Tag: 2022

Please Help David Tuller, Our Champion!

UPDATE: David Tuller’s fundraiser made its goal! A HUGE thank you to everyone who donated. You are helping David continue his important work on our behalf. Thank you to everybody!

David Tuller’s spring fundraiser is now live! Tuller has been tireless in his battle against the GET/CBT ideological onslaught! He has much more work to do and he needs our support.

Tuller has written more than seventy-five  posts on Vincent Racaniello’s Virology Blog, spanning ten years. His articles comprise a full history of how the PACE trial was used to mislead health care providers into thinking ME/CFS could be cured with “a walk and a talk.” Tuller has taken on some of the authors of the PACE study and, despite threats from them, has continued to challenge their findings.

In 2021, Tuller explored the intersections between the pandemic and ME, including the overlap between ME/CFS and long Covid. He kept an eye out for new bad research (CBT/GET, Lightning Process) as well as keeping an eye on goings-on at the CDC, the NIH and elsewhere.

This year, Tuller will continue in his efforts. “Because of long Covid’s range of reported symptoms, many people with the illness have medical issues unrelated to ME and will not receive an ME diagnosis. But a great many will,” he says. “So examining long Covid in the context of these scientific debates over the source and cause of the devastating symptoms is critical to sustain the momentum of change in the ME domain and affirming the advances in the ME field that have been made to date.”

Last year, Tuller successfully raised money through Crowdrise  in order to continue investigating and blogging about the PACE trial. The funds went to the School of Public Health at the University of California, Berkeley, which created a position for Tuller to continue his investigative work. Now, a year later, the funds have run out, and Tuller has to depend on the generosity of our community to continue his work.

The struggle continues! And David is fighting hard for us!

PLEASE DONATE HERE!

Persistent Brain Fog After Mild COVID Infection Tied to CSF Markers

Abstract:

As cases of coronavirus disease 2019 (COVID-19) mount worldwide, attention is needed on potential long-term neurologic impacts for the majority of patients who experience mild to moderate illness managed as outpatients. To date, there has not been discussion of persistent neurocognitive deficits in patients with milder COVID-19. We present two cases of non-hospitalized patients recovering from COVID-19 with persistent neurocognitive symptoms. Commonly used cognitive screens were normal, while more detailed testing revealed working memory and executive functioning deficits.

An observational cohort study of individuals recovering from COVID-19 (14 or more days following symptom onset) identified that among the first 100 individuals enrolled, 14 were non-hospitalized patients reporting persistent cognitive issues. These 14 participants had a median age of 39 years (interquartile range: 35-56), and cognitive symptoms were present for at least a median of 98 days (interquartile range: 71-120 following acute COVID-19 symptoms); no participants with follow-up evaluation reported symptom resolution. We discuss potential mechanisms to be explored in future studies, including direct viral effects, indirect consequences of immune activation, and immune dysregulation causing auto-antibody production.

Source: Hellmuth J, Barnett TA, Asken BM, Kelly JD, Torres L, Stephens ML, Greenhouse B, Martin JN, Chow FC, Deeks SG, Greene M, Miller BL, Annan W, Henrich TJ, Peluso MJ. Persistent COVID-19-associated neurocognitive symptoms in non-hospitalized patients. J Neurovirol. 2021 Feb;27(1):191-195. doi: 10.1007/s13365-021-00954-4. Epub 2021 Feb 2. PMID: 33528824; PMCID: PMC7852463. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7852463/ (Full text)

Post COVID fatigue: Can we really ignore it?

Abstract:

Long-COVID, also referred to as post-acute COVID-19, chronic COVID-19, post-COVID syndrome, or post-acute sequelae of SARS-CoV-2 infection (PASC), generally refers to symptoms that develop during or after acute COVID-19 illness, continue for ≥12 weeks, and are not explained by an alternative diagnosis. It is not yet known whether “long-COVID” represents a new syndrome unique to COVID-19 or overlaps with recovery from similar illnesses. It’s difficult for physicians to predict when symptoms will improve as it varies differently in different people. Patient’s recovery depends on various factors including age, associated comorbidities, severity of COVID-19 infection. Some symptoms, like fatigue, might continue even while others improve or go away. This review addresses the pathogenesis, presentation of post covid fatigue, its severity and its management.

Source: Sharma P, Bharti S, Garg I. Post COVID fatigue: Can we really ignore it? Indian J Tuberc. 2022 Apr;69(2):238-241. doi: 10.1016/j.ijtb.2021.06.012. Epub 2021 Jun 23. PMID: 35379408. https://pubmed.ncbi.nlm.nih.gov/35379408/

Magnetic Resonance Imaging Confirmed Olfactory Bulb Reduction in Long COVID-19: Literature Review and Case Series

Abstract:

An altered sense of smell and taste was recognized as one of the most characteristic symptoms of coronavirus infection disease (COVID-19). Despite most patients experiencing a complete functional resolution, there is a 21.3% prevalence of persistent alteration at 12 months after infection. To date, magnetic resonance imaging (MRI) findings in these patients have been variable and not clearly defined. We aimed to clarify radiological alterations of olfactory pathways in patients with long COVID-19 characterized by olfactory dysfunction.
A comprehensive review of the English literature was performed by analyzing relevant papers about this topic. A case series was presented: all patients underwent complete otorhinolaryngology evaluation including the Sniffin’ Sticks battery test. A previous diagnosis of SARS-CoV-2 infection was confirmed by positive swabs. The MRIs were acquired using a 3.0T MR scanner with a standardized protocol for olfactory tract analysis. Images were first analysed by a dedicated neuroradiologist and subsequently reviewed and compared with the previous available MRIs.
The review of the literature retrieved 25 studies; most cases of olfactory dysfunction more than 3 months after SARS-CoV-2 infection showed olfactory bulb (OB) reduction. Patients in the personal case series had asymmetry and a reduction in the volume of the OB. This evidence was strengthened by the comparison with a previous MRI, where the OBs were normal. The results preliminarily confirmed OB reduction in cases of long COVID-19 with an altered sense of smell. Further studies are needed to clarify the epidemiology, pathophysiology and prognosis.
Source: Frosolini A, Parrino D, Fabbris C, Fantin F, Inches I, Invitto S, Spinato G, Filippis CD. Magnetic Resonance Imaging Confirmed Olfactory Bulb Reduction in Long COVID-19: Literature Review and Case Series. Brain Sciences. 2022; 12(4):430. https://doi.org/10.3390/brainsci12040430 (Full text)

Post-COVID-19 syndrome and humoral response association after one year in vaccinated and unvaccinated patients

Abstract:

Objectives: To describe the impact of vaccination and the role of humoral responses on post-coronavirus disease 2019 (COVID-19) syndrome one year after the onset of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Methods: A prospective study. Interviews investigated post-COVID-19 syndrome 6 and 12 months after the disease onset of all adult in- and outpatients with COVID-19 attending Udine Hospital (March-May 2020). Vaccination status and two different serological assays to distinguish between response to vaccination (receptor-binding domain -RBD SARS-CoV-2 IgG) and/or natural infection (non-RBD- SARS-CoV-2 IgG) were also assessed.

Results: 479 individuals (52.6% female, mean age 53 years) were interviewed 13.5 months (0.6 SD) after acute infection. Post-COVID-19 syndrome was observed in 47.2% (226/479) of patients after one year. There were no significant differences in the worsening of post-COVID 19 symptoms (22.7% vs 15.8%, p = 0.209) among vaccinated (n=132) and unvaccinated (n=347) patients. The presence of non-RBD SARS-CoV-2 IgG induced by natural infection showed a significant association with post-COVID-19 syndrome (OR 1.35, 95% CI 1.11-1.64, p = 0.003), and median non-RBD SARS-CoV-2 IgG titres were significantly higher in long-haulers than in patients without symptoms 22 (IQR 9.7-37.2) vs 14.1 (IQR 5.4-31.3) kAU/L, p = 0.009) after one year.

In contrast, the presence of RBD SARS-CoV-2 IgG was not associated with the occurrence of post-COVID-19 syndrome (>2500 U/mL vs 0.9-2500 U/mL, OR 1.36, 95% CI 0.62-3.00, p = 0.441) and RBD SARS-CoV-2 IgG titres were similar in long-haulers than in patients without symptoms (50% values > 2500 U/mL vs 55.6% values > 2500 U/mL, p = 0.451)

Conclusions: The SARS-CoV-2 vaccination is not associated with the emergence of post-COVID-19 symptoms over one year after acute infection. The persistence of high serological titres response induced by natural infection but not by vaccination, may play a role in long-COVID-19.

Source: Peghin M, De Martino M, Palese A, Gerussi V, Bontempo G, Graziano E, Visintini E, Elia D, Dellai F, Marrella F, Fabris M, Curcio F, Sartor A, Isola M, Tascini C. Post-COVID-19 syndrome and humoral response association after one year in vaccinated and unvaccinated patients. Clin Microbiol Infect. 2022 Mar 23:S1198-743X(22)00155-0. doi: 10.1016/j.cmi.2022.03.016. Epub ahead of print. PMID: 35339673; PMCID: PMC8940723.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8940723/ (Full text)

A Causal-Pathway Phenotype of Chronic Fatigue Syndrome due to Hemodialysis in Patients with End-Stage Renal Disease

Abstract:

Background: End-stage renal disease (ESRD) is associated with fatigue and physio-somatic symptoms.

Objective: To delineate the associations between severity of fatigue and physio-somatic symptoms and glomerular filtration rate, inflammatory biomarkers, and Wnt/catenin-pathway proteins.

Methods: The Wnt-pathway related proteins β-catenin, Dickkopf-related protein 1 (DKK1), R-spondin-1, and sclerostin were measured by ELISA technique in 60 ESRD patients and 30 controls. The Fibromyalgia and Chronic Fatigue Syndrome (FF) Rating Scale was used to assess the severity of FF symptoms.

Results: ESRD is characterized by a significant increase in the total FF score, muscle tension, fatigue, sadness, sleep disorders, gastro-intestinal (GI) symptoms, and a flu-like malaise. The total-FF score was significantly correlated with serum levels of urea, creatinine, and copper (positively), and β-catenin, eGFR, hemoglobin, albumin, and zinc (inversely). The total-FF score was associated with the number of total dialysis and weekly dialysis sessions, and these dialysis characteristics were more important in predicting FF scores than eGFR measurements. Partial Least Squares analysis showed that the FF score comprised two factors that are differently associated with biomarkers: a) 43.0% of the variance in fatigue, GI symptoms, muscle tension, sadness, and insomnia is explained by hemoglobin, albumin, zinc, β-catenin, and R-spondin-1; and b) 22.3% of the variance in irritability, concentration and memory impairments by increased copper and cations/chloride ratio, and male sex.

Conclusion: ESRD patients show high levels of fatigue and physio-somatic symptoms, which are associated with hemodialysis and mediated by dialysis-induced changes in inflammatory pathways, the Wnt/catenin pathway, and copper.

Source: Asad HN, Al-Hakeim HK, Moustafa SR, Maes M. A Causal-Pathway Phenotype of Chronic Fatigue Syndrome due to Hemodialysis in Patients with End-Stage Renal Disease. CNS Neurol Disord Drug Targets. 2022 Apr 1. doi: 10.2174/1871527321666220401140747. Epub ahead of print. PMID: 35366785. https://pubmed.ncbi.nlm.nih.gov/35366785/

Metabolomics study of the effect of Danggui Buxue Tang on rats with chronic fatigue syndrome

Abstract:

Danggui Buxue Tang (DBT), a traditional Chinese medicine formula for “invigorating qi and enriching blood”, has been reported to produce a good effect on chronic fatigue syndrome (CFS). However, the related mechanism remains largely unresolved. In this study, a metabolomics approach with gas chromatography coupled to mass spectrometry combined with pattern recognition was devised to estimate the extent to which DBT alleviated CFS induced by food restriction and force swimming in rats.

After four weeks of treatment, the endurance capability of rats was significantly better and the motionless time was significantly shorter in the DBT group than in CFS model group. Moreover, the activities of SOD and GSH-Px were increased, while the levels of MDA, IL-6 and TNF-α were decreased in the DBT treatment group. Fifteen significantly changed metabolites were observed in the serum of rats with CFS, which was reversed markedly by DBT treatment. Metabolic pathway analysis showed that DBT could possibly alleviate CFS in rats by regulating phenylalanine, tyrosine and tryptophan biosynthesis, glycine, serine and the metabolism of threonine, glycerolipid, glyoxylate, dicarboxylate and tyrosine. It was observed that the metabolism of glycine, serine and threonine was most closely related to the improvement of CFS by DBT treatment. This study showed that DBT could improve CFS effectively and metabolomics was a powerful means to gain insights into the traditional Chinese medicine formulas against CFS.

Source: Miao X, Li S, Xiao B, Yang J, Huang R. Metabolomics study of the effect of Danggui Buxue Tang on rats with chronic fatigue syndrome. Biomed Chromatogr. 2022 Apr 4:e5379. doi: 10.1002/bmc.5379. Epub ahead of print. PMID: 35373377.  https://pubmed.ncbi.nlm.nih.gov/35373377/

Sulodexide: A Benefit for Cardiovascular Sequelae of Long COVID Patients?

Dear Editor,

The elaborate and precise review of Harry N. Magnani didactically demonstrates the complex pathophysiological aspects of coronavirus disease 2019 (COVID-19) emphasizing the roles of vascular endothelial dysfunction and coagulation cascade as key features of disease progression.  Moreover, this article brings up that glycosaminoglycane (GAG) antithrombotics likely interfere with inflammatory and coagulation activity in an effective fashion.  Thereafter this postulate has become advocated as the application of sulodexide (Vessel Due F; ALFASIGMA, Italy) (SDX), an unexpensive and orally administrable GAG antithrombotic drug reduced the necessity for both hospital admission and oxygen supplementation in the early phase of SARS-Cov-2 infection under a randomized placebo-controlled out-patient trial.  Interestingly, these patients also showed lower serum levels of C-reactive protein (CRP) and D-dimer as markers of inflammation and prothrombotic state. Of note, instead of regularly recommended and prescribed 250 RLU twice-daily dose, the clinical trial applied the higher, 500 RLU twice-daily dosing regimen in which an antithrombotic effect was safely achieved in a clinical setting.

Read the rest of this article HERE.

Source: Szolnoky G, González-Ochoa AJ. Sulodexide: A Benefit for Cardiovascular Sequelae of Long COVID Patients? Clin Appl Thromb Hemost. 2022 Jan-Dec;28:10760296221084300. doi: 10.1177/10760296221084300. PMID: 35333125; PMCID: PMC8961374. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8961374/ (Full text)

Sex-Related Differences in Long-COVID-19 Syndrome

Abstract:

Background: Sex differences have been demonstrated in the acute phase of COVID-19. Women (F) were found to be less prone to develop a severe disease than men (M), but few studies have assessed sex-differences in Long-COVID-19 syndrome.

Methods: The aim of this prospective/retrospective study was to characterize the long-term consequences of this infection based on sex. For this purpose, we enrolled 223 patients (89 F and 134 M) who were infected by SARS-CoV-2. In the acute phase of the illness, F reported the following symptoms more frequently than M: weakness, dysgeusia, anosmia, thoracic pain, palpitations, diarrhea, and myalgia-all without significant differences in breathlessness, cough, and sleep disturbance.

Results: After a mean follow-up time of 5 months after the acute phase, F were significantly more likely than M to report dyspnea, weakness, thoracic pain, palpitations, and sleep disturbance but not myalgia and cough. At the multivariate logistic regression, women were statistically significantly likely to experience persistent symptoms such as dyspnea, fatigue, chest pain, and palpitations. On the contrary, myalgia, cough, and sleep disturbance were not influenced by sex.

Conclusion: We demonstrated that F were more symptomatic than M not only in the acute phase but also at follow-up. Sex was found to be an important determinant of Long-COVID-19 syndrome because it is a significant predictor of persistent symptoms in F, such as dyspnea, fatigue, chest pain, and palpitations. Our results suggest the need for long-term follow-up of these patients from a sex perspective to implement early preventive and personalized therapeutic strategies.

Source: Pelà G, Goldoni M, Solinas E, Cavalli C, Tagliaferri S, Ranzieri S, Frizzelli A, Marchi L, Mori PA, Majori M, Aiello M, Corradi M, Chetta A. Sex-Related Differences in Long-COVID-19 Syndrome. J Womens Health (Larchmt). 2022 Mar 25. doi: 10.1089/jwh.2021.0411. Epub ahead of print. PMID: 35333613. https://www.liebertpub.com/doi/10.1089/jwh.2021.0411 (Full text)

Efficacy of Adaptogens in Patients with Long COVID-19: A Randomized, Quadruple-Blind, Placebo-Controlled Trial

Abstract:

Currently, no effective treatment of comorbid complications or COVID-19 long-haulers during convalescence is known. This randomized, quadruple-blind, placebo-controlled trial aimed to assess the efficacy of adaptogens on the recovery of patients with Long COVID symptoms. One hundred patients with confirmed positive SARS-CoV-2 test, discharged from COVID Hotel isolation, Intensive Care Unit (ICU), or Online Clinics, and who experienced at least three of nine Long COVID symptoms (fatigue, headache, respiratory insufficiency, cognitive performance, mood disorders, loss of smell, taste, and hair, sweatiness, cough, pain in joints, muscles, and chest) in the 30 days before randomization were included in the study of the efficacy of Chisan®/ADAPT-232 (a fixed combination of adaptogens Rhodiola, Eleutherococcus, and Schisandra) supplementation for two weeks.

Chisan® decreased the duration of fatigue and pain for one and two days, respectively, in 50% of patients. The number of patients with lack of fatigue and pain symptoms was significantly less in the Chisan® treatment group than in the placebo group on Days 9 (39% vs. 57%, pain relief, p = 0.0019) and 11 (28% vs. 43%, relief of fatigue, * p = 0.0157). Significant relief of severity of all Long COVID symptoms over the time of treatment and the follow-up period was observed in both groups of patients, notably decreasing the level of anxiety and depression from mild and moderate to normal, as well as increasing cognitive performance in patients in the d2 test for attention and increasing their physical activity and workout (daily walk time).

However, the significant difference between placebo and Chisan® treatment was observed only with a workout (daily walk time) and relieving respiratory insufficiency (cough). A clinical assessment of blood markers of the inflammatory response (C-reactive protein) and blood coagulation (D-dimer) did not reveal any significant difference over time between treatment groups except significantly lower IL-6 in the Chisan® treatment group. Furthermore, a significant difference between the placebo and Chisan® treatment was observed for creatinine: Chisan® significantly decreased blood creatinine compared to the placebo, suggesting prevention of renal failure progression in Long COVID. In this study, we, for the first time, demonstrate that adaptogens can increase physical performance in Long COVID and reduce the duration of fatigue and chronic pain. It also suggests that Chisan®/ADAPT-232 might be useful for preventing the progression of renal failure associated with increasing creatinine.

Source: Karosanidze I, Kiladze U, Kirtadze N, Giorgadze M, Amashukeli N, Parulava N, Iluridze N, Kikabidze N, Gudavadze N, Gelashvili L, Koberidze V, Gigashvili E, Jajanidze N, Latsabidze N, Mamageishvili N, Shengelia R, Hovhannisyan A, Panossian A. Efficacy of Adaptogens in Patients with Long COVID-19: A Randomized, Quadruple-Blind, Placebo-Controlled Trial. Pharmaceuticals (Basel). 2022 Mar 11;15(3):345. doi: 10.3390/ph15030345. PMID: 35337143; PMCID: PMC8953947. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8953947/ (Full text)