Tag: long Covid

Insights from myalgic encephalomyelitis/chronic fatigue syndrome may help unravel the pathogenesis of postacute COVID-19 syndrome

Abstract:

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause chronic and acute disease. Postacute 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-coronavirus disease 2019 (COVID-19) syndrome (‘long COVID’) with features that can follow other acute infectious diseases and 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 we 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 we suggest a research agenda for both ME/CFS and post-COVID-19 syndrome.

Source: Komaroff AL, Lipkin WI. Insights from myalgic encephalomyelitis/chronic fatigue syndrome may help unravel the pathogenesis of postacute COVID-19 syndrome. Trends Mol Med. 2021 Jun 7:S1471-4914(21)00134-9. doi: 10.1016/j.molmed.2021.06.002. Epub ahead of print. PMID: 34175230. https://pubmed.ncbi.nlm.nih.gov/34175230/

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)

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 Twomey, Jessica DeMars, Kelli Franklin, S. Nicole Culos-Reed, Jason Weatherald, James G. Wrightson. Chronic fatigue and post-exertional malaise in people living with long COVID. medRxiv 2021.06.11.21258564; doi: https://doi.org/10.1101/2021.06.11.21258564 https://www.medrxiv.org/content/10.1101/2021.06.11.21258564v1

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)

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/

Post-COVID-19 Syndrome: The Persistent Symptoms at the Post-viral Stage of the Disease. A Systematic Review of the Current Data

Abstract:

Whilst the entire world is battling the second wave of COVID-19, a substantial proportion of patients who have suffered from the condition in the past months are reporting symptoms that last for months after recovery, i. e., long-term COVID-19 symptoms. We aimed to assess the current evidence on the long-term symptoms in COVID-19 patients. We did a systematic review on PubMed, Web of Science, EMBASE, and Google Scholar from database inception to February 15, 2021, for studies on long-term COVID-19 symptoms.

We included all type of papers that reported at least one long-term COVID-19 symptom. We screened studies using a standardized data collection form and pooled data from published studies. Cohort cross-sectional, case-report, cases-series, case-control studies, and review were graded using specific quality assessment tools. Of 11,361 publications found following our initial search we assessed 218 full-text articles, of which 145 met all selection criteria. We found that 20.70% of reports on long-term COVID-19 symptoms were on abnormal lung functions, 24.13% on neurologic complaints and olfactory dysfunctions, and 55.17% on specific widespread symptoms, mainly chronic fatigue, and pain.

Despite the relatively high heterogeneity of the reviewed studies, our findings highlighted that a noteworthy proportion of patients who have suffered from SARS-CoV-2 infection present a “post-COVID syndrome.” The multifaceted understanding of all aspects of the COVID-19 pandemic, including these long-term symptoms, will allow us to respond to all the global health challenges, thus paving the way to a stronger public health.

Source: Salamanna F, Veronesi F, Martini L, Landini MP, Fini M. Post-COVID-19 Syndrome: The Persistent Symptoms at the Post-viral Stage of the Disease. A Systematic Review of the Current Data. Front Med (Lausanne). 2021 May 4;8:653516. doi: 10.3389/fmed.2021.653516. PMID: 34017846; PMCID: PMC8129035. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129035/ (Full text)

Editorial: The Pathogenesis of Long-Term Neuropsychiatric COVID-19 and the Role of Microglia, Mitochondria, and Persistent Neuroinflammation: A Hypothesis

Abstract:

Persistent comorbidities occur in patients who initially recover from acute coronavirus disease 2019 (COVID-19) due to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). ‘Long COVID’ involves the central nervous system (CNS), resulting in neuropsychiatric symptoms and signs, including cognitive impairment or ‘brain fog’ and chronic fatigue syndrome. There are similarities in these persistent complications between SARS-CoV-2 and the Ebola, Zika, and influenza A viruses. Normal CNS neuronal mitochondrial function requires high oxygen levels for oxidative phosphorylation and ATP production. Recent studies have shown that the SARS-CoV-2 virus can hijack mitochondrial function. Persistent changes in cognitive functioning have also been reported with other viral infections. SARS-CoV-2 infection may result in long-term effects on immune processes within the CNS by causing microglial dysfunction. This short opinion aims to discuss the hypothesis that the pathogenesis of long-term neuropsychiatric COVID-19 involves microglia, mitochondria, and persistent neuroinflammation.

Source: Stefano GB, Büttiker P, Weissenberger S, Martin A, Ptacek R, Kream RM. Editorial: The Pathogenesis of Long-Term Neuropsychiatric COVID-19 and the Role of Microglia, Mitochondria, and Persistent Neuroinflammation: A Hypothesis. Med Sci Monit. 2021 May 10;27:e933015. doi: 10.12659/MSM.933015. PMID: 34016942. https://pubmed.ncbi.nlm.nih.gov/34016942/

Case Study Suggests Young People Susceptible To Chronic Fatigue Syndrome After Covid-19

Press Release:

With more adolescents and young adults being treated for COVID-19, clinicians are concerned that these people also will start showing post-COVID — or “long haul” — symptoms from their bouts with the virus. A recent Johns Hopkins Medicine review of three case studies provides some of the first evidence that one serious post-COVID problem may be myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), the complex, multisystem disorder previously known as chronic fatigue syndrome.

The findings were published April 29 in the journal Frontiers in Medicine.

“In the three patients studied — all of whom had confirmed or highly probable COVID-19 infections early in the pandemic — we observed ME/CFS-like symptoms within the first two weeks of illness,” says Peter Rowe, M.D., director of the Chronic Fatigue Clinic at Johns Hopkins Children’s Center and professor of pediatrics at the Johns Hopkins University School of Medicine. “At six months following their illness, all three still met the criteria for being diagnosed with ME/CFS.”

In a recent report, the U.S. Centers for Disease Control and Prevention (CDC) noted that U.S. hospitals are seeing more adolescents and young adults admitted with COVID-19 as more contagious variants of SARS-CoV-2 — the virus that causes the disease — spread. The agency believes that the youthful case surge may be the result of those ages 10 to 24 being among the last prioritized to get the coronavirus vaccines, and the fact that many who are eligible have yet to receive their shots. Also, the CDC says, this group is more likely to be involved in high-risk behaviors such as playing close-contact sports and going out to bars.

The three patients evaluated in the recent study were a 19-year-old man and two women, ages 22 and 30, whose COVID-19 symptoms began between April and June 2020, and who were referred to the Chronic Fatigue Clinic between August and October of the same year. Symptoms of orthostatic intolerance — a group of clinical conditions that includes fatigue, lightheadedness and difficulty concentrating, and are linked with greater than 90% of the people with ME/CFS — were prominent in all three from the outset of their COVID-19 illness.

A six-month post-COVID symptom onset examination, including evaluations of movement, neurological function and continued orthostatic intolerance, was conducted on each of the patients to determine if ME/CFS could be diagnosed. All three easily met the criteria.

Interestingly, Rowe says, all three patients had relatively mild COVID-19 respiratory symptoms and none required hospitalization, yet it appears to have translated into the more serious secondary problem of ME/CFS for them all.

“This finding is consistent with previous studies in older patients with COVID-19 who showed persistent fatigue months after infection, regardless of the severity of the initial infection,” he explains. “This raises the question of how many ME/CFS cases before the COVID-19 pandemic might have been due to mild, subclinical or asymptomatic viral infections [such as Epstein-Barr virus or human herpesvirus 6], including cases in adolescents, young adults and older people.”

Rowe and his colleagues feel that further research is needed to define the biological mechanism by which ME/CFS arises from COVID-19, and then use that insight to develop treatment strategies that can return patients with post-COVID ME/CFS back to their previous quality of life.

Rowe is available for interviews.

https://www.hopkinsmedicine.org/news/newsroom/news-releases/covid-19-story-tip-case-study-suggests-young-people-may-be-susceptible-to-chronic-fatigue-following-covid-19

Media Contact: Michael E. Newman, mnewma25@jhmi.edu