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)

New Clinical Phenotype of the Post-Covid Syndrome: Fibromyalgia and Joint Hypermobility Condition

Abstract:

Fibromyalgia can be defined as a chronic pain condition, affecting the musculoskeletal system, etiology and pathophysiology of which is sufficiently understudied. Despite the fact that many authors consider this entity to be a manifestation of central sensitization, and not an autoimmune disease, the high prevalence of fibromyalgia in patients with post-COVID-19 conditions requires taking a fresh look at the causes of the disease development.

During the patient examination, the authors identified a combination of symptoms that occurs so often, that they can be carefully described as a clinical pattern. These manifestations include young age, female gender, joint hypermobility, the onset of pain after COVID-19, physical traumatization of one particular tendon and the development of the fibromyalgia pain syndrome during the next several weeks. As well as an increase in the titer of antinuclear antibodies and some other systemic inflammation factors. It can be assumed with great caution that local damage to the connective tissue in patients with joint hypermobility, having COVID-19 as a trigger factor can lead to the development of fibromyalgia syndrome. This article presents three clinical cases that illustrated this hypothesis.

Source: Gavrilova N, Soprun L, Lukashenko M, Ryabkova V, Fedotkina TV, Churilov LP, Shoenfeld Y. New Clinical Phenotype of the Post-Covid Syndrome: Fibromyalgia and Joint Hypermobility Condition. Pathophysiology. 2022 Jan 19;29(1):24-29. doi: 10.3390/pathophysiology29010003. PMID: 35366287. https://www.mdpi.com/1873-149X/29/1/3/htm (Full text)

The Journey Towards Becoming Diagnosed with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome – Patients’ Experiences

Abstract:

Background: Myalgic encephalomyelitis/chronic fatigue syndrome is a disease that negatively affects patients’ quality of life. Previous research has shown that these patients are commonly not taken seriously when seeking medical attention.

Aim: The aim was to examine the experiences of patients with ME/CFS regarding their interaction with Swedish primary healthcare professionals.

Method: The study used a qualitative and exploratory design, taking place in a specialist clinic in Sweden. Data consisted of interviews with 13 patients with ME/CFS, which were analysed using content analysis.

Findings: For patients, it was Feeling truly connected during the period before they received a diagnosis. Time is an important factor, and in the phase from initial symptoms to diagnosis, Knowledge is power.

Conclusion: Patients with ME/CFS were met with different levels of knowledge and interest from healthcare professionals. These challenges might be related to the relative unawareness and lack of knowledge of the disease and the underlying cultural scepticism still present.

Source: Bo Christer Bertilson., et al. “The Journey Towards Becoming Diagnosed with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome – Patients’ Experiences”. EC Neurology 14.2 (2022): 49-56.  https://www.ecronicon.com/ecne/pdf/ECNE-14-01012.pdf (Full text as PDF file)

Plasma metabolomics reveals disrupted response and recovery following maximal exercise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Post-exertional malaise (PEM) is a hallmark symptom of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). We monitored the evolution of 1,157 plasma metabolites in 60 ME/CFS cases (45 females, 15 males) and in 45 matched healthy control subjects (30 females, 15 males) before and after two maximal Cardiopulmonary Exercise Test (CPET) challenges separated by 24 hours, with the intent of provoking PEM in patients. Four timepoints allowed exploration of the metabolic response to maximal energy-producing capacity and the recovery pattern of ME/CFS cases compared to the healthy control group.

Baseline comparison identified several significantly different metabolites, along with an enriched percentage of yet-to-be identified compounds. Additionally, temporal measures demonstrated an increased metabolic disparity between cohorts, including unknown metabolites. The effects of exertion in the ME/CFS cohort predominantly highlighted lipid- as well as energy-related pathways and chemical structure clusters, which were disparately affected by the first and second exercise sessions.

The 24-hour recovery period was distinct in the ME/CFS cohort, with over a quarter of the identified pathways statistically different. The pathways that are uniquely different 24 hours after an exercise challenge provide clues to metabolic disruptions that lead to PEM. Numerous altered pathways were observed to depend on glutamate metabolism, a crucial component to the homeostasis of many organs in the body, including the brain.

Source: Germain A, Giloteaux L, Moore GE, Levine SM, Chia JK, Keller BA, Stevens J, Franconi CJ, Mao X, Shungu DC, Grimson A, Hanson MR. Plasma metabolomics reveals disrupted response and recovery following maximal exercise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. JCI Insight. 2022 Mar 31:e157621. doi: 10.1172/jci.insight.157621. Epub ahead of print. PMID: 35358096. https://pubmed.ncbi.nlm.nih.gov/35358096/

Volumetric differences in hippocampal subfields and associations with clinical measures in myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients suffer from a cognitive and memory dysfunction. Because the hippocampus plays a key role in both cognition and memory, we tested for volumetric differences in the subfields of the hippocampus in ME/CFS.

We estimated hippocampal subfield volumes for 25 ME/CFS patients who met Fukuda criteria only (ME/CFSFukuda ), 18 ME/CFS patients who met the stricter ICC criteria (ME/CFSICC ), and 25 healthy controls (HC). Group comparisons with HC detected extensive differences in subfield volumes in ME/CFSICC but not in ME/CFSFukuda . ME/CFSICC patients had significantly larger volume in the left subiculum head (p < 0.001), left presubiculum head (p = 0.0020), and left fimbria (p = 0.004).

Correlations of hippocampus subfield volumes with clinical measures were stronger in ME/CFSICC than in ME/CFSFukuda patients. In ME/CFSFukuda patients, we detected positive correlations between fatigue and hippocampus subfield volumes and a negative correlation between sleep disturbance score and the right CA1 body volume.

In ME/CFSICC patients, we detected a strong negative relationship between fatigue and left hippocampus tail volume. Strong negative relationships were also detected between pain and SF36 physical scores and two hippocampal subfield volumes (left: GC-ML-DG head and CA4 head).

Our study demonstrated that volumetric differences in hippocampal subfields have strong statistical inference for patients meeting the ME/CFSICC case definition and confirms hippocampal involvement in the cognitive and memory problems of ME/CFSICC patients.

Source: Thapaliya K, Staines D, Marshall-Gradisnik S, Su J, Barnden L. Volumetric differences in hippocampal subfields and associations with clinical measures in myalgic encephalomyelitis/chronic fatigue syndrome. J Neurosci Res. 2022 Mar 31. doi: 10.1002/jnr.25048. Epub ahead of print. PMID: 35355311. https://onlinelibrary.wiley.com/doi/10.1002/jnr.25048  (Full study)