Tag: long Covid

Chronic Fatigue and Postexertional Malaise in People Living with Long COVID: An Observational Study

Abstract:

Objectives: People living with long COVID describe a high symptom burden, and a more detailed assessment is needed to inform rehabilitation recommendations. The objectives 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 postexertional malaise (PEM); and assess symptoms of dysfunctional breathing, self-reported physical activity, and health-related quality of life.

Methods: This was an observational study with a cross-sectional survey design (data collection from February 2021 to April 2021). Eligible participants were adults experiencing persistent symptoms due to COVID-19 that did not predate the confirmed or suspected infection. Questionnaires included the Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F) and the DePaul Symptom Questionnaire-Post-Exertional Malaise.

Results: After data cleaning, 213 participants were included in the analysis. The total FACIT-F score was 18 (SD = 10) (where the score can range from 0 to 52 and a lower score indicates more severe fatigue), and 71.4% were experiencing chronic fatigue. Postexertional symptom exacerbation affected most participants, and 58.7% met the PEM scoring thresholds used in people living with myalgic encephalomyelitis/chronic fatigue syndrome.

Conclusion: Long COVID is characterized by chronic fatigue that is clinically relevant and at least as severe as fatigue in several other clinical conditions. PEM is a significant challenge for this patient group. Because of the potential for setbacks and deteriorated function following overexertion, fatigue and postexertional symptom exacerbation must be monitored and reported in clinical practice and in studies involving interventions for people with long COVID.

Impact: Physical therapists working with people with long COVID should measure and validate the patient’s experience. Postexertional symptom exacerbation must be considered, and rehabilitation needs to be carefully designed based on individual presentation. Beneficial interventions might first ensure symptom stabilization via pacing, a self-management strategy for the activity that helps minimize postexertional malaise.

Source: Twomey R, DeMars J, Franklin K, Culos-Reed SN, Weatherald J, Wrightson JG. Chronic Fatigue and Postexertional Malaise in People Living with Long COVID: An Observational Study. Phys Ther. 2022 Jan 13:pzac005. doi: 10.1093/ptj/pzac005. Epub ahead of print. PMID: 35079817. https://pubmed.ncbi.nlm.nih.gov/35079817/

Letter: Could endothelial dysfunction and vascular damage contribute to pain, inflammation and post-exertional malaise in individuals with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)?

To the Editor,

In their hypothesis paper, Wirth, Scheibenbogen, and Paul describe how endothelial dysfunction could produce a wide range of neurological symptoms in people with ME/CFS [1]. As they and others work to refine their understanding of ME/CFS and the related Long COVID syndrome, I would encourage consideration of the possibility that endothelial dysfunction and vascular damage could also explain other symptoms, including widespread pain and inflammation and post-exertional malaise.

For the past four years, my wife and I have been caregivers for our teenage daughter, who has ME/CFS, hypermobile Ehlers-Danlos syndrome, craniocervical instability, Chiari malformation and several other comorbid conditions. Through observation and trial and error, I have developed a number of hypotheses on these matters that I offer here in the hope they might prompt formal research into how to effectively treat these conditions [2].

Widespread pain and inflammation

Discussion of endothelial dysfunction and vascular damage in ME/CFS and Long COVID generally focuses on how leakages from dysfunctional blood vessels lead to reduced blood flow, which has many consequences, including reduced oxygenation of muscles and reduced cerebral brain flow. As researchers study this phenomenon, I would encourage consideration of the additional possibility that the leaking fluid causes independent damage. Lipedema researchers have found that leakages from microangiopathic blood vessels cause an excess of interstitial fluid that stimulates the formation of subcutaneous adipose tissue [3], which generates hypoxic conditions and becomes fibrotic, contributing to pain and inflammation [4].

I hypothesize that a similar process happens when fluid leaks from faulty blood vessels in ME/CFS, possibly exacerbated by endothelial dysfunction in lymphatic vessels that inhibit the fluid’s removal, causing widespread pain and inflammation. This mechanism appears most pronounced among people with hypermobility or other connective tissue disorders, a common trait among people with both ME/CFS and lipedema.

My daughter experiences pain from fibrotic adipose tissue as well as what appears to be nerve compression from accumulated interstitial / lymphatic fluid. Manual lymphatic drainage, the squeezing of affected tissue, and the manual break-up of fibrotic adipose tissue have helped to ameliorate these symptoms.

In my daughter, I have also observed impaired drainage of fluid from the glymphatic system, both at the cribriform plate and down her spine. Could this be related to damaged lymphatic vessels or blockages from fibrotic adipose tissue?

Post-exertional malaise

Like many people with moderate or severe ME/CFS, my daughter struggles to recover from even small amounts of physical exertion. In addition to mitigating her pain, manual lymphatic drainage and the squeezing of affected tissue greatly accelerates this recovery process. We have observed a direct dose–response relationship: the more exercise, the more fluid is present in her tissues, and the more manual draining / squeezing is necessary for her to recover.

Based on this experience, I hypothesize that excess interstitial fluid resulting from dysfunctional blood and lymphatic vessels contributes to the experience of post-exertional malaise, with fluid literally drowning affected tissue, leading to hypoxic conditions and inflammation. Possible explanations for the increased interstitial fluid are increases in blood pressure during physical exertion, hypermobile joints going out of place, prompting localized increases in interstitial fluid, and increases in cortisol that generate an increase in fluid and blood volume. Increases in fluid leakage due to elevated cortisol levels may also explain why some people with ME/CFS feel worse when stressed or anxious. The role of cortisol (or another mediator with fluid retaining properties) may explain why cognitive exertion can also generate post-exertional malaise. When present, elevated estrogen levels may exacerbate leakage by increasing fluid volume.

I am not sure why there is typically a delay between physical exertion and the experience of the most acute symptoms of post-exertional malaise. One possibility is that it takes time for the tissue inundated with fluid to feel the full effects of the hypoxic conditions. Another possibility is that a biphasic reaction triggered during physical exertion leads to the release of a mediator that causes heightened endothelial dysfunction and fluid release.

Further research is needed into the causes of endothelial dysfunction and damage (in addition to initial infection and inflammatory overreaction, consider major “crashes,” mast cell activations, surgeries and microclots as additional contributors) and appropriate treatment.

References

1. Wirth KJ, Scheibenbogen C, Paul F. An attempt to explain the neurological symptoms of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. J Transl Med. 2021;19:471. https://doi.org/10.1186/s12967-021-03143-3.

Article PubMed PubMed Central Google Scholar

2. For background, see Lubell, J. To speed progress in treating chronic conditions, engage patients and caregivers as research partners. 2021 Sept.20 In: BMJ Opinion. https://blogs.bmj.com/bmj/2021/09/20/to-speed-progress-in-treating-chronic-conditions-engage-patients-and-caregivers-as-research-partners/

3. Allen M, Schwartz M, Herbst KL. Interstitial Fluid in Lipedema and Control Skin. Womens Health Rep (New Rochelle). 2020;1(1):480–7. https://doi.org/10.1089/whr.2020.0086.PMID:33786515;PMCID:PMC7784769.

Article Google Scholar

4. Herbst KL. Subcutaneous Adipose Tissue Diseases: Dercum Disease, Lipedema, Familial Multiple Lipomatosis, and Madelung Disease. [Updated 2019 Dec 14]. In: Feingold KR, Anawalt B, Boyce A, et al., editors. South Dartmouth (MA).

Source: Lubell J. Letter: Could endothelial dysfunction and vascular damage contribute to pain, inflammation and post-exertional malaise in individuals with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)? J Transl Med. 2022 Jan 24;20(1):40. doi: 10.1186/s12967-022-03244-7. PMID: 35073915. https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-022-03244-7

Nervous system consequences of COVID-19

Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is considered a respiratory pathogen, myriad neurologic complications—including confusion, stroke, and neuromuscular disorders—manifest during acute COVID-19. Furthermore, maladies such as impaired concentration, headache, sensory disturbances, depression, and even psychosis may persist for months after infection, as part of a constellation of symptoms now called Long Covid. Even young people with mild initial disease can develop acute COVID-19 and Long Covid neuropsychiatric syndromes. The pathophysiological mechanisms are not well understood, although evidence primarily implicates immune dysfunction, including nonspecific neuroinflammation and antineural autoimmune dysregulation. It is uncertain whether unforeseen neurological consequences may develop years after initial infection. With millions of individuals affected, nervous system complications pose public health challenges for rehabilitation and recovery and for disruptions in the workforce due to loss of functional capacity. There is an urgent need to understand the pathophysiology of these disorders and develop disease-modifying therapies.

Read the rest of this article HERE.

Source: Serena Spudich and Avindra Nath. Nervous system consequences of COVID-19. Science, Volume 375 | Issue 6578, 21 January 2022.

Researchers highlight COVID-19 neurological symptoms and need for rigorous studies

Press Release, NINDS/NIH, Jan 20, 2022:

SARS-CoV-2 was initially identified as a respiratory virus, but it can affect the entire body, including the nervous system. In a new Viewpoint published in Science, Avindra Nath, M.D., clinical director of the National Institutes of Health’s National Institute of Neurological Disorders and Stroke (NINDS), and Serena Spudich, M.D., Yale School of Medicine, New Haven, Connecticut, highlight what is currently known about the effects of SARS-CoV-2 on the brain, the importance of increased research into the underlying causes of Long Covid and possible ways to treat its symptoms.

Neurological symptoms that have been reported with acute COVID-19 include loss of taste and smell, headaches, stroke, delirium, and brain inflammation. There does not seem to be extensive infection of brain cells by the virus, but the neurological effects may be caused by immune activation, neuroinflammation, and damage to brain blood vessels.

Acute COVID-19 infection can sometimes lead to long-lasting effects, that have collectively been termed “Long Covid,” and can include a wide variety of symptoms in the brain and nervous system that range from a loss of taste and smell, impaired concentration, fatigue, pain, sleep disorders, autonomic disorders and/or headache to psychological effects such as depression or psychosis.

Drs. Nath and Spudich outline the current scientific understanding of the potential body responses to acute COVID-19 infection and how those responses could lead to Long Covid symptoms. They also draw parallels between the symptoms experienced by individuals with Long Covid to those living with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) or post-Lyme disease, which suggests there could be common risk factors involved.

Finally, owing to the significant variability in symptoms from person to person and the fact that many individuals with Long Covid were healthy prior to a relatively mild COVID-19 infection, the authors highlight the urgent need for significant research efforts into identifying the full extent of Long Covid complications and their causes. This kind of research, which would include the careful study of individuals with Long Covid categorized by their specific symptoms, is crucial to the development of diagnostic and therapeutic tools to identify and treat what is becoming an ever-increasing public health concern. The NIH RECOVER COVID initiative is an ambitious research program to reach these goals.

WHO:

Avindra Nath, M.D., clinical director, NINDS. To arrange an interview, please contact NINDSPressTeam@ninds.nih.gov.

ARTICLE:

Spudich S. and Nath A. “Nervous system consequences of COVID-19” Science. January 21, 2022. DOI: 10.1126/science.abm2052.

Chronic fatigue syndrome and cognitive deficit are associated with acute-phase neuropsychiatric manifestations of COVID-19: A 9-month follow-up study

Abstract:

The prevalence of long-COVID symptoms is rising but it is not still possible to predict which patients will present them, and which types of symptoms they will present. We followed up 95 patients with confirmed COVID-19 for 9 months to identify and characterize long-COVID symptoms.

Easy fatigability was the most common symptom (51.04%), followed by anxiety (38.54%), dyspnea (38.54%), and new-onset headache (38.54%). There was no association between COVID-19 severity in the acute phase and the number of long-COVID symptoms (F(1,93) = 0.75, p = 0.45), and cognitive function (MoCA) scores (F(1,90) = 0.073, p = 0.787) at follow-up. Being female (F(1,92) = – 2.27, p = 0.02), having a higher number of symptoms (F(1,93) = 2.76, p = 0.0068), and experiencing constitutional neuropsychiatric symptoms (F(1,93) = 2.529, p = 0.01) in the acute phase were associated with having chronic fatigue syndrome at follow-up.

Moreover, constitutional neuropsychiatric symptoms in the acute phase were associated with a lower MoCA score (F(1,93) = 10.84, p = 0.001) at follow-up. Specific clinical presentations such as constitutional neuropsychiatric symptoms in the acute phase might be predictors of debilitating long-COVID symptoms such as chronic fatigue syndrome and cognitive deficits.

Source: Mirfazeli FS, Sarabi-Jamab A, Pereira-Sanchez V, Kordi A, Shariati B, Shariat SV, Bahrami S, Nohesara S, Almasi-Dooghaee M, Faiz SHR. Chronic fatigue syndrome and cognitive deficit are associated with acute-phase neuropsychiatric manifestations of COVID-19: A 9-month follow-up study. Neurol Sci. 2022 Jan 21. doi: 10.1007/s10072-021-05786-y. Epub ahead of print. PMID: 35059902. https://pubmed.ncbi.nlm.nih.gov/35059902/

Prevalence, characteristics, and predictors of Long COVID among diagnosed cases of COVID-19

Abstract:

Background: Long COVID or long-term complication after COVID-19 has the ability to affect health and quality of life. Knowledge about the burden and predictors could aid in their prevention and management. Most of the studies are from high-income countries and focus on severe cases. We did this study to estimate the prevalence and identify the characteristics and predictors of Long COVID among our patients.

Methodology: We recruited adult (≥18 years) patients who were diagnosed as Reverse Transcription Polymerase Chain Reaction (RTPCR) confirmed SARS-COV-2 infection and were either hospitalized or tested on outpatient basis. Eligible participants were followed up telephonically after four weeks of diagnosis of SARS-COV-2 infection to collect data on sociodemographic, clinical history, vaccination history, Cycle threshold (Ct) values during diagnosis and other variables. Characteristics of Long COVID were elicited, and multivariable logistic regression was done to find the predictors of Long COVID.

Results: We have analyzed 487 individual data with a median follow-up of 44 days (Inter quartile range (IQR): 39,47). Overall, Long COVID was reported by 29.2% (95% Confidence interval (CI): 25.3%,33.4%) participants. Prevalence of Long COVID among patients with mild/moderate disease (n = 415) was 23.4% (95% CI: 19.5%,27.7%) as compared to 62.5% (95% CI: 50.7%,73%) in severe/critical cases(n=72). The most common Long COVID symptom was fatigue (64.8%) followed by cough (32.4%). Statistically significant predictors of Long COVID were – Pre-existing medical conditions (Adjusted Odds ratio (aOR)=2.00, 95% CI: 1.16,3.44), having a more significant number of symptoms during acute phase of COVID-19 disease (aOR=11.24, 95% CI: 4.00,31.51), two doses of COVID-19 vaccination (aOR=2.32, 95% CI: 1.17,4.58), the severity of illness (aOR=5.71, 95% CI: 3.00,10.89) and being admitted to hospital (Odds ratio (OR)=3.89, 95% CI: 2.49,6.08).

Conclusion: A considerable proportion of COVID-19 cases reported Long COVID symptoms. More research is needed in Long COVID to objectively assess the symptoms and find the biological and radiological markers.

Source: M. C. Arjun, Arvind Kumar Singh, Debkumar Pal, Kajal Das, Alekhya Gajjala, Mahalingam Venkateshan, Baijayantimala Mishra, Binod Kumar Patro, Prasanta Raghab Mohapatra, Sonu Hangma Subba. Prevalence, characteristics, and predictors of Long COVID among diagnosed cases of COVID-19. medRxiv 2022.01.04.21268536; doi: https://doi.org/10.1101/2022.01.04.21268536 https://www.medrxiv.org/content/10.1101/2022.01.04.21268536v1.full-text (Full text)

Symptoms Experienced at the Acute Phase of SARS-CoV-2 Infection as Risk Factor of Long-term Post-COVID Symptoms: The LONG-COVID-EXP-CM Multicenter Study

Abstract:

Objective: This multicenter study investigated clinical risk factors associated with the number of long-term post-COVID symptoms.

Methods: Clinical features, symptoms at hospital admission, hospitalization data, and the number of post-COVID symptoms was systematically assessed from patients recovered from COVID-19 at four hospitals in Madrid (Spain) from February 20 to May 31, 2020.

Results: Overall, 1,969 patients (46.5% women, age: 61, SD: 16 years) were randomly assessed at 8.4 months (SD 1.5) after hospital discharge. Female gender (OR1.82, 95%CI 1.57-2.10), number of morbidities (OR1.182, 95%CI 1.08-1.29), number of symptoms at hospital admission (OR1.309, 95%CI 1.15-1.49) and days at the hospital (OR1.01, 95%CI 1.007-1.017) were associated (all, P<0.001) with more long-term post-COVID symptoms. Further, vomiting (OR1.78, 95%CI 1.26-2.52), throat pain (OR1.36, 95%CI 1.02-1.81), diarrhoea (OR1.51, 95%CI 1.25-1.82), dyspnea (OR1.20, 95%CI 1.01-1.41), or headache (OR1.50, 95%CI 1.28-1.75) as symptoms at hospital admission were also associated (all, P<0.01) with a higher number of post-COVID symptoms.

Conclusion: This multicenter study found that a higher number of symptoms at hospital admission was the most relevant risk factor for developing more post-COVID symptoms, supporting the assumption that a higher symptom load at the acute phase is associated with a greater likelihood of long-term post-COVID symptoms.

Source: Fernández-de-Las-Peñas C, Pellicer-Valero OJ, Navarro-Pardo E, Palacios-Ceña D, Florencio LL, Guijarro C, Martín-Guerrero JD. Symptoms Experienced at the Acute Phase of SARS-CoV-2 Infection as Risk Factor of Long-term Post-COVID Symptoms: The LONG-COVID-EXP-CM Multicenter Study. Int J Infect Dis. 2022 Jan 8:S1201-9712(22)00007-8. doi: 10.1016/j.ijid.2022.01.007. Epub ahead of print. PMID: 35017102; PMCID: PMC8743274. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8743274/ (Full text)

Premorbid vulnerability and disease severity impact on Long-COVID cognitive impairment

Abstract:

Background: Cognitive deficits have been increasingly reported as possible long-term manifestations after SARS-CoV-2 infection.

Aims: In this study we aimed at evaluating the factors associated with cognitive deficits 6 months after hospitalization for Coronavirus Disease 2019 (COVID-19).

Methods: One hundred and six patients, discharged from a pneumology COVID-19 unit between March 1 and May 30 2020, accepted to be evaluated at 6 months according to an extensive neurological protocol, including the Montreal Cognitive Assessment (MoCA).

Results: Abnormal MoCA scores at 6 months follow-up were associated with higher pre-hospitalization National Health System (NHS) score (Duca et al. in Emerg Med Pract 22:1-2, 2020) (OR 1.27; 95% CI 1.05-1.6; p = 0.029) and more severe pulmonary disease expressed by the Brescia-COVID Respiratory Severity Scale (Duca et al. in Emerg Med Pract 22:1-2, 2020) (BCRSS > 1OR 4.73; 95% CI 1.53-14.63; p = 0.003) during the acute phase of the disease.

Discussion: This longitudinal study showed that the severity of COVID-19, indicated by BCRSS, and a complex score given by age and premorbid medical conditions, expressed by NHS, play a major role in modulating the long-term cognitive consequences of COVID-19 disease.

Conclusions: These findings indicate that the association of age and premorbid factors might identify people at risk for long-term neurological consequences of COVID-19 disease, thus deserving longer and proper follow-up.

Source: Cristillo V, Pilotto A, Cotti Piccinelli S, Bonzi G, Canale A, Gipponi S, Bezzi M, Leonardi M, Padovani A; Neuro Covid Next Study group. Premorbid vulnerability and disease severity impact on Long-COVID cognitive impairment. Aging Clin Exp Res. 2022 Jan 11:1–4. doi: 10.1007/s40520-021-02042-3. Epub ahead of print. PMID: 35014002; PMCID: PMC8747881. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8747881/ (Full text)

Evaluation of 3-month follow-up of patients with post-acute COVID-19 syndrome

Abstract:

Background: In addition to the highly variable clinical presentation of acute COVID-19 infection, it can also cause various post-acute signs and symptoms. This study aimed to evaluate patients with post-acute COVID-19 over 12 weeks of follow-up.

Methods: The study included 151 patients who were diagnosed with COVID-19 by real-time PCR of a nasopharyngeal swab 1 month earlier, had radiologic findings consistent with COVID-19 pneumonia, and presented to the post-COVID-19 outpatient clinic between May and August 2021. The patients were divided into three groups based on COVID-19 severity: non-severe pneumonia (group 1), severe pneumonia (group 2), and severe pneumonia requiring intensive care (group 3).

Results: Evaluation of laboratory parameters at 4 and 12 weeks showed that group 3 had higher lactose dehydrogenase (LDH) level and lower mean platelet volume than the other groups at both time points (p=0.001 for all). Group 3 also had lower FVC%, FEV1%, and DLCO/VA% compared to groups 1 and 2 at week 4 (p=0.001, 0.004, 0.001, respectively) and compared to group 1 at 12 weeks (p=0.002, 0.03, 0.001, respectively). Patients with persistent dyspnea at 12 weeks had significantly lower FEV1%, FVC%, DLCO/VA%, and saturation levels in room air and significantly higher LDH, pro-BNP, D-dimer, and heart rate compared to those without dyspnea (p=0.001 for all).

Conclusion: Although the lungs are most commonly affected after COVID-19 infection, vascular and endothelial damage also causes multisystem involvement. Our study indicates that laboratory values, radiological signs, and pulmonary functional capacity improved in most patients after 12 weeks of follow-up. This article is protected by copyright. All rights reserved.

Source: Kerget B, Çelik E, Kerget F, Aksakal A, Uçar EY, Araz Ö, Akgün M. Evaluation of 3-month follow-up of patients with post-acute COVID-19 syndrome. J Med Virol. 2022 Jan 9. doi: 10.1002/jmv.27579. Epub ahead of print. PMID: 35001367. https://pubmed.ncbi.nlm.nih.gov/35001367/

Successful application of pulsed electromagnetic fields in a patient with post-COVID-19 fatigue: a case report

Abstract:

in English, German

Background: Post-COVID-19 fatigue is a frequent symptom in COVID-19 survivors, which substantially limits patients to achieve full recovery and potentially restrains return to work. The previous literature has not yet reported the use of pulsed electromagnetic fields in this indication.

Methods: Over the course of 5 weeks, 10 sessions of pulsed electromagnetic field treatment with a high magnetic flux density were applied to a patient suffering from post-COVID-19 fatigue syndrome. Fatigue, work ability, quality of life as well as anxiety, depression, stress level, and resilience were evaluated using validated patient-reported outcome measures.

Results: Fatigue, work ability, quality of life, and psychological well-being improved clearly over the course of the treatment and showed stable results 6 weeks later.

Conclusion: The use of pulsed electromagnetic field therapy with a device that allows sufficient penetration of the body tissue might be a promising physical modality to manage post-COVID-19 fatigue syndrome, which could reduce clinical and economic health consequences. Clinical sham-controlled studies are needed to evaluate the effect of pulsed electromagnetic fields in this indication.

Source: Wagner B, Steiner M, Markovic L, Crevenna R. Successful application of pulsed electromagnetic fields in a patient with post-COVID-19 fatigue: a case report. Wien Med Wochenschr. 2022 Jan 10:1–6. doi: 10.1007/s10354-021-00901-2. Epub ahead of print. PMID: 35006516; PMCID: PMC8743351. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8743351/ (Full text)