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

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)

Onset Patterns and Course of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Background: Epidemiologic studies of myalgic encephalomyelitis/ chronic fatigue syndrome (ME/CFS) have examined different aspects of this disease separately but few have explored them together.

Objective: Describe ME/CFS onset and course in one United States-based cohort.

Methods: One hundred and fifty subjects fitting Fukuda 1994 CFS criteria completed a detailed survey concerning the initial and subsequent stages of their illness. Descriptive statistics, graphs, and tables were used to illustrate prevalence and patterns of characteristics.

Results: The most common peri-onset events reported by subjects were infection-related episodes (64%), stressful incidents (39%), and exposure to environmental toxins (20%). For 38% of subjects, more than 6 months elapsed from experiencing any initial symptom to developing the set of symptoms comprising their ME/CFS. Over time, the 12 most common symptoms persisted but declined in prevalence, with fatigue, unrefreshing sleep, exertion-related sickness, and flu-like symptoms declining the most (by 20–25%). Conversely, cognitive symptoms changed the least in prevalence, rising in symptom ranking. Pregnancy, menopause, and menstrual cycles exacerbated many women’s symptoms. Fatigue-related function was not associated with duration of illness or age; during the worst periods of their illness, 48% of subjects could not engage in any productive activity. At the time of survey, 47% were unable to work and only 4% felt their condition was improving steadily with the majority (59%) describing a fluctuating course. Ninety-seven percent suffered from at least one other illness: anxiety (48%), depression (43%), fibromyalgia (39%), irritable bowel syndrome (38%), and migraine headaches (37%) were the most diagnosed conditions. Thirteen percent came from families where at least one other first-degree relative was also afflicted, rising to 27% when chronic fatigue of unclear etiology was included.

Conclusions: This paper offers a broad epidemiologic overview of one ME/CFS cohort in the United States. While most of our findings are consistent with prior studies, we highlight underexamined aspects of this condition (e.g., the evolution of symptoms) and propose new interpretations of findings. Studying these aspects can offer insight and solutions to the diagnosis, etiology, pathophysiology, and treatment of this condition.

Source: Lily Chu, Ian J. Valencia, Donn W. Garvert and Jose G. Montoya. Onset Patterns and Course of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Front. Pediatr., 05 February 2019. https://doi.org/10.3389/fped.2019.00012  https://www.frontiersin.org/articles/10.3389/fped.2019.00012/full (Full article)

Onset Patterns of Chronic Fatigue Syndrome and Myalgic Encephalomyelitis: A Mixed Method Approach

Abstract:

The onset of Chronic fatigue syndrome (CFS) and Myalgic Encephalomyelitis (ME) is considered a key area of inquiry. Case criteria for ME and CFS and much of the academic literature suggest that patients typically experience one of two possible onset patterns: sudden or gradual. The current study provided an in-depth investigation of ME and CFS onset in order to provide insight into early symptoms, onset duration, and the progression of functional disability. We collected qualitative descriptive data to gain a rich description of illness onset from the patients’ point of view.

Overall, qualitative findings revealed detailed descriptions of ME and CFS onset experiences. Major themes that emerged from the data included: onset/illness progression patterns, illness causes, methods of adapting and coping, hardworking and active lives prior to onset, healthy lives prior to onset, prior health problems, comorbid health conditions, emotional responses to onset, exertional effects, the illness as life limiting, stress, traumatic experiences, lack of support, support, and treatment limitations. A closer examination of the onset/illness progression patterns that emerged from the data provided evidence that individuals with ME and CFS experience complex onset patterns.

Furthermore, the study findings suggest that the method of categorizing individuals into sudden versus gradual onset groups fails to capture the more nuanced and varied onset experiences. Prospective research studies that capture the onset period as it is developing could lead to improvements in the way we define and assess ME and CFS onset, and may also lead to methods for early detection, prevention, and individualized treatment approaches.

Source: Meredyth Anne Evans & Leonard A. Jason. Onset Patterns of Chronic Fatigue Syndrome and Myalgic Encephalomyelitis: A Mixed Method Approach. Res Chron Dis (2018) 2(1), 001–0030 (Full article)

Birth order and its association with the onset of chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is a medically unexplained illness that is diagnosed on the basis of a clinical case definition; so it probably is an illness with multiple causes producing the same clinical picture. One way of dealing with this heterogeneity is to stratify patients based on illness onset. We hypothesized that either the whole group of CFS patients or that group which developed CFS gradually would show a relation with birth order, while patients who developed CFS suddenly, probably due to a viral illness, would not show such a relation. We hypothesized the birth order effect in the gradual onset group because those patients have more psychological problems, and birth order effects have been shown for psychological characteristics.

We compared birth order in our CFS patients to that in a comparison group derived from U.S. demographic data. We found a tendency that did not reach formal statistical significance for a birth order effect in the gradual onset group, but not in either the sudden onset or combined total group. However, the birth order effect we found was due to relatively increased rates of CFS in second-born children; prior birth order studies of personality characteristics have found such effects to be skewed toward first-born children. Thus, our data do support a birth order effect in a subset of patients with CFS. The results of this study should encourage a larger multicenter study to further explore and understand this relation.

Comment in: Response to Brimacombe et al., birth order and its association with the onset of chronic fatigue syndrome. [Hum Biol. 2003]

 

Source: Brimacombe M, Helmer DA, Natelson BH. Birth order and its association with the onset of chronic fatigue syndrome. Hum Biol. 2002 Aug;74(4):615-20. http://www.ncbi.nlm.nih.gov/pubmed/12371687

 

Longitudinal analysis of symptoms reported by patients with chronic fatigue syndrome

Abstract:

PURPOSE: To determine the effect of chronic fatigue syndrome (CFS) illness duration and onset type on the likelihood of reporting a symptom during successive follow-up periods.

METHODS: In 1997, a two-phase RDD survey in Wichita, Kansas, was conducted to estimate the prevalence of CFS. Phase I identified 56,154 respondents 18-69 years of age and screened for severe fatigue, extreme tiredness or exhaustion lasting for 1 month or longer. In phase II an equal number of fatigued (n = 7,176) and randomly selected non-fatigued subjects were asked about 8 CFS and 13 non-CFS symptoms, as well as the presence of specific medical and psychiatric conditions. Eligible respondents were clinically evaluated to establish CFS diagnosis. Phase II respondents were re-contacted at 12- (n = 4,331) and 24-months (n = 4,266) for additional follow-up and diagnosis. In this study we considered symptoms reported as being present most of the time during each successive observation period. Generalized estimating equations were used to model symptoms over time and to address study questions. Such a model accounts for correlations among repeated symptoms for each subject. We used an auto-regressive structure for the correlation matrix, assuming the correlations between each pair of repeated symptoms should decrease as the time between symptoms increased.

RESULTS: There were 74 CFS patients who had been ill for 1 to 20 years (median = 6.3 years). Among these, 46 reported gradual and 28 reported sudden onset. Symptoms fluctuated over the course of illness. However, only stomach pain (non-CFS symptom) was more likely to be reported as duration of illness increased (p < 0.05). There was no association between onset type and the likelihood of reporting a symptom during an interview, except that chills and severe headaches were more likely to be reported by sudden cases.

CONCLUSIONS: The likelihood of expressing CFS and non-CFS symptom “most of the time” is the same across years of illness. More analyses are warranted to consider expression of symptoms for >/=6 months and severe symptoms.

 

Source: Nisenbaum R, Jones A, Jones J, Reeves W. Longitudinal analysis of symptoms reported by patients with chronic fatigue syndrome. Ann Epidemiol. 2000 Oct 1;10(7):458. http://www.ncbi.nlm.nih.gov/pubmed/11018368

 

Sudden vs gradual onset of chronic fatigue syndrome differentiates individuals on cognitive and psychiatric measures

Abstract:

To examine the influence of mode of illness onset on psychiatric status and neuropsychological performance, 36 patients with CFS were divided into two groups: sudden vs gradual onset of symptoms.

These two CFS subgroups were compared to each other and to sedentary healthy controls on standardized neuropsychological tests of attention/concentration, information processing efficiency, memory, and higher cortical functions. In addition, the distribution of comorbid Axis I psychiatric disease between the two CFS groups was examined.

The rate of concurrent psychiatric disease was significantly greater in the CFS-gradual group relative to the CFS-sudden group. While both CFS groups showed a significant reduction in information processing ability relative to controls, impairment in memory was more severe in the CFS-sudden group. Because of the significant heterogeneity of the CFS population, the need for subgroup analysis is discussed.

 

Source: DeLuca J, Johnson SK, Ellis SP, Natelson BH. Sudden vs gradual onset of chronic fatigue syndrome differentiates individuals on cognitive and psychiatric measures. J Psychiatr Res. 1997 Jan-Feb;31(1):83-90. http://www.ncbi.nlm.nih.gov/pubmed/9201650

 

Chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) has emerged as a public health concern over the past decade. A working case definition was created in 1988 and revised in 1994, and this has been used to establish prevalence estimates using physician-based surveillance and an a random digit dial telephone survey. Although CFS has some characteristics of an infectious disease, so far no infectious agent has been associated with the illness. Studies of immune function in CFS patients failed to detect differences between cases and healthy controls. However, when cases were subgrouped according to whether they had a sudden or gradual onset, differences in immunologic markers were detected between cases and their matched controls.

 

Source: Mawle AC. Chronic fatigue syndrome. Immunol Invest. 1997 Jan-Feb;26(1-2):269-73. http://www.ncbi.nlm.nih.gov/pubmed/9037629

 

Immune responses associated with chronic fatigue syndrome: a case-control study

Abstract:

An exploratory case-control study was conducted to assess whether the many reported differences in the immune function of chronic fatigue syndrome (CFS) patients are detectable in rigorously defined cases of CFS. Although many studies have reported differences between cases and controls in various measures of immune function, none of these differences were found in all studies.

In this study, no differences were found in white blood cell numbers; immune complex, complement, or serum immunoglobulin levels; delayed type hypersensitivity and allergic responses; NK cell function; and proliferative responses to mitogens and antigens. Marginal differences were detected in cytokine responses and in cell surface markers in the total CFS population.

However, when the patients were subgrouped by type of disease onset (gradual or sudden) or by how well they were feeling on the day of testing, more pronounced differences were seen

 

Source: Mawle AC, Nisenbaum R, Dobbins JG, Gary HE Jr, Stewart JA, Reyes M, Steele L, Schmid DS, Reeves WC. Immune responses associated with chronic fatigue syndrome: a case-control study. J Infect Dis. 1997 Jan;175(1):136-41. http://jid.oxfordjournals.org/content/175/1/136.long (Full article)