Tag: POTS

Autonomic function testing in long-COVID syndrome patients with orthostatic intolerance

Abstract:

The association between dysautonomia and long-COVID syndrome has gained considerable interest. This study retrospectively characterized the findings of autonomic reflex screen (ARS) in long-COVID patients presenting with orthostatic intolerance (OI). Fourteen patients were identified. All patients had normal cardiovagal function and 2 patients had abnormal sudomotor function. The head-up tilt table (HUTT) was significantly abnormal in 3 patients showing postural orthostatic tachycardia syndrome (POTS). CASS ranged from 0 to 2. The most common clinical scenario was symptoms of orthostatic intolerance without demonstrable HUTT orthostatic tachycardia or orthostatic hypotension (OH) (n = 8, 57 %). In our case series, most long-COVID patients presenting to our laboratory with OI had no significant HUTT abnormalities; only 3 patients met the criteria for POTS.

Source: Eldokla AM, Ali ST. Autonomic function testing in long-COVID syndrome patients with orthostatic intolerance. Auton Neurosci. 2022 Jun 2;241:102997. doi: 10.1016/j.autneu.2022.102997. Epub ahead of print. PMID: 35679657. https://pubmed.ncbi.nlm.nih.gov/35679657/

Post-Acute Sequelae of SARS-CoV-2 infection (PASC) – Lessons Learned From a Coordinated Health Systems Response

Abstract:

Objective: To outline a consensus designed process for triaging and managing patients with Post COVID syndrome at the Mayo Clinic.

Patients and methods: We convened a central multidisciplinary team including members from General Internal Medicine, Occupational Medicine, Physical Medicine & Rehabilitation, Psychology, Allergy and Immunology, Infectious Disease, Pulmonology, Neurology, Cardiology, Pediatrics and Otorhinolaryngology, with membership from all the Mayo Clinic sites in Arizona, Florida, Iowa, Minnesota, and Wisconsin.

Results: Consensus recommendations were made for best practice guidelines on triaging and managing patients. Several innovations were agreed upon including a PASC specific appointment request form for data collection, a bio-registry, a bio-repository, and a PASC specific treatment program.

Conclusions: Given that each clinical site had individual clinical practices, these recommendations were implemented using different models, which may provide broad applicability to other clinical settings.

Source: Ganesh R, Vanichkachorn GS, Munipalli B, Hanson SN, Abu Dabrh AM, Croghan IT, Dawson NL, Hurt RT. Post-Acute Sequelae of SARS-CoV-2 infection (PASC) – Lessons Learned From a Coordinated Health Systems Response. Mayo Clin Proc Innov Qual Outcomes. 2022 Jun 1. doi: 10.1016/j.mayocpiqo.2022.05.007. Epub ahead of print. PMID: 35669936; PMCID: PMC9156955. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9156955/ (Full text)

A case series of cutaneous phosphorylated α-synuclein in Long-COVID POTS

Dear Editors,

As case numbers of coronavirus disease 19 (COVID-19) increase, chronic symptoms, including those of autonomic dysfunction, are being reported with increasing frequency [], leading to the diagnosis of post-acute sequelae of COVID-19 (PASC), or Long-COVID. In addition, small fiber neuropathy (SFN) has been reported after viral infections, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) []. These associations have prompted our group to systematically perform autonomic testing and skin biopsies in a cohort of patients who have developed postural tachycardia syndrome (POTS) as a consequence of PASC (Long-COVID POTS). As part of this evaluation, all skin biopsy samples undergo immunohistochemical analysis of both intraepidermal nerve fiber density (IENFD) and phosphorylated α-synuclein (p-syn) [], the pathological form of α-synuclein associated with the neurodegenerative diseases of Parkinson’s disease (PD), dementia with Lewy bodies (DLB), multiple system atrophy (MSA), and pure autonomic failure (PAF), as well as isolated REM sleep behavior disorder (iRBD), a prodromal manifestation of synucleinopathy for the majority of patients.

Read the rest of this article HERE. 

Source: Miglis MG, Seliger J, Shaik R, Gibbons CH. A case series of cutaneous phosphorylated α-synuclein in Long-COVID POTS. Clin Auton Res. 2022 May 16:1–4. doi: 10.1007/s10286-022-00867-0. Epub ahead of print. PMID: 35570247; PMCID: PMC9108014. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9108014/ (Full text)

Autonomic dysfunction and post-COVID-19 syndrome: A still elusive link

Editorial:

Infection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing the long-lasting pandemic coronavirus disease 2019 (COVID-19), with dramatic clinical, social, and economic implications. Importantly, evolving experience consistently shows that, in addition to issues related to the acute phase, patients who recover from COVID-19 may present a wide variety of bothersome symptoms, which may be debilitating and significantly impair their quality of life. This condition, when it persists beyond 12 weeks after recovery, is defined as “post–COVID-19” or “long COVID-19” syndrome.

Some of the symptoms, including tachycardia/palpitations, chest pain, fatigue, and dyspnea with reduced effort tolerance, suggest a possible cardiovascular cause, whereas others (eg, muscle and/or joint pain, headache, memory loss, nausea, mood disturbances) suggest involvement of other systems. Symptoms may occur independently of the severity of COVID-19, although patients with more severe symptoms in the acute phase experience a higher rate of symptom persistence during follow-up. , 

Importantly, careful diagnostic assessment usually fails to identify specific causes of post–COVID-19 syndrome. However, it has been suggested that at least some post–COVID-19 symptoms, including those of potential cardiovascular origin, might be related to abnormalities of the autonomic nervous system (ANS). The pathophysiological mechanisms responsible for ANS impairment remain speculative and might include direct damage of the ANS (ganglia and/or nerve terminations) by the virus, a toxic effect of inflammatory cytokines released during the acute infection, and an immune-mediated response triggered by some viral component(s). ,  Independent of the mechanism, the possibility of ANS involvement in SARS-CoV-2 infection is supported by the frequent occurrence of neurologic symptoms (eg, anosmia, dysgeusia) as well as the sporadic occurrence of clinical conditions typically related to ANS dysfunction (eg, orthostatic hypotension, orthostatic tachycardia) in post–COVID-19 syndrome. Furthermore, patients with COVID-19, compared to healthy subjects, have been found to show reduced heart rate variability (HRV) parameters 20 weeks after recovery from the illness. However, a pathogenetic relationship between dysautonomia and post–COVID-19 syndrome remains to be demonstrated. Establishing such a relationship would be of importance because it might help guide the management of this clinical condition.

The study by Ladlow et al in this issue of Heart Rhythm Journal is welcome because it attempts to clarify whether any association exists between dysautonomia and symptoms, as well as objective evidence of exercise intolerance, in patients with post–COVID-19 syndrome. In their study, Ladlow et al enrolled 205 patients referred to a post–COVID-19 clinic who fulfilled specific eligibility criteria (hospitalization and desaturation ≤95% on a Harvard step test or chest pain with electrocardiographic [ECG] changes during acute illness and life-limiting symptoms persisting for >12 weeks). All patients underwent bicycle cardiopulmonary exercise testing (CPET) and were divided into 1 of 2 groups according to evidence or no evidence of dysautonomia.

Dysautonomia was diagnosed based on 3 heart rate (HR) parameters that Jouven et al found to be associated with total mortality and sudden death in a population of asymptomatic subjects: (1) resting HR >75 bpm; (2) increase in HR during exercise <89 bpm; and (3) HR reduction <25 bpm during the first minute of recovery from peak exercise. HRV was also assessed by calculating the root mean square of the squared differences of adjacent RR intervals (RMSSD) on a 1-minute 12-lead ECG at rest and on 30-second ECGs during the first 3 minutes of recovery after peak exercise.

Patients were studied 183 ± 77 days (∼6 months) from COVID-19 disease, and dysautonomia was found in 51 patients (25%). Per definition, these patients had higher HR at rest (95 ± 12 bpm vs 81 ± 12 bpm; P <.001) and lower HR increase during CPET (75 ± 12 bpm vs 96 ± 13 bpm; P <.001) and HR recovery after peak exercise (17 ± 4 bpm vs 31 ± 17 bpm; P <.001) compared to those without dysautonomia.

Patients with dysautonomia were older, had a higher body mass index (BMI) (P = .013) and waist circumference (WC) (P = .003), and had a lower basal RMSSD (P <.001). Furthermore, at rest, dysautonomic patients showed a higher breathing rate (P = .006) and lower forced vital capacity (P = .031), forced expiratory volume in 1 second (P = .036), and ventilatory efficiency (Ve/Vco 2) (P = .036).

When assessing symptoms that showed prevalence >25%, a significant association with dysautonomia was found for low mood (P = .007), headache (P = .026), and poor attention (P = .047). However, other symptoms, including some of potential cardiovascular origin (eg, shortness of breath, fatigue), showed no significant association with dysautonomia.

Patients with dysautonomia, however, showed a lower performance on CPET. In particular, HR at peak exercise (170 ± 13 bpm vs 177 ± 15 bpm; P = .003), maximal work rate (219 ± 37 W vs 253 ± 52 W; P <.001), and maximal oxygen consumption (V⋅O2) (30.6 ± 5.5 mL/kg/min vs 35.8 ± 7.6 mL/kg/min; P <.001) all were significantly lower in patients with dysautonomia than in those without dysautonomia, suggesting a role of ANS dysfunction in their physical limitation.

Ladlow et al should be congratulated for performing this large study on post–COVID-19 syndrome. However, possible alternative interpretations of the data suggest caution in deriving definitive conclusions from their results.

Although the study shows the lack of significant relationship between dysautonomia and most post–COVID-19 symptoms, including, in particular, some symptoms of possible cardiovascular origin, the method applied to identify patients with an impairment of ANS function presents some limitations. Both higher HR at rest and lower HR recovery after exercise suggest an imbalance of sympathovagal tone toward adrenergic predominance in their patients with dysautonomia. However, rather than reflecting a primary impairment of the ANS, these findings simply might have been related to differences between the 2 groups with regard to some basal clinical characteristics, including higher BMI/WC, lower efficiency in respiratory function, and lower mood in dysautonomic patients. In addition, the lower increase in HR during maximal exercise in patients with dysautonomia might have been a mere consequence of their having a higher HR at rest and, given their older age, a lower maximal theoretical HR for age. The percent of predicted maximal HR for age achieved during CPET, in fact, did not differ between the 2 groups. The possibility that the differences in HR behavior might have not been related to a primary abnormality of the ANS is also suggested by the fact that, despite the basal difference, RMSSD values were similar during exercise recovery in the 2 groups of patients, suggesting a similar ANS response to exercise interruption in the 2 groups.

Future studies should clarify whether different results regarding the relationship between ANS dysfunction and post–COVID-19 symptoms might be obtained using more comprehensive and better validated methods for the diagnosis of ANS dysfunction, such as standard tests of autonomic function and HRV assessed from its multiple (short-term and long-term) components.

Of note, although the results of CPET in the study by Ladlow et al suggest lower performance by patients classified with dysautonomia, exercise tolerance was largely normal in these subjects, who achieved >100% of the predicted maximal oxygen consumption and an average maximal work rate of 219 W, with only small differences compared to patients without dysautonomia, possibly explained, again, and at least in part, by some demographic (age) and clinical (BMI, respiratory function) differences.

In conclusion, the study by Ladlow et al provides interesting data on the clinical characteristics and objective physical performance of patients with post–COVID-19 syndrome. However, the role of ANS in determining symptoms (particularly those of potential cardiovascular origin) and physical limitation in these patients still has not been fully elucidated by their data, making necessary further studies applying more comprehensive and valuable methods for the assessment of ANS function.

Source: Lanza GA. Autonomic dysfunction and post-COVID-19 syndrome: A still elusive link. Heart Rhythm. 2022 Apr;19(4):621-622. doi: 10.1016/j.hrthm.2021.12.027. Epub 2021 Dec 28. PMID: 34968741; PMCID: PMC8712711. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8712711/ (Full study)

Platelet Storage Pool Deficiency and Elevated Inflammatory Biomarkers Are Prevalent in Postural Orthostatic Tachycardia Syndrome

Abstract:

A significant number of postural orthostatic tachycardia syndrome (POTS) patients have platelet delta granule storage pool deficiency (δ-SPD).

The etiology of POTS is unknown but a number of laboratories, including ours, have reported elevations of G-protein-coupled adrenergic receptor and muscarinic acetylcholine receptor autoantibodies in POTS patients, detected by a variety of techniques, suggesting that the disorder is an autoimmune condition. Thus, it could also be considered an inflammatory disease.

In a pilot study, we investigated a limited number of platelet-related cytokines and chemokines and discovered many that were elevated.

This case–control study validates our pilot study results that POTS patients have an activated innate immune system.

Plasma of 35 POTS patients and 35 patients with unexplained bleeding symptoms and categorized as “non-POTS” subjects was analyzed by multiplex flow cytometry to quantify 16 different innate immune system cytokines and chemokines. Electron microscopy was used to quantify platelet dense granules.

Ten of 16 biomarkers of inflammation were elevated in plasma from POTS patients compared to non-POTS subjects, with most of the differences extremely significant, with p values < 0.0001.

Of particular interest were elevations of IL-1β and IL-18 and decreased or normal levels of type 1 interferons in POTS patients, suggesting that the etiology of POTS might be autoinflammatory.

All POTS patients had δ-SPD. With a growing body of evidence that POTS is an autoimmune disease and having elevations of the innate immune system, our results suggest a potential T-cell-mediated autoimmunity in POTS characteristic of a mixed-pattern inflammatory disease similar to rheumatoid arthritis.

Source: Gunning WT, Kramer PM, Cichocki JA, Karabin BL, Khuder SA, Grubb BP. Platelet Storage Pool Deficiency and Elevated Inflammatory Biomarkers Are Prevalent in Postural Orthostatic Tachycardia Syndrome. Cells. 2022; 11(5):774. https://doi.org/10.3390/cells11050774  https://www.mdpi.com/2073-4409/11/5/774/htm (Full text)

Psychogenic Pseudosyncope: Real or Imaginary? Results from a Case-Control Study in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Patients

Abstract:

Background and objectives: Orthostatic intolerance (OI) is a clinical condition in which symptoms worsen upon assuming and maintaining upright posture and are ameliorated by recumbency. OI has a high prevalence in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Exact numbers on syncopal spells especially if they are on a weekly or even daily basis are not described. Although not a frequent phenomenon, this symptomatology is of very high burden to the patient if present. To explore whether patients with very frequent (pre)syncope spells diagnosed elsewhere with conversion or psychogenic pseudosyncope (PPS) might have another explanation of their fainting spells than behavioral psychiatric disorders, we performed a case-control study comparing ME/CFS patients with and without PPS spells.

Methods and results: We performed a case-control study in 30 ME/CFS patients diagnosed elsewhere with PPS and compared them with 30 control ME/CFS patients without syncopal spells. Cases were gender, age and ME/CFS disease duration matched. Each underwent a tilt test with extracranial Doppler measurements for cerebral blood flow (CBF). ME/CFS cases with PPS had a significant larger CBF reduction at end tilt than controls: 39 (6)% vs. 25 (4)%; (p < 0.0001). Cases had more severe disease compared with controls (chi-square p < 0.01 and had a p = 0.01) for more postural orthostatic tachycardia syndrome in cases compared with controls. PETCO2 end-tilt differed also, but the magnitude of difference was smaller than compared with the CBF reduction: there were no differences in heart rate and blood pressure at either end-tilt testing period. Compared with the test with the stockings off, the mean percentage reduction in cardiac output during the test with compression stockings on was lower, 25 (5) mmHg versus 29 (4) mmHg (p < 0.005).

Conclusions: This study demonstrates that in ME/CFS patients suspected of having PPS, or conversion, CBF measurements end-tilt show a large decline compared with a control group of ME/CFS patients. Therefore, hypoperfusion offers an explanation of the orthostatic intolerance and syncopal spells in these patients, where it is clear that origin might not be behavioral or psychogenic, but have a clear somatic pathophysiologic background.

Source: van Campen CLMC, Visser FC. Psychogenic Pseudosyncope: Real or Imaginary? Results from a Case-Control Study in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Patients. Medicina (Kaunas). 2022 Jan 9;58(1):98. doi: 10.3390/medicina58010098. PMID: 35056406. https://pubmed.ncbi.nlm.nih.gov/35056406/

Orthostatic Symptoms and Reductions in Cerebral Blood Flow in Long‐Haul COVID‐19 Patients: Similarities with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Background and Objectives: Symptoms and hemodynamic findings during orthostatic stress have been reported in both long-haul COVID-19 and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), but little work has directly compared patients from these two groups. To investigate the overlap in these clinical phenotypes, we compared orthostatic symptoms in daily life and during head-up tilt, heart rate and blood pressure responses to tilt, and reductions in cerebral blood flow in response to orthostatic stress in long-haul COVID-19 patients, ME/CFS controls, and healthy controls.
Materials and Methods: We compared 10 consecutive long-haul COVID-19 cases with 20 age- and gender-matched ME/CFS controls with postural tachycardia syndrome (POTS) during head-up tilt, 20 age- and gender-matched ME/CFS controls with a normal heart rate and blood pressure response to head-up tilt, and 10 age- and gender-matched healthy controls. Identical symptom questionnaires and tilt test procedures were used for all groups, including measurement of cerebral blood flow and cardiac index during the orthostatic stress.
Results: There were no significant differences in ME/CFS symptom prevalence between the long-haul COVID-19 patients and the ME/CFS patients. All long-haul COVID-19 patients developed POTS during tilt. Cerebral blood flow and cardiac index were more significantly reduced in the three patient groups compared with the healthy controls. Cardiac index reduction was not different between the three patient groups. The cerebral blood flow reduction was larger in the long-haul COVID-19 patients compared with the ME/CFS patients with a normal heart rate and blood pressure response.
Conclusions: The symptoms of long-haul COVID-19 are similar to those of ME/CFS patients, as is the response to tilt testing. Cerebral blood flow and cardiac index reductions during tilt were more severely impaired than in many patients with ME/CFS. The finding of early-onset orthostatic intolerance symptoms, and the high pre-illness physical activity level of the long-haul COVID-19 patients, makes it unlikely that POTS in this group is due to deconditioning. These data suggest that similar to SARS-CoV-1, SARS-CoV-2 infection acts as a trigger for the development of ME/CFS.
Source: Campen CMCv, Rowe PC, Visser FC. Orthostatic Symptoms and Reductions in Cerebral Blood Flow in Long-Haul COVID-19 Patients: Similarities with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Medicina. 2022; 58(1):28. https://doi.org/10.3390/medicina58010028  (Full text)

Autonomic dysfunction post-acute COVID-19 infection

Introduction:

SARS-CoV-2 infection which causes the disease COVID-19 is most known for its severe respiratory complications. However, a variety of extrapulmonary effects have since been described, with cardiovascular complications being amongst the most common [ 1 ]. Those who recover from the acute phase of COVID-19 may be left with residual symptoms such as chest pain and dyspnea, resulting in a decreased quality of life and a syndrome sometimes described as “long COVID”[ 2 ].

Recent evidence suggests that survivors with some of these chronic symptoms may have autonomic dysfunction with features of postural orthostatic tachycardia syndrome (POTS) and/or inappropriate sinus tachycardia (IST)3 , 4. POTS is characterized by symptoms that occur with standing, an increase in heart rate of ≥30 beats per minute (or heart rate >120 bpm) when moving from a supine to a standing position, and the absence of orthostatic hypotension[ 5 ]. IST is defined as a sinus heart rate >100 beats per minute at rest without an identifiable cause of sinus tachycardia[ 6 ]. Cardiac manifestations of autonomic dysfunction lie on a wide spectrum and can therefore be classified as either POTS, IST, or other unspecified symptoms such as tachycardia and palpitations without a clear, single underlying pathological mechanism.[ 7 ]

The treatment of these arrhythmias includes nonpharmacologic management, such as increasing salt and fluid intake, as well as the use of oral medications. Beta-blockers or off label use of ivabradine have used reported to be used in both syndromes with the goal of controlling heart rate to reduce the symptoms 8 , 9. Other therapies more common in POTS include fludrocortisone, midodrine, pyridostigmine, and alpha-2 agonists[ 8 ].

There is a need to understand the patient characteristics and risk factors for developing AD as a sequela of COVID-19. Furthermore, there is limited management information specific to patients suffering from AD following COVID-19. It is unclear how treatment of these patients and their prognoses may differ from other cases of POTS or IST. In this study, we investigated a small cohort of patients diagnosed with suspected AD post SARS-CoV-2 infection to elucidate possible risk factors and treatment strategies in this population.

Source: Desai AD, Boursiquot BC, Moore CJ, Gopinathannair R, Waase MP, Rubin GA, Wan EY. Autonomic dysfunction post-acute COVID-19 infection. HeartRhythm Case Rep. 2021 Nov 27. doi: 10.1016/j.hrcr.2021.11.019. Epub ahead of print. PMID: 34868880; PMCID: PMC8626157. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8626157/ (Full text)

Post-COVID-19 Tachycardia Syndrome: A Distinct Phenotype of Post-Acute COVID-19 Syndrome

Abstract:

In this paper we highlight the presence of tachycardia in post-acute COVID-19 syndrome by introducing a new label for this phenomenon—post-COVID-19 tachycardia syndrome—and argue that this constitutes a phenotype or sub-syndrome in post-acute COVID-19 syndrome. We also discuss epidemiology, putative mechanisms, treatment options, and future research directions in this novel clinical syndrome.

Source: Ståhlberg M, Reistam U, Fedorowski A, et al. Post-COVID-19 Tachycardia Syndrome: A Distinct Phenotype of Post-Acute COVID-19 Syndrome [published online ahead of print, 2021 Aug 11]. Am J Med. 2021;S0002-9343(21)00472-1. doi:10.1016/j.amjmed.2021.07.004  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8356730/ (Full text)

Delineating the Association Between Soluble CD26 and Autoantibodies Against G-Protein Coupled Receptors, Immunological and Cardiovascular Parameters Identifies Distinct Patterns in Post-Infectious vs. Non-Infection-Triggered Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Soluble cluster of differentiation 26 (sCD26) has a wide range of enzymatic functions affecting immunological, metabolic and vascular regulation. Diminished sCD26 concentrations have been reported in various autoimmune diseases and also in Myalgic Encephalomyelitis/Chronic fatigue syndrome (ME/CFS). Here we re-evaluate sCD26 as a diagnostic marker and perform a comprehensive correlation analysis of sCD26 concentrations with clinical and paraclinical parameters in ME/CFS patients. Though this study did find significantly lower concentrations of sCD26 only in the female cohort and could not confirm diagnostic suitability, results from correlation analyses provide striking pathomechanistic insights.

In patients with infection-triggered onset, the associations of low sCD26 with elevated autoantibodies (AAB) against alpha1 adrenergic (AR) and M3 muscarinic acetylcholine receptors (mAChR) point to a pathomechanism of infection-triggered autoimmune-mediated vascular and immunological dysregulation. sCD26 concentrations in infection-triggered ME/CFS were found to be associated with activated T cells, liver enzymes, creatin kinase (CK) and lactate dehydrogenase (LDH) and inversely with Interleukin-1 beta (IL-1b). Most associations are in line with the known effects of sCD26/DPP-4 inhibition.

Remarkably, in non-infection-triggered ME/CFS lower sCD26 in patients with higher heart rate after orthostatic challenge and postural orthostatic tachycardia syndrome (POTS) suggest an association with orthostatic regulation. These findings provide evidence that the key enzyme sCD26 is linked to immunological alterations in infection-triggered ME/CFS and delineate a different pathomechanism in the non-infectious ME/CFS subset.

Source: Szklarski M, Freitag H, Lorenz S, Becker SC, Sotzny F, Bauer S, Hartwig J, Heidecke H, Wittke K, Kedor C, Hanitsch LG, Grabowski P, Sepúlveda N, Scheibenbogen C. Delineating the Association Between Soluble CD26 and Autoantibodies Against G-Protein Coupled Receptors, Immunological and Cardiovascular Parameters Identifies Distinct Patterns in Post-Infectious vs. Non-Infection-Triggered Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Front Immunol. 2021 Apr 6;12:644548. doi: 10.3389/fimmu.2021.644548. PMID: 33889154; PMCID: PMC8056217. https://www.frontiersin.org/articles/10.3389/fimmu.2021.644548/full  (Full text)