Who has long-COVID? A big data approach

Abstract:

Background Post-acute sequelae of SARS-CoV-2 infection (PASC), otherwise known as long-COVID, have severely impacted recovery from the pandemic for patients and society alike. This new disease is characterized by evolving, heterogeneous symptoms, making it challenging to derive an unambiguous long-COVID definition. Electronic health record (EHR) studies are a critical element of the NIH Researching COVID to Enhance Recovery (RECOVER) Initiative, which is addressing the urgent need to understand PASC, accurately identify who has PASC, and identify treatments.

Methods Using the National COVID Cohort Collaborative’s (N3C) EHR repository, we developed XGBoost machine learning (ML) models to identify potential long-COVID patients. We examined demographics, healthcare utilization, diagnoses, and medications for 97,995 adult COVID-19 patients. We used these features and 597 long-COVID clinic patients to train three ML models to identify potential long-COVID patients among (1) all COVID-19 patients, (2) patients hospitalized with COVID-19, and (3) patients who had COVID-19 but were not hospitalized.

Findings Our models identified potential long-COVID patients with high accuracy, achieving areas under the receiver operator characteristic curve of 0.91 (all patients), 0.90 (hospitalized); and 0.85 (non-hospitalized). Important features include rate of healthcare utilization, patient age, dyspnea, and other diagnosis and medication information available within the EHR. Applying the “all patients” model to the larger N3C cohort identified 100,263 potential long-COVID patients.

Interpretation Patients flagged by our models can be interpreted as “patients likely to be referred to or seek care at a long-COVID specialty clinic,” an essential proxy for long-COVID diagnosis in the current absence of a definition. We also achieve the urgent goal of identifying potential long-COVID patients for clinical trials. As more data sources are identified, the models can be retrained and tuned based on study needs.

Source: Pfaff ER, Girvin AT, Bennett TD, Bhatia A, Brooks IM, Deer RR, Dekermanjian JP, Jolley SE, Kahn MG, Kostka K, McMurry JA, Moffitt R, Walden A, Chute CG, Haendel MA, The N3C Consortium. (2021). Who has long-COVID? A big data approach [preprint]. UMass Center for Clinical and Translational Science Supported Publications. https://doi.org/10.1101/2021.10.18.21265168. Retrieved from https://escholarship.umassmed.edu/umccts_pubs/253

Nationwide epidemiological characteristics of chronic fatigue syndrome in South Korea

Abstract:

Background: Chronic fatigue syndrome (CFS) is a long-term disabling illness accompanied by medically unexplained fatigue. This study aimed to explore the epidemiological characteristics of CFS in South Korea.

Methods: Using the nationwide medical records provided by the Korean Health Insurance Review & Assessment Service (HIRA), we analyzed the entire dataset for CFS patients diagnosed by physicians in South Korea from January 2010 to December 2020.

Results: The annual mean incidence of CFS was estimated to be 44.71 ± 6.10 cases per 100,000 individuals [95% CI: 40.57, 48.76], and the prevalence rate was 57.70 ± 12.20 cases per 100,000 individuals [95% CI: 49.40, 65.79]. These two rates increased by 1.53- and 1.94-fold from 2010 to 2020, respectively, and showed an increasing trend with aging and an approximately 1.5-fold female predominance.

Conclusions: This study is the first to report the nationwide epidemiological features of CFS, which reflects the clinical reality of CFS diagnosis and care in South Korea. This study will be a valuable reference for studies of CFS in the future.

Source: Lim EJ, Lee JS, Lee EJ, Jeong SJ, Park HY, Ahn YC, Son CG. Nationwide epidemiological characteristics of chronic fatigue syndrome in South Korea. J Transl Med. 2021 Dec 7;19(1):502. doi: 10.1186/s12967-021-03170-0. PMID: 34876158. https://pubmed.ncbi.nlm.nih.gov/34876158/

Systematic Review of the Epidemiological Burden of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Across Europe: Current Evidence and EUROMENE Research Recommendations for Epidemiology

Abstract:

This review aimed at determining the prevalence and incidence of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) in Europe. We conducted a primary search in Scopus, PubMed and Web of Science for publications between 1994 and 15 June 2019 (PROSPERO: CRD42017078688). Additionally, we performed a backward-(reference lists) and forward-(citations) search of the works included in this review. Grey literature was addressed by contacting all members of the European Network on ME/CFS (EUROMENE). Independent reviewers searched, screened and selected studies, extracted data and evaluated the methodological and reporting quality. For prevalence, two studies in adults and one study in adolescents were included. Prevalence ranged from 0.1% to 2.2%. Two studies also included incidence estimates.

In conclusion, studies on the prevalence and incidence of ME/CFS in Europe were scarce. Our findings point to the pressing need for well-designed and statistically powered epidemiological studies. To overcome the shortcomings of the current state-of-the-art, EUROMENE recommends that future research is better conducted in the community, reviewing the clinical history of potential cases, obtaining additional objective information (when needed) and using adequate ME/CFS case definitions; namely, the Centers for Disease Control & Prevention−1994, Canadian Consensus Criteria, or Institute of Medicine criteria

Source: Estévez-López F, Mudie K, Wang-Steverding X, et al. Systematic Review of the Epidemiological Burden of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Across Europe: Current Evidence and EUROMENE Research Recommendations for Epidemiology. J Clin Med. 2020;9(5):E1557. Published 2020 May 21. doi:10.3390/jcm9051557 (Full article) https://www.mdpi.com/2077-0383/9/5/1557

Systematic review and meta-analysis of the prevalence of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME)

Abstract:

BACKGROUND: Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) has been emerging as a significant health issue worldwide. This study aimed to systemically assess the prevalence of CFS/ME in various aspects of analyses for precise assessment.

METHODS: We systematically searched prevalence of CFS/ME from public databases from 1980 to December 2018. Data were extracted according to 7 categories for analysis: study participants, gender and age of the participants, case definition, diagnostic method, publication year, and country of the study conducted. Prevalence data were collected and counted individually for studies adopted various case definitions. We analyzed and estimated prevalence rates in various angles: average prevalence, pooled prevalence and meta-analysis of all studies.

RESULTS: A total of 1291 articles were initially identified, and 45 articles (46 studies, 56 prevalence data) were selected for this study. Total 1085,976 participants were enrolled from community-based survey (540,901) and primary care sites (545,075). The total average prevalence was 1.40 ± 1.57%, pooled prevalence 0.39%, and meta-analysis 0.68% [95% CI 0.48-0.97]. The prevalence rates were varied by enrolled participants (gender, study participants, and population group), case definitions and diagnostic methods. For example, in the meta-analysis; women (1.36% [95% CI 0.48-0.97]) vs. men (0.86% [95% CI 0.48-0.97]), community-based samples (0.76% [95% CI 0.53-1.10]) vs. primary care sites (0.63% [95% CI 0.37-1.10]), adults ≥ 18 years (0.65% [95% CI 0.43-0.99]) vs. children and adolescents < 18 years (0.55% [95% CI 0.22-1.35]), CDC-1994 (0.89% [95% CI 0.60-1.33]) vs. Holmes (0.17% [95% CI 0.06-0.49]), and interviews (1.14% [95% CI 0.76-1.72]) vs. physician diagnosis (0.09% [95% CI 0.05-0.13]), respectively.

CONCLUSIONS: This study comprehensively estimated the prevalence of CFS/ME; 0.89% according to the most commonly used case definition CDC-1994, with women approximately 1.5 to 2 folds higher than men in all categories. However, we observed the prevalence rates are widely varied particularly by case definitions and diagnostic methods. An objective diagnostic tool is urgently required for rigorous assessment of the prevalence of CFS/ME.

Source: Lim EJ, Ahn YC, Jang ES, Lee SW, Lee SH, Son CG. Systematic review and meta-analysis of the prevalence of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). J Transl Med. 2020 Feb 24;18(1):100. doi: 10.1186/s12967-020-02269-0. https://www.ncbi.nlm.nih.gov/pubmed/32093722

Prevalence and characteristics of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) in Poland: a cross-sectional study

Abstract:

OBJECTIVES: The aim of this study was to estimate the prevalence of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) and describe illness characteristics in a community population in Poland.

DESIGN: cross-sectional study.

SETTING: Poland.

PARTICIPANTS: Of the cohort of 1400 who self-presented with fatigue only 69 subsequently were confirmed as having CFS/ME using the Fukuda criteria.

MAIN OUTCOME MEASURES: Participants completed the following screening symptom assessment tools: Chalder Fatigue Scale, Hospital Anxiety and Depression Scale (HADS), Epworth Sleepiness Scale (ESS), Composite Autonomic Symptom Score 31 (COMPASS 31), Quality of Life Scale (QOLS). Haemodynamic and autonomic parameters were automatically measured at rest with a Task Force Monitor.

RESULTS: In 1308, from 1400 (93%) individuals who identified themselves as fatigued, recognised chronic conditions were identified, for example, neurological (n=280, 21.5%), neurodegenerative (n=200, 15%), psychiatric (n=654, 50%) and immunologic (n=174, 13.5%) disorders. The remaining 69 participants (mean age 38.3±8.5) met the Fukuda defintion for CFS/ME and had baseline objective assessment. The majority had experienced symptoms for over 2 years with 37% having symptoms for 2-5 years and 21.7% for more than 10 years. The COMPASS 31 indicated that 50% have symptoms consistent with orthostatic intolerance. About 43/69 (62%) had Epworth sleepiness scores ≥10, ie, consistent with excessive daytime sleepiness, 26/69 (38%) had significant anxiety and 22/69 (32%) depression measured by HADS A & D. Quality of life is significantly impaired in those with Fukuda criteria CFS (QLS score 64±11) with significant negative relationships between quality of life and fatigue (p<0.0001), anxiety (p=0.0009), depression (p<0.0001) and autonomic symptoms (p=0.04).

CONCLUSION: This is the first study to summarise illness characteristics of Polish CFS/ME patients. Our study has confirmed that fatigue is a common and under-recognised symptom affecting the Polish population.

Source: Słomko J, Newton JL, Kujawski S, Tafil-Klawe M, Klawe J, Staines D, Marshall-Gradisnik S, Zalewski P. Prevalence and characteristics of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) in Poland: a cross-sectional study. BMJ Open. 2019 Mar 7;9(3):e023955. doi: 10.1136/bmjopen-2018-023955. https://bmjopen.bmj.com/content/9/3/e023955.long (Full study)

Chronic fatigue syndrome: study of a consecutive series of 824 cases assessed in two specialized units

Abstract:

BACKGROUND AND OBJECTIVE: The chronic fatigue syndrome (CFS) is a disabling disorder. Few studies are available in our area on the prevalence and characteristics of CFS. Therefore, we carried out a study of a consecutive series of 824 cases diagnosed in two specialized units.

PATIENTS AND METHODS: We evaluated all of the CFS patients seen from January 2008 to June 2010. We analyzed social and demographic data, employment status, time of clinical evolution, trigger factors and onset, Fukuda and Canadian criteria, associated comorbidities and treatment.

RESULTS: A total of 824 patients were included, 748 (91%) woman, mean age 48±9 years. Average age of onset of symptoms was 35±11 years, time to diagnosis 108±88 month. A precipitating factor was identified in 481 (58%) patients, the onset was gradual in 517 (63%) and 515 (62.5%) were not employed. The most outstanding diagnostic criteria of Fukuda were prolonged generalized fatigue after exercise, sleep disturbance and impairments in concentration and short-term memory. The different groups of symptoms defined by the Canadian consensus showed that CFS is a homogeneous entity. Accompanying comorbidity phenomena were anxiety 691 (83%), sicca syndrome 678 (82%), fibromyalgia 450 (55%). A total of 63% of patients (520) received pharmacological treatment.

CONCLUSIONS: CFS is an illness that preferentially affects young women and results in employment absenteeism. The most relevant clinical features were prolonged generalized fatigue after exercise, neurocognitive impairment and sleep disturbance. In the evaluation of the patient, it is very important to apply the Canadian criteria and to assess comorbidity.

Copyright © 2011 Elsevier España, S.L. All rights reserved.

Comment in: Chronic fatigue syndrome: current situation. [Rev Clin Esp. 2011]

 

Source: Ruiz E, Alegre J, García Quintana AM, Aliste L, Blázquez A, Fernández de Sevilla T. Chronic fatigue syndrome: study of a consecutive series of 824 cases assessed in two specialized units. Rev Clin Esp. 2011 Sep;211(8):385-90. doi: 10.1016/j.rce.2011.02.013. Epub 2011 Jul 27. [Article in Spanish] https://www.ncbi.nlm.nih.gov/pubmed/21794854

 

Epidemiology of chronic fatigue syndrome

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) is a controversial disorder with different case definitions, aetiological models and proposed treatments. An epidemiological approach is likely to bring some clarity to the field.

AIM: The aim of this article is to review the literature on the epidemiology of fatigue, chronic fatigue and CFS.

METHOD: A literature search was conducted using the databases Medline and Pubmed as well as the reference lists of recent reviews to identify the relevant studies. The aim was not to do a systematic review but to review the key studies in the area to highlight the methodological issues.

RESULTS: The review is organized according to the following areas: the prevalence of fatigue and chronic fatigue, the prevalence and incidence of CFS, epidemiological associations such as gender, social class and psychiatric co-morbidity and CFS in special groups such as those recovering from a viral infection, specific occupational groups and Gulf War veterans.

CONCLUSION: While fatigue as a symptom is very common, CFS is relatively rare. Many of the epidemiological associations seen in specialist clinics are not found in community samples. It is unlikely that one specific causal factor can explain CFS. Future studies should go beyond estimating the prevalence to testing more complex aetiological models.

 

Source: Ranjith G. Epidemiology of chronic fatigue syndrome. Occup Med (Lond). 2005 Jan;55(1):13-9. http://occmed.oxfordjournals.org/content/55/1/13.long (Full article)

 

Politics, science, and the emergence of a new disease. The case of chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) emerged as a diagnostic category during the last decade. Initial research suggested that CFS was a relatively rare disorder with a high level of psychiatric comorbidity. Many physicians minimized the seriousness of this disorder and also interpreted the syndrome as being equivalent to a psychiatric disorder. These attitudes had negative consequences for the treatment of CFS.

By the mid-1990s, findings from more representative epidemiological studies indicated considerably higher CFS prevalence rates. However, the use of the revised CFS case definition might have produced heterogeneous patient groups, possibly including some patients with pure psychiatric disorders.

Social scientists have the expertise to more precisely define this syndrome and to develop appropriate and sensitive research strategies for understanding this disease.

Comment in: The biopsychosocial model and chronic fatigue syndrome. [Am Psychol. 1998]

 

Source: Jason LA, Richman JA, Friedberg F, Wagner L, Taylor R, Jordan KM. Politics, science, and the emergence of a new disease. The case of chronic fatigue syndrome. Am Psychol. 1997 Sep;52(9):973-83. http://www.ncbi.nlm.nih.gov/pubmed/9301342

 

Chronic fatigue syndrome in young persons

Abstract:

The prevalence of chronic fatigue syndrome (CFS) in teenagers is 10-20 per 100,000 inhabitants in the Netherlands. The natural course of the disorder is not favourable according to the literature.

Proposed criteria for the diagnosis ‘CFS’ in adolescence are: absence of a physical explanation for the complaints, a disabling fatigue for at least six months and prolonged school absenteeism or severe motor and social disabilities. Exclusion criterion should be a psychiatric disorder.

Factors that attribute to the persistence of fatigue are somatic attributions, illness enhancing cognitions and behaviour of parents as well as physical inactivity. The role of the physician and the role of parents can enhance the problems.

The treatment should focus on decreasing the somatic attributions, on reinforcement by the parents of healthy adolescent behaviour, on the gradual increase of physical activity and on decreasing attention (including medical attention) for the somatic complaints.

 

Source: de Jong LW, Prins JB, Fiselier TJ, Weemaes CM, Meijer-van den Bergh EM, Bleijenberg G. Chronic fatigue syndrome in young persons. Ned Tijdschr Geneeskd. 1997 Aug 2;141(31):1513-6.[Article in Dutch] http://www.ncbi.nlm.nih.gov/pubmed/9543737

 

Managing chronic fatigue syndrome in children

Last month the British press made much of a study purporting to show that chronic fatigue syndrome was the single commonest cause of long term absence from school in Britain.1 The authors claimed to have calculated prevalence figures for both pupils (0.07%) and teachers (0.5%) similar to previously reported figures for the general population.2-4 Dowsett and Colby make much of “clusters” of cases, defined as three or more cases in a school. The press release distributed by one of the authors states that 39% of cases occurred in such clusters, saying that this “suggests that ME results from an infection.” It refers to one cluster extending over several schools in an area where there was “recreational water heavily polluted by sewage.” The published paper contains no reference to pollution by sewage or anything else, but only to several cases in “schools near two new towns in a rural environment alongside recreational water.”

You can read the full article here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2126833/pdf/9193280.pdf

Comment in:

Graded exercise in chronic fatigue syndrome. Including patients who rated themselves as a little better would have altered results. [BMJ. 1997]

Chronic fatigue syndrome in children. Journal was wrong to critizise study in schoolchildren. [BMJ. 1997]

Chronic fatigue syndrome in children. Patient organisations are denied a voice. [BMJ. 1997]

Comment on:

Randomised controlled trial of graded exercise in patients with the chronic fatigue syndrome. [BMJ. 1997]

 

Source: Marcovitch H. Managing chronic fatigue syndrome in children. BMJ. 1997 Jun 7;314(7095):1635-6. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2126833/pdf/9193280.pdf (Full article)