Physical and Mental Fatigue in Subjects Recovered from COVID-19 Infection: A Case–Control Study

Abstract:

Purpose: Much effort has been directed toward studying COVID-19 symptoms; however, the post–COVID-19 phase remains mysterious. The aim of this work was to conduct a clinical and neurophysiological evaluation of physical and mental fatigue in COVID-19 long-haulers and to study whether markers of COVID-19 severity are able to predict the likelihood of developing postinfectious fatigue syndrome (PIFS) in such patients.

Patients and Methods: This case–control study was conducted on 46 COVID-19 long-haulers who met the criteria for PIFS and 46 recovered COVID-19 subjects without any residuals. Clinical assessment of fatigue was done using a fatigue questionnaire. Repetitive nerve stimulation and single-fiber electromyography were done after excluding neuropathy and myopathy.

Results: The median value for physical fatigue was 4 (IQR 2– 7), while that for mental fatigue was 2 (IQR 0– 3). Each day’s increase in the period of COVID-19 illness increased the odds of PIFS in COVID-19 long-haulers 1.104-fold, and each unit increase in ferritin increased the odds of PIFS 1.006-fold. A significant decrement in at least one muscle was observed in 50% of patients. Patients with PIFS had significantly higher mean consecutive difference (MCD) in the extensor digitorum communis than the control group. There were statistically significant positive correlations between MCD values and physical, mental, and total fatigue scores.

Conclusion: Higher ferritin levels and prolonged COVID-19 infection were independent predictors of PIFS in COVID-19 long-haulers. There was electrophysiological evidence of abnormalities in the peripheral portion of the motor unit in COVID-19 long-haulers with PIFS.

Source: Elanwar R, Hussein M, Magdy R, Eid RA, Yassien A, Abdelsattar AS, Alsharaway LA, Fathy W, Hassan A, Kamal YS. Physical and Mental Fatigue in Subjects Recovered from COVID-19 Infection: A Case–Control Study. Neuropsychiatr Dis Treat. 2021;17:2063-2071 https://doi.org/10.2147/NDT.S317027 https://www.dovepress.com/physical-and-mental-fatigue-in-subjects-recovered-from-covid-19-infect-peer-reviewed-fulltext-article-NDT (Full text)

Migraine Is More Than Just Headache: Is the Link to Chronic Fatigue and Mood Disorders Simply Due to Shared Biological Systems?

Abstract:

Migraine is a symptomatically heterogeneous condition, of which headache is just one manifestation. Migraine is a disorder of altered sensory thresholding, with hypersensitivity among sufferers to sensory input. Advances in functional neuroimaging have highlighted that several brain areas are involved even prior to pain onset. Clinically, patients can experience symptoms hours to days prior to migraine pain, which can warn of impending headache. These symptoms can include mood and cognitive change, fatigue, and neck discomfort. Some epidemiological studies have suggested that migraine is associated in a bidirectional fashion with other disorders, such as mood disorders and chronic fatigue, as well as with other pain conditions such as fibromyalgia. This review will focus on the literature surrounding alterations in fatigue, mood, and cognition in particular, in association with migraine, and the suggested links to disorders such as chronic fatigue syndrome and depression.

We hypothesize that migraine should be considered a neural disorder of brain function, in which alterations in aminergic networks integrating the limbic system with the sensory and homeostatic systems occur early and persist after headache resolution and perhaps interictally. The associations with some of these other disorders may allude to the inherent sensory sensitivity of the migraine brain and shared neurobiology and neurotransmitter systems rather than true co-morbidity.

Source: Karsan N, Goadsby PJ. Migraine Is More Than Just Headache: Is the Link to Chronic Fatigue and Mood Disorders Simply Due to Shared Biological Systems? Front Hum Neurosci. 2021 Jun 3;15:646692. doi: 10.3389/fnhum.2021.646692. PMID: 34149377; PMCID: PMC8209296. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209296/ (Full text)

Chronic post-COVID-19 syndrome and chronic fatigue syndrome: Is there a role for extracorporeal apheresis?

Abstract:

As millions of patients have been infected by SARS-CoV-2 virus a vast number of individuals complain about continuing breathlessness and fatigue even months after the onset of the disease. This overwhelming phenomenon has not been well defined and has been called “post-COVID syndrome” or “long-COVID” [1]. There are striking similarities to myalgic encephalomyelitis also called chronic fatigue syndrome linked to a viral and autoimmune pathogenesis. In both disorders neurotransmitter receptor antibodies against ß-adrenergic and muscarinic receptors may play a key role. We found similar elevation of these autoantibodies in both patient groups.

Extracorporeal apheresis using a special filter seems to be effective in reducing these antibodies in a significant way clearly improving the debilitating symptoms of patients with chronic fatigue syndrome. Therefore, such a form of neuropheresis may provide a promising therapeutic option for patients with post-COVID-19 syndrome. This method will also be effective when other hitherto unknown antibodies and inflammatory mediators are involved.

Source: Bornstein SR, Voit-Bak K, Donate T, Rodionov RN, Gainetdinov RR, Tselmin S, Kanczkowski W, Müller GM, Achleitner M, Wang J, Licinio J, Bauer M, Young AH, Thuret S, Bechmann N, Straube R. Chronic post-COVID-19 syndrome and chronic fatigue syndrome: Is there a role for extracorporeal apheresis? Mol Psychiatry. 2021 Jun 17. doi: 10.1038/s41380-021-01148-4. Epub ahead of print. PMID: 34140635. https://pubmed.ncbi.nlm.nih.gov/34140635/

Chronic fatigue and post-exertional malaise in people living with long COVID

Abstract:

Purpose People living with long COVID describe a high symptom burden, and a more detailed assessment of chronic fatigue and post-exertional malaise (PEM) may inform the development of rehabilitation recommendations. The aims of this study were to use validated questionnaires to measure the severity of fatigue and compare this with normative data and thresholds for clinical relevance in other diseases; measure and describe the impact of PEM; and describe symptoms of dysfunctional breathing, self-reported physical activity/sitting time, and health-related quality of life.

Methods This was an observational study involving an online survey for adults living with long COVID (data collection from February-April, 2021) following a confirmed or suspected SARS-CoV-2 infection. Questionnaires included the Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F) and DePaul Symptom Questionnaire-Post-Exertional Malaise.

Results After data cleaning, n=213 participants were included in the analysis. Participants primarily identified as women (85.5%), aged 40-59 (78.4%), who had been experiencing long COVID symptoms for ≥6 months (72.3%). The total FACIT-F score was 18±10 (where the score can range from 0-52, and a lower score indicates more severe fatigue), and 71.4% were experiencing chronic fatigue. Post-exertional symptom exacerbation affected most participants, and 58.7% met the scoring thresholds used in people living with myalgic encephalomyelitis/chronic fatigue syndrome. PEM occurred alongside a reduced capacity to work, be physically active, and function both physically and socially.

Conclusion Long COVID is characterized by chronic fatigue that is clinically relevant and is at least as severe as fatigue in several other clinical conditions, including cancer. PEM appears to be a common and significant challenge for the majority of this patient group. Patients, researchers, and allied health professionals are seeking information on safe rehabilitation for people living with long COVID, particularly regarding exercise. Fatigue and post-exertional symptom exacerbation must be monitored and reported in studies involving interventions for people with long COVID.

Source: Rosie TwomeyJessica DeMarsKelli FranklinS. Nicole Culos-ReedJason WeatheraldJames G. Wrightson. Chronic fatigue and post-exertional malaise in people living with long COVID.

Insights from Myalgic Encephalomyelitis/Chronic Fatigue Syndrome May Help Unravel the Pathogenesis of Post-Acute COVID-19 Syndrome

Abstract:

SARS-CoV-2 can cause chronic and acute disease. Post-Acute Sequelae of SARS-CoV-2 infection (PASC) include injury to the lungs, heart, kidneys and brain, that may produce a variety of symptoms. PASC also includes a post-COVID-19 syndrome (“long COVID”) with features that can follow other acute infectious diseases as well as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Here we summarize what is known about the pathogenesis of ME/CFS and of acute COVID-19, and speculate that the pathogenesis of post-COVID-19 syndrome in some people may be similar to that of ME/CFS. We propose molecular mechanisms that might explain the fatigue and related symptoms in both illnesses, and suggest a research agenda for both ME/CFS and post-COVID-19 syndrome.

Source: A.L. Komaroff and W.I. Lipkin, Insights from Myalgic Encephalomyelitis/Chronic Fatigue Syndrome May Help Unravel the Pathogenesis of Post-Acute COVID-19 Syndrome, Trends in Molecular Medicine (2021), https://doi.org/ 10.1016/j.molmed.2021.06.002  https://www.cell.com/trends/molecular-medicine/fulltext/S1471-4914(21)00134-9 (Full text)

Postdengue chronic fatigue syndrome in an adolescent boy

Abstract:

Chronic fatigue syndrome (CFS) is often preceded by a viral illness and has recurrent ‘flulike’ symptoms which include a wide spectrum of musculoskeletal and neurological clinical features. The condition is also known as myalgic encephalomyelitis and systemic exertional intolerance syndrome. CFS has been reported following dengue among adult patients. We report the case of an 11-year-old boy who developed CFS following recovery of dengue haemorrhagic fever (DHF). The reported child was initially managed as for DHF and was clinically asymptomatic on post-discharge day 3. He was re-admitted after 3 weeks with severe joint pains, myalgia and unbearable headache. As his symptoms persisted, he was investigated in-depth. All investigations were normal except mild elevation of liver functions. The diagnosis of CFS secondary to DHF was made by exclusion of differential diagnosis. At 1-year follow-up, patient continues to have symptoms after treatment with physiotherapy and nutrition counselling.

Source: Thadchanamoorthy V, Dayasiri K. Postdengue chronic fatigue syndrome in an adolescent boy. BMJ Case Rep. 2021 Jun 7;14(6):e238605. doi: 10.1136/bcr-2020-238605. PMID: 34099442. https://pubmed.ncbi.nlm.nih.gov/34099442/

Report on the impact of Covid-19 on ME

Summary:

This summary report provides the preliminary findings from responses to the survey we are carrying out, in partnership with Action for ME, to identify the impact that Covid-19 has on people with ME. The report is based on the analysis of the 220 responses received in the three weeks after the survey went live in late March.

These initial responses show clearly that Covid-19 had a significant impact on respondents, with more than three quarters (76%) of respondents saying that Covid-19 made their ME symptoms worse. This impact appears to be long lasting, with over two thirds of respondents reporting that the worsening in symptoms has lasted more than 6 months and have still not resolved.

The wider impact of Covid-19 is illustrated by the negative impacts on the health of respondents, including 72% reporting new symptoms. The analysis also shows that respondents’ ability to attend education or work had decreased and their use of health services had increased significantly, highlighting the potential economic impact of Covid-19.

Read the full report HERE.

Utility of positron emission tomography imaging in the diagnosis of chronic Q fever: A Systematic Review

Abstract:

Chronic Q fever is a diagnostic challenge. Diagnosis relies on serology and/or the detection of DNA from blood or tissue samples. PET-CT identifies tissues with increased glucose metabolism, thus identifying foci of inflammation. Our aim was to review the existing literature on the use of PET-CT to help diagnose chronic Q fever. A literature search was conducted in PubMed and Google Scholar to ascertain publications that included the terms ‘Positron Emission Tomography’ and ‘PET CT’ in combination with subheadings ‘chronic Q fever’ and ‘Coxiella burnetii’ within the search. To broaden our search retrieval, we used the terms ‘chronic Q fever’ and ‘PET-CT’.

Published literature up to 16th April 2020 was included. 274 articles were initially identified. Post-exclusion criteria, 46 articles were included. Amongst case reports and series, the most frequent focus of infection was vascular, followed by musculoskeletal then cardiac. 79.5% of patients had a focus detected with 55.3% of these having proven infected prosthetic devices. Amongst the retrospective and prospective studies, a total of 394 positive sites of foci were identified with 186 negative cases. Some had follow-up scans (53), with 75.5% showing improvement or resolution. Average timeframe for documented radiological resolution post-initiating treatment was 8.86 months.

PET-CT is a useful tool in the management of chronic Q fever. Knowledge of a precise focus enables for directed surgical management helping reduce microbial burden, preventing future complications. Radiological resolution of infection can give clinicians reassurance on whether antimicrobial therapy can be ceased earlier, potentially limiting side effects.

Source: Sivabalan P, Visvalingam R, Grey V, Blazak J, Henderson A, Norton R. Utility of positron emission tomography imaging in the diagnosis of chronic Q fever: A Systematic Review. J Med Imaging Radiat Oncol. 2021 May 30. doi: 10.1111/1754-9485.13244. Epub ahead of print. PMID: 34056851. https://pubmed.ncbi.nlm.nih.gov/34056851/

Post-COVID-19 syndrome: epidemiology, diagnostic criteria and pathogenic mechanisms involved

Abstract in English, Spanish:

Introduction: Many patients with mild or severe COVID-19 do not make a full recovery and have a wide range of chronic symptoms for weeks or months after infection, often of a neurological, cognitive or psychiatric nature. The epidemiological evidence, diagnostic criteria and pathogenesis of post-COVID-19 syndrome are reviewed.

Development: Post-COVID-19 syndrome is defined by persistent clinical signs and symptoms that appear while or after suffering COVID-19, persist for more than 12 weeks and cannot be explained by an alternative diagnosis. The symptoms can fluctuate or cause relapses. It is a heterogeneous condition that includes post-viral chronic fatigue syndrome, sequelae in multiple organs and the effects of severe hospitalisation/post-intensive care syndrome. It has been reported in patients with mild or severe COVID-19 and irrespective of the severity of the symptoms in the acute phase. Between 10% and 65% of survivors who had mild/moderate COVID-19 present symptoms of post-COVID-19 syndrome for 12 weeks or more. At six months, subjects report an average of 14 persistent symptoms. The most common symptoms are fatigue, dyspnoea, anxiety, depression, and impaired attention, concentration, memory and sleep. The underlying biological mechanisms are unknown, although an abnormal or excessive autoimmune and inflammatory response may play an important role.

Conclusions: Clinical manifestations are diverse, fluctuating and variable, although fatigue and neurocognitive complaints predominate. There is no defined consensus on post-COVID-19 syndrome and its diagnostic criteria have not been subjected to adequate psychometric evaluation.

Source: Carod-Artal FJ. Síndrome post-COVID-19: epidemiología, criterios diagnósticos y mecanismos patogénicos implicados [Post-COVID-19 syndrome: epidemiology, diagnostic criteria and pathogenic mechanisms involved]. Rev Neurol. 2021 Jun 1;72(11):384-396. Spanish. doi: 10.33588/rn.7211.2021230. PMID: 34042167. https://pubmed.ncbi.nlm.nih.gov/34042167/

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/