A Case Study of Successful Application of the Principles of ME/CFS Care to an Individual with Long COVID

Abstract:

Persistent fatigue is one of the most common symptoms of post-COVID conditions, also termed long COVID. At the extreme end of the severity spectrum, some individuals with long COVID also meet the criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), raising the possibility that symptom management approaches for ME/CFS may benefit some long COVID patients.

We describe the long-term outcomes of a 19-year-old male who developed profound impairment consistent with ME/CFS after a SARS-CoV-2 infection early in the pandemic.

We evaluated and treated him using our clinic’s approach to ME/CFS. This included a history and physical examination that ascertained joint hypermobility, pathological reflexes, physical therapy maneuvers to look for a range of motion restrictions in the limbs and spine, orthostatic testing, and screening laboratory studies.

He was found to have profound postural tachycardia syndrome, several ranges of motion restrictions, and mast cell activation syndrome. He was treated according to our clinic’s guidelines for managing ME/CFS, which included manual physical therapy maneuvers and both non-pharmacologic measures and medications directed at postural tachycardia syndrome and mast cell activation.

He experienced significant improvement in his symptoms over 30 months. His case emphasizes how the application of the principles of treating ME/CFS has the potential to provide a direction for treating long COVID.

Source: Petracek LS, Broussard CA, Swope RL, Rowe PC. A Case Study of Successful Application of the Principles of ME/CFS Care to an Individual with Long COVID. Healthcare. 2023; 11(6):865. https://doi.org/10.3390/healthcare11060865 (Full text)

Validity of 2-Day Cardiopulmonary Exercise Testing in Male Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Introduction: Among the main characteristics of patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are effort intolerance along with a prolonged recovery from exercise and post-exertional exacerbation of ME/CFS symptoms. The gold standard for measuring the severity of physical activity intolerance is cardiopulmonary exercise testing (CPET). Multiple studies have shown that peak oxygen consumption is reduced in the majority of ME/CFS patients. A consecutive day CPET protocol has shown a difference on day 2 in ME/CFS patients in contrast to sedentary controls. Because of the low number of male ME/CFS patients in the published literature, and because of a possible gender difference in the clinical phenotype, the aim of this study was to examine whether the response to a 2-day CPET protocol in a larger sample of male ME/CFS patients was similar to that observed in females.

Methods: From 77 male patients, 25 male ME/CFS patients fulfilled the criteria of a 2-day CPET protocol for analysis. Measures of oxygen consumption (VO2), heart rate (HR), systolic and diastolic blood pressure, workload (Work), and respiratory exchange ratio (RER) were made at maximal (peak) and ventilatory threshold (VT) intensities. Data were analysed using a paired t-test.

Results: Baseline characteristics of the group were as follows. Mean age was 44 (12) years, mean BMI was 27.1 (4.4) kg/m2. Median disease duration was 10 years (IQR 7 – 13). Heart rate, systolic and diastolic blood pressure at rest and the RER did not differ significantly between CPET 1 and CPET 2. All other CPET parameters at the ventilatory threshold and maximum exercise differed significantly (p-value between <0.005 and <0.0001). All patients experienced a deterioration of performance on CPET2 as measured by the predicted and actual VO2 and workload at peak exercise and ventilatory threshold.

Conclusion: This study confirms that male ME/CFS patients have a reduction in exercise capacity in response to a consecutive day CPET. These results are similar to published results in female ME/CFS populations.

Source:

 

Orthostatic intolerance as a potential contributor to prolonged fatigue and inconsistent performance in elite swimmers

Abstract:

Background: Athletic underperformance is characterized by fatigue and an inability to sustain a consistent exercise workload. We describe five elite swimmers with prolonged fatigue and athletic underperformance. Based on our work in myalgic encephalomyelitis /chronic fatigue syndrome, we focused on orthostatic intolerance as a possible contributor to symptoms.

Methods: Participants were referred for evaluation of fatigue and underperformance to the Chronic Fatigue Clinic at the Johns Hopkins Children’s Center. All patients were evaluated for overtraining syndrome, as well as for features commonly seen in myalgic encephalomyelitis/chronic fatigue syndrome. The latter included joint hypermobility, orthostatic intolerance, and non-IgE mediated milk protein intolerance. Orthostatic intolerance was tested by performing a ten-minute passive standing test or a head-up tilt table test.

Results: Orthostatic testing provoked fatigue and other symptoms in all five swimmers, two of whom met heart rate criteria for postural tachycardia syndrome. Treatment was individualized, primarily consisting of an increased intake of sodium chloride and fluids to address orthostasis. All patients experienced a relatively prompt improvement in fatigue and other orthostatic symptoms and were able to either return to their expected level of performance or improve their practice consistency.

Conclusions: Orthostatic intolerance was an easily measured and treatable contributor to athletic underperformance in the five elite swimmers we describe. We suggest that passive standing tests or formal tilt table tests be incorporated into the clinical evaluation of athletes with fatigue and underperformance as well as into scientific studies of this topic. Recognition and treatment of orthostatic intolerance provides a new avenue for improving outcomes in underperforming athletes.

Source: Petracek LS, Eastin EF, Rowe IR, Rowe PC. Orthostatic intolerance as a potential contributor to prolonged fatigue and inconsistent performance in elite swimmers. BMC Sports Sci Med Rehabil. 2022 Jul 23;14(1):139. doi: 10.1186/s13102-022-00529-8. PMID: 35870963. https://bmcsportsscimedrehabil.biomedcentral.com/articles/10.1186/s13102-022-00529-8 (Full text)

Long-Term COVID 19 Sequelae in Adolescents: the Overlap with Orthostatic Intolerance and ME/CFS

Abstract

Purpose of Review: To discuss emerging understandings of adolescent long COVID or post-COVID-19 conditions, including proposed clinical definitions, common symptoms, epidemiology, overlaps with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and orthostatic intolerance, and preliminary guidance on management.

Recent Findings: The recent World Health Organization clinical case definition of post-COVID-19 condition requires a history of probable or confirmed SARS-CoV-2 infection, with symptoms starting within 3 months of the onset of COVID-19. Symptoms must last for at least 2 months and cannot be explained by an alternative diagnosis.

Common symptoms of the post-COVID-19 condition include, but are not limited to, fatigue, shortness of breath, and cognitive dysfunction. These symptoms generally have an impact on everyday functioning.

The incidence of prolonged symptoms following SARS-CoV-2 infection has proven challenging to define, but it is now clear that those with relatively mild initial infections, without severe initial respiratory disease or end-organ injury, can still develop chronic impairments, with symptoms that overlap with conditions like ME/CFS (profound fatigue, unrefreshing sleep, post-exertional malaise, cognitive dysfunction, and orthostatic intolerance).

Summary: We do not yet have a clear understanding of the mechanisms by which individuals develop post-COVID-19 conditions. There may be several distinct types of long COVID that require different treatments.

At this point, there is no single pharmacologic agent to effectively treat all symptoms. Because some presentations of post-COVID-19 conditions mimic disorders such as ME/CFS, treatment guidelines for this and related conditions can be helpful for managing post-COVID-19 symptoms.

Source: Morrow, A.K., Malone, L.A., Kokorelis, C. et al. Long-Term COVID 19 Sequelae in Adolescents: the Overlap with Orthostatic Intolerance and ME/CFS. Curr Pediatr Rep (2022). https://doi.org/10.1007/s40124-022-00261-4  (Full text)

Pediatric Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Overlaps and Opportunities

David Spodick once wrote: “We must view published material critically (if not biblically), for too often the ‘Conclusions’ giveth, but the ‘Materials and Methods’ taketh away.” In the December 2021 issue of the Pediatric Infectious Diseases Journal, Zimmermann et al provide a masterful application of Spodick’s exhortation. Their review of the existing evidence regarding long COVID in children enumerates important methodologic challenges in interpreting this literature, including the heterogeneity of available case definitions for long COVID, differences in the time intervals in which symptoms are ascertained, variability regarding which symptoms are included under the rubric of long COVID, and whether laboratory confirmation of the initial COVID infection is required. Additionally, the authors emphasize that without control groups in many of these studies, and in light of the overlap of some long COVID symptoms with symptoms of prolonged social isolation, it is difficult to discern which symptoms are attributable to the general pandemic circumstances rather than the COVID-19 infection itself. Despite such limitations, it is clear that pediatric patients are at risk for prolonged symptoms following acute SARS-CoV-2 infection. Although many persistent symptoms, such as anosmia, dysgeusia and shortness of breath are unique to the post-COVID state, many other symptoms such as fatigue, cognitive dysfunction, lightheadedness and postexertional malaise overlap with symptoms found in myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS). In this commentary, we review case definitions for long COVID and ME/CFS, emphasize recent research findings on the biologic basis of ME/CFS, discuss the overlap with long COVID, and consider opportunities posed by the pandemic to improve the understanding of both conditions

Read the rest of this article HERE.

Source: Siberry VGR, Rowe PC. Pediatric Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Overlaps and Opportunities. Pediatr Infect Dis J. 2022 Feb 4. doi: 10.1097/INF.0000000000003477. Epub ahead of print. PMID: 35121715. https://journals.lww.com/pidj/Citation/9000/Pediatric_Long_COVID_and_Myalgic.95546.aspx (Full text)

Compression Stockings Improve Cardiac Output and Cerebral Blood Flow during Tilt Testing in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Patients: A Randomized Crossover Trial

Background and Objectives: Orthostatic intolerance (OI) is a clinical condition in which symptoms worsen upon assuming and maintaining upright posture and are ameliorated by recumbency. OI has a high prevalence in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Limited data are available to guide the treatment of OI in ME/CFS patients. We and others have previously described patient-reported subjective improvement in symptoms using compression stockings. We hypothesized that these subjective reports would be accompanied by objective hemodynamic improvements.
Materials and Methods: We performed a randomized crossover trial in 16 ME/CFS patients. Each underwent two 15-min head-up tilt table tests, one with and one without wearing knee-high compression stockings that provided 20–25 mm Hg compression. The order of the tests was randomized. We measured heart rate and blood pressure as well as cardiac output and cerebral blood flow (CBF) using extracranial Doppler of the internal carotid and vertebral arteries.
Results: There were no differences in supine measurements between the 2 baseline measurements. There were no differences in heart rate and blood pressure at either end-tilt testing period. Compared to the test with the stockings off, the mean percentage reduction in cardiac output during the test with compression stockings on was lower, 15 (4)% versus 27 (6)% (p < 0.0001), as was the mean percentage CBF reduction, 14 (4)% versus 25 (5)% (p < 0.0001).
Conclusion: In ME/CFS patients with orthostatic intolerance symptoms, cardiac output and CBF are significantly reduced during a tilt test. These abnormalities were present without demonstrable heart rate and blood pressure changes and were ameliorated by the use of compression stockings.
Source: van Campen CMC, Rowe PC, Visser FC. Compression Stockings Improve Cardiac Output and Cerebral Blood Flow during Tilt Testing in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Patients: A Randomized Crossover Trial. Medicina. 2022; 58(1):51. https://doi.org/10.3390/medicina58010051 https://www.mdpi.com/1648-9144/58/1/51/htm  (Full text)

Orthostatic Symptoms and Reductions in Cerebral Blood Flow in Long‐Haul COVID‐19 Patients: Similarities with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Background and Objectives: Symptoms and hemodynamic findings during orthostatic stress have been reported in both long-haul COVID-19 and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), but little work has directly compared patients from these two groups. To investigate the overlap in these clinical phenotypes, we compared orthostatic symptoms in daily life and during head-up tilt, heart rate and blood pressure responses to tilt, and reductions in cerebral blood flow in response to orthostatic stress in long-haul COVID-19 patients, ME/CFS controls, and healthy controls.
Materials and Methods: We compared 10 consecutive long-haul COVID-19 cases with 20 age- and gender-matched ME/CFS controls with postural tachycardia syndrome (POTS) during head-up tilt, 20 age- and gender-matched ME/CFS controls with a normal heart rate and blood pressure response to head-up tilt, and 10 age- and gender-matched healthy controls. Identical symptom questionnaires and tilt test procedures were used for all groups, including measurement of cerebral blood flow and cardiac index during the orthostatic stress.
Results: There were no significant differences in ME/CFS symptom prevalence between the long-haul COVID-19 patients and the ME/CFS patients. All long-haul COVID-19 patients developed POTS during tilt. Cerebral blood flow and cardiac index were more significantly reduced in the three patient groups compared with the healthy controls. Cardiac index reduction was not different between the three patient groups. The cerebral blood flow reduction was larger in the long-haul COVID-19 patients compared with the ME/CFS patients with a normal heart rate and blood pressure response.
Conclusions: The symptoms of long-haul COVID-19 are similar to those of ME/CFS patients, as is the response to tilt testing. Cerebral blood flow and cardiac index reductions during tilt were more severely impaired than in many patients with ME/CFS. The finding of early-onset orthostatic intolerance symptoms, and the high pre-illness physical activity level of the long-haul COVID-19 patients, makes it unlikely that POTS in this group is due to deconditioning. These data suggest that similar to SARS-CoV-1, SARS-CoV-2 infection acts as a trigger for the development of ME/CFS.
Source: Campen CMCv, Rowe PC, Visser FC. Orthostatic Symptoms and Reductions in Cerebral Blood Flow in Long-Haul COVID-19 Patients: Similarities with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Medicina. 2022; 58(1):28. https://doi.org/10.3390/medicina58010028  (Full text)

Cerebral blood flow remains reduced after tilt testing in myalgic encephalomyelitis/chronic fatigue syndrome patients

Abstract:

Objective: Orthostatic symptoms in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) may be caused by an abnormal reduction in cerebral blood flow. An abnormal cerebral blood flow reduction was shown in previous studies, without information on the recovery pace of cerebral blood flow. This study examined the prevalence and risk factors for delayed recovery of cerebral blood flow in ME/CFS patients.

Methods: 60 ME/CFS adults were studied: 30 patients had a normal heart rate and blood pressure response during the tilt test, 4 developed delayed orthostatic hypotension, and 26 developed postural orthostatic tachycardia syndrome (POTS) during the tilt. Cerebral blood flow measurements, using extracranial Doppler, were made in the supine position pre-tilt, at end-tilt, and in the supine position at 5 min post-tilt. Also, cardiac index measurements were performed, using suprasternal Doppler imaging, as well as end-tidal PCO2 measurements. The change in cerebral blood flow from supine to end-tilt was expressed as a percent reduction with mean and (SD). Disease severity was scored as mild (approximately 50% reduction in activity), moderate (mostly housebound), or severe (mostly bedbound).

Results: End-tilt cerebral blood flow reduction was -29 (6)%, improving to -16 (7)% at post-tilt. No differences in either end-tilt or post-tilt measurements were found when patients with a normal heart rate and blood pressure were compared to those with POTS, or between patients with normocapnia (end-tidal PCO2 ≥ 30 mmHg) versus hypocapnia (end-tidal PCO2 < 30 mmHg) at end-tilt. A significant difference was found in the degree of abnormal cerebral blood flow reduction in the supine post-test in mild, moderate, and severe ME/CFS: mild: cerebral blood flow: -7 (2)%, moderate: -16 (3)%, and severe :-25 (4)% (p all < 0.0001). Cardiac index declined significantly during the tilt test in all 3 severity groups, with no significant differences between the groups. In the supine post-test cardiac index returned to normal in all patients.

Conclusions: During tilt testing, extracranial Doppler measurements show that cerebral blood flow is reduced in ME/CFS patients and recovery to normal supine values is incomplete, despite cardiac index returning to pre-tilt values. The delayed recovery of cerebral blood flow was independent of the hemodynamic findings of the tilt test (normal heart rate and blood pressure response, POTS, or delayed orthostatic hypotension), or the presence/absence of hypocapnia, and was only related to clinical ME/CFS severity grading. We observed a significantly slower recovery in cerebral blood flow in the most severely ill ME/CFS patients.

Significance: The finding that orthostatic stress elicits a post-stress cerebral blood flow reduction and that disease severity greatly influences the cerebral blood flow reduction may have implications on the advice of energy management after a stressor and on the advice of lying down after a stressor in these ME/CFS patients.

Source: van Campen CLMC, Rowe PC, Visser FC. Cerebral blood flow remains reduced after tilt testing in myalgic encephalomyelitis/chronic fatigue syndrome patients. Clin Neurophysiol Pract. 2021 Sep 23;6:245-255. doi: 10.1016/j.cnp.2021.09.001. PMID: 34667909; PMCID: PMC8505270. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8505270/  (Full text)

The Presentation of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Is Not Influenced by the Presence or Absence of Joint Hypermobility

Abstract:

Objective: To examine demographic and clinical characteristics of individuals with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) with and without joint hypermobility We hypothesized that JH+ patients would have an earlier onset of ME/CFS symptoms as well as increased severity, greater number of co-morbid conditions, and lower health related quality of life.

Study design: From an observational cohort study of 55 individuals meeting the Fukuda criteria for ME/CFS, we compared groups using a Beighton score cut-off of 4 or higher to indicate JH. Chart data were collected to examine the age and type of onset of ME/CFS, and the presence of comorbid conditions. The impact on quality of life was assessed through questionnaires that included the Peds QL, Functional Disability Inventory, Peds QL Multidimensional Fatigue Scale, and Anxiety Subscale of the Symptom Checklist 90.

Results: There was no significant difference between groups in mean (SD) age at onset of ME/CFS (13.3 [3.3] years vs 13.3 [2.3] years; P = .92), sex, frequency, and severity of ME/CFS symptoms, orthostatic intolerance symptoms, or comorbid conditions. There was no significant difference between groups in measures of health-related quality of life using a Beighton score cut-off of 4 or a cut-off of 5 to define joint hypermobility.

Conclusions: Despite being a risk factor for the development of ME/CFS, JH as defined in this study was not associated with other clinical characteristics of the illness.

Source: Vogel SK, Primavera IR, Marden CL, Jasion SE, Cranston EM, Flaherty MAK, Violand RL, Rowe PC. The Presentation of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Is Not Influenced by the Presence or Absence of Joint Hypermobility. J Pediatr. 2021 Sep 16:S0022-3476(21)00887-8. doi: 10.1016/j.jpeds.2021.09.014. Epub ahead of print. PMID: 34537220. https://pubmed.ncbi.nlm.nih.gov/34537220/

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