Tag: long covid vs ME/CFS

Brain fog of post-COVID-19 condition and Chronic Fatigue Syndrome, same medical disorder?

Abstract:

Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is characterized by persistent physical and mental fatigue. The post-COVID-19 condition patients refer physical fatigue and cognitive impairment sequelae. Given the similarity between both conditions, could it be the same pathology with a different precipitating factor?

Objective: To describe the cognitive impairment, neuropsychiatric symptoms, and general symptomatology in both groups, to find out if it is the same pathology. As well as verify if the affectation of smell is related to cognitive deterioration in patients with post-COVID-19 condition.

Methods: The sample included 42 ME/CFS and 73 post-COVID-19 condition patients. Fatigue, sleep quality, anxiety and depressive symptoms, the frequency and severity of different symptoms, olfactory function and a wide range of cognitive domains were evaluated.

Results: Both syndromes are characterized by excessive physical fatigue, sleep problems and myalgia. Sustained attention and processing speed were impaired in 83.3% and 52.4% of ME/CFS patients while in post-COVID-19 condition were impaired in 56.2% and 41.4% of patients, respectively. Statistically significant differences were found in sustained attention and visuospatial ability, being the ME/CFS group who presented the worst performance. Physical problems and mood issues were the main variables correlating with cognitive performance in post-COVID-19 patients, while in ME/CFS it was anxiety symptoms and physical fatigue.

Conclusions: The symptomatology and cognitive patterns were similar in both groups, with greater impairment in ME/CFS. This disease is characterized by greater physical and neuropsychiatric problems compared to post-COVID-19 condition. Likewise, we also propose the relevance of prolonged hyposmia as a possible marker of cognitive deterioration in patients with post-COVID-19.

Source: Azcue N, Gómez-Esteban JC, Acera M, Tijero B, Fernandez T, Ayo-Mentxakatorre N, Pérez-Concha T, Murueta-Goyena A, Lafuente JV, Prada Á, López de Munain A, Ruiz-Irastorza G, Ribacoba L, Gabilondo I, Del Pino R. Brain fog of post-COVID-19 condition and Chronic Fatigue Syndrome, same medical disorder? J Transl Med. 2022 Dec 6;20(1):569. doi: 10.1186/s12967-022-03764-2. PMID: 36474290. https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-022-03764-2 (Full text)

The Prevalence, Severity, and Impact of Post-COVID Persistent Fatigue, Post-Exertional Malaise, and Chronic Fatigue Syndrome

Background: Fatigue is common after viral infections, including SARS-CoV-2.1 Our purpose was to report the prevalence and impact of persistent fatigue 6 months after SARS-CoV-2 infection, considering post-exertional malaise2 and criteria for chronic fatigue syndrome.3

Methods: Since March 2020, individuals tested for SARS-CoV-2 at the Geneva University Hospitals outpatient testing center benefit from remote ambulatory follow-up (COVICARE). This study included all individuals tested between March 2020 and December 2020 and whose follow-up was at 6 months or more after their test date.

Follow-up included questions about the prevalence of symptoms (yes/no) and their severity using a Likert scale (mild, moderate, or severe). Fatigue was assessed using the Eastern Cooperative Oncology Group (ECOG) scale and the Chalder fatigue scale. The Chalder fatigue scale was scored using the 4-item Likert and the bimodal scoring schemes. A score of ≥ 4 on bimodal scoring indicated severe fatigue.

The DePaul brief questionnaire was used to identify post-exertional malaise and criteria for chronic fatigue syndrome.

The Sheehan Disability Scale was used to assess functional impairment. Reduced work capacity was defined as missing days off work or having a reduced productivity on the Sheehan disability scale.

Comorbidities were considered present if pre-existing prior to SARS-CoV-2 infection. Statistical analysis included descriptive comparisons of percentages using chi-square tests and Student’s t test.

Results: Overall, 5515 individuals participated in this study (response rate 70.7%), with 5406 participants at 6 months or more after their test date. A total of 1497 (27.7%) participants had a documented positive SARS-CoV-2 test and were ultimately included in the study. The median time for follow-up was 225 days (interquartile range 207–398). Respectively, fatigue was reported by 17.2%, post-exertional malaise by 8.2%, and the presence of criteria for chronic fatigue syndrome by 1.1% of SARS-CoV-2-positive individuals, compared to 8.9%, 3.5%, and 0.5% of SARS-CoV-2-negative individuals. Characteristics are presented in Table 1.

Out of SARS-CoV-2-positive participants with fatigue (n = 258), 35.3% had moderate to severe limitations on the ECOG scale, and 83.0% had a score ≥ 4 on the Chalder fatigue scale. The Chalder fatigue scale revealed a mean score of 19 out of 33, SD 5.4, and a mean score of 6.7 out of 11, SD 3.3 using bimodal scoring. After adjusting for age and sex, 47.7% of SARS-CoV-2-positive individuals with fatigue at 6 months or more had the frequency and severity criteria for post-exertional malaise, and 6.2% had criteria for chronic fatigue syndrome.

Individuals had a higher prevalence of insomnia, cognitive impairment, headaches, generalized pain, functional impairment, reduced work capacity, and decreased physical activity, after SARS-CoV-2 infection. The prevalence of these sequelae was adjusted for age and sex and was increasingly higher with severe fatigue, with post-exertional malaise, or when criteria for chronic fatigue syndrome were present (Fig. 1).

Discussion: Fatigue is the most common and persistent post-COVID symptom. The spectrum of fatigue severity in post-COVID individuals ranges from feeling tired to having severe fatigue, post-exertional malaise, or criteria for chronic fatigue syndrome with an increasing impact on health, functional capacity, and physical activity.

Almost half of individuals experiencing fatigue at 6 months after the infection had post-exertional malaise, and 6.2% had criteria for chronic fatigue syndrome, prompting physicians to consider pacing as a management option, in the absence of other treatment options at this stage. SARS-CoV-2 infection was positively associated with fatigue and post-exertional malaise.

Results showed that individuals with fatigue were more likely to be vaccinated. This was partially explained by the baseline distribution as older individuals and those with more comorbidities were more likely to get vaccinated.

Results compare to recent reviews showing an overlap between post-COVID condition and chronic fatigue syndrome. Our study graded post-COVID fatigue by severity in correlation with functional capacity, and showed the high prevalence of post-exertional malaise.

Limitations include the self-reported nature of this follow-up with individuals infected in 2020 and follow-up in 2021, lacking comparisons to individuals infected with other variants. Additionally, this study considered having received at least 2 doses as full vaccination, a concept that continues to evolve with time.

Physicians, employers, and insurance companies should address fatigue on a spectrum, accounting for the correlated functional impairment, decreased activity levels, and potentially poorer quality of life.

Source: Nehme M, Chappuis F, Kaiser L, Assal F, Guessous I. The Prevalence, Severity, and Impact of Post-COVID Persistent Fatigue, Post-Exertional Malaise, and Chronic Fatigue Syndrome. J Gen Intern Med. 2022 Nov 10:1–5. doi: 10.1007/s11606-022-07882-x. Epub ahead of print. PMID: 36357723; PMCID: PMC9648889. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9648889/ (Full text)

 

Global prevalence of chronic fatigue syndrome among long COVID-19 patients: A systematic review and meta-analysis

Abstract:

Background: Chronic fatigue syndrome is a persistent and debilitating disorder. According to several studies, chronic fatigue syndrome has been identified among recovered COVID-19 patients as the most common symptom of long COVID. The aim of this systematic review and meta-analysis study was to obtain the prevalence of chronic fatigue syndrome in long COVID cases.

Methods: In this systematic review and meta-analysis, we analysed reported results of studies that assessed the occurrence of chronic fatigue syndrome among COVID-19 patients four weeks after the onset of symptoms. The study selection was commenced by searching PubMed, Web of Science, Science Direct, Scopus, Embase, and Google scholar using the keywords of Chronic fatigue syndrome, COVID-19, and post-COVID-19 syndrome. The searches were without a lower time limit and until April 2022. Heterogeneity of studies was assessed using the I2 index, and a random effects model was used for analysis. Data analysis was performed within the Comprehensive Meta-Analysis software (version 2).

Results: The pooled prevalence of chronic fatigue syndrome four weeks after the onset of COVID-19 symptoms, in 52 studies with a sample size of 127,117, was 45.2% (95% CI: 34.1-56.9%). Meta-regression analysis in examining the effects of the two factors of sample size, and year of study on the changes in the overall prevalence, showed that with increasing sample size, and year of study, the prevalence of chronic fatigue syndrome among long COVID patients (p < 0.05).

Conclusion: Our results show that the overall prevalence of chronic fatigue syndrome as a long COVID symptom is 45.2%. Chronic fatigue after infection with COVID-19 can negatively affect personal and social lives. Given such significant negative consequences caused by the syndrome, it is recommended that health policymakers allocate funds to reduce the adverse effects of this syndrome, by creating programs to support long COVID patients.

Source: Salari N, Khodayari Y, Hosseinian-Far A, Zarei H, Rasoulpoor S, Akbari H, Mohammadi M. Global prevalence of chronic fatigue syndrome among long COVID-19 patients: A systematic review and meta-analysis. Biopsychosoc Med. 2022 Oct 23;16(1):21. doi: 10.1186/s13030-022-00250-5. PMID: 36274177; PMCID: PMC9589726. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9589726/ (Full text)

Long-haul COVID: heed the lessons from other infection-triggered illnesses

According to the Johns Hopkins Coronavirus Resource Center, more than 115 million people worldwide have been infected with SARS-CoV-2 during the COVID-19 pandemic, with extensive implications for morbidity and mortality. Description of long-term effects of COVID-19 are apparing in the medical literature; the first large cohort study with 6-months’ follow-up has been published, and more data are sure to follow. A small number of studies point not only to persistent imaging and testing abnormalities across several organ systems in the postacute period, but to a high frequency of patient-reported symptoms such as fatigue, insomnia, anxiety and depression, autonomic disturbances, cognitive difficulties, pain, and others. The presence of patient support groups, and the rapid expansion of clinics to manage or treat these symptoms, validate further their existence and impact.
Although the frequency, severity, and potentially the etiology of persistent symptoms can vary, sequelae after COVID-19 appears poised to join the range of other postinfectious syndromes described in the field of infectious diseases.

These often share a common symptom phenotype, which might also meet case definitions for myalgic encephalomyelitis/chronic fatigue syndrome, fibromyalgia, or post-treatment Lyme disease. We hope that researchers and clinicians will draw on these other conditions as they continue to advance scientific understanding of so-called long-haul or persistent COVID-19. We would also argue that there are important lessons to learn and pitfalls to avoid; our specific area of clinical care and research (post-treatment Lyme disease) has remained a fiercely contentious condition for more than 30 years.

Read the rest of this article HERE.
Source: John N Aucott, Alison W Rebman. Long-haul COVID: heed the lessons from other infection-triggered illnesses. The Lancet, CORRESPONDENCE| VOLUME 397, ISSUE 10278, P967-968, MARCH 13, 2021 https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00446-3/fulltext (Full text) 

Orthostatic Intolerance in Long-Haul COVID after SARS-CoV-2: A Case-Control Comparison with Post-EBV and Insidious-Onset Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients

Abstract:

Background: As complaints of long-haul COVID patients are similar to those of ME/CFS patients and as orthostatic intolerance (OI) plays an important role in the COVID infection symptomatology, we compared 14 long-haul COVID patients with 14 ME/CFS patients with a post-viral Ebstein-Barr (EBV) onset and 14 ME/CFS patients with an insidious onset of the disease.
Methods: In all patients, OI analysis by history taking and OI assessed during a tilt test, as well as cerebral blood flow measurements by extracranial Doppler, and cardiac index measurements by suprasternal Doppler during the tilt test were obtained in all patients.
Results: Except for disease duration no differences were found in clinical characteristics. The prevalence of POTS was higher in the long-haul patients (100%) than in post-EBV (43%) and in insidious-onset (50%) patients (p = 0.0002). No differences between the three groups were present in the prevalence of OI, heart rate and blood pressure changes, changes in cerebral blood flow or in cardiac index during the tilt test.
Conclusion: OI symptomatology and objective abnormalities of OI (abnormal cerebral blood flow and cardiac index reduction during tilt testing) are comparable to those in ME/CFS patients. It indicates that long-haul COVID is essentially the same disease as ME/CFS.
Source: van Campen CMC, Visser FC. Orthostatic Intolerance in Long-Haul COVID after SARS-CoV-2: A Case-Control Comparison with Post-EBV and Insidious-Onset Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients. Healthcare. 2022; 10(10):2058. https://doi.org/10.3390/healthcare10102058 (Full text)

Saliva antibody-fingerprint of reactivated latent viruses after mild/asymptomatic COVID-19 is unique in patients with myalgic-encephalomyelitis/chronic fatigue syndrome

Abstract:

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic disease considered to be triggered by viral infections in a majority of cases. Symptoms overlap largely with those of post-acute sequelae of COVID-19/long-COVID implying common pathogenetic mechanisms. SARS-CoV-2 infection is risk factor for sustained latent virus reactivation that may account for the symptoms of post-viral fatigue syndromes. The aim of this study was first to investigate whether patients with ME/CFS and healthy donors (HDs) differed in their antibody response to mild/asymptomatic SARS-CoV-2 infection. Secondly, to analyze whether COVID-19 imposes latent virus reactivation in the cohorts.

Methods: Anti-SARS-CoV-2 antibodies were analyzed in plasma and saliva from non-vaccinated ME/CFS (n=95) and HDs (n=110) using soluble multiplex immunoassay. Reactivation of human herpesviruses 1-6 (HSV1, HSV2, VZV, EBV, CMV, HHV6), and human endogenous retrovirus K (HERV-K) was detected by anti-viral antibody fingerprints in saliva.

Results: At 3-6 months after mild/asymptomatic SARS-CoV-2 infection, virus-specific antibodies in saliva were substantially induced signifying a strong reactivation of latent viruses (EBV, HHV6 and HERV-K) in both cohorts. In patients with ME/CFS, antibody responses were significantly stronger, in particular EBV-encoded nuclear antigen-1 (EBNA1) IgG were elevated in patients with ME/CFS, but not in HDs. EBV-VCA IgG was also elevated at baseline prior to SARS-infection in patients compared to HDs.

Conclusion: Our results denote an altered and chronically aroused anti-viral profile against latent viruses in ME/CFS. SARS-CoV-2 infection even in its mild/asymptomatic form is a potent trigger for reactivation of latent herpesviruses (EBV, HHV6) and endogenous retroviruses (HERV-K), as detected by antibody fingerprints locally in the oral mucosa (saliva samples). This has not been shown before because the antibody elevation is not detected systemically in the circulation/plasma.

Source: Apostolou Eirini, Rizwan Muhammad, Moustardas Petros, Sjögren Per, Bertilson Bo Christer, Bragée Björn, Polo Olli, Rosén Anders. Saliva antibody-fingerprint of reactivated latent viruses after mild/asymptomatic COVID-19 is unique in patients with myalgic-encephalomyelitis/chronic fatigue syndrome. Frontiers in Immunology, Vol 13, 2022. https://www.frontiersin.org/articles/10.3389/fimmu.2022.949787/full (Full text)

A new clinical challenge: Supporting patients coping with the long-term effects of COVID-19

Abstract:

Mental Health Practitioners (MHPs) have a unique opportunity to provide resources and support to those suffering from Long COVID (LC), the post infectious illness that often follows an acute SARS-CoV-2 infection. In working with these individuals, MHPs can learn from the experiences of patients with another post-infectious disease known as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). ME/CFS was once thought to be a psychologically mediated disorder caused by deconditioning and the fear of exertion following a precipitating event such as a viral infection. Research now shows that LC and ME/CFS are biomedical, multisystem, complex physiologic diseases. This article provides a framework to MHPs for the treatment of LC patients using knowledge derived from three decades of research on ME/CFS.

Source: Neal C. Goldberg, Sabrina Poirier, Allison Kanas, Lisa McCorkell, Carrie Anna McGinn, Yochai Re’em, Kathi Kuehnel, Nina Muirhead, Tahlia Ruschioni, Susan Taylor-Brown & Leonard A. Jason (2022) A new clinical challenge: supporting patients coping with the long-term effects of COVID-19, Fatigue: Biomedicine, Health & Behavior, DOI: 10.1080/21641846.2022.2128576 (Full text)

The significance of oxidative stress in the pathophysiology of Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Abstract:

Long COVID is now well accepted as an ongoing post-viral syndrome resulting from infection of a single virus, the pandemic SARS-CoV-2. It mirrors the post-viral fatigue syndrome, Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome, a global debilitating illness arising mainly from sporadic geographically-specific viral outbreaks, and from community endemic infections, but also from other stressors. Core symptoms of both syndromes are post-exertional malaise (a worsening of symptoms following mental or physical activity), pervasive fatigue, cognitive dysfunction (brain fog), and sleep disturbance. Long COVID patients frequently also suffer from shortness of breath, relating to the lung involvement of the SARS-CoV-2 virus.

There is no universally accepted pathophysiology, or recognized biomarkers yet for Long COVID or indeed for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Clinical case definitions with very similar characteristics for each have been defined. Chronic inflammation, immune dysfunction, and disrupted energy production in the peripheral system has been confirmed in Long COVID and has been well documented in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Neuroinflammation occurs in the brain in Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome as shown from a small number of positron emission tomography and magnetic resonance spectroscopy studies, and has now been demonstrated for Long COVID. Oxidative stress, an increase in reactive oxygen and reactive nitrogen species, and free radicals, has long been suggested as a potential cause for many of the symptoms seen in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, resulting from both activation of the brain’s immune system and dysregulation of mitochondrial function throughout the body. The brain as a high producer of energy may be particularly susceptible to oxidative stress. It has been shown in peripheral immune cells that the balanced production of proteins involved in regulation of the reactive oxygen species in mitochondria is disturbed in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Fluctuations in the chronic low level neuroinflammation during the ongoing course of Long COVID as well as Myalgic Encephalomyelitis/Chronic Fatigue Syndrome have been proposed to cause the characteristic severe relapses in patients.

This review explores oxidative stress as a likely significant contributor to the pathophysiology of Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, and the mechanisms by which oxidative stress could cause the symptoms seen in both syndromes. Treatments that could mitigate oxidative stress and thereby lessen the debilitating symptoms to improve the life of patients are discussed.

Source: WALKER, Max Oliver Mackay et al. The significance of oxidative stress in the pathophysiology of Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Medical Research Archives, [S.l.], v. 10, n. 9, sep. 2022. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/3050>. Date accessed: 09 oct. 2022. doi: https://doi.org/10.18103/mra.v10i9.3050.

Association of SARS-CoV-2 Seropositivity With Myalgic Encephalomyelitis and/or Chronic Fatigue Syndrome Among Children and Adolescents in Germany

Abstract:

Importance: During the COVID-19 pandemic, a reduction in quality of life and physical and mental health among children and adolescents has been reported that may be associated with SARS-CoV-2 infection and/or containment measures.

Objective: To assess the association of SARS-CoV-2 seropositivity with symptoms that may be related to myalgic encephalomyelitis and/or chronic fatigue syndrome (ME/CFS) among children and adolescents.

Design, setting, and participants: This substudy of the cross-sectional SARS-CoV-2 seroprevalence surveys in Germany (SARS-CoV-2 KIDS) was performed in 9 pediatric hospitals from May 1 to October 31, 2021. Pediatric patients were recruited during an inpatient or outpatient visit regardless of the purpose of the visit. Parental questionnaires and serum samples were collected during clinically indicated blood draws. The parental questionnaire on demographic and clinical information was extended by items according to the DePaul Symptom Questionnaire, a pediatric screening tool for ME/CFS in epidemiological studies in patients aged 5 to 17 years.

Exposures: Seropositivity was determined by SARS-CoV-2 IgG antibodies in serum samples using enzyme-linked immunosorbent assays.

Main outcomes and measures: Key symptoms of ME/CFS were evaluated separately or as clustered ME/CFS symptoms according to the DePaul Symptom Questionnaire, including fatigue.

Results: Among 634 participants (294 male [46.4%] and 340 female [53.6%]; median age, 11.5 [IQR, 8-14] years), 198 (31.2%) reported clustered ME/CFS symptoms, including 40 of 100 SARS-CoV-2-seropositive (40.0%) and 158 of 534 SARS-CoV-2-seronegative (29.6%) children and adolescents. After adjustment for sex, age group, and preexisting disease, the risk ratio for reporting clustered ME/CFS symptoms decreased from 1.35 (95% CI, 1.03-1.78) to 1.18 (95% CI, 0.90-1.53) and for substantial fatigue from 2.45 (95% CI, 1.24-4.84) to 2.08 (95% CI, 1.05-4.13). Confinement to children and adolescents with unknown previous SARS-CoV-2 infection status (n = 610) yielded lower adjusted risks for all symptoms except joint pain ME/CFS-related symptoms. The adjusted risk ratio was 1.08 (95% CI, 0.80-1.46) for reporting clustered ME/CFS symptoms and 1.43 (95% CI, 0.63-3.23) for fatigue.

Conclusions and relevance: These findings suggest that the risk of ME/CFS in children and adolescents owing to SARS-CoV-2 infection may be very small. Recall bias may contribute to risk estimates of long COVID-19 symptoms in children. Extensive lockdowns must be considered as an alternative explanation for complex unspecific symptoms during the COVID-19 pandemic.

Source: Sorg AL, Becht S, Jank M, Armann J, von Both U, Hufnagel M, Lander F, Liese JG, Niehues T, Verjans E, Wetzke M, Stojanov S, Behrends U, Drosten C, Schroten H, von Kries R. Association of SARS-CoV-2 Seropositivity With Myalgic Encephalomyelitis and/or Chronic Fatigue Syndrome Among Children and Adolescents in Germany. JAMA Netw Open. 2022 Sep 1;5(9):e2233454. doi: 10.1001/jamanetworkopen.2022.33454. PMID: 36166227.  https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2796733 (Full text)