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)

Editorial: Current Insights Into Complex Post-infection Fatigue Syndromes With Unknown Aetiology: The Case of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Beyond

Introduction:

Black plague epidemics in Medieval Europe, the Spanish Flu pandemic during the first world war, and the pandemic of COVID-19 disease are just three devastating examples of the fragile co-existence between human beings and the microbial world. Remarkably, the human immune system with its innate and adaptive arms recognizes and clears the invading pathogens in most cases. However, like a scar after an injury, some people who had suffered from acute infections remain ill long after the clearance of the pathogen itself. These individuals develop complex fatigue-related syndromes whose pathological mechanisms remain poorly understood. A prime example of such syndromes is the Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) characterized by persistent fatigue and post-exertional malaise among other symptoms (1). Unfortunately, its diagnosis remains challenging due to the inexistence of objective biomarkers that could identify cases. However, researchers are gathering around multidisciplinary networks, such as the US ME/CFS Clinician Coalition and the European Network on ME/CFS, with the aim of fostering collaboration, standardizing research and clinical practices, while accelerating biomarker discovery (2–5). Less-known fatigue-related syndromes have been recently reported after the outbreaks of Ebola virus, Dengue virus, and Chikungunya virus in the Tropics (6–8). However, it is still unclear whether these syndromes constitute clinical entities beyond ME/CFS itself.

Read the rest of this article HERE.

Source: Westermeier F, Lacerda EM, Scheibenbogen C and Sepúlveda N (2022) Editorial: Current Insights Into Complex Post-infection Fatigue Syndromes With Unknown Aetiology: The Case of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Beyond. Front. Med. 9:862953. doi: 10.3389/fmed.2022.862953  https://www.frontiersin.org/articles/10.3389/fmed.2022.862953/full (Full text)

Evaluating case diagnostic criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): toward an empirical case definition

Abstract:

Purpose: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is an illness characterized by a variety of symptoms including post-exertional malaise, unrefreshing sleep, and cognitive impairment. A variety of case definitions (e.g., the Canadian Consensus Criteria (CCC), the Myalgic Encephalomyelitis International Consensus Criteria (ME-ICC), and the Institute of Medicine (IOM) criteria) have been used to diagnose patients. However, these case definitions are consensus-based rather than empirical.

Materials and methods: The aim of the current study was to evaluate the validity of the aforementioned case definitions by factor analyzing a large, international sample (N = 2308) of ME/CFS symptom data. We performed primary and secondary exploratory factor analyses on the DePaul Symptom Questionnaire’s 54-item symptom inventory. These results were compared to the CCC, the ME-ICC, and the IOM criteria.

Results: We identified seven symptom domains, including post-exertional malaise, cognitive dysfunction, and sleep dysfunction. Contrary to many existing case criteria, our analyses did not identify pain as an independent factor.

Conclusions: Although our results implicate a factor solution that best supports the CCC, revisions to the criteria are recommended. Implications for rehabilitation: ME/CFS is a chronic illness with no consensus regarding case diagnostic criteria, which creates difficulty for patients seeking assistance and disability benefits. The current study compared three commonly used case definitions for ME/CFS by factor analyzing symptomological data from an international sample of patients. Our results suggest three primary and four secondary symptom domains which differed from all three case definitions. These findings could help reduce barriers to care for those disabled with ME/CFS by guiding the development of an empirically-based case definition.

Source: Conroy KE, Islam MF, Jason LA. Evaluating case diagnostic criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): toward an empirical case definition. Disabil Rehabil. 2022 Mar 2:1-8. doi: 10.1080/09638288.2022.2043462. Epub ahead of print. PMID: 35236205. https://pubmed.ncbi.nlm.nih.gov/35236205/

The impact of post-traumatic stress on quality of life and fatigue in women with Gulf War Illness

Abstract:

Background: Gulf War Illness (GWI) is a chronic, multi-symptomatic disorder characterized by fatigue, muscle pain, cognitive problems, insomnia, rashes, and gastrointestinal issues affecting an estimated 30% of the ~ 750,000 returning military Veterans of the 1990-1991 Persian Gulf War. Female Veterans deployed to combat in this war report medical symptoms, like cognition and respiratory troubles, at twice the rate compared to non-deployed female Veterans of the same era. The heterogeneity of GWI symptom presentation complicates diagnosis as well as the identification of effective treatments. This is exacerbated by the presence of co-morbidities. Defining subgroups of the illness may help alleviate these complications. One clear grouping is along the lines of gender. Our aim is to determine if women with GWI can be further subdivided into distinct subgroups based on post-traumatic stress disorder (PTSD) symptom presentation.

Methods: Veterans diagnosed with GWI (n = 35) and healthy sedentary controls (n = 35) were recruited through the Miami Veterans Affairs Medical Health Center. Symptoms were assessed via the RAND short form health survey, the multidimensional fatigue inventory, and the Davidson trauma scale. Hierarchal regression modeling was performed on measures of health and fatigue with PTSD symptoms as a covariate. This was followed by univariate analyses conducted with two separate GWI groups based on a cut-point of 70 for their total Davidson trauma scale value and performing heteroscedastic t-tests across all measures.

Results: Based on the distinct differences found in PTSD symptomology regarding all health and trauma symptoms, two subgroups were derived within female GWI Veterans. Hierarchical regression models displayed the comorbid effects of GWI and PTSD, as both conditions had measurable impacts on quality of life and fatigue (ΔR2 = 0.08-0.672), with notable differences in mental and emotional measures. Overall, a cut point analysis indicated poorer quality of life and greater fatigue within all measures for women with GWI and PTSD symptoms in comparison to those women with GWI without PTSD symptoms and healthy controls.

Conclusions: Our current findings support the understanding that comorbid symptoms of GWI and PTSD subsequently result in poorer quality of life and fatigue, along with establishing the possibility of varying clinical presentations.

Source: Shastry N, Sultana E, Jeffrey M, Collado F, Kibler J, DeLucia C, Fletcher MA, Klimas N, Craddock TJA. The impact of post-traumatic stress on quality of life and fatigue in women with Gulf War Illness. BMC Psychol. 2022 Feb 25;10(1):42. doi: 10.1186/s40359-022-00752-5. PMID: 35216624; PMCID: PMC8876751. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8876751/ (Full text)

Does Dietary Coenzyme Q10 plus Selenium Supplementation Ameliorate Clinical Outcomes by Modulating Oxidative Stress and Inflammation in Individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome?

Abstract:

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a neuroinflammatory, multifaceted chronic disorder of unknown cause. Accumulating data indicates a link between a redox imbalance, mitochondrial dysfunction, and inflammation status in ME/CFS. CoQ10 and selenium as effective antioxidant and anti-inflammatory agents have shown potential clinical implications in chronic diseases; however, their therapeutic benefits on ME/CFS remain elusive.

This open-label exploratory study aimed to evaluate the effectiveness of combined CoQ10 plus selenium supplementation on clinical features and circulating biomarkers in ME/CFS. Twenty-seven ME/CFS patients received an oral combination of 400 mg of CoQ10 and 200 µg of selenium daily for 8-weeks. The primary endpoint was patient-reported changes in outcome measures from baseline to 8 weeks post-intervention.

Secondary endpoint included changes in circulating biomarkers from baseline to each participant. After an 8-week intervention, a significant improvement was found for overall fatigue severity (p = 0.021) and global quality of life (p = 0.002), while there was no significant effect on the sleep disturbances (p = 0.480) among participants. After 8-weeks’ intervention, there was significantly increased total antioxidant capacity, and there were reduced lipoperoxides levels from the participants (p < 0.0001 for both). Circulating cytokine levels decreased significantly (p < 0.01 for all), but with no significant changes on the CRP, FGF21, and NT-proBNP biomarkers after supplementation.

Based on these findings, we hypothesized that long-term supplementation of combined CoQ10 and selenium may indicate a potentially beneficial synergistic effect in ME/CFS.

Source: Castro-Marrero J, Domingo JC, Cordobilla B, Ferrer R, Giralt M, Sanmartin-Sentañes R, Alegre-Martin J. Does Dietary Coenzyme Q10 plus Selenium Supplementation Ameliorate Clinical Outcomes by Modulating Oxidative Stress and Inflammation in Individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome? Antioxid Redox Signal. 2022 Mar 1. doi: 10.1089/ars.2022.0018. Epub ahead of print. PMID: 35229657. https://pubmed.ncbi.nlm.nih.gov/35229657/

Spontaneously reported persistent symptoms related to coronavirus disease 2019 one year after hospital discharge : A retrospective cohort single-center study

Abstract:

in English, German

Background: There are no outcome studies for coronavirus disease 2019 (COVID-19) survivors one year after hospital discharge in Germany.

Methods: This retrospective cohort study included all patients with polymerase chain reaction (PCR)-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) hospitalized in the departments of internal medicine of the Klinikum Saarbrücken, a tertiary care hospital, between March 15 and December 31, 2020. A telephone interview with survivors was conducted at least 12 months after discharge. The interview was initiated with an open-ended question whether the patient had fully recovered from the disease. In the event of a subjective incomplete recovery, the patient was prompted to report any continuous or frequent symptoms that had not occurred prior to COVID-19. Finally, independent of the open-ended question response, all patients were asked closed questions which addressed new symptom onset of persistent fatigue, cognitive dysfunction, headache, muscle and joint pain following COVID-19.

Results: In all, 235 survivors were contacted and 162 could be included in the analysis. In 55 of 162 interviews (34.0%) at least one persistent COVID-19 symptom (PCS) was spontaneously reported. Four of 55 survivors with PCS reported five additional symptoms on the closed questions. One survivor, who responded positively to the open-ended question, reported new onset PCS in response to the closed questions. Physical fatigue (24.7%), cognitive dysfunction (14.8%), shortness of breath (8.6%), muscle and joint pain (6.8%) and headache (6.2%) were the most frequently reported PCS.

Conclusions: Despite an interview technique aimed to reduce attribution bias by patients, one third of COVID-19 inpatient survivors report PCS one year after hospitalization.

The complete article is written in English.

Source: Zuschlag D, Grandt D, Custodis F, Braun C, Häuser W. Spontaneously reported persistent symptoms related to coronavirus disease 2019 one year after hospital discharge : A retrospective cohort single-center study. Schmerz. 2022 Feb 25:1–9. doi: 10.1007/s00482-022-00626-0. Epub ahead of print. PMID: 35217881; PMCID: PMC8877740. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8877740/ (Full study)

COVID-19 and Mitochondrial Non-Coding RNAs: New Insights From Published Data

Abstract:

Scientists all around the world are working to investigate new ways to prevent and treat COVID-19, and recent research has been focusing on the effects of a syndrome commonly called “long COVID.” People affected by this syndrome usually suffer from symptoms like the ones observed in several types of fatigue syndrome. As these syndromes are often linked to mitochondrial dysfunction, researchers hypothesized that a dysfunction in the mitochondrial metabolism might be part of the causes of long COVID. However, while there are a few studies investigating the effect of SARS-CoV-2 infection on mitochondrial metabolism, the effect on the transcription of mitochondrial non-coding RNAs has not been investigated yet. Thus, using publicly available data, I explored the effect of SARS-CoV-2 on the expression of several mitochondrial non-coding RNAs in patients recovering from COVID-19.

No change in the expression of long non-coding RNAs was detected at any stage of the infection, but up to 43 small mitochondrial RNAs have their expression altered during the recovery from COVID-19. This result suggests that the SARS-CoV-2 infection somehow affected the metabolism of small mitochondrial RNAs specifically without altering the overall mitochondrial transcription. Despite these being only preliminary results on a small cohort, the analyses clearly showed that individuals infected by SARS-CoV-2 retain an altered expression of these small RNAs. This persistent alteration in the expression of small mitochondrial RNAs might be involved in the long COVID syndrome and further studies are needed to confirm the possibility.

Source: Pozzi A. COVID-19 and Mitochondrial Non-Coding RNAs: New Insights From Published Data. Front Physiol. 2022 Feb 4;12:805005. doi: 10.3389/fphys.2021.805005. PMID: 35185603; PMCID: PMC8856670. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8856670/ (Full text)

Pain Burden in Post-COVID-19 Syndrome following Mild COVID-19 Infection

Abstract:

The global pandemic of SARS-CoV-2 has affected several hundred million people, and many infected people have suffered from a milder initial infection but have never fully recovered. This observational study investigates the pain burden in sufferers of post-COVID-19 syndrome after a milder initial infection.

One hundred post-COVID-19 patients filled out questionnaires regarding sociodemographic data, previous comorbidities, present pharmacological treatment, pain intensity and pain localisation. Health-related quality of life, fatigue, emotional status, and insomnia were measured by validated questionnaires. Multiple post-COVID-19 symptoms, including post-exertional malaise, were evaluated by a symptom questionnaire. Among the 100 participants (mean age 44.5 years), 82% were women, 61% had higher education, and 56% were working full or part time. Nine participants reported previous pain or inflammatory conditions. Among the most painful sites were the head/face, chest, lower extremities, and migrating sites. Generalised pain was self-reported by 75 participants and was estimated in 50 participants. Diagnosis of fibromyalgia according to the 2016 criteria was suspected in 40 participants. Subgroup analyses indicated that comorbidities might play a role in the development of pain.

In conclusion, a major part of sufferers from post-COVID-19 syndrome develop pain, and in addition to its many disabling symptoms, there is an urgent need for pain management in post-COVID-19 syndrome.

Source: Bileviciute-Ljungar I, Norrefalk JR, Borg K. Pain Burden in Post-COVID-19 Syndrome following Mild COVID-19 Infection. J Clin Med. 2022 Jan 31;11(3):771. doi: 10.3390/jcm11030771. PMID: 35160223; PMCID: PMC8836662. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8836662/ (Full text)

Covid-19: Vaccinated people are less likely to get long covid, review finds

People who had been fully vaccinated against covid-19 were around half as likely to develop long covid symptoms as people who had received only one vaccine dose or were unvaccinated, the UK Health Security Agency has said.1

The agency conducted a rapid review of evidence, including 15 UK and international studies up to January 2022. Being vaccinated was defined as having two doses of the Pfizer-BioNTech, Oxford-AstraZeneca, or Moderna vaccine or one dose of the Janssen vaccine.

The review found that vaccine effectiveness against most post-covid symptoms in adults was highest in people over 60 and lowest in those aged 19 to 35.

Around 2% of the UK population have reported symptoms of long covid (or “post-covid syndrome”), which can last for more than four weeks after the initial SARS-CoV-2 infection. The most common symptoms are fatigue, shortness of breath, and muscle or joint pain.

Read the rest of this article HERE.

Source: Mahase E. Covid-19: Vaccinated people are less likely to get long covid, review finds. BMJ. 2022 Feb 16;376:o407. doi: 10.1136/bmj.o407. PMID: 35172970. https://www.bmj.com/content/376/bmj.o407 (Full text)

Long COVID: post-acute sequelae of COVID-19 with a cardiovascular focus

Abstract:

Emerging as a new epidemic, long COVID or post-acute sequelae of coronavirus disease 2019 (COVID-19), a condition characterized by the persistence of COVID-19 symptoms beyond 3 months, is anticipated to substantially alter the lives of millions of people globally. Cardiopulmonary symptoms including chest pain, shortness of breath, fatigue, and autonomic manifestations such as postural orthostatic tachycardia are common and associated with significant disability, heightened anxiety, and public awareness. A range of cardiovascular (CV) abnormalities has been reported among patients beyond the acute phase and include myocardial inflammation, myocardial infarction, right ventricular dysfunction, and arrhythmias.

Pathophysiological mechanisms for delayed complications are still poorly understood, with a dissociation seen between ongoing symptoms and objective measures of cardiopulmonary health. COVID-19 is anticipated to alter the long-term trajectory of many chronic cardiac diseases which are abundant in those at risk of severe disease.

In this review, we discuss the definition of long COVID and its epidemiology, with an emphasis on cardiopulmonary symptoms. We further review the pathophysiological mechanisms underlying acute and chronic CV injury, the range of post-acute CV sequelae, and impact of COVID-19 on multiorgan health. We propose a possible model for referral of post-COVID-19 patients to cardiac services and discuss future directions including research priorities and clinical trials that are currently underway to evaluate the efficacy of treatment strategies for long COVID and associated CV sequelae.

Source: Raman B, Bluemke DA, Lüscher TF, Neubauer S. Long COVID: post-acute sequelae of COVID-19 with a cardiovascular focus. Eur Heart J. 2022 Feb 18:ehac031. doi: 10.1093/eurheartj/ehac031. Epub ahead of print. PMID: 35176758. https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehac031/6529562 (Full text)