Tag: 2022

Genetic risk factors for ME/CFS identified using combinatorial analysis

Abstract:

Background:Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating chronic disease that lacks known pathogenesis, distinctive diagnostic criteria, and effective treatment options. Understanding the genetic (and other) risk factors associated with the disease would begin to help to alleviate some of these issues for patients.

Methods: We applied both GWAS and the PrecisionLife combinatorial analytics platform to analyze ME/CFS cohorts from UK Biobank, including the Pain Questionnaire cohort, in a case-control design with 1,000 cycles of fully random permutation. Results from this study were supported by a series of replication and cohort comparison experiments, including use of disjoint Verbal Interview CFS, post-viral fatigue syndrome and fibromyalgia cohorts also derived from UK Biobank, and results compared for overlap and reproducibility.

Results: Combinatorial analysis revealed 199 SNPs mapping to 14 genes, that were significantly associated with 91% of the cases in the ME/CFS population. These SNPs were found to stratify by shared cases into 15 clusters (communities) made up of 84 high-order combinations of between 3-5 SNPs. p-values for these communities range from 2.3 × 10−10 to 1.6 × 10−72. Many of the genes identified are linked to the key cellular mechanisms hypothesized to underpin ME/CFS, including vulnerabilities to stress and/or infection, mitochondrial dysfunction, sleep disturbance and autoimmune development. We identified 3 of the critical SNPs replicated in the post-viral fatigue syndrome cohort and 2 SNPs replicated in the fibromyalgia cohort. We also noted similarities with genes associated with multiple sclerosis and long COVID, which share some symptoms and potentially a viral infection trigger with ME/CFS.

Conclusions: This study provides the first detailed genetic insights into the pathophysiological mechanisms underpinning ME/CFS and offers new approaches for better diagnosis and treatment of patients

Source: Sayoni Das, Krystyna Taylor, James Kozubek, Jason Sardell, Steve Gardner. Genetic Risk Factors for ME/CFS Identified using Combinatorial Analysis. medRxiv 2022.09.09.22279773; doi: https://doi.org/10.1101/2022.09.09.22279773  https://www.medrxiv.org/content/10.1101/2022.09.09.22279773v2.full-text (Full text)

Mechanism of the Huangguoshu waterfall forest environment’s promotive effect on human health in Guizhou, China

Abstract:

Background: The aim of this study was to investigate the specific mechanisms underlying the human health-promoting effects of the forest environment at Huangguoshu Falls, Guizhou, China.

Methods: Ninety-five participants were recruited and an eye tracker was used to record fixation and sweep indices. A questionnaire was also used to evaluate the effects of different subject environments on human emotions, perceived recovery and preferences. Thereafter, 24 participants with chronic fatigue syndrome (CFS) were recruited and the participants’ fatigue and stress-related scale indices and inflammatory factor levels were examined. Serum metabolites of the participants under different time waterfall forest interventions were detected by ultra performance liquid chromatography-quadrupole-time of flight mass spectrometry (UHPLC-Q/TOF-MS).

Results: Eye tracking paradigm analysis showed that the “waterfall” element was the most interesting element for participants and that the “charm” of the waterfall forest environment could be well perceived by participants. Scores on the Fatigue Scale, Anxiety Scale and Depression Scale decreased as the duration of treatment in the waterfall forest environment increased. Levels of inflammatory factors decreased after treatment in the waterfall forest environment. At the same time the level of antioxidants, represented by L-ascorbic acid, increased significantly.

Conclusions: The charm of the Huangguoshu waterfall scenery could be perceived by the participants and have a positive modulating effect on mood and cognitive function. In addition, the unique mixture of negative oxygen ions in this environment can increase the content of endogenous antioxidants and balance the metabolism of choline and amino acids.

Source: Zhu Z, Zhao X, Ouyang Q, Cong S, Zhou M, Xiong Y, Zhang M, Luo X, Cheng M. Mechanism of the Huangguoshu waterfall forest environment’s promotive effect on human health in Guizhou, China. Ann Transl Med. 2022 Aug;10(16):894. doi: 10.21037/atm-22-3787. PMID: 36110995; PMCID: PMC9469133. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9469133/ (Full text)

A preliminary estimate of the economic impact of long COVID in the United States

Abstract:

Post-Acute Sequelae of SARS CoV-2 infection (PASC), more commonly referred to as Long COVID, is one of the most daunting health-care grand challenges facing the United States today. Affecting millions of Americans, Long COVID extracts a huge cost both socially and economically. In this article, we provide a preliminary estimate of the annual income loss and medical costs due to Long COVID in the United States. With many Long COVID patients either meeting the diagnostic criteria for myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) or exhibiting symptoms consistent with ME/CFS, we utilize ME/CFS to help guide our estimates. Based on the nearly 86 million documented US COVID survivors as of June 25, 2022, and considering a range of 5% to 20% of those survivors currently afflicted with Long COVID, we estimate annual medical costs to range from $43 billion to $172 billion, and lost income to range from $101 billion to $430 billion. This corresponds to an annual economic impact (exclusive of costs of disability services, social services, and lost income on the part of caretakers) ranging from roughly $140 billion to $600 billion.

Source: Arthur A. Mirin (2022) A preliminary estimate of the economic impact of long COVID in the United States, Fatigue: Biomedicine, Health & Behavior, DOI: 10.1080/21641846.2022.2124064

Chronic Fatigue Associated with Post-COVID Syndrome versus Transient Fatigue Caused by High-Intensity Exercise: Are They Comparable in Terms of Vascular Effects?

Abstract:

Purpose: The pathophysiology of chronic fatigue associated with post-COVID syndrome is not well recognized. It is assumed that this condition is partly due to vascular dysfunction developed during an acute phase of infection. There is great demand for a diagnostic tool that is able to clinically assess post-COVID syndrome and monitor the rehabilitation process.

Patients and methods: The Flow Mediated Skin Fluorescence (FMSF) technique appears uniquely suitable for the analysis of basal microcirculatory oscillations and reactive hyperemia induced by transient ischemia. The FMSF was used to measure vascular circulation in 45 patients with post-COVID syndrome. The results were compared with those for a group of 26 amateur runners before and after high-intensity exercise as well as for a control group of 32 healthy age-matched individuals.

Results: Based on the observed changes in the NOI (Normoxia Oscillatory Index) and RHR (Reactive Hyperemia Response) parameters measured with the FMSF technique, it was found that chronic fatigue associated with post-COVID syndrome is comparable with transient fatigue caused by high-intensity exercise in terms of vascular effects, which are associated with vascular stress in the macrocirculation and microcirculation. Acute and chronic fatigue symptomatology shared similarly altered changes in the NOI and RHR parameters and both can be linked to calcium homeostasis modification.

Conclusion: The NOI and RHR parameters measured with the FMSF technique can be used for non-invasive clinical assessment of post-COVID syndrome as well as for monitoring the rehabilitation process.

Source: Chudzik M, Cender A, Mordaka R, Zielinski J, Katarzynska J, Marcinek A, Gebicki J. Chronic Fatigue Associated with Post-COVID Syndrome versus Transient Fatigue Caused by High-Intensity Exercise: Are They Comparable in Terms of Vascular Effects? Vasc Health Risk Manag. 2022 Sep 6;18:711-719. doi: 10.2147/VHRM.S371468. PMID: 36097586; PMCID: PMC9464031.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9464031/ (Full text)

Post COVID-19 Conditions: The New Challenge to Mankind

Abstract:

After the waves of acute COVID-19 that swept mankind in 2020 and 2021, now we are confronted with the challenge of post COVID-19 conditions. According to the definition, post COVID-19 conditions comprise all signs and symptoms of COVID-19 that persist after the acute phase (3–4 weeks), without an upper limit of duration (as for the present state of knowledge). The symptoms of post COVID-19 conditions are highly variable, could affect every system, often overlap, and typically fluctuate and change over time.

In regard to this disease and its long-term burden, the Bulgarian Cardiac Institute initiated a campaign “Life after COVID-19” and the data we gathered showed that a substantial proportion of patients having suffered from COVID-19 continue to have persistent symptoms that require special medical attention. Our biggest concern was the acute vascular manifestations of post COVID-19 conditions, such as acute coronary syndromes and acute pulmonary embolism, and for these we shared our personal experience.

Post COVID-19 conditions have and will have a major significance for the healthcare and economic systems in the upcoming years. This derives from the simple facts that it is highly prevalent, affects people regardless of age (including young and active people) or severity of the acute illness (even asymptomatic cases), and that we still must learn a lot about its pathogenesis, natural history, treatment, and prognosis.

Source: Simova, I. et al. (2022). Post COVID-19 Conditions: The New Challenge to Mankind. In: Adibi, S., Griffin, P., Sanicas, M., Rashidi, M., Lanfranchi, F. (eds) Frontiers of COVID-19. Springer, Cham. https://doi.org/10.1007/978-3-031-08045-6_15 https://link.springer.com/chapter/10.1007/978-3-031-08045-6_15

Long covid and medical gaslighting: Dismissal, delayed diagnosis, and deferred treatment

Abstract:

While we know a lot more about Long Covid today, patients who were infected with Covid-19 early on in the pandemic and developed Long Covid had to contend with medical professionals who lacked awareness of the potential for extended complications from Covid-19. Long Covid patients have responded by labeling their contentious interactions with medical professionals, organizations, and the broader medical system as “gaslighting.” We argue that the charge of medical gaslighting can be understood as a form of ontological politics. Not only do patients demand that their version of reality be recognized, but they also blame the experts who hold gatekeeping power over their medical care for producing a distorted version of said reality.

By analyzing results from an online survey of Long Covid patients active on social media in the United States (n ​= ​334), we find that experiences of contention and their reframing as “gaslighting” were common amongst our respondents. In short answer responses about their experience obtaining medical care for Long Covid, our respondents described encountering medical professionals who dismissed their experience, leading to lengthy diagnostic odysseys and lack of treatment options for Long Covid. Even though we are limited by characteristics of our sample, there is good reason to believe that these experiences and their contentious reframing as medical gaslighting are exacerbated by gender, class, and racial inequalities.

Source: Au L, Capotescu C, Eyal G, Finestone G. Long covid and medical gaslighting: Dismissal, delayed diagnosis, and deferred treatment. SSM Qual Res Health. 2022 Sep 7;2:100167. doi: 10.1016/j.ssmqr.2022.100167. Epub ahead of print. PMID: 36092770; PMCID: PMC9448633.  https://www.sciencedirect.com/science/article/pii/S2667321522001299 (Full text)

Understanding myalgic encephalomyelitis

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a severe condition characterized by post-exertional neuroimmune exhaustion (PENE) accompanied by neurological, immunological, gastrointestinal (GI), and mitochondrial disturbances (1). The global prevalence of ME/CFS is ∼1%, affecting 17 million to 24 million people (2). ME/CFS is heterogeneous not only in symptom presentation but also illness trajectories, which can be worsening, plateauing, improving, or relapsing-remitting. Approximately 25% of patients with ME/CFS are considered severe and are bound to their homes. Although the etiology of ME/CFS is elusive, a large proportion of patients (∼60%) report post-infectious onset, such as after Epstein-Barr virus infection (3). The recent emergence of a chronic post-infectious condition, called Long Covid, overlaps considerably with ME/CFS in immunological, mitochondrial, and neurological dysfunctions (4). These similarities have resulted in increased interest and acceptance of ME/CFS as a disease and may stimulate research, the development of a diagnostic test, and pharmacotherapeutic interventions in ME/CFS that may be applied to Long Covid.

Read the rest of this article HERE.

Source: Sonya Marshall-Gradisnik and Natalie Eaton-Fitch. Understanding myalgic encephalomyelitis. SCIENCE, 8 Sep 2022, Vol 377, Issue 6611, pp. 1150-1151, DOI: 10.1126/science.abo126 https://www.science.org/doi/10.1126/science.abo1261 (Full text)

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)

The prevalence of SARS-CoV-2 infection and long COVID in US adults during the BA.5 surge, June-July 2022

Abstract:

Due to changes in SARS-CoV-2 testing practices, passive case-based surveillance may be an increasingly unreliable indicator for monitoring the burden of SARS-CoV-2, especially during surges. We conducted a cross-sectional survey of a population-representative sample of 3,042 U.S. adults between June 30 and July 2, 2022, during the Omicron BA.5 surge. Respondents were asked about SARS-CoV-2 testing and outcomes, COVID-like symptoms, contact with cases, and experience with prolonged COVID-19 symptoms following prior infection.

We estimated the weighted age and sex-standardized SARS-CoV-2 prevalence, during the 14-day period preceding the interview. We estimated age and gender adjusted prevalence ratios (aPR) for current SARS-CoV-2 infection using a log-binomial regression model.

An estimated 17.3% (95% CI 14.9, 19.8) of respondents had SARS-CoV-2 infection during the two-week study period, equating to 44 million cases as compared to 1.8 million per the CDC during the same time period. SARS-CoV-2 prevalence was higher among those 18-24 years old (aPR 2.2, 95% CI 1.8, 2.7) and among non-Hispanic Black (aPR 1.7, 95% CI 1.4 ,2.2) and Hispanic (aPR 2.4, 95% CI 2.0 , 2.9). SARS-CoV-2 prevalence was also higher among those with lower income (aPR 1.9, 95% CI 1.5, 2.3), lower education (aPR 3.7 95% CI 3.0,4.7), and those with comorbidities (aPR 1.6, 95% CI 1.4, 2.0). An estimated 21.5% (95% CI 18.2, 24.7) of respondents with a SARS-CoV-2 infection more than 4 weeks prior reported long COVID symptoms.

The inequitable distribution of SARS-CoV-2 prevalence during the BA.5 surge will likely drive inequities in the future burden of long COVID.

Source: Saba Qasmieh, McKaylee Robertson, Chloe A Teasdale, Sarah Kulkarni, Heidi E Jones, Margaret McNairy, Luisa N Borrell, Denis Nash. The prevalence of SARS-CoV-2 infection and long COVID in US adults during the BA.5 surge, June-July 2022. medRxiv 2022.09.04.22279588; doi: https://doi.org/10.1101/2022.09.04.22279588 (Full text available as PDF file)

The long COVID syndrome: A conundrum for the allergist/immunologist

Abstract:

Background: The long coronavirus disease 2019 (COVID-19) syndrome includes a group of patients who, after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibit lingering mild-to-moderate symptoms and develop medical complications that can have lasting health problems.

Objective: The purpose of this report was to examine the current body of evidence that deals with the relationship of COVID-19 infection with the long COVID syndrome to define the possible immunologic mechanisms involved in the pathogenesis of long COVID and to describe potential strategies for the diagnosis and clinical management of the condition.

Methods: Extensive research was conducted in medical literature data bases by applying terms such as long COVID, post-COVID-19 condition, pathogenesis of long COVID, management of the long COVID syndrome.

Results: The post-COVID conditions, a more recent and less anxiety-inducing term for the patient than long COVID or “long haul,” is an umbrella term for a wide range of physical and mental health symptoms similar to those seen in patients with the myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), experienced by some patients and are present ≥ 4 weeks after SARS-CoV-2 infection. Although the precise reason why long COVID develops is unknown, one of the major causes is thought to be related to chronic inflammation with overproduction of inflammatory cytokines responsible for the symptoms of the disorder.

Conclusion: Long COVID is a growing burden for millions of patients, health-care providers, and global health-care systems, and is a particular challenge for the allergist/immunologist. Many survivors of COVID-19 struggle with multiple symptoms, increased disability, reduced function, and poor quality of life. The allergist/immunologist can assist the total health-care team’s efforts in providing a comprehensive and coordinated approach to the management of these patients by promoting comprehensive vaccination and rehabilitation and social services that focus on improving physical, mental, and social well-being, and by establishing partnerships with specialists and other health-care professionals who can provide behavioral, lifestyle, and integrative approaches that may have much to offer in helping patients cope with their symptoms.

Source: Bellanti JA. The long COVID syndrome: A conundrum for the allergist/immunologist. Allergy Asthma Proc. 2022 Sep 1;43(5):368-374. doi: 10.2500/aap.2022.43.220059. PMID: 36065103. https://www.ingentaconnect.com/content/ocean/aap/2022/00000043/00000005/art00007;jsessionid=2d46805mm1b04.x-ic-live-02 (Full text available as PDF file)