Long COVID Patient Symptoms and its Evaluation and Management

Abstract:

While the acute case burdens and deaths from the COVID-19 pandemic (in Nepal approaching 700,000 and 10,000 respectively) have been costly, the characteristics and potentially huge dimensions of the chronic disease sequelae of this infectious disease are only slowly becoming apparent. We reviewed Pub Med, major medical meeting and medical journal, and investigative journalist materials seeking to frame and describe COVID-19 chronic disease.

The consequences of COVID-19 infections follow major organ damage, and induction of immunological and hormonal systems dysfunction. The first injuries are consequent to direct viral effects on tissues, and vasculitis, endothelialitis, thrombosis and inflammatory events. Pulmonary, cardiac, brain, and kidney tissues incur function-limiting damage, with dyspnea, arrythmias, decreased exercise capacity, cognitive dysfunction, and decreased glomerular filtration rates.

The second process is characterized by immune dysregulation and autoimmunity, and dysfunction of hormonal regulation systems, with high, fluctuating levels of physical and mental fatigue, multiple-site pain and ache, and non-restorative sleep, in 10-30% of cases.

This communication proposes evaluation and management of chronic COVID-19 patients with efficient assessment of commonest symptoms, targeted physical examination and organ function testing, and interventions based on specific organ functional status, and experience with similar chronic immune syndromes, such as myalgic encephalomyelitis.

Source: Sundar Shrestha D, Love R. Long COVID Patient Symptoms and its Evaluation and Management. JNMA J Nepal Med Assoc. 2021 Aug 12;59(240):823-831. doi: 10.31729/jnma.6355. PMID: 34508486. https://pubmed.ncbi.nlm.nih.gov/34508486/

COVID-19 symptoms over time: comparing long-haulers to ME/CFS

Abstract:

Introduction: Our objective was to determine which symptoms among long-hauler COVID-19 patients change over time, and how their symptoms compare to another chronic illness group.

Methods: 278 long-haulers completed two symptom questionnaires at one time point, with one recounting experiences during the first two weeks of their illness, an average of 21.7 weeks prior. We used a comparison group of 502 patients diagnosed with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Participants completed a standardized symptom questionnaire and a list of additional CDC COVID-19 symptoms.

Results: Over time, the long-haulers reported an overall reduction of most symptoms including unrefreshing sleep and post-exertional malaise, but an intensification of neurocognitive symptoms. When compared to ME/CFS, the COVID-19 sample was initially more symptomatic for the immune and orthostatic domains but over time, the long-haulers evidenced significantly less severe symptoms than those with ME/CFS, except in the orthostatic domain. Among the COVID-19 long haulers, several neurocognitive symptoms got worse over time, whereas improvements occurred in most other areas.

Conclusions: These types of differential patterns of symptoms over time might contribute to helping better understand the pathophysiology of those reporting prolonged illness following COVID-19.

Source: Leonard A. Jason, Mohammed F. Islam, Karl Conroy, Joseph Cotler, Chelsea Torres, Mady Johnson & Brianna Mabie (2021) COVID-19 symptoms over time: comparing long-haulers to ME/CFS, Fatigue: Biomedicine, Health & Behavior, DOI: 10.1080/21641846.2021.1922140 https://www.tandfonline.com/doi/full/10.1080/21641846.2021.1922140

Exploratory study into the relationship between the symptoms of chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (ME) and fibromyalgia (FM) using a quasiexperimental design

Abstract:

Objective: To explore the relationship between symptoms of chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (ME) and fibromyalgia (FM). The hypothesis predicated that there would be no significant differences between the group’s symptom experience.

Design: A quasiexperimental design. Structural equation modelling (SEM) and invariance testing.

Participants: Males (M) and females (F) >16 with a confirmed diagnosis of CFS/ME or FM by a general practitioner or specialist. CFS/ME (n=101, F: n=86, M: n=15, mean (M) age M=45.5 years). FM (n=107, F: n=95, M: n=12, M=47.2 years).

Outcome measures: Diagnostic criteria: the American Centers for Disease Control and Prevention (CDC) for CFS/ME and the American College of Rheumatology (ACR) criteria for FM. Additional symptom questionnaires measuring: pain, sleep quality, fatigue, quality of life, anxiety and depression, locus of control and self-esteem.

Results: Invariance was confirmed with the exception of the American CDC Symptom Inventory, Fibromyalgia Impact Questionnaire and Hospital Anxiety and Depression Scale (p<0.05) based on five questions. Consequently, it was erroneous to conclude differences. Therefore, the Syndrome Model was created. SEM could not have tested the ACR previously, as it comprised a single data point. Thus, it was combined with these three questionnaires, increasing the data points, to create this new measurable model. Results confirmed no significant differences between groups (p=0.07 (p<0.05)).

Conclusion: Participants responded in a similar manner to the questionnaire, confirming the same symptom experience. It is important to consider this in context with differing criteria and management guidelines, as this may influence diagnosis and the trajectory of patient’s management. With the biomedical cause currently unclear, it is the symptom experience and the impact on quality of life that is important. These findings are meaningful for patients, clinicians and policy development and support the requirement for future research.

Source: Mckay PG, Walker H, Martin CR, Fleming M. Exploratory study into the relationship between the symptoms of chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (ME) and fibromyalgia (FM) using a quasiexperimental design. BMJ Open. 2021 Feb 1;11(2):e041947. doi: 10.1136/bmjopen-2020-041947. PMID: 33526500. https://bmjopen.bmj.com/content/11/2/e041947.long (Full text)

Treatment Avenues in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Split-gender Pharmacogenomic Study of Gene-expression Modules

Abstract:

PURPOSE: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating multisymptom illness impacting up to 1 million people in the United States. As the pathogenesis and etiology of this complex condition are unclear, prospective treatments are limited. Identifying US Food and Drug Administration-approved drugs that may be repositioned as treatments for ME/CFS may offer a rapid and cost-effective solution.

METHODS: Here we used gene-expression data from 33 patients with Fukuda-defined ME/CFS (23 females, 10 males) and 21 healthy demographically comparable controls (15 females, 6 males) to identify differential expression of predefined gene-module sets based on nonparametric statistics. Differentially expressed gene modules were then annotated via over-representation analysis using the Consensus Pathway database. Differentially expressed modules were then regressed onto measures of fatigue and cross-referenced with drug atlas and pharmacogenomics databases to identify putative treatment agents.

FINDINGS: The top 1% of modules identified in males indicated small effect sizes in modules associated with immune regulation and mitochondrial dysfunction. In females, modules identified included those related to immune factors and cardiac/blood factors, returning effect sizes ranging from very small to intermediate (0.147 < Cohen δ < 0.532). Regression analysis indicated that B-cell receptors, T-cell receptors, tumor necrosis factor α, transforming growth factor β, and metabolic and cardiac modules were strongly correlated with multiple composite measures of fatigue. Cross-referencing identified genes with pharmacogenomics data indicated immunosuppressants as potential treatments of ME/CFS symptoms.

IMPLICATIONS: The findings from our analysis suggest that ME/CFS symptoms are perpetuated by immune dysregulation that may be approached via immune modulation-based treatment strategies. (Clin Ther. 2019;41:XXX-XXX) © 2019 Elsevier Inc.

Copyright © 2019. Published by Elsevier Inc.

Source: Jeffrey MG, Nathanson L, Aenlle K, Barnes ZM, Baig M, Broderick G, Klimas NG, Fletcher MA, Craddock TJA. Treatment Avenues in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Split-gender Pharmacogenomic Study of Gene-expression Modules. Clin Ther. 2019 Mar 6. pii: S0149-2918(19)30047-5. doi: 10.1016/j.clinthera.2019.01.011. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/30851951

Examining case definition criteria for chronic fatigue syndrome and myalgic encephalomyelitis

Abstract:

BACKGROUND: Considerable controversy has transpired regarding the core features of myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS). Current case definitions differ in the number and types of symptoms required. This ambiguity impedes the search for biological markers and effective treatments.

PURPOSE: This study sought to empirically operationalize symptom criteria and identify which symptoms best characterize the illness.

METHODS: Patients (n=236) and controls (n=86) completed the DePaul Symptom Questionnaire, rating the frequency and severity of 54 symptoms. Responses were compared to determine the threshold of frequency/severity ratings that best distinguished patients from controls. A Classification and Regression Tree (CART) algorithm was used to identify the combination of symptoms that most accurately classified patients and controls.

RESULTS: A third of controls met the symptom criteria of a common CFS case definition when just symptom presence was required; however, when frequency/severity requirements were raised, only 5% met criteria. Employing these higher frequency/severity requirements, the CART algorithm identified three symptoms that accurately classified 95.4% of participants as patient or control: fatigue/extreme tiredness, inability to focus on multiple things simultaneously, and experiencing a dead/heavy feeling after starting to exercise.

CONCLUSIONS: Minimum frequency/severity thresholds should be specified in symptom criteria to reduce the likelihood of misclassification. Future research should continue to seek empirical support of the core symptoms of ME and CFS to further progress the search for biological markers and treatments.

 

Source: Jason LA, Sunnquist M, Brown A, Evans M, Vernon SD, Furst J, Simonis V. Examining case definition criteria for chronic fatigue syndrome and myalgic encephalomyelitis. Fatigue. 2014 Jan 1;2(1):40-56. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3912876/ (Full article)

 

Symptom occurrence in persons with chronic fatigue syndrome

Abstract:

This investigation compared differences in the occurrence of symptoms in participants with CFS, melancholic depression, and no fatigue (controls). The following Fukuda et al. [Ann. Intern. Med. 121 (1994) 953] criteria symptoms differentiated the CFS group from controls, but did not differentiate the melancholic depression group from controls: headaches, lymph node pain, sore throat, joint pain, and muscle pain. In addition, participants with CFS uniquely differed from controls in the occurrence of muscle weakness at multiple sites as well as in the occurrence of various cardiopulmonary, neurological, and other symptoms not currently included in the current case definition. Implications of these findings are discussed.

 

Source: Jason LA, Torres-Harding SR, Carrico AW, Taylor RR. Symptom occurrence in persons with chronic fatigue syndrome. Biol Psychol. 2002 Feb;59(1):15-27. http://www.ncbi.nlm.nih.gov/pubmed/11790441

 

Co-existence of chronic fatigue syndrome with fibromyalgia syndrome in the general population. A controlled study

Abstract:

OBJECTIVE: To determine the proportion of adults with fibromyalgia syndrome (FMS) in the general population who also meet the 1988 Centre for Disease Control (CDC) criteria for chronic fatigue syndrome (CFS).

METHODS: Seventy-four FMS cases were compared with 32 non-FMS controls with widespread pain and 23 with localized pain, all recruited in a general population survey.

RESULTS: Among females, 58.0% of fibromyalgia cases met the full criteria for CFS, compared to 26.1% and 12.5% of controls with widespread and localized pain, respectively (p=0.0006). Male percentages were 80.0, 22.2, and zero, respectively (p=0.003). Compared to those with FMS alone, those meeting the case definitions for both FMS and CFS reported a worse course, worse overall health, more dissatisfaction with health, more non-CFS symptoms, and greater disease impact. The number of total symptoms and non-CFS symptoms were the best predictors of co-morbid CFS.

CONCLUSIONS: There is significant clinical overlap between CFS and FMS.

 

Source: White KP, Speechley M, Harth M, Ostbye T. Co-existence of chronic fatigue syndrome with fibromyalgia syndrome in the general population. A controlled study. Scand J Rheumatol. 2000;29(1):44-51. http://www.ncbi.nlm.nih.gov/pubmed/10722257

 

Monitoring and assessing symptoms of chronic fatigue syndrome: use of time series regression

Abstract:

Chronic Fatigue Syndrome’s principal symptoms are severe and include prolonged fatigue and a number of other minor symptoms. Behavioral data collection methods were used in a case study to show some of the benefits that can be derived from monitoring symptoms hourly and daily. Using time series regression, several statistically significant correlates of fatigue were found both within days and between days. Perceived energy, physical exertion, and mental exertion were significantly related to fatigue in both analyses. Collection of such data may help resolve a number of theoretical and methodological problems in research on the Chronic Fatigue Syndrome.

 

Source: Jason LA, Tryon WW, Taylor RR, King C, Frankenberry EL, Jordan KM. Monitoring and assessing symptoms of chronic fatigue syndrome: use of time series regression. Psychol Rep. 1999 Aug;85(1):121-30. http://www.ncbi.nlm.nih.gov/pubmed/10575979

 

Correlates of somatic causal attributions in primary care patients with fatigue

Abstract:

Researchers in the field of chronic fatigue in tertiary care found that patients’ somatic (e.g. viral) explanations for their condition may lead to chronicity of symptoms. We studied the influence of a somatic attributional bias on outcome and reported symptoms in primary care patients with fatigue.

We compared fatigue scores on a specific scale, and number of presented symptoms, in two groups of primary care patients with ‘functional’ fatigue: 75 with a high score on the somatic subscale of the Fatigue Attribution Scale (S-FAS), and 95 with a low score on the S-FAS. At the index visit, patients with low and high scores on the S-FAS were not different for age, sex, fatigue scores, and levels of depressive symptoms.

Patients with high scores on the S-FAS presented significantly more somatic and psychological symptoms-a total of 36 symptoms for 24 patients (25.3%) in the low-score group, and a total of 52 symptoms for 31 patients (41.3%) in the high-score group.

Forty-two days later, at the follow-up visit, the fatigue scores were similar in both groups. In primary care patients with fatigue not due to somatic illness or major depression, the tendency to attribute fatigue to somatic causes is not associated with a worse outcome, but with a higher number of reported symptoms.

 

Source: Cathébras P, Jacquin L, le Gal M, Fayol C, Bouchou K, Rousset H. Correlates of somatic causal attributions in primary care patients with fatigue. Psychother Psychosom. 1995;63(3-4):174-80. http://www.ncbi.nlm.nih.gov/pubmed/7624463

 

Chronic fatigue syndrome–symptoms, signs, laboratory tests, and prognosis

Abstract:

Chronic fatigue syndrome (CFS) is an undefined clinical problem and is perceived as a complex of multiple symptomatology with an unexplained persistent fatigue. Major symptoms include fatigue lasting for more than 6 months, low-grade fever, moderate lymphadenopathy, muscle and joint pain, and various psychological presentations. Since no specific laboratory tests are available, clinical diagnosis demands that known causes of chronic fatigue should be excluded. The pathogenesis is at present unknown, but it is suspected that CFS is a physical and psychological condition associated with some unrecognized infectious agent. Further study is needed to clarify the precise pathophysiology of this newly recognized entity.

 

Source: Kanayama Y. Chronic fatigue syndrome–symptoms, signs, laboratory tests, and prognosis. Nihon Rinsho. 1992 Nov;50(11):2586-90. [Article in Japanese] http://www.ncbi.nlm.nih.gov/pubmed/1287234