Most patients with Post COVID Syndrome (PCS) present with a plethora of symptoms without clear evidence of organ dysfunction. A subset of them fulfills diagnostic criteria of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Symptom severity of ME/CFS correlates with natural regulatory autoantibody (AAB) levels targeting several G-protein coupled receptors (GPCR). In this exploratory study, we analyzed serum AAB levels against vaso- and immunoregulatory receptors, mostly GPCRs, in 80 PCS patients following mild-to-moderate COVID-19, with 40 of them fulfilling diagnostic criteria of ME/CFS. Healthy seronegative (n=38) and asymptomatic post COVID-19 controls (n=40) were also included in the study as control groups. We found lower levels for various AABs in PCS compared to at least one control group, accompanied by alterations in the correlations among AABs. Classification using random forest indicated AABs targeting ADRB2, STAB1, and ADRA2A as the strongest classifiers (AABs stratifying patients according to disease outcomes) of post COVID-19 outcomes. Several AABs correlated with symptom severity in PCS groups. Remarkably, severity of fatigue and vasomotor symptoms were associated with ADRB2 AAB levels in PCS/ME/CFS patients. Our study identified dysregulation of AAB against various receptors involved in the autonomous nervous system (ANS), vaso-, and immunoregulation and their correlation with symptom severity, pointing to their role in the pathogenesis of PCS.
ObjectiveTo assess the safety and efficacy of epigallocatechin-3-gallate (EGCG) add-on to glatiramer acetate (GA) in patients with relapsing-remitting multiple sclerosis (RRMS).MethodsWe enrolled patients with RRMS (aged 18–60 years, Expanded Disability Status Scale [EDSS] score 0–6.5), receiving stable GA treatment in a multicenter, prospective, double-blind, phase II, randomized controlled trial. Participants received up to 800 mg oral EGCG daily over a period of 18 months. The primary outcome was the proportion of patients without new hyperintense lesions on T2-weighted (T2w) brain MRI within 18 months. Secondary end points included additional MRI and clinical parameters. Immunologic effects of EGCG were investigated in exploratory experiments.ResultsA total of 122 patients on GA were randomly assigned to EGCG treatment (n = 62) or placebo (n = 60). We could not demonstrate a difference between groups after 18 months for the primary outcome or other radiologic (T2w lesion volume, T1w hypointense lesion number or volume, number of cumulative contrast-enhancing lesions, percent brain volume change), or clinical (EDSS, MS functional composite, and annualized relapse rate) parameter. EGCG treatment did not affect immune response to GA. Pharmacologic analysis revealed wide ranging EGCG plasma levels. The treatment was well tolerated with a similar incidence of mostly mild adverse events similar in both groups.ConclusionIn RRMS, oral EGCG add-on to GA was not superior to placebo in influencing MRI and clinical disease activity over 18 months. The treatment was safe at a daily dosage up to 800 mg EGCG. It did not influence immune parameters, despite indication of EGCG being bioavailable in patients.Classification of EvidenceThis study provides Class II evidence that for patients with RRMS, EGCG added to GA did not significantly affect the development of new hyperintense lesions on T2-weighted brain MRI.Trial Registration InformationClinical trial registration number: NCT00525668.
This manuscript presents practical recommendations for managing acute attacks and implementing preventive immunotherapies for neuromyelitis optica spectrum disorders (NMOSD), a rare autoimmune disease that causes severe inflammation in the central nervous system (CNS), primarily affecting the optic nerves, spinal cord, and brainstem. The pillars of NMOSD therapy are attack treatment and attack prevention to minimize the accrual of neurological disability. Aquaporin-4 immunoglobulin G antibodies (AQP4-IgG) are a diagnostic marker of the disease and play a significant role in its pathogenicity. Recent advances in understanding NMOSD have led to the development of new therapies and the completion of randomized controlled trials. Four preventive immunotherapies have now been approved for AQP4-IgG-positive NMOSD in many regions of the world: eculizumab, ravulizumab - most recently-, inebilizumab, and satralizumab. These new drugs may potentially substitute rituximab and classical immunosuppressive therapies, which were as yet the mainstay of treatment for both, AQP4-IgG-positive and -negative NMOSD. Here, the Neuromyelitis Optica Study Group (NEMOS) provides an overview of the current state of knowledge on NMOSD treatments and offers statements and practical recommendations on the therapy management and use of all available immunotherapies for this disease. Unmet needs and AQP4-IgG-negative NMOSD are also discussed. The recommendations were developed using a Delphi-based consensus method among the core author group and at expert discussions at NEMOS meetings.
Background: Epigallocatechin gallate (EGCG) is an anti-inflammatory agent and has proven neuroprotective properties in animal models of multiple sclerosis (MS). Optical coherence tomography (OCT) assessed retinal thickness analysis can reflect treatment responses in MS.Objective: To analyze the influence of EGCG treatment on retinal thickness analysis as secondary and exploratory outcomes of the randomized controlled Sunphenon in Progressive Forms of MS trial (SUPREMES, NCT00799890).Methods: SUPREMES patients underwent OCT with the Heidelberg Spectralis device at a subset of visits. We determined peripapillary retinal nerve fiber layer (pRNFL) thickness from a 12° ring scan around the optic nerve head and thickness of the ganglion cell/inner plexiform layer (GCIP) and inner nuclear layer (INL) within a 6 mm diameter grid centered on the fovea from a macular volume scan. Longitudinal OCT data were available for exploratory analysis from 31 SUPREMES participants (12/19 primary/secondary progressive MS (PPMS/SPMS); mean age 51 ± 7 years; 12 female; mean time since disease onset 16 ± 11 years). We tested the null hypothesis of no treatment*time interaction using nonparametric analysis of longitudinal data in factorial experiments.Results: After 2 years, there were no significant differences in longitudinal retinal thickness changes between EGCG treated and placebo arms in any OCT parameter (Mean change [confidence interval] ECGC vs. Placebo: pRNFL: −0.83 [1.29] μm vs. −0.64 [1.56] μm, p = 0.156; GCIP: −0.67 [0.67] μm vs. −0.14 [0.47] μm, p = 0.476; INL: −0.06 [0.58] μm vs. 0.22 [0.41] μm, p = 0.455).Conclusion: Retinal thickness analysis did not reveal a neuroprotective effect of EGCG. While this is in line with the results of the main SUPREMES trial, our study was probably underpowered to detect an effect.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT00799890.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.