Tag: severely ill patients

Predictors of Long COVID in Patients without Comorbidities: Data from the Polish Long-COVID Cardiovascular (PoLoCOV-CVD) Study

Abstract:

Background: The SARS-CoV-2 pandemic has become an enormous worldwide challenge over the last two years. However, little is still known about the risk of Long COVID (LC) in patients without comorbidities. Thus, we aimed to assess the predictors of LC in patients without comorbidities.

Methods: Patients’ information, the course of the disease with symptoms, and post-COVID-19 complaints were collected within 4-12 weeks after COVID-19 recovery. Next, the patients were followed for at least 3 months. ECG, 24-h ECG monitoring, 24-h blood pressure (BP) monitoring, echocardiography, and selected biochemical tests were performed. LC was recognized based on the WHO definition.

Results: We identified 701 consecutive patients, 488 of whom completed a 3-month follow-up (63% women). Comparisons were made between the LC group (n = 218) and patients without any symptoms after SARS-CoV-2 recovery (non-LC group) (n = 270). Patients with a severe course of acute-phase COVID-19 developed LC complications more often (34% vs. 19%, p < 0.0001). The persistent symptoms were observed in 45% of LC patients. The LC group also had significantly more symptoms during the acute phase of COVID-19, and they suffered significantly more often from dyspnoea (48 vs. 33%), fatigue (72 vs. 63%), chest pain (50 vs. 36%), leg muscle pain (41 vs. 32%), headache (66 vs. 52%), arthralgia (44 vs. 25%), and chills (34 vs. 25%). In LC patients, significant differences regarding sex and body mass index were observed-woman: 69% vs. 56% (p = 0.003), and BMI: 28 [24-31] vs. 26 kg/m2 [23-30] (p < 0.001), respectively. The number of symptoms in the acute phase was significantly greater in the LC group than in the control group (5 [2-8] vs. 2 [1-5], p = 0.0001). The LC group also had a higher 24-h heart rate (77 [72-83] vs. 75 [70-81], p = 0.021) at admission to the outpatient clinic. Multivariate regression analysis showed that LC patients had a higher BMI (odds ratio (OR): 1.06, 95% confidence intervals [CI]: 1.02-1.10, p = 0.007), almost twice as often had a severe course of COVID-19 (OR: 1.74, CI: 1.07-2.81, p = 0.025), and presented with joint pain in the acute phase (OR: 1.90, CI: 1.23-2.95, p = 0.004).

Conclusions: A severe course of COVID-19, BMI, and arthralgia are independently associated with the risk of Long COVID in healthy individuals.

Source: Chudzik M, Lewek J, Kapusta J, Banach M, Jankowski P, Bielecka-Dabrowa A. Predictors of Long COVID in Patients without Comorbidities: Data from the Polish Long-COVID Cardiovascular (PoLoCOV-CVD) Study. J Clin Med. 2022 Aug 25;11(17):4980. doi: 10.3390/jcm11174980. PMID: 36078910. https://www.mdpi.com/2077-0383/11/17/4980/htm (Full text)

Autoimmune Gene Expression Proling 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 2 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: Zheng Wang, Michelle F. Waldman, Tara J. Basavanhally, Aviva R. Jacobs, et al. Autoimmune Gene Expression Proling of Fingerstick Whole Blood in Chronic Fatigue Syndrome. https://doi.org/10.21203/rs.3.rs-1942047/v1  (Full text)

Phenotypic characteristics of peripheral immune cells of Myalgic encephalomyelitis/chronic fatigue syndrome via transmission electron microscopy: A pilot study

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex chronic multi-systemic disease characterized by extreme fatigue that is not improved by rest, and worsens after exertion, whether physical or mental. Previous studies have shown ME/CFS-associated alterations in the immune system and mitochondria.

We used transmission electron microscopy (TEM) to investigate the morphology and ultrastructure of unstimulated and stimulated ME/CFS immune cells and their intracellular organelles, including mitochondria. PBMCs from four participants were studied: a pair of identical twins discordant for moderate ME/CFS, as well as two age- and gender- matched unrelated subjects-one with an extremely severe form of ME/CFS and the other healthy.

TEM analysis of CD3/CD28-stimulated T cells suggested a significant increase in the levels of apoptotic and necrotic cell death in T cells from ME/CFS patients (over 2-fold). Stimulated Tcells of ME/CFS patients also had higher numbers of swollen mitochondria. We also found a large increase in intracellular giant lipid droplet-like organelles in the stimulated PBMCs from the extremely severe ME/CFS patient potentially indicative of a lipid storage disorder. Lastly, we observed a slight increase in platelet aggregation in stimulated cells, suggestive of a possible role of platelet activity in ME/CFS pathophysiology and disease severity.

These results indicate extensive morphological alterations in the cellular and mitochondrial phenotypes of ME/CFS patients’ immune cells and suggest new insights into ME/CFS biology.

Source: Jahanbani F, Maynard RD, Sing JC, Jahanbani S, Perrino JJ, Spacek DV, Davis RW, Snyder MP. Phenotypic characteristics of peripheral immune cells of Myalgic encephalomyelitis/chronic fatigue syndrome via transmission electron microscopy: A pilot study. PLoS One. 2022 Aug 9;17(8):e0272703. doi: 10.1371/journal.pone.0272703. PMID: 35943990. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0272703 (Full text)

Ensuring the Voice of the Very Severely Affected Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patient Is Heard in Research—A Research Model

Abstract:

Most of the research about Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) has focused on ambulant patients who are able to attend clinics. It is estimated that 25% of people with ME/CFS are severely, or very severely, affected and are housebound or bedbound; some require tube feeding. Due to the severity of their illness, these patients have largely been excluded from research and are often described as ‘hard to reach.’ A questionnaire was devised to gather data about their experiences of accessing tube feeding. By making the necessary reasonable adjustments, such as direct outreach and the option to complete the questionnaire by telephone or texting, very severely affected patients were enabled to participate and provided invaluable contributions. This study aimed to act as a model for future researchers.
Source: Baxter H. Ensuring the Voice of the Very Severely Affected Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patient Is Heard in Research—A Research Model. Healthcare. 2022; 10(7):1278. https://doi.org/10.3390/healthcare10071278  https://www.mdpi.com/2227-9032/10/7/1278 (Full text)

Comparative Analysis of Extracellular Vesicles in Patients with Severe and Mild Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Myalgic encephalomyelitis, or chronic fatigue syndrome (ME/CFS) is a serious disease whose cause has yet to be identified. Objective markers of the disease are also not well understood and would serve as important tools in diagnosis and management.

One potential biomarker or transmitter of immune signals in ME/CFS is the extracellular vesicle (EV) compartment. These small, membrane bound particles have been shown to play a key role in intercellular signaling. Our laboratory has focused on methods of detection of EVS in clinical samples. In this study we explored whether the prevalence of EVs in the plasma of participants with mild or severe ME/CFS differed from the plasma of healthy control participants. By staining for multiple cell surface molecules, plasma EVs could be fingerprinted as to their cell of origin.

Our study revealed a significant correlation between severe ME/CSF and levels of EVs bearing the B cell marker CD19 and the platelet marker CD41a, though these changes were not significant after correction for multiple comparisons. These findings point to potential dysregulation of B cell and platelet activation or homeostasis in ME/CFS, which warrants validation in a replication cohort and further exploration of potential mechanisms underlying the association.

Source: Bonilla H, Hampton D, Marques de Menezes EG, Deng X, Montoya JG, Anderson J, Norris PJ. Comparative Analysis of Extracellular Vesicles in Patients with Severe and Mild Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Front Immunol. 2022 Mar 4;13:841910. doi: 10.3389/fimmu.2022.841910. PMID: 35309313; PMCID: PMC8931328. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8931328/ (Full text)

Predictors for Developing Severe Myalgic Encephalomyelitis/Chronic Fatigue Syndrome following Infectious Mononucleosis

Abstract:

Background: About 10% of individuals who contract infectious mononucleosis (IM) have symptoms 6 months later that meet criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).  Our study for the first time examined whether it is possible to predict who will develop ME/CFS following IM.

Methods: We have reported on a prospectively recruited cohort of 4,501 college students, of which 238 (5.3%) developed IM.  Those who developed IM were followed-up at six months to determine whether they recovered or met criteria for ME/CFS. The present study focuses on 48 students who after six months had a diagnosis of ME/CFS, and a matched control group of 58 students who had no further symptoms after their IM. All of these 106 students  had data at baseline (at least 6 weeks prior to the development of IM), when experiencing IM, and 6 months following IM. Of those who did not recover from IM, there were two groups: 30 were classified as ME/CFS and 18 were classified as severe ME/CFS. We measured the results of 7 questionnaires, physical examination findings, the severity of mononucleosis and cytokine analyses at baseline (pre-illness) and at the time of IM.  We examined predictors (e.g., pre-illness variables as well as variables at onset of IM) of  those who developed ME/CFS and severe ME/CFS following IM.

Results: From analyses using receiver operating characteristic statistics, the students who had had severe gastrointestinal symptoms of stomach pain, bloating, and an irritable bowel at baseline  and who also had abnormally low levels of the immune markers IL-13 and/or IL-5 at baseline, as well as severe gastrointestinal symptoms when then contracted IM,  were found to have a nearly 80% chance of having severe ME/CFS persisting six months following IM.

Conclusions: Our findings are consistent with emerging literature that gastrointestinal distress and autonomic symptoms, along with several immune markers, may be implicated in the development of severe ME/CFS.

Source: Jason, Leonard & Cotler, Joseph & Islam, Mohammed & Furst, Jacob & Katz, Ben. (2022). Predictors for Developing Severe Myalgic Encephalomyelitis/Chronic Fatigue Syndrome following Infectious Mononucleosis. Journal of Rehabilitation Therapy. 4. 1-5. 10.29245/2767-5122/2021/1.1129. https://www.rehabiljournal.com/articles/predictors-for-developing-severe-myalgic-encephalomyelitischronic-fatigue-syndrome-following-infectious-mononucleosis.html  (Full text)

Risk Factors for Severe ME/CFS

Abstract:

ME/CFS is a serious illness affecting several hundred thousand British people. Some 25% of people with ME/CFS may be severely ill (housebound or bedbound), sometimes for decades. This observational, questionnaire-based study was designed to identify risk factors for severe disease. Exposure to potential risk factors, including familial risks, personality, and early management of the illness, was compared in 124 people with severe disease and 619 mildly ill controls. Severity was determined by self-report and the Barthel (activities of daily living) Index.

Premorbid personality was assessed using the Neuroticism and Conscientiousness domains of the IPIP scale. Analysis was by tests of association and logistic regression. Early management of the illness appeared the most important determinant of severity. Having a mother with ME/CFS was also important. Smoking and personality were not risk factors, neurotic traits being more frequent among the less severely ill. Conscientiousness overall was not related to severity.

Source: Derek Pheby, Lisa Saffron. Risk Factors for Severe ME/CFS. Biology and Medicine, Vol 1 (4): 50-74, 2009. https://meassociation.org.uk/wp-content/uploads/2013/04/Biology-and-Medicine_Published-paper_vol1_4_50-74.pdf  (Full text)

Chronic Fatigue Syndrome: A Case Report Highlighting Diagnosing and Treatment Challenges and the Possibility of Jarisch-Herxheimer Reactions If High Infectious Loads Are Present

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex multi-system disease with no cure and no FDA-approved treatment. Approximately 25% of patients are house or bedbound, and some are so severe in function that they require tube-feeding and are unable to tolerate light, sound, and human touch.

The overall goal of this case report was to (1) describe how past events (e.g., chronic sinusitis, amenorrhea, tick bites, congenital neutropenia, psychogenic polydipsia, food intolerances, and hypothyroidism) may have contributed to the development of severe ME/CFS in a single patient, and (2) the extensive medical interventions that the patient has pursued in an attempt to recover, which enabled her to return to graduate school after becoming bedridden with ME/CFS 4.5 years prior.

This paper aims to increase awareness of the harsh reality of ME/CFS and the potential complications following initiation of any level of intervention, some of which may be necessary for long-term healing. Treatments may induce severe paradoxical reactions (Jarisch-Herxheimer reaction) if high infectious loads are present. It is our hope that sharing this case will improve research and treatment options for ME/CFS.

Source: Straub RK, Powers CM. Chronic Fatigue Syndrome: A Case Report Highlighting Diagnosing and Treatment Challenges and the Possibility of Jarisch-Herxheimer Reactions If High Infectious Loads Are Present. Healthcare (Basel). 2021 Nov 10;9(11):1537. doi: 10.3390/healthcare9111537. PMID: 34828583. https://pubmed.ncbi.nlm.nih.gov/34828583/

Cerebral blood flow remains reduced after tilt testing in myalgic encephalomyelitis/chronic fatigue syndrome patients

Abstract:

Objective: Orthostatic symptoms in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) may be caused by an abnormal reduction in cerebral blood flow. An abnormal cerebral blood flow reduction was shown in previous studies, without information on the recovery pace of cerebral blood flow. This study examined the prevalence and risk factors for delayed recovery of cerebral blood flow in ME/CFS patients.

Methods: 60 ME/CFS adults were studied: 30 patients had a normal heart rate and blood pressure response during the tilt test, 4 developed delayed orthostatic hypotension, and 26 developed postural orthostatic tachycardia syndrome (POTS) during the tilt. Cerebral blood flow measurements, using extracranial Doppler, were made in the supine position pre-tilt, at end-tilt, and in the supine position at 5 min post-tilt. Also, cardiac index measurements were performed, using suprasternal Doppler imaging, as well as end-tidal PCO2 measurements. The change in cerebral blood flow from supine to end-tilt was expressed as a percent reduction with mean and (SD). Disease severity was scored as mild (approximately 50% reduction in activity), moderate (mostly housebound), or severe (mostly bedbound).

Results: End-tilt cerebral blood flow reduction was -29 (6)%, improving to -16 (7)% at post-tilt. No differences in either end-tilt or post-tilt measurements were found when patients with a normal heart rate and blood pressure were compared to those with POTS, or between patients with normocapnia (end-tidal PCO2 ≥ 30 mmHg) versus hypocapnia (end-tidal PCO2 < 30 mmHg) at end-tilt. A significant difference was found in the degree of abnormal cerebral blood flow reduction in the supine post-test in mild, moderate, and severe ME/CFS: mild: cerebral blood flow: -7 (2)%, moderate: -16 (3)%, and severe :-25 (4)% (p all < 0.0001). Cardiac index declined significantly during the tilt test in all 3 severity groups, with no significant differences between the groups. In the supine post-test cardiac index returned to normal in all patients.

Conclusions: During tilt testing, extracranial Doppler measurements show that cerebral blood flow is reduced in ME/CFS patients and recovery to normal supine values is incomplete, despite cardiac index returning to pre-tilt values. The delayed recovery of cerebral blood flow was independent of the hemodynamic findings of the tilt test (normal heart rate and blood pressure response, POTS, or delayed orthostatic hypotension), or the presence/absence of hypocapnia, and was only related to clinical ME/CFS severity grading. We observed a significantly slower recovery in cerebral blood flow in the most severely ill ME/CFS patients.

Significance: The finding that orthostatic stress elicits a post-stress cerebral blood flow reduction and that disease severity greatly influences the cerebral blood flow reduction may have implications on the advice of energy management after a stressor and on the advice of lying down after a stressor in these ME/CFS patients.

Source: van Campen CLMC, Rowe PC, Visser FC. Cerebral blood flow remains reduced after tilt testing in myalgic encephalomyelitis/chronic fatigue syndrome patients. Clin Neurophysiol Pract. 2021 Sep 23;6:245-255. doi: 10.1016/j.cnp.2021.09.001. PMID: 34667909; PMCID: PMC8505270. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8505270/  (Full text)

Caring for the patient with severe or very severe Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) can cause a wide range of severity and functional impairment, leaving some patients able to work while others are homebound or bedbound. The most severely ill patients may need total care. Yet, patients with severe or very severe ME/CFS struggle to receive appropriate medical care because they cannot travel to doctors’ offices and their doctors lack accurate information about the nature of this disease and how to diagnose and manage it. Recently published clinical guidance provides updated information about ME/CFS but advice on caring for the severely ill is limited. This article is intended to fill that gap.
Based on published clinical guidance and clinical experience, we describe the clinical presentation of severe ME/CFS and provide patient-centered recommendations on diagnosis, assessment and approaches to treatment and management. We also provide suggestions to support the busy provider in caring for these patients by leveraging partnerships with the patient, their caregivers, and other providers and by using technology such as telemedicine. Combined with compassion, humility, and respect for the patient’s experience, such approaches can enable the primary care provider and other healthcare professionals to provide the care these patients require and deserve.
Source: Montoya JG, Dowell TG, Mooney AE, Dimmock ME, Chu L. Caring for the Patient with Severe or Very Severe Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Healthcare. 2021; 9(10):1331. https://doi.org/10.3390/healthcare9101331 https://www.mdpi.com/2227-9032/9/10/1331/htm (Full text)