajectory. In the absence of a diagnostic test and treatment, this study aims to confirm the symptoms and their severity, which may infer a relationship and influence future research.

Method: A quasi-experimental design was utilised, using Internet-based self-assessment questionnaires focusing on nine symptom areas: criteria, pain, sleep, fatigue, anxiety and depression, health-related quality of life, self-esteem and locus of control. The questionnaires used for data collection are as follows: the American Centre for Disease Control and Prevention Symptom Inventory for CFS/ME (American CDC Symptom Inventory); the American College of Rheumatology (ACR) Criteria for FM; Fibromyalgia Impact Questionnaire (FIQ); McGill Pain Questionnaire (MPQ); Multidimensional Fatigue Inventory (MFI); Pittsburgh Sleep Quality Index (PSQI); Health-Related Quality of Life SF-36 V2 (HRQoL SF-36 V2); Hospital Anxiety and Depression Scale (HADS); Multidimensional Health Locus of Control (MHLOC) and the Rosenberg Self-Esteem Scale (RSES).

Setting and participants: Participants were recruited from two distinct community groups, namely CFS/ME (n = 101) and FM (n = 107). Participants were male and female aged 17 (CFS/ME mean age 45.5 years; FM mean age 47.2 years).

Results: All participants in the CFS/ME and FM groups satisfied the requirements of their individual criteria. Results confirmed that both groups experienced the debilitating symptoms measured, with the exception of anxiety and depression, impacting on their quality of life. Results suggest a relationship between CFS/ME and FM, indicating the requirement for future research.

Source: Mckay PG, Martin CR, Walker H, Fleming M. Chronic fatigue syndrome (CFS)/Myalgic Encephalomyelitis (ME) and Fibromyalgia (FM): the foundation of a relationship. Br J Pain. 2021 Feb;15(1):26-39. doi: 10.1177/2049463719875164. Epub 2019 Oct 5. PMID: 33633851; PMCID: PMC7882776. https://pubmed.ncbi.nlm.nih.gov/33633851/

Historical Insight into Infections and Disorders Associated with Neurological and Psychiatric Sequelae Similar to Long COVID

Abstract:

Long-term sequelae of coronavirus disease 2019 (COVID-19) due to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are now recognized. However, there is still a lack of consensus regarding the terminology for this emerging chronic clinical syndrome, which includes long COVID, chronic COVID syndrome, post-COVID-19 syndrome, post-acute COVID-19, and long-hauler COVID-19. In this review, I will use the term “long COVID”. A review of the medical history and epidemiology of past pandemics and epidemics in modern literature review identifies common long-term post-infectious disorders, with the common finding of altered cognition.

In the brain, the cerebral hypoxia induced by SARS-CoV-2 infection may be caused by mitochondrial dysfunction, resulting in “brain fog”. Historically, the common symptom of altered cognition has been reported during earlier pandemics, which include the influenza pandemics of 1889 and 1892 (Russian flu), the Spanish flu pandemic (1918-1919), encephalitis lethargica, diphtheria, and myalgic encephalomyelitis (chronic fatigue syndrome or post-viral fatigue syndrome).

There are similarities between chronic fatigue syndrome and the “brain fog” described in long COVID. During past viral epidemics and pandemics, a commonality of neural targets may have increased viral survival by conformational matching. The neurological and psychiatric sequelae of SARS-CoV-2 infection, or long COVID, may have emerged from neural effects that have emerged from an invertebrate and vertebrate virosphere. This review aims to present a historical overview of infections and disorders associated with neurological and psychiatric sequelae that have shown similarities with long COVID.

Source: Stefano GB. Historical Insight into Infections and Disorders Associated with Neurological and Psychiatric Sequelae Similar to Long COVID. Med Sci Monit. 2021 Feb 26;27:e931447. doi: 10.12659/MSM.931447. PMID: 33633106; PMCID: PMC7924007. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7924007/ (Full text)

Co-occurrence of immune-mediated conditions and endometriosis among adolescents and adult women

Abstract:

Problem: Associations between immune dysfunction conditions (eg, systemic lupus erythematous, rheumatoid arthritis) and endometriosis have been observed in adult women, but not assessed among a younger population. We investigated the association between immune-mediated conditions and endometriosis among young women.

Method of study: This cross-sectional analysis in the Women’s Health Study: From Adolescence to Adulthood included 551 participants with surgically diagnosed endometriosis (median age=19) and 652 controls without endometriosis (median age=24). Participants completed an expanded Endometriosis Phenome and Biobanking Harmonization Project questionnaire. We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) to investigate the associations between autoimmune/inflammatory, atopic, chronic pain/fatigue, and endocrine disorders with endometriosis, adjusting for confounders.

Results: Participants with any autoimmune and/or inflammatory condition had an increased odds of co-occurring endometriosis (OR: 1.87; CI: 0.92-3.80), as did participants with allergies (OR: 1.76; CI: 1.32-2.36), asthma (OR: 1.35; CI: 0.97-1.88), chronic fatigue syndrome and/or fibromyalgia (OR: 5.81; CI: 1.89-17.9), or previous mononucleosis (OR: 1.75; CI: 1.14-2.68). Odds of endometriosis were lower among participants with eczema (OR: 0.68; CI: 0.44-1.04). We observed a positive trend between the number of immune-mediated conditions and the odds of endometriosis (p-trend=0.0002). Endocrine disorders were not associated with endometriosis.

Conclusions: Among this population of adolescents and adult women, endometriosis was more likely among participants with autoimmune and/or inflammatory diseases, allergies, asthma, previous mononucleosis infection, and chronic fatigue and/or fibromyalgia. We observed that an increasing number of immune-mediated conditions were positively associated with endometriosis risk. It is important for clinicians who care for adolescents and women with these conditions to consider endometriosis as a comorbidity.

Source: Shafrir AL, Palmor MC, Fourquet J, DiVasta AD, Farland LV, Vitonis AF, Harris HR, Laufer MR, Cramer DW, Terry KL, Missmer SA. Co-occurrence of immune-mediated conditions and endometriosis among adolescents and adult women. Am J Reprod Immunol. 2021 Feb 14:e13404. doi: 10.1111/aji.13404. Epub ahead of print. PMID: 33583078. https://pubmed.ncbi.nlm.nih.gov/33583078/

Sequelae in Adults at 6 Months After COVID-19 Infection

Abstract:

Introduction: Many individuals experience persistent symptoms and a decline in health-related quality of life (HRQoL) after coronavirus disease 2019 (COVID-19) illness.1 Existing studies have focused on hospitalized individuals 30 to 90 days after illness onset2-4 and have reported symptoms up to 110 days after illness.3 Longer-term sequelae in outpatients have not been well characterized.

Methods: A longitudinal prospective cohort of adults with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was enrolled at the University of Washington with a concurrent cohort of healthy patients in a control group (eAppendix in the Supplement). Electronic informed consent was obtained, and the study was approved by the University of Washington human participants institutional review board. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline. COVID-19 symptom data were obtained at the time of acute illness or retrospectively recounted at a 30-day enrollment visit. A total of 234 participants with COVID-19 were contacted between August and November 2020 to complete a single follow-up questionnaire between 3 and 9 months after illness onset. We did not perform statistical tests for this descriptive analysis because of the small numbers in each subgroup. Data analysis was conducted in R version 4.0.2 (R Project for Statistical Computing).

Results: A total of 177 of 234 participants (75.6%; mean [range] age, 48.0 [18-94] years; 101 [57.1%] women) with COVID-19 completed the survey. Overall, 11 (6.2%) were asymptomatic, 150 (84.7%) were outpatients with mild illness, and 16 (9.0%) had moderate or severe disease requiring hospitalization (Table). Hypertension was the most common comorbidity (23 [13.0%]). The follow-up survey was completed a median (range) of 169 (31-300) days after illness onset among participants with COVID-19 (Figure, A) and 87 (71-144) days after enrollment among 21 patients in the control group. Among participants with COVID-19, persistent symptoms were reported by 17 of 64 patients (26.6%) aged 18 to 39 years, 25 of 83 patients (30.1%) aged 40 to 64 years, and 13 of 30 patients (43.3%) aged 65 years and older. Overall, 49 of 150 outpatients (32.7%), 5 of 16 hospitalized patients (31.3%), and 1 of 21 healthy participants (4.8%) in the control group reported at least 1 persistent symptom. Of 31 patients with hypertension or diabetes, 11 (35.5%) experienced ongoing symptoms.

The most common persistent symptoms were fatigue (24 of 177 patients [13.6%]) and loss of sense of smell or taste (24 patients [13.6%]) (Figure, B). Overall, 23 patients (13.0%) reported other symptoms, including brain fog (4 [2.3%]). A total of 51 outpatients and hospitalized patients (30.7%) reported worse HRQoL compared with baseline vs 4 healthy participants and asymptomatic patients (12.5%); 14 patients (7.9%) reported negative impacts on at least 1 activity of daily living (ADL), the most common being household chores.

Discussion: In this cohort of individuals with COVID-19 who were followed up for as long as 9 months after illness, approximately 30% reported persistent symptoms. A unique aspect of our cohort is the high proportion of outpatients with mild disease. Persistent symptoms were reported by one-third of outpatients in our study, consistent with a previously reported study,4 in which 36% of outpatients had not returned to baseline health by 14 to 21 days following infection. However, this has not been previously described 9 months after infection.

Consistent with existing literature, fatigue was the most commonly reported symptom.2-4 This occurred in 14% of individuals in this study, lower than the 53% to 71%2-4 reported in cohorts of hospitalized patients, likely reflecting the lower acuity of illness in our cohort. Furthermore, impairment in HRQoL has previously been reported among hospitalized patients who have recovered from COVID-19; we found 29% of outpatients reported worsened HRQoL.5

Notably, 14 participants, including 9 nonhospitalized individuals, reported negative impacts on ADLs after infection. With 57.8 million cases worldwide, even a small incidence of long-term debility could have enormous health and economic consequences.6

Study limitations include a small sample size, single study location, potential bias from self-reported symptoms during illness episode, and loss to follow-up of 57 participants. To our knowledge, this study presents the longest follow-up symptom assessment after COVID-19 infection. Our research indicates that the health consequences of COVID-19 extend far beyond acute infection, even among those who experience mild illness. Comprehensive long-term investigation will be necessary to fully understand the impact of this evolving viral pathogen.

Source: Jennifer K. Logue, BS; Nicholas M. Franko, BS; Denise J. McCulloch, MD, MPH; et al Dylan McDonald, BA; Ariana Magedson, BS; Caitlin R. Wolf, BS; Helen Y. Chu, MD, MPH. Sequelae in Adults at 6 Months After COVID-19 Infection. JAMA Netw Open. 2021;4(2):e210830. doi:10.1001/jamanetworkopen.2021.0830 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2776560

Managing COVID-19 post viral Fatigue Syndrome

Abstract:

In online surveys, over 50% of persons who contract COVD-19 experience symptoms lasting longer than 90 days [Pelanti S, Grassi E, Markris N, et al. J Psych Res. 2020. doi:10.1016/j.jpsychires.2020.08.008] Despite an estimated 3 million Americans being affected by COVID post-viral fatigue, there has been little discussion about the care of these patients, most of whom report feeling unsupported or dismissed by their providers [Amitay O, Komaroff AL. The Guardian, 20 Aug 2020]. This article points out the similarity between this post-viral fatigue syndrome and Chronic Fatigue Syndrome (ME/CFS) or Systemic Exertion Intolerance Disease (SEID), and offers evidence-based suggestions for management.

Source: Charles W. Lapp & Joseph F. John (2021) Managing COVID-19 post viral Fatigue Syndrome, Fatigue: Biomedicine, Health & Behavior, DOI: 10.1080/21641846.2021.1890347  (Full text) https://www.tandfonline.com/doi/full/10.1080/21641846.2021.1890347

Sex-Based Differences in Plasma Autoantibodies to Central Nervous System Proteins in Gulf War Veterans versus Healthy and Symptomatic Controls

Abstract:

Veterans from the 1991 Gulf War (GW) have suffered from Gulf War illness (GWI) for nearly 30 years. This illness encompasses multiple body systems, including the central nervous system (CNS). Diagnosis and treatment of GWI is difficult because there has not been an objective diagnostic biomarker. Recently, we reported on a newly developed blood biomarker that discriminates GWI from GW healthy controls, and symptomatic controls with irritable bowel syndrome (IBS) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The present study was designed to compare levels of these biomarkers between men and women with GWI, as well as sex-specific effects in comparison to healthy GW veterans and symptomatic controls (IBS, ME/CFS).

The results showed that men and women with GWI differ in 2 of 10 plasma autoantibodies, with men showing significantly elevated levels. Men and women with GWI showed significantly different levels of autoantibodies in 8 of 10 biomarkers to neuronal and glial proteins in plasma relative to controls. In summary, the present study addressed the utility of the use of plasma autoantibodies for CNS proteins to distinguish among both men and women veterans with GWI and other healthy and symptomatic control groups.

Source: Abou-Donia MB, Krengel MH, Lapadula ES, Zundel CG, LeClair J, Massaro J, Quinn E, Conboy LA, Kokkotou E, Nguyen DD, Abreu M, Klimas NG, Sullivan K. Sex-Based Differences in Plasma Autoantibodies to Central Nervous System Proteins in Gulf War Veterans versus Healthy and Symptomatic Controls. Brain Sci. 2021 Jan 23;11(2):148. doi: 10.3390/brainsci11020148. PMID: 33498629. https://pubmed.ncbi.nlm.nih.gov/33498629/

Postural orthostatic tachycardia syndrome in patients of orthostatic intolerance symptoms: an ambispective study

Abstract:

Background: A Postural orthostatic tachycardia syndrome (POTS) is infrequently diagnosed in routine practice because of the variable range of symptoms that could be seen in cardiac rhythm disorders, vertigo, chronic fatigue syndrome and anxiety panic disorder. POTS is a chronic debilitating condition that affects day to day efficient working of an individual. We have planned a study to look for POTS in patients who are having orthostatic intolerance symptoms and underwent a head-up tilt table test (HUTT).

Aim: To study the prevalence of POTS in patients of orthostatic intolerance (OI) symptoms and to analyze symptomatology, its association with neurocardiogenic syncope (NCS), and its outcome.

Methods: We reviewed the medical records of 246 patients presented with symptoms of OI seen at our centre from January 2010 till March 2019. Out of them, 40 patients included, those qualifying the criteria for POTS on HUTT.

Results: The mean age of the cohort was 25.90 ± 10.33 years with a range of 15 to 55 years, and males comprised 52.5% (21/40) of total patients. The most frequent presenting orthostatic symptoms of POTS patients are loss of consciousness (77.5%), lightheadedness (75%), and palpitation (67.5%). A total of 18 patients (45%) had coexisting neurocardiogenic syncope.

Conclusion: POTS is a prevalent condition and have a significant impact on the quality of life, and the majority of patients may not present with OI symptoms during HUTT. We have to keep this possibility in young patients of transient loss of consciousness because it may coexist with NCS.

Source: Chouksey D, Rathi P, Sodani A, Jain R, Ishar HS. Postural orthostatic tachycardia syndrome in patients of orthostatic intolerance symptoms: an ambispective study. AIMS Neurosci. 2020 Dec 8;8(1):74-85. doi: 10.3934/Neuroscience.2021004. PMID: 33490373; PMCID: PMC7815479. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815479/ (Full text)

Beyond bones: The relevance of variants of connective tissue (hypermobility) to fibromyalgia, ME/CFS and controversies surrounding diagnostic classification: an observational study

Abstract:

Background: Fibromyalgia and myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) are poorly understood conditions with overlapping symptoms, fuelling debate as to whether they are manifestations of the same spectrum or separate entities. Both are associated with hypermobility, but this remains significantly undiagnosed, despite impact on quality of life.

Objective: We planned to understand the relevance of hypermobility to symptoms in fibromyalgia and ME/CFS.

Method: Sixty-three patient participants presented with a confirmed diagnosis of fibromyalgia and/or ME/CFS; 24 participants were healthy controls. Patients were assessed for symptomatic hypermobility.

Results: Evaluations showed exceptional overlap in patients between fibromyalgia and ME/CFS, plus 81% met Brighton criteria for hypermobility syndrome (odds ratio 7.08) and 18% met 2017 hypermobile Ehlers-Danlos syndrome (hEDS) criteria. Hypermobility scores significantly predicted symptom levels.

Conclusion: Symptomatic hypermobility is particularly relevant to fibromyalgia and ME/CFS, and our findings highlight high rates of mis-/underdiagnosis. These poorly understood conditions have a considerable impact on quality of life and our observations have implications for diagnosis and treatment targets.

Source: Eccles JA, Thompson B, Themelis K, Amato ML, Stocks R, Pound A, Jones AM, Cipinova Z, Shah-Goodwin L, Timeyin J, Thompson CR, Batty T, Harrison NA, Critchley HD, Davies KA. Beyond bones: The relevance of variants of connective tissue (hypermobility) to fibromyalgia, ME/CFS and controversies surrounding diagnostic classification: an observational study. Clin Med (Lond). 2021 Jan;21(1):53-58. doi: 10.7861/clinmed.2020-0743. PMID: 33479068. https://pubmed.ncbi.nlm.nih.gov/33479068/