Co-occurrence of immune-mediated conditions and endometriosis among adolescents and adult women

Abstract:

Problem: Associations between immune dysfunction conditions (eg, systemic lupus erythematous, rheumatoid arthritis) and endometriosis have been observed in adult women, but not assessed among a younger population. We investigated the association between immune-mediated conditions and endometriosis among young women.

Method of study: This cross-sectional analysis in the Women’s Health Study: From Adolescence to Adulthood included 551 participants with surgically diagnosed endometriosis (median age=19) and 652 controls without endometriosis (median age=24). Participants completed an expanded Endometriosis Phenome and Biobanking Harmonization Project questionnaire. We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) to investigate the associations between autoimmune/inflammatory, atopic, chronic pain/fatigue, and endocrine disorders with endometriosis, adjusting for confounders.

Results: Participants with any autoimmune and/or inflammatory condition had an increased odds of co-occurring endometriosis (OR: 1.87; CI: 0.92-3.80), as did participants with allergies (OR: 1.76; CI: 1.32-2.36), asthma (OR: 1.35; CI: 0.97-1.88), chronic fatigue syndrome and/or fibromyalgia (OR: 5.81; CI: 1.89-17.9), or previous mononucleosis (OR: 1.75; CI: 1.14-2.68). Odds of endometriosis were lower among participants with eczema (OR: 0.68; CI: 0.44-1.04). We observed a positive trend between the number of immune-mediated conditions and the odds of endometriosis (p-trend=0.0002). Endocrine disorders were not associated with endometriosis.

Conclusions: Among this population of adolescents and adult women, endometriosis was more likely among participants with autoimmune and/or inflammatory diseases, allergies, asthma, previous mononucleosis infection, and chronic fatigue and/or fibromyalgia. We observed that an increasing number of immune-mediated conditions were positively associated with endometriosis risk. It is important for clinicians who care for adolescents and women with these conditions to consider endometriosis as a comorbidity.

Source: Shafrir AL, Palmor MC, Fourquet J, DiVasta AD, Farland LV, Vitonis AF, Harris HR, Laufer MR, Cramer DW, Terry KL, Missmer SA. Co-occurrence of immune-mediated conditions and endometriosis among adolescents and adult women. Am J Reprod Immunol. 2021 Feb 14:e13404. doi: 10.1111/aji.13404. Epub ahead of print. PMID: 33583078. https://pubmed.ncbi.nlm.nih.gov/33583078/

Sequelae in Adults at 6 Months After COVID-19 Infection

Abstract:

Introduction: Many individuals experience persistent symptoms and a decline in health-related quality of life (HRQoL) after coronavirus disease 2019 (COVID-19) illness.1 Existing studies have focused on hospitalized individuals 30 to 90 days after illness onset2-4 and have reported symptoms up to 110 days after illness.3 Longer-term sequelae in outpatients have not been well characterized.

Methods: A longitudinal prospective cohort of adults with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was enrolled at the University of Washington with a concurrent cohort of healthy patients in a control group (eAppendix in the Supplement). Electronic informed consent was obtained, and the study was approved by the University of Washington human participants institutional review board. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline. COVID-19 symptom data were obtained at the time of acute illness or retrospectively recounted at a 30-day enrollment visit. A total of 234 participants with COVID-19 were contacted between August and November 2020 to complete a single follow-up questionnaire between 3 and 9 months after illness onset. We did not perform statistical tests for this descriptive analysis because of the small numbers in each subgroup. Data analysis was conducted in R version 4.0.2 (R Project for Statistical Computing).

Results: A total of 177 of 234 participants (75.6%; mean [range] age, 48.0 [18-94] years; 101 [57.1%] women) with COVID-19 completed the survey. Overall, 11 (6.2%) were asymptomatic, 150 (84.7%) were outpatients with mild illness, and 16 (9.0%) had moderate or severe disease requiring hospitalization (Table). Hypertension was the most common comorbidity (23 [13.0%]). The follow-up survey was completed a median (range) of 169 (31-300) days after illness onset among participants with COVID-19 (Figure, A) and 87 (71-144) days after enrollment among 21 patients in the control group. Among participants with COVID-19, persistent symptoms were reported by 17 of 64 patients (26.6%) aged 18 to 39 years, 25 of 83 patients (30.1%) aged 40 to 64 years, and 13 of 30 patients (43.3%) aged 65 years and older. Overall, 49 of 150 outpatients (32.7%), 5 of 16 hospitalized patients (31.3%), and 1 of 21 healthy participants (4.8%) in the control group reported at least 1 persistent symptom. Of 31 patients with hypertension or diabetes, 11 (35.5%) experienced ongoing symptoms.

The most common persistent symptoms were fatigue (24 of 177 patients [13.6%]) and loss of sense of smell or taste (24 patients [13.6%]) (Figure, B). Overall, 23 patients (13.0%) reported other symptoms, including brain fog (4 [2.3%]). A total of 51 outpatients and hospitalized patients (30.7%) reported worse HRQoL compared with baseline vs 4 healthy participants and asymptomatic patients (12.5%); 14 patients (7.9%) reported negative impacts on at least 1 activity of daily living (ADL), the most common being household chores.

Discussion: In this cohort of individuals with COVID-19 who were followed up for as long as 9 months after illness, approximately 30% reported persistent symptoms. A unique aspect of our cohort is the high proportion of outpatients with mild disease. Persistent symptoms were reported by one-third of outpatients in our study, consistent with a previously reported study,4 in which 36% of outpatients had not returned to baseline health by 14 to 21 days following infection. However, this has not been previously described 9 months after infection.

Consistent with existing literature, fatigue was the most commonly reported symptom.2-4 This occurred in 14% of individuals in this study, lower than the 53% to 71%2-4 reported in cohorts of hospitalized patients, likely reflecting the lower acuity of illness in our cohort. Furthermore, impairment in HRQoL has previously been reported among hospitalized patients who have recovered from COVID-19; we found 29% of outpatients reported worsened HRQoL.5

Notably, 14 participants, including 9 nonhospitalized individuals, reported negative impacts on ADLs after infection. With 57.8 million cases worldwide, even a small incidence of long-term debility could have enormous health and economic consequences.6

Study limitations include a small sample size, single study location, potential bias from self-reported symptoms during illness episode, and loss to follow-up of 57 participants. To our knowledge, this study presents the longest follow-up symptom assessment after COVID-19 infection. Our research indicates that the health consequences of COVID-19 extend far beyond acute infection, even among those who experience mild illness. Comprehensive long-term investigation will be necessary to fully understand the impact of this evolving viral pathogen.

Source: Jennifer K. Logue, BS; Nicholas M. Franko, BS; Denise J. McCulloch, MD, MPH; et al Dylan McDonald, BA; Ariana Magedson, BS; Caitlin R. Wolf, BS; Helen Y. Chu, MD, MPH. Sequelae in Adults at 6 Months After COVID-19 Infection. JAMA Netw Open. 2021;4(2):e210830. doi:10.1001/jamanetworkopen.2021.0830 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2776560

Long COVID Advocates Join Together To Form Alliance To Make Policy Recommendations, Secure Research Funding, And Transform Understanding Of Post-Viral Illnesses

Press Release:

LOS ANGELES, Feb. 25, 2021 /PRNewswire/ — Today, leaders of 50 organizations and patient groups announced the formation of the Long COVID Alliance. The Alliance includes a network of patient-advocates, scientists, public health and disease experts, and drug developers who have joined together to leverage their collective knowledge and resources to educate policymakers and accelerate research that will address the challenges faced by ‘COVID long haulers’ and related post-viral illnesses.

Their goal is to transform the current understanding of Long COVID and related post-infectious illnesses such as:  myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), postural orthostatic tachycardia syndrome (POTS), other forms of dysautonomia, Ehlers-Danlos syndrome (EDS), hypermobility spectrum disorder (HSD) and mast cell activation syndrome (MCAS), autoimmune diseases and other related illnesses.

“The Long COVID Alliance is a critical collaboration based on the current reality that doctors and researchers are reporting that millions of COVID-19 patients continue to experience chronic and often debilitating post-viral symptoms. This state of extended illness is presently labeled Long COVID,” said Oved Amitay, Solve M.E. President and Chief Executive Officer, one of the three Alliance founders. “Even though tests might reveal that no virus remains in the body, COVID-19 ‘long haulers’ continue to struggle, often alone. Our community brings past experiences that are relevant to the current crisis.”

In 2020, this same group came together to successfully call for urgent government investments for Long COVID, and $1.15 billion for long-term COVID-19 research at the National Institutes of Health shortly followed. The effort laid the foundation for the new Long COVID Alliance, which will prioritize:

  • Health equity and confronting systemic bias and racism in the Long COVID response;
  • Facilitating data harmonization (i.e., combine data from different sources and provide users with a comparable view of data from different studies);
  • Deploying financial resources from the NIH to create a public-private post-viral research infrastructure and translate research results into treatments and cures for millions;
  • Providing expert guidance and resources to media and policymakers;
  • Expanding public-private partnerships;
  • Leveraging existing post-viral disease knowledge and infrastructure;
  • Connecting policymakers with patients and scientists; and
  • Ensuring meaningful patient participation.

“So many patients have bonded together as the healthcare community has not understood why some patients are asymptomatic and others are suffering moderate to debilitating issues a year later,” said Hunter Howard, chairman of the Global Pandemic Coalition, a founder of the Alliance. “As one of the first infected in Texas, and a healthcare executive, I immediately noticed doctor friends did not understand my lingering symptoms or the novel coronavirus.  We started the Global Pandemic Coalition to bring together private companies to support the public sector pandemic initiatives.  If the vaccines continue to drive down mortalities, nothing may be more important now than coming together to drive understanding and fund research for the COVID survivors.”

To accompany the Long COVID Alliance’s launch, the initial partners from 2020 have drafted key recommendations and guidance for the National Institutes of Health (NIH), which can be found by visiting https://longcovidalliance.org/wp-content/uploads/2021/02/NIH-Long-COVID-Alliance-NIH-Recommendations-Letter-Final-with-signers.pdf

Current Long COVID Alliance partners include:

  • Action for M.E.
  • American Medical Women’s Association (AMWA)
  • Bateman Horne Center
  • Body Politic
  • Covid-19 Longhauler Advocacy Project
  • Dysautonomia International
  • ENIGMA COVID-19 Working Group
  • Florida Society of Neurology
  • HADASSAH
  • Health Rising
  • Healthy Women
  • Institute for Neuro-Immune Medicine (INIM)
  • Kantor Neurology, LLC
  • Long COVID Physio
  • Massachusetts ME/CFS & FM
  • #MEACTION
  • ME International
  • Medical Partnership 4 MS+
  • Minnesota ME/CFS Alliance
  • National Association for Nurse Practitioners in Women’s Health
  • National Health Council
  • National Organization for Women (NOW)
  • Nurse Practitioners in Women’s Health (NPWH)
  • Open Medicine Foundation
  • PandoraORG
  • PolyBio Research Foundation
  • Pulmonary Wellness Foundation
  • Sex and Gender Health Collaboration
  • Simmaron Research
  • Solve M.E.
  • The American Dysautonomia Institute (ADI)
  • The Mast Cell Disease Society, Inc.
  • The SHANE Foundation
  • Utah COVID-19 Long Hauler
  • Whittemore Peterson Institute
  • YOU + ME Registry (Solve M.E.)

“Many long haulers are now approaching a full year post-infection. We have lost jobs, lost significant quality of life, and lost pieces of who we once were. It’s been a long road with an uncertain future and we’ve finally found hope,” said Karyn Bishof, Founder of the COVID-19 Longhauler Advocacy Project and of the Long COVID Alliance. “With the help of our partners, we will ensure that Long haulers are not left out in the cold. The Long COVID Alliance will fight with us for awareness, answers, and ensuring that patient voices are included at every step of solving this ‘second wave’ Long COVID health crisis.”

To learn more, join the Long COVID Alliance, or become a signatory to the NIH letter, visit: www.longcovidalliance.org.

About Solve M.E.
The Solve ME/CFS Initiative (Solve M.E.) is the leading, national non-profit organization solely dedicated to solving ME/CFS. We are committed to making ME/CFS understood, diagnosable, and treatable. Solve M.E. is the largest U.S. provider of private competitive research funding exclusively for ME/CFS working to accelerate the discovery of safe and effective treatments; we strive for an aggressive expansion of funding for research that will lead to a cure, and seek to engage the entire ME/CFS community.

Media Inquiries Only 
Contact Emily Taylor
Director of Advocacy and Communications
714-296-1661
ETaylor@solvecfs.org

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: The Human Herpesviruses Are Back!

Abstract:

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) or Systemic Exertion Intolerance Disease (SEID) is a chronic multisystem illness of unconfirmed etiology. There are currently no biomarkers and/or signatures available to assist in the diagnosis of the syndrome and while numerous mechanisms have been hypothesized to explain the pathology of ME/CFS, the triggers and/or drivers remain unknown. Initial studies suggested a potential role of the human herpesviruses especially Epstein-Barr virus (EBV) in the disease process but inconsistent and conflicting data led to the erroneous suggestion that these viruses had no role in the syndrome. New studies using more advanced approaches have now demonstrated that specific proteins encoded by EBV could contribute to the immune and neurological abnormalities exhibited by a subgroup of patients with ME/CFS. Elucidating the role of these herpesvirus proteins in ME/CFS may lead to the identification of specific biomarkers and the development of novel therapeutics.

Source: Ariza ME. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: The Human Herpesviruses Are Back! Biomolecules. 2021 Jan 29;11(2):185. doi: 10.3390/biom11020185. PMID: 33572802. https://www.mdpi.com/2218-273X/11/2/185 (Full text)

Managing COVID-19 post viral Fatigue Syndrome

Abstract:

In online surveys, over 50% of persons who contract COVD-19 experience symptoms lasting longer than 90 days [Pelanti S, Grassi E, Markris N, et al. J Psych Res. 2020. doi:10.1016/j.jpsychires.2020.08.008] Despite an estimated 3 million Americans being affected by COVID post-viral fatigue, there has been little discussion about the care of these patients, most of whom report feeling unsupported or dismissed by their providers [Amitay O, Komaroff AL. The Guardian, 20 Aug 2020]. This article points out the similarity between this post-viral fatigue syndrome and Chronic Fatigue Syndrome (ME/CFS) or Systemic Exertion Intolerance Disease (SEID), and offers evidence-based suggestions for management.

Source: Charles W. Lapp & Joseph F. John (2021) Managing COVID-19 post viral Fatigue Syndrome, Fatigue: Biomedicine, Health & Behavior, DOI: 10.1080/21641846.2021.1890347  (Full text) https://www.tandfonline.com/doi/full/10.1080/21641846.2021.1890347

Will COVID-19 Lead to Myalgic Encephalomyelitis/Chronic Fatigue Syndrome?

Introduction:

“Recovering” from COVID-19 does not guarantee a return to a person’s usual state of health. For one thing, some people with multi-system injury—particularly to the brain, heart and kidneys—may develop permanent dysfunction of those organs.

In addition, a more subtle form of chronic illness may develop. For some people with COVID-19, even those who are only mildly affected at first, the ensuing weeks and months of “recovery” bring a surprise and a betrayal: they do not return to full health. Although nucleic acid tests no longer detect the virus, people still suffer from ongoing symptoms. They call themselves “long haulers,” and the condition is being called “long COVID.”

Source: Komaroff AL, Bateman L. Will COVID-19 Lead to Myalgic Encephalomyelitis/Chronic Fatigue Syndrome? Front Med (Lausanne). 2021 Jan 18;7:606824. doi: 10.3389/fmed.2020.606824. PMID: 33537329; PMCID: PMC7848220. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848220/ (Full text)

Off label use of shows promise as a treatment for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): a retrospective study of 101 patients treated with a low dose of Aripiprazole

In a retrospective study, we reviewed the medical records of 101 patients who met the criteria for a ME/CFS diagnosis according to three separate case definitions (Fukuda, CCC, and IOM) and who received off-label aripiprazole (Table ​(Table1).1). Medical records were included for individuals evaluated in the clinic at least twice, representing periods before and after the use of the medication. The age range was from 18 to 84 years old (mean 50 years), with a gender distribution of 67% female and 33% male, and the duration of illness was from 1 to 54 years (median 13 years).

The daily oral dose of aripiprazole ranged from 0.2 to 2.0 mg/day (mean 1.1 mg/day). Dosage started at 0.25 mg/day and titrated up or down based on each patient’s observations and feedback. The duration of aripiprazole therapy ranged from less than one month to 17 months (mean 7.8 months). Patient records were also evaluated for concurrent use of various classes of antidepressants, including selective serotonin reuptake inhibitors (SSRI), serotonin-norepinephrine reuptake inhibitors (SNRI), serotonin modulators, norepinephrine–dopamine reuptake inhibitors (NDRIs), and tri-cyclic antidepressants. The difference in antidepressant use between responders vs. non-responders was not statistically significant (p = 0.145) using the test for proportions, suggesting that antidepressant use does not predict or preclude a clinical response to aripiprazole.

Source: Crosby LD, Kalanidhi S, Bonilla A, Subramanian A, Ballon JS, Bonilla H. Off label use of Aripiprazole shows promise as a treatment for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): a retrospective study of 101 patients treated with a low dose of Aripiprazole. J Transl Med. 2021 Feb 3;19(1):50. doi: 10.1186/s12967-021-02721-9. PMID: 33536023; PMCID: PMC7860172. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7860172/ (Full text)

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Where Will the Drugs Come From?

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic debilitating disease characterized by severe and disabling fatigue that fails to improve with rest; it is commonly accompanied by multifocal pain, as well as sleep disruption, and cognitive dysfunction. Even mild exertion can exacerbate symptoms. The prevalence of ME/CFS in the U.S. is estimated to be 0.5-1.5% and is higher among females. Viral infection is an established trigger for the onset of ME/CFS symptoms, raising the possibility of an increase in ME/CFS prevalence resulting from the ongoing COVID-19 pandemic. Current treatments are largely palliative and limited to alleviating symptoms and addressing the psychological sequelae associated with long-term disability.

While ME/CFS is characterized by broad heterogeneity, common features include immune dysregulation and mitochondrial dysfunction. However, the underlying mechanistic basis of the disease remains poorly understood. Herein, we review the current understanding, diagnosis and treatment of ME/CFS and summarize past clinical studies aimed at identifying effective therapies. We describe the current status of mechanistic studies, including the identification of multiple targets for potential pharmacological intervention, and ongoing efforts towards the discovery of new medicines for ME/CFS treatment.

Source: Toogood PL, Clau DJ, Phadke S, Hoffman D. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Where Will the Drugs Come From? Pharmacol Res. 2021 Jan 30:105465. doi: 10.1016/j.phrs.2021.105465. Epub ahead of print. PMID: 33529750. https://pubmed.ncbi.nlm.nih.gov/33529750/

Persistent Brainstem Dysfunction in Long-COVID: A Hypothesis

Abstract:

Long-COVID is a postviral illness that can affect survivors of COVID-19, regardless of initial disease severity or age. Symptoms of long-COVID include fatigue, dyspnea, gastrointestinal and cardiac problems, cognitive impairments, myalgia, and others. While the possible causes of long-COVID include long-term tissue damage, viral persistence, and chronic inflammation, the review proposes, perhaps for the first time, that persistent brainstem dysfunction may also be involved.

This hypothesis can be split into two parts. The first is the brainstem tropism and damage in COVID-19. As the brainstem has a relatively high expression of ACE2 receptor compared with other brain regions, SARS-CoV-2 may exhibit tropism therein. Evidence also exists that neuropilin-1, a co-receptor of SARS-CoV-2, may be expressed in the brainstem. Indeed, autopsy studies have found SARS-CoV-2 RNA and proteins in the brainstem. The brainstem is also highly prone to damage from pathological immune or vascular activation, which has also been observed in autopsy of COVID-19 cases.

The second part concerns functions of the brainstem that overlap with symptoms of long-COVID. The brainstem contains numerous distinct nuclei and subparts that regulate the respiratory, cardiovascular, gastrointestinal, and neurological processes, which can be linked to long-COVID. As neurons do not readily regenerate, brainstem dysfunction may be long-lasting and, thus, is long-COVID. Indeed, brainstem dysfunction has been implicated in other similar disorders, such as chronic pain and migraine and myalgic encephalomyelitis or chronic fatigue syndrome.

Source: Yong SJ. Persistent Brainstem Dysfunction in Long-COVID: A Hypothesis. ACS Chem Neurosci. 2021 Feb 4;12(4):573–80. doi: 10.1021/acschemneuro.0c00793. Epub ahead of print. PMID: 33538586; PMCID: PMC7874499. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874499/ (Full text)

Insights from Invasive Cardiopulmonary Exercise Testing of Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Background

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) affects tens of millions worldwide; the causes of exertional intolerance are poorly understood. The ME/CFS label overlaps with postural orthostatic tachycardia (POTS) and fibromyalgia, and objective evidence of small fiber neuropathy (SFN) is reported in ∼50% of POTS and fibromyalgia patients.

Research Question

Can invasive cardiopulmonary exercise testing (iCPET) and PGP9.5-immunolabeled lower-leg skin biopsies inform the pathophysiology of ME/CFS exertional intolerance and potential relationships with SFN?

Study Design and Methods

We analyzed 1516 upright invasive iCPETs performed to investigate exertional intolerance. After excluding patients with intrinsic heart or lung disease and selecting those with right atrial pressures (RAP) <6.5 mmHg, results from 160 patients meeting ME/CFS criteria who had skin-biopsy test results were compared to 36 controls. Rest-to-peak changes in cardiac output (Qc) were compared to oxygen uptake (Qc/VO 2 slope) to identify participants with low, normal, or high pulmonary blood flow by Qc/VO 2 tertiles.

Results

During exercise, the 160 ME/CFS patients averaged lower RAP (1.9±2 vs. 8.3±1.5; P<0.0001) and peak VO 2 (80%±21 vs. 101.4%±17; P<0.0001) than controls. The low-flow tertile had lower peak Qc than the normal and high-flow tertiles (88.4±19% vs. 99.5±23.8% vs. 99.9±19.5% predicted; P<0.01). In contrast, systemic oxygen extraction was impaired in high-flow versus low and normal-flow participants (0.74±0.1% vs. 0.88±0.11 vs. 0.86±0.1; P<0.0001) in association with peripheral left-to-right shunting. Among the 160 ME/CFS patient biopsies, 31% was consistent with SFN (epidermal innervation ≤5.0% of predicted; P < 0.0001). Denervation severity did not correlate with exertional measures.

Interpretation

These results identify two types of peripheral neurovascular dysregulation that are biologically plausible contributors to ME/CFS exertional intolerance–depressed Qc from impaired venous return, and impaired peripheral oxygen extraction. In patients with small-fiber pathology, neuropathic dysregulation causing microvascular dilation may limit exertion by shunting oxygenated blood from capillary beds and reducing cardiac return.

Abbreviation:

Ca-vO2/[Hb] ( Arterial–mixed venous oxygen content difference/hemoglobin concentration), iCPET ( Invasive cardiopulmonary exercise test), NAM ( National Academy of Medicine, formerly the Institute of Medicine), ME/CFS ( Myalgic encephalomyelitis/chronic fatigue syndrome), MM ( Mitochondrial myopathy), mPAP ( Mean pulmonary artery pressure), PAWP ( Pulmonary arterial wedge pressure), PLF ( Preload failure), POTS ( Postural orthostatic tachycardia syndrome), PVR ( Pulmonary vascular resistance), RAP ( Right atrial pressure), Qc ( Cardiac output), SFN ( Small fiber neuropathy), VO2 ( Oxygen uptake), vPO2 ( Venous oxygen tension)

Source: Phillip Joseph, MD, Carlo Arevalo, MD, Rudolf K.F. Oliveira, MD, PhD, Donna Felsenstein, MD, Anne Louise Oaklander, MD, PhD, David M. Systrom, MD. Insights from Invasive Cardiopulmonary Exercise Testing of Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. February 09, 2021. DOI:https://doi.org/10.1016/j.chest.2021.01.082 https://journal.chestnet.org/article/S0012-3692(21)00256-7/fulltext