Observational Study of Repeat Immunoadsorption (RIA) in Post-COVID ME/CFS Patients with Elevated ß2-Adrenergic Receptor Autoantibodies—An Interim Report

Abstract:

There is increasing evidence for an autoimmune aetiology in post-infectious Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). SARS-CoV-2 has now become the main trigger for ME/CFS. We have already conducted two small proof-of-concept studies on IgG depletion by immunoadsorption (IA) in post-infectious ME/CFS, which showed efficacy in most patients.
This observational study aims to evaluate the efficacy of IA in patients with post-COVID-19 ME/CFS. The primary objective was to assess the improvement in functional ability. Due to the urgency of finding therapies for post-COVID-Syndrome (PCS), we report here the interim results of the first ten patients, with seven responders defined by an increase of between 10 and 35 points in the Short-Form 36 Physical Function (SF36-PF) at week four after IA. The results of this observational study will provide the basis for patient selection for a randomised controlled trial (RCT), including sham apheresis, and for an RCT combining IA with B-cell depletion therapy. Trial registration number: NCT05629988.
Source: Stein E, Heindrich C, Wittke K, Kedor C, Kim L, Freitag H, Krüger A, Tölle M, Scheibenbogen C. Observational Study of Repeat Immunoadsorption (RIA) in Post-COVID ME/CFS Patients with Elevated ß2-Adrenergic Receptor Autoantibodies—An Interim Report. Journal of Clinical Medicine. 2023; 12(19):6428. https://doi.org/10.3390/jcm12196428 https://www.mdpi.com/2077-0383/12/19/6428 (Full text)

Low-dose naltrexone use for the management of post-acute sequelae of COVID-19

Abstract:

The global prevalence of Post-Acute Sequelae of SARS-CoV-2 Infection (PASC) stands at approximately 43 % among individuals who have previously had acute COVID-19. In contrast, in the United States, the National Center for Health Statistics (NCHS) estimates that around 11 % of individuals who have been infected with SARS-CoV-2 go on to experience long COVID. The underlying causes of PASC remains under investigation, and there are no currently established FDA-approved therapies.

One of the leading hypotheses for the cause of PASC is the persistent activation of innate immune cells with increase systemic inflammation. Naltrexone is a medication with anti-inflammatory and immunomodulatory properties that has been used in other conditions that overlap with PASC.

We performed a retrospective review of a clinical cohort of 59 patients at a single academic center who received low-dose naltrexone (LDN) off-label as a potential therapeutic intervention for PASC. The use of LDN was associated with a fewer number of symptoms, improved clinical symptoms (fatigue, post-exertional malaise, unrefreshing sleep, and abnormal sleep pattern), and a better functional status. This observation warrants testing in rigorous, randomized, placebo-controlled clinical trials.

Source: Bonilla H, Tian L, Marconi VC, Shafer R, McComsey GA, Miglis M, Yang P, Bonilla A, Eggert L, Geng LN. Low-dose naltrexone use for the management of post-acute sequelae of COVID-19. Int Immunopharmacol. 2023 Oct 5;124(Pt B):110966. doi: 10.1016/j.intimp.2023.110966. Epub ahead of print. PMID: 37804660. https://www.sciencedirect.com/science/article/pii/S1567576923012912 (Full text)

A brief overview of SARS-CoV-2 infection and its management strategies: a recent update

Abstract:

The COVID-19 pandemic has become a global health crisis, inflicting substantial morbidity and mortality worldwide. A diverse range of symptoms, including fever, cough, dyspnea, and fatigue, characterizes COVID-19. A cytokine surge can exacerbate the disease’s severity. This phenomenon involves an increased immune response, marked by the excessive release of inflammatory cytokines like IL-6, IL-8, TNF-α, and IFNγ, leading to tissue damage and organ dysfunction.

Efforts to reduce the cytokine surge and its associated complications have garnered significant attention. Standardized management protocols have incorporated treatment strategies, with corticosteroids, chloroquine, and intravenous immunoglobulin taking the forefront. The recent therapeutic intervention has also assisted in novel strategies like repurposing existing medications and the utilization of in vitro drug screening methods to choose effective molecules against viral infections.

Beyond acute management, the significance of comprehensive post-COVID-19 management strategies, like remedial measures including nutritional guidance, multidisciplinary care, and follow-up, has become increasingly evident. As the understanding of COVID-19 pathogenesis deepens, it is becoming increasingly evident that a tailored approach to therapy is imperative.

This review focuses on effective treatment measures aimed at mitigating COVID-19 severity and highlights the significance of comprehensive COVID-19 management strategies that show promise in the battle against COVID-19.

Source: Das A, Pathak S, Premkumar M, Sarpparajan CV, Balaji ER, Duttaroy AK, Banerjee A. A brief overview of SARS-CoV-2 infection and its management strategies: a recent update. Mol Cell Biochem. 2023 Sep 24. doi: 10.1007/s11010-023-04848-3. Epub ahead of print. PMID: 37742314. https://link.springer.com/article/10.1007/s11010-023-04848-3 (Full text)

Hyperbaric Oxygen Therapy Counters Oxidative Stress/Inflammation-Driven Symptoms in Long COVID-19 Patients: Preliminary Outcomes

Abstract:

Long COVID-19 patients show systemic inflammation and persistent symptoms such as fatigue and malaise, profoundly affecting their quality of life. Since improving oxygenation can oppose inflammation at multiple tissue levels, we hypothesized that hyperbaric oxygen therapy (HBOT) could arrest inflammation progression and thus relieve symptoms of COVID-19.
We evaluated oxy-inflammation biomarkers in long COVID-19 subjects treated with HBOT and monitored with non-invasive methods. Five subjects (two athletes and three patients with other comorbidities) were assigned to receive HBOT: 100% inspired O2 at 2.4 ATA in a multiplace hyperbaric chamber for 90 min (three athletes: 15 HBOT × 5 days/wk for 3 weeks; two patients affected by Idiopathic Sudden Sensorineural Hearing Loss: 30 HBOT × 5 days/wk for 6 weeks; and one patient with osteomyelitis: 30 HBOT × 5 days/wk for week for 6 weeks and, after a 30-day break, followed by a second cycle of 20 HBOT).
Using saliva and/or urine samples, reactive oxygen species (ROS), antioxidant capacity, cytokines, lipids peroxidation, DNA damage, and renal status were assessed at T1_pre (basal level) and at T2_pre (basal level after treatment), and the results showed attenuated ROS production, lipid peroxidation, DNA damage, NO metabolites, and inflammation biomarker levels, especially in the athletes post-treatment. Thus, HBOT may represent an alternative non-invasive method for treating long COVID-19-induced long-lasting manifestations of oxy-inflammation.
Source: Mrakic-Sposta S, Vezzoli A, Garetto G, Paganini M, Camporesi E, Giacon TA, Dellanoce C, Agrimi J, Bosco G. Hyperbaric Oxygen Therapy Counters Oxidative Stress/Inflammation-Driven Symptoms in Long COVID-19 Patients: Preliminary Outcomes. Metabolites. 2023; 13(10):1032. https://doi.org/10.3390/metabo13101032 https://www.mdpi.com/2218-1989/13/10/1032 (Full text)

Effects of six-month creatine supplementation on patient- and clinician-reported outcomes, and tissue creatine levels in patients with post-COVID-19 fatigue syndrome

Abstract:

Dietary creatine has been recently put forward as a possible intervention strategy to reduce post-COVID-19 fatigue syndrome yet no clinical study so far evaluated its efficacy and safety for this perplexing condition. In this parallel-group, randomized placebo-controlled double-blind trial, we analyzed the effects of 6-month creatine supplementation (4 g of creatine monohydrate per day) on various patient- and clinician-reported outcomes, and tissue creatine levels in 12 patients with post-COVID-19 fatigue syndrome.

Creatine intake induced a significant increase in tissue creatine levels in vastus medialis muscle and right parietal white matter compared to the baseline values at both 3-month and 6-month follow-ups (p < .05). Two-way analysis of variance with repeated measures revealed a significant difference (treatment vs. time interaction) between interventions in tissue creatine levels (p < .05), with the creatine group was superior to placebo to augment creatine levels at vastus medialis muscle, left frontal white matter, and right parietal white matter.

Creatine supplementation induced a significant reduction in general fatigue after 3 months of intake compared to baseline values (p = .04), and significantly improved scores for several post-COVID-19 fatigue syndrome-related symptoms (e.g., ageusia, breathing difficulties, body aches, headache, and difficulties concentrating) at 6-month follow-up (p < .05). Taking creatine for 6 months appears to improve tissue bioenergetics and attenuate clinical features of post-COVID-19 fatigue syndrome; additional studies are warranted to confirm our findings in various post-COVID-19 cohorts.

Source: Slankamenac, J.Ranisavljev, M.Todorovic, N.Ostojic, J.Stajer, V., & Ostojic, S. M. (2023). Effects of six-month creatine supplementation on patient- and clinician-reported outcomes, and tissue creatine levels in patients with post-COVID-19 fatigue syndromeFood Science & Nutrition0017https://doi.org/10.1002/fsn3.3597 (Full text)

Clinical Rationale for Dietary Lutein Supplementation in Post COVID-19 and mRNA Vaccine Injury Syndromes

Abstract:

Lutein, a plant-derived xanthophyl-carotenoid, is an exceptional antioxidant and anti-inflammatory constituent found in food. Elevated concentrations of lutein found in human blood and plasma, due to high dietary intake, are beneficial against eye disease and improve cardiometabolic health.

Lutein plays an important protective role against the development of neurological disorders, including Alzheimer’s disease (AD), multiple sclerosis (MS) and Parkinson’s disease (PD). It has also been shown to be beneficial for liver, kidney and respiratory health. Lutein, acting as a very strong antioxidant, can alleviate oxidative stress and downgrade reactive oxygen species (ROS). Oxidative stress is one of the key pathogenic mechanisms in post-COVID and mRNA vaccine injury syndromes.

Recent in silico studies suggest that lutein and other naturally derived antioxidants, by docking at the site where the SARS-CoV-2 spike protein (SP) binds to the angiotensin enzyme type 2 (ACE2) receptor, may neutralize the SP-ACE2 interactions. Lutein can be added to a detoxification regimen to aid in clearing Spike protein and relieving symptoms.

In agreement with Hippocrates’ dictum to “Let food be thy medicine,” this review establishes dietary lutein as a valuable therapy in the treatment of post-COVID syndrome, mRNA vaccine injury syndromes, and a wide range of other chronic illnesses.

Source: Kyriakopoulos, A.M.; Nigh, G.; McCullough, P.A.; Seneff, S. Clinical Rationale for Dietary Lutein Supplementation in Post COVID-19 and mRNA Vaccine Injury Syndromes. Preprints 2023, 2023091385. https://doi.org/10.20944/preprints202309.1385.v1 https://www.preprints.org/manuscript/202309.1385/v1 https://www.preprints.org/manuscript/202309.1385/v1 (Full text available as PDF file)

Immune Adsorption for the Treatment of Fatigue-Dominant Long-/Post-COVID Syndrome

Introduction:

Following an infection with SARS-CoV-2, a relevant proportion of patients suffer from fatigue-dominant long-/post-COVID syndrome. In 57% of patients with long-/post-COVID syndrome, who were treated in a university hospital, increased levels of autoantibodies (AABs) to G-protein-coupled neurotransmitter receptors (including ß-adrenergic and muscarinic) were detected ().

Reduction of ß-adrenergic AABs by immunoadsorption therapy was associated with clinical improvement in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) (). Increasingly, reports of individual cases of successful treatment of long/post-COVID syndrome with the help of apheresis techniques have been widely disseminated via social media. By contrast, cases or studies with negative outcomes are much less likely to receive proper attention. Given the overall lack of data to date, medical societies are calling for a broader scientific basis, to which we would like to contribute with this case series.

Source: Ruhe J, Giszas B, Schlosser M, Reuken PA, Wolf G, Stallmach A. Immune Adsorption for the Treatment of Fatigue-Dominant Long-/Post-COVID Syndrome: A Series of Cases With Standardized Individual Experimental Therapy. Dtsch Arztebl Int. 2023 Jul;120(29-30):499–500. doi: 10.3238/arztebl.m2023.0073. Epub 2023 Jul 24. PMCID: PMC10511006. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10511006/ (Full text)

Neuroimmunological Effect of Vitamin D on Neuropsychiatric Long COVID Syndrome: A Review

Abstract:

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the coronavirus disease 2019 (COVID-19). COVID-19 is now recognized as a multiorgan disease with a broad spectrum of manifestations. A substantial proportion of individuals who have recovered from COVID-19 are experiencing persistent, prolonged, and often incapacitating sequelae, collectively referred to as long COVID. To date, definitive diagnostic criteria for long COVID diagnosis remain elusive.
An emerging public health threat is neuropsychiatric long COVID, encompassing a broad range of manifestations, such as sleep disturbance, anxiety, depression, brain fog, and fatigue. Although the precise mechanisms underlying the neuropsychiatric complications of long COVID are presently not fully elucidated, neural cytolytic effects, neuroinflammation, cerebral microvascular compromise, breakdown of the blood–brain barrier (BBB), thrombosis, hypoxia, neurotransmitter dysregulation, and provoked neurodegeneration are pathophysiologically linked to long-term neuropsychiatric consequences, in addition to systemic hyperinflammation and maladaptation of the renin–angiotensin–aldosterone system.
Vitamin D, a fat-soluble secosteroid, is a potent immunomodulatory hormone with potential beneficial effects on anti-inflammatory responses, neuroprotection, monoamine neurotransmission, BBB integrity, vasculometabolic functions, gut microbiota, and telomere stability in different phases of SARS-CoV-2 infection, acting through both genomic and nongenomic pathways.
Here, we provide an up-to-date review of the potential mechanisms and pathophysiology of neuropsychiatric long COVID syndrome and the plausible neurological contributions of vitamin D in mitigating the effects of long COVID.
Source: Chen T-B, Chang C-M, Yang C-C, Tsai I-J, Wei C-Y, Yang H-W, Yang C-P. Neuroimmunological Effect of Vitamin D on Neuropsychiatric Long COVID Syndrome: A Review. Nutrients. 2023; 15(17):3802. https://doi.org/10.3390/nu15173802 https://www.mdpi.com/2072-6643/15/17/3802 (Full text)

The global challenges of the long COVID-19

Abstract:

COVID-19 may lead to a perseverance of symptoms after recovery from the disease, a condition known as long COVID, characterized by continual cognitive, somatic and behavioral symptoms. SARS-CoV-2 infection triggers different molecular to tissue level events, given by the inherent features of each patient. The potential pathological changes which determine the array of symptoms are arduous to anticipate.

There is an increasing interest to develop treatment strategies for survivors who experience a long COVID. In this respect, considering the anti-inflammatory, anti-oxidative and cytoprotective effects of melatonin (MEL) on viral infections, its potential links with COVID-19 should be researched. Several studies suggest that administration of MEL may prevent clinical deterioration and even death in patients with acute and long COVID-19.

This paper briefly reviews the current status of knowledge of the pathogenic, clinical, and therapeutic features of Long COVID-19 and forthcoming directions for research and implications for the management and therapy of the disease are analyzed.

Source: Leonor Chacin-Bonilla. The global challenges of the long COVID-19. Journal of Clinical Images and Medical Case Reports. ISSN 2766-7820 https://jcimcr.org/pdfs/JCIMCR-v4-2512.pdf (Full text)

Efficiency of comprehensive rehabilitation of chronic fatigue syndrome due to coronavirus infections COVID-19

Abstract:

The aim of the study was to study the effectiveness of complex rehabilitation in patients with chronic fatigue syndrome caused by coronavirus infections.

In 120 patients with a confirmed diagnosis of SARS-CoV-2 (COVID-19) aged 20-58 years, post-COVID syndrome or chronic fatigue syndrome was detected, 52 men and 68 women. Patients had asthenic, cognitive, vegetative manifestations, sleep disorders, smell and taste disorders, anxiety and depression.

Patients received drug therapy: succinic acid preparations, brain metabolic drugs, stimulating antidepressants, sleeping pills – melatonin and B vitamins, among other things, received micropolarization of the head and translingualneurostimulation.

The results of treatment confirmed the effectiveness of the proposed conservative therapy. The neurological symptoms of post-COVID syndrome – chronic fatigue syndrome (CFS) were studied in 120 patients with a confirmed diagnosis of SARS-CoV-2 (COVID-19), aged 20-58 years.

Patients were examined according to the “Questionnaire for the detection of asthenia”, “Mini Mental State Assessment (MMSE)”, et.al. Sleep disorders were studied using the Epworth Sleepiness Scale, anxiety and depression were studied using the “Questionnaire for Determining Anxiety and Depression”.

The patients were divided into 2 groups: the main group (MG) – 69 patients and the control group (CG) – 51 patients. Patients with MG and CG received drug therapy: succinic acid preparations, brain metabolic drugs, stimulating antidepressants, sleeping pills – melatonin and B vitamins. And patients with MG, among other things, received micropolarization of the head and translingualneurostimulation.

Source: Z.I. Adambaev, I.A. Kilichev, A.B. Nurzhonov, N.Yu. Khudoyberganov, and M.R. Niyazmetov. Efficiency of comprehensive rehabilitation of chronic fatigue syndrome due to coronavirus infections COVID-19. BIO Web of Conferences 65, 05039 (2023) https://www.bio-conferences.org/articles/bioconf/abs/2023/10/bioconf_ebwff2023_05039/bioconf_ebwff2023_05039.html (Full text available as PDF file)