Tag: severely ill patients

Occupational differences in the prevalence and severity of long-COVID: Analysis of the ONS Coronavirus (COVID-19) Infection Survey

Abstract:

Objectives To establish whether prevalence and severity of long-COVID symptoms vary by industry and occupation.

Methods We utilised ONS Coronavirus Infection Survey (CIS) data (February 2021-April 2022) of working-age participants (16-65 years). Exposures were industrial sector, occupation and major Standard Occupational Classification (SOC) group. Outcomes were self-reported: (1) long-COVID symptoms; and (2) reduced function due to long-COVID. Binary (outcome 1) and ordered (outcome 2) logistic regression were used to estimate odds ratios (OR) and prevalence (marginal means) for all exposures.

Results Public facing industries, including teaching and education, social care, healthcare, civil service, retail and transport industries and occupations had highest odds ratios for long-COVID. By major SOC group, those in caring, leisure and other services (OR 1.44, CIs: 1.38-1.52) had substantially elevated odds than average. For almost all exposures, the pattern of odds ratios for long-COVID symptoms followed that for SARS-CoV-2 infections, except for professional occupations (OR<1 for infection; OR>1 for long-COVID). The probability of reporting long-COVID for industry ranged from 7.7% (financial services) to 11.6% (teaching and education); whereas the prevalence of reduced function by ‘a lot’ ranged from 17.1% (arts, entertainment and recreation) to 22-23% (teaching and education and armed forces) and to 27% (those not working).

Conclusions The risk and prevalence of long-COVID differs across industries and occupations. Generally, it appears that likelihood of developing long-COVID symptoms follows likelihood of SARS-CoV-2 infection, except for professional occupations. These findings highlight sectors and occupations where further research is needed to understand the occupational factors resulting in long-COVID.

Source: Theocharis Kromydas, Evangelia Demou, Rhiannon Edge, Matthew Gittins, S Vittal Katikireddi, Neil Pearce, Martie van Tongeren, Jack Wilkinson, Sarah Rhodes. Occupational differences in the prevalence and severity of long-COVID: Analysis of the ONS Coronavirus (COVID-19) Infection Survey. medRxiv 2023.03.24.23287666; doi: https://doi.org/10.1101/2023.03.24.23287666 https://www.medrxiv.org/content/10.1101/2023.03.24.23287666v1.full-text (Full text)

Unfavorable Outcome and Long-Term Sequelae in Cases with Severe COVID-19

Abstract:

Emerging evidence shows that individuals with COVID-19 who survive the acute phase of illness may experience lingering symptoms in the following months. There is no clear indication as to whether these symptoms persist for a short time before resolving or if they persist for a long time. In this review, we will describe the symptoms that persist over time and possible predictors in the acute phase that indicate long-term persistence.
Based on the literature available to date, fatigue/weakness, dyspnea, arthromyalgia, depression, anxiety, memory loss, slowing down, difficulty concentrating and insomnia are the most commonly reported persistent long-term symptoms. The extent and persistence of these in long-term follow-up is not clear as there are still no quality studies available.
The evidence available today indicates that female subjects and those with a more severe initial disease are more likely to suffer permanent sequelae one year after the acute phase. To understand these complications, and to experiment with interventions and treatments for those at greater risk, we must first understand the physio-pathological mechanisms that sustain them.
Source: Fabbri A, Voza A, Riccardi A, Vanni S, De Iaco F on behalf of the Study & Research Center of the Italian Society of Emergency Medicine (SIMEU). Unfavorable Outcome and Long-Term Sequelae in Cases with Severe COVID-19. Viruses. 2023; 15(2):485. https://doi.org/10.3390/v15020485 (Full text)

Severe and Very Severe Myalgic Encephalopathy/Chronic Fatigue Syndrome ME/CFS in Norway: Symptom Burden and Access to Care

Abstract:

There is a striking lack of systematic knowledge regarding the symptom burden, capacity for activities of daily living, and supportive measures for the most severely ill ME/CFS patients. The present study seeks to address this through a national, Internet-based survey targeting patients with severe and very severe ME/CFS and their carers.
Responses from 491 patients were included, with 444 having severe and 47 very severe ME/CFS with the classification based on the best estimate from patient responses. In addition, 95 respondents were reclassified from patients’ own classification to moderate and included for comparison. The onset was before 15 years of age for 45% in the very severe and 32% in the severe group. Disease duration was more than 15 years for 19% in the very severe and 27% in the severe group. Patient symptom burden was extensive. The most severely affected were totally bedridden, unable to talk, and experienced dramatic worsening of symptoms after minimal activity or sensory stimuli.
Care and assistance from healthcare and social services were often described as insufficient or inadequate, often worsening the symptom load and burden of care. A substantial lack of disease knowledge among healthcare providers in general was reported. Yet approximately 60% in the severe and very severe groups found services provided by occupational therapists and family doctors (general practitioners) helpful, while a smaller proportion experienced appropriate help from other health personnel groups. This indicates that help and support are highly needed and possible to provide. On the other hand, this must be approached carefully, as a substantial number of patients experienced deterioration from contact with healthcare personnel. Family carers described an extensive burden of care with often inadequate help from healthcare providers or municipal authorities.
Patient care by family members of very severe ME/CFS patients constituted more than 40 h a week for 71% of this patient group. The carers described a large negative impact on their work and financial situation, and on their mental wellbeing. We conclude that childhood onset was common, burden of disease was extensive, and support from responsible societal health and social support providers was commonly grossly inadequate.
Source: Sommerfelt K, Schei T, Angelsen A. Severe and Very Severe Myalgic Encephalopathy/Chronic Fatigue Syndrome ME/CFS in Norway: Symptom Burden and Access to Care. Journal of Clinical Medicine. 2023; 12(4):1487. https://doi.org/10.3390/jcm12041487 https://www.mdpi.com/2077-0383/12/4/1487 (Full text)

The Role of Leptin and Inflammatory Related Biomarkers in Individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Purpose: Leptin is a member of the cytokine family; its receptor (LEPR-b) is the longest form receptor expressed in cells of the immune system; wherein LEPR-b deficiency causes a decrease in CD4+ cells. LEPR-b is located in hypothalamic and brain stem nuclei, and it primarily regulates energy status. As well, leptin indirectly regulates widespread pain and exercise tolerance by decreasing circulating cortisol.

Hyperinsulinemia increases leptin production in adipocytes on a diurnal rhythm; however, the precise relationship between insulin, leptin and pro-inflammatory markers remains uncertain. In clinical settings, high-sensitivity C-reactive protein (hsCRP) has been widely used, as an inflammatory predictor for leptin-related cardiometabolic outcomes and chronic inflammatory symptoms.

Leptin-related metabolic and inflammation dysregulations have been clinically reported in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), but not fully elucidated. We examined the association of plasma insulin, leptin, and hsCRP levels with ME/CFS self-reported symptom severity.

Methods: Prospective analyses were conducted on ME/CFS patients who met Fukuda/CDC criteria at Birmingham hospital, Alabama, U.S.A. The independent variables were hyperinsulinemia (>174 μIU/mL), hyperleptinemia/hypoleptinemia (>18.3/<3.3 ng/mL), residual inflammation risk (hsCRP ≥2 and ≠26.2 mg/L) and within-individual-variability (WIV) for each biomarker.

WIV was defined for each individual as standard deviation/sample residuals adjusting for time and calculated from once-daily random plasma samples over 10–12 weeks.

The primary outcomes were:

(1) ME/CFS symptom score trends [generalized pain, persistent fatigue, sleep disturbance, impairment of concentration and memory (brain fog), and post-exertional malaise (PEM)] calculated from the MFI-20 questionnaire with anchors from 0 to 100 and recorded once daily over a matching 12–14 weeks, and

(2) dichotomized symptom severity, with severe symptoms defined as scores > 60/100. After adjusting for age and time, we reported: (1) standard errors (SEM) and p-values for symptom trends using multivariable mixed-effect linear regression models, and (2) odds ratios for severe symptoms using multivariable alternating logistic regression models.

Results: We included 29 ME/CFS patients. All were females and >18 years old. Hyperinsulinemia, hyperleptinemia/hypoleptinemia, and residual inflammation risk were 7%, 80%/7%, and 74%, respectively.

The medians of insulin-WIV, leptin-WIV and hsCRP-WIV were [(0.24; IQR 0.15–0.38), (0.25; IQR 0.15–0.40), (0.33; IQR 0.18–0.51)] respectively. On average, hyperleptinemic patients had the highest leptin-WIV and 50% of them had residual inflammation risk.

Severe (fatigue, pain, brain fog, sleep disturbance, and PEM) were reported in 50%, 29%, 41%, 30%, and 57% of patients, respectively. In the adjusted analysis, worse fatigue scores (7.49; SEM, 2.23; p = 0.002) were associated with higher insulin-WIV.

Hyperleptinemia (OR 1.54; 95% CI 1.13–2.09) compared to hypoleptinemia, and residual inflammation risk (OR 1.65; 95% CI 1.21–2.25) were associated with higher odds of severe fatigue. Worse pain scores (7.17; SEM, 2.30; p = 0.005) were associated with higher leptin-WIV, and (8.45; SEM, 2.25; p = 0.0009) higher hsCRP-WIV, and residual inflammation risk (OR 1.75; 95% CI 1.34–2.29) was associated with higher odds of severe pain.

Severe brain fog scores (9.20; SEM, 2.44; p = 0.0008) were associated with higher insulin-WIV, higher leptin-WIV (4.73; SEM, 2.12; p = 0.03). Residual inflammation risk (OR 1.40; 95% CI 1.16–1.77) was associated with higher odds of severe brain fog.

Hyperleptinemia (OR 0.60; 95% CI 0.43–1.19) was associated with lower odds of severe PEM compared to hypoleptinemia, and better sleep quality was associated (6.07; SEM, 1.70; p = 0.001) with higher insulin-WIV, and (3.37; SEM, 1.47; p = 0.03) higher leptin-WIV.

Conclusions: In patients with ME/CFS, symptoms severity was associated with hyperleptinemia, inflammation and within-individual-variability of these biomarkers. Leptin and hsCRP may be clinically useful in predicting symptom severity.

Larger clinical trials are needed to further examine the prediction and causality of these biomarkers in the development of ME/CFS diagnosis. The efficacy and safety of anti-inflammatory therapies may be evaluated in sub-clusters of ME/CFS with metabolic responses and inflammation dysregulations to improve patient-reported symptoms.

Source: Rahaf Al Assil and Jarred W Younger. “The Role of Leptin and Inflammatory Related Biomarkers in Individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome” in Karandrea S, Agarwal N, Organizing Committee of Cardiometabolic Health Congress. Report from the Scientific Poster Session at the 16th Annual Cardiometabolic Health Congress in National Harbor, USA, 14–17 October 2021. Proceedings. 2022; 80(1):6. https://doi.org/10.3390/proceedings2022080006 (Full text)

Autoantibody Correlation Signatures in Fibromyalgia and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Association with Symptom Severity

Abstract:

Background: Recent studies provide some evidence for the contribution of antibody-mediated autoimmune mechanisms to the nature of fibromyalgia (FM) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Much attention was paid to the autoantibodies (AAb) targeting G protein-coupled receptors as natural components of the immune system. However, natural AAb network is much more extensive, and has not been previously investigated in these disorders;

Methods: The enzyme immunoassays ELI-Viscero-Test and ELI-Neuro-Test were used to determine changes in serum content of a 33 natural AAb to neural, organ-specific and non-tissue-specific autoantigens a) in 11 FM patients with comorbid ME/CFS; b) in 11 ME/CFS patients without FM; c) in 11 healthy controls. Individual autoantibody profiles and their correlation with some clinical symptoms were analyzed.

Results: Both patients with ME/CFS and ME/CFS+FM were characterized by more frequent and pronounced deviations in the immunoreactivity to GABA-receptors than healthy controls. Although the level of other natural AAb did not differ between study groups, AAb correlation signatures were changing in patients compared to healthy controls. Both in patients and healthy controls the level of natural AAb to various neural and tissue-specific antigens correlated with the severity of fatigue, bodily pain, depression, anxiety, physical and mental-health related quality of life. Notably, that widely different correlation patterns were observed between study groups.

Conclusions: Findings from this pilot study provide some evidence that the homeostasis of autoimmune relationships, which are possibly a physiological part of our immune system, may break down in FM and ME/CFS. The correlation of disease-induced perturbations in individual AAb profiles with some clinical symptoms may arise from the immune system’s ability to reflect qualitative and quantitative changes in antigenic composition of the body.

Source: Ryabkova, V.A.; Gavrilova, N.Y.; Poletaeva, A.A.; Pukhalenko, A.I.; Koshkina, I.A.; Churilov, L.P.; Shoenfeld, Y. Autoantibody Correlation Signatures in Fibromyalgia and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Association with Symptom Severity . Preprints 2022, 2022120224 (doi: 10.20944/preprints202212.0224.v1). https://www.preprints.org/manuscript/202212.0224/v1 (Full text available as PDF file)

Severe myalgic encephalomyelitis/chronic fatigue syndrome in children and young people: a British Paediatric Surveillance Unit study

Abstract:

Objectives: Primary objective: to determine the point prevalence and incidence rate of severe myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in children aged 5-16 years over 13 months.

Secondary objectives: to describe the demographic features, symptoms, impact on activities of daily living, school attendance and time to diagnosis.

Design: Prospective surveillance study conducted by the British Paediatric Surveillance Unit. Paediatricians was asked if they had assessed a child with severe ME/CFS (screening definition for prevalence and incidence: children (5-16 years) diagnosed with ME/CFS so severe that they are unable to attend school for more than 1 hour a week during the last 6 weeks of the school term).

Participants: Patients 5-16 years of age, seen by paediatricians and two large ME/CFS specialist services across the UK and Ireland.

Outcome measures: Paediatrician-completed questionnaires describing demographics, symptoms, function and treatment, (applying National Institute for Health and Care Excellence (NICE)-recommended criteria to assess severity of ME/CFS). Diagnosis of severe, probable severe or possible severe ME/CFS was made only with evidence of NICE-recommended screening blood tests.

Results: 285 cases were reported, of which of which 33 were severe, 4 probable severe and 55 possible severe. Estimated prevalence was 3.2 per million children (95% CI 2.2 to 4.5). Including possible/probable severe ME/CFS gave 8.9 per million children (95% CI 7.2 to 11). The incidence rate was 0.90 per million children-years (95% CI 0.43 to 1.65) (1.97 per million children-years (95% CI 1.24 to 2.99)). Median age was 13 years and 58% of cases were female. Median time to diagnosis was 0.47 years.

Conclusions: Although the incidence of children presenting with severe ME/CFS is low, all were very disabled. In addition, the majority receive little or no education. Paediatricians need to consider how to provide rehabilitation and education for these disabled young people.

Source: Royston AP, Rai M, Brigden A, Burge S, Segal TY, Crawley EM. Severe myalgic encephalomyelitis/chronic fatigue syndrome in children and young people: a British Paediatric Surveillance Unit study. Arch Dis Child. 2022 Dec 1:archdischild-2022-324319. doi: 10.1136/archdischild-2022-324319. Epub ahead of print. PMID: 36456114. https://adc.bmj.com/content/early/2022/11/30/archdischild-2022-324319 (Full text)

COVID-19 disease severity to predict persistent symptoms: a systematic review and meta-analysis

Abstract:

Background: It is unclear, whether the initial disease severity may help to predict which COVID-19 patients at risk of developing persistent symptoms.

Aim: The aim of this study was to examine whether the initial disease severity affects the risk of persistent symptoms in post-acute COVID-19 syndrome and long COVID.

Methods: A systematic search was conducted using PUBMED, Google Scholar, EMBASE, and ProQuest databases to identify eligible articles published after January 2020 up to and including 30 August 2021. Pooled odds ratio (OR) and confidence intervals (CIs) were calculated using random effects meta-analysis.

Findings: After searching a total of 7733 articles, 20 relevant observational studies with a total of 7840 patients were selected for meta-analysis. The pooled OR for persistent dyspnea in COVID-19 survivors with a severe versus nonsevere initial disease was 2.17 [95%CI 1.62 to 2.90], and it was 1.33 [95%CI 0.75 to 2.33] for persistent cough, 1.30 [95%CI 1.06 to 1.58] for persistent fatigue, 1.02 [95%CI 0.73 to 1.40] for persistent anosmia, 1.22 [95%CI 0.69 to 2.16] for persistent chest pain, and 1.30 [95%CI 0.93 to 1.81] for persistent palpitation.

Conclusions: Contrary to expectations, we did not observe an association between the initial COVID-19 disease severity and common persistent symptoms except for dyspnea and fatigue. In addition, it was found that being in the acute or prolonged post-COVID phase did not affect the risk of symptoms. Primary care providers should be alert to potential most prevalent persistent symptoms in all COVID-19 survivors, which are not limited to patients with critical-severe initial disease.

Source: Dirican E, Bal T. COVID-19 disease severity to predict persistent symptoms: a systematic review and meta-analysis. Prim Health Care Res Dev. 2022 Nov 10;23:e69. doi: 10.1017/S1463423622000585. PMID: 36352492.  https://www.cambridge.org/core/journals/primary-health-care-research-and-development/article/covid19-disease-severity-to-predict-persistent-symptoms-a-systematic-review-and-metaanalysis/479FC1E900E22673895FDAC1CF5C12B2 (Full text)

Autoimmune gene expression profiling of fingerstick whole blood in Chronic Fatigue Syndrome

Abstract:

Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating condition that can lead to severe impairment of physical, psychological, cognitive, social, and occupational functions. The cause of ME/CFS remains incompletely understood. There is no clinical diagnostic test for ME/CFS. Although many therapies have been used off-label to manage symptoms of ME/CFS, there are limited, if any, specific therapies or cure for ME/CFS. In this study, we investigated the expression of genes specific to key immune functions, and viral infection status in ME/CFS patients with an aim of identifying biomarkers for characterization and/or treatment of the disease.

Methods: In 2021, one-hundred and sixty-six (166) patients diagnosed with ME/CFS and 83 healthy controls in the US participated in this study via a social media-based application (app). The patients and heathy volunteers consented to the study and provided self-collected finger-stick blood and first morning void urine samples from home. RNA from the fingerstick blood was tested using DxTerity’s 51-gene autoimmune RNA expression panel (AIP). In addition, DNA from the same fingerstick blood sample was extracted to detect viral load of 4 known ME/CFS associated viruses (HHV6, HHV7, CMV and EBV) using a real-time PCR method.

Results: Among the 166 ME/CFS participants in the study, approximately half (49%) of the ME/CFS patients reported being house-bound or bedridden due to severe symptoms of the disease. From the AIP testing, ME/CFS patients with severe, bedridden conditions displayed significant increases in gene expression of IKZF2, IKZF3, HSPA8, BACH2, ABCE1 and CD3D, as compared to patients with mild to moderate disease conditions. These six aforementioned genes were further upregulated in the 22 bedridden participants who suffer not only from ME/CFS but also from other autoimmune diseases. These genes are involved in T cell, B cell and autoimmunity functions. Furthermore, IKZF3 (Aiolos) and IKZF2 (Helios), and BACH2 have been implicated in other autoimmune diseases such as systemic lupus erythematosus (SLE) and Rheumatoid Arthritis (RA). Among the 240 participants tested with the viral assays, 9 samples showed positive results (including 1 EBV positive and 8 HHV6 positives).

Conclusions: Our study indicates that gene expression biomarkers may be used in identifying or differentiating subsets of ME/CFS patients having different levels of disease severity. These gene targets may also represent opportunities for new therapeutic modalities for the treatment of ME/CFS. The use of social media engaged patient recruitment and at-home sample collection represents a novel approach for conducting clinical research which saves cost, time and eliminates travel for office visits.

Source: Wang Z, Waldman MF, Basavanhally TJ, Jacobs AR, Lopez G, Perichon RY, Ma JJ, Mackenzie EM, Healy JB, Wang Y, Hersey SA. Autoimmune gene expression profiling of fingerstick whole blood in Chronic Fatigue Syndrome. J Transl Med. 2022 Oct 25;20(1):486. doi: 10.1186/s12967-022-03682-3. PMID: 36284352; PMCID: PMC9592873.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9592873/ (Full study)

Acute COVID-19 Syndrome Predicts Severe Long COVID-19: An Observational Study

Abstract:

Introduction Tissue damage, chronic dysfunction, and symptoms that last more than 12 weeks are hallmarks of long-term chronic opportunistic viral infection (COVID-19), and the disease may have a permanent, relapsing/remitting, or gradually improving course. This study aimed to determine the risk factors of severe long COVID-19.

Methods In October 2021, primary care clinics enrolled consenting 18- to 89-year-olds to complete an online questionnaire on self-diagnosis, clinician diagnosis, testing, symptom presence, and duration of COVID-19. Long COVID-19 was identified if symptoms were beyond 12 weeks. Patients with long-lasting COVID-19 symptoms were assessed using multivariable regression to identify potential predictors of severe long COVID-19.

Results Of the 220 respondents, 108 (49%) patients were self- or clinician-diagnosed with COVID-19 or had a confirmed positive laboratory test result. Patients aged >45 years and with at least 15 COVID-19 symptoms were 5.55 and 6.02 times, respectively, more likely to acquire severe long COVID-19. Most patients with severe and moderate post-acute COVID-19 syndrome had no relevant comorbidities (p=0.0402; odds ratio [OR]=0.4; 95% confidence interval [CI]=0.18-0.98). Obesity was a significant predictor (p=0.0307; OR=6.2; 95% CI=1.1-33.2).

Conclusion The simultaneous presence of 15 or more COVID-19 symptoms, age >45 years, and obesity were related to a higher probability of severe long COVID-19.

Source: Menezes AS Jr, Botelho SM, Santos LR, Rezende AL. Acute COVID-19 Syndrome Predicts Severe Long COVID-19: An Observational Study. Cureus. 2022 Oct 2;14(10):e29826. doi: 10.7759/cureus.29826. PMID: 36204261; PMCID: PMC9527039.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9527039/ (Full text)

Biomarkers in the diagnostic algorithm of myalgic encephalomyelitis/chronic fatigue syndrome

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex disease that is mainly diagnosed based on its clinical symptoms. Biomarkers that could facilitate the diagnosis of ME/CFS are not yet available; therefore, reliable and clinically useful disease indicators are of high importance. The aim of this work was to analyze the association between ME/CFS clinical course severity, presence of HHV-6A/B infection markers, and plasma levels of autoantibodies against adrenergic and muscarinic acetylcholine receptors.

A total of 134 patients with ME/CFS and 33 healthy controls were analyzed for the presence of HHV-6A/B using PCRs, and antibodies against beta2-adrenergic receptors (β2AdR) and muscarinic acetylcholine receptors (M3 AChR and M4 AChR) using ELISAs. HHV-6A/B U3 genomic sequence in whole-blood DNA was detected in 19/31 patients with severe ME/CFS, in 18/73 moderate ME/CFS cases, and in 7/30 mild ME/CFS cases. Severity-related differences were found among those with a virus load of more than 1,000 copies/106 PBMCs.

Although no disease severity-related differences in anti-β2AdR levels were observed in ME/CFS patients, the median concentration of these antibodies in plasma samples of ME/CFS patients was 1.4 ng/ml, while in healthy controls, it was 0.81 ng/ml, with a statistically significant increased level in those with ME/CFS (p = 0.0103). A significant difference of antibodies against M4 AChR median concentration was found between ME/CFS patients (8.15 ng/ml) and healthy controls (6.45 ng/ml) (p = 0.0250). The levels of anti-M4 plotted against disease severity did not show any difference; however, increased viral load correlates with the increase in anti-M4 level.

ME/CFS patients with high HHV-6 load have a more severe course of the disease, thus confirming that the severity of the disease depends on the viral load—the course of the disease is more severe with a higher viral load. An increase in anti-M4 AchR and anti-β2AdR levels is detected in all ME/CFS patient groups in comparison to the control group not depending on ME/CFS clinical course severity. However, the increase in HHV-6 load correlates with the increase in anti-M4 level, and the increase in anti-M4 level, in turn, is associated with the increase in anti-β2AdR level. Elevated levels of antibodies against β2AdR and M4 receptors in ME/CFS patients support their usage as clinical biomarkers in the diagnostic algorithm of ME/CFS.

Source: Gravelsina S, Vilmane A, Svirskis S, Rasa-Dzelzkaleja S, Nora-Krukle Z, Vecvagare K, Krumina A, Leineman I, Shoenfeld Y and Murovska M (2022) Biomarkers in the diagnostic algorithm of myalgic encephalomyelitis/chronic fatigue syndrome. Front. Immunol. 13:928945. doi: 10.3389/fimmu.2022.928945 https://www.frontiersin.org/articles/10.3389/fimmu.2022.928945/full (Full text)