Tag: long covid treatment

Cystatin-c May Indicate Subclinical Renal Involvement, While Orosomucoid Is Associated with Fatigue in Patients with Long-COVID Syndrome

Abstract:

Long-COVID syndrome is associated with high healthcare costs, but its pathophysiology is not yet fully understood. Inflammation, renal impairment or disturbance of the NO system emerge as potential pathogenetic factors. We aimed to investigate the relationship between symptoms of long-COVID syndrome and serum levels of cystatin-c (CYSC), orosomucoid (ORM), l-arginine, symmetric dimethylarginine (SDMA) and asymmetric dimethylarginine (ADMA). A total of 114 patients suffering from long-COVID syndrome were included in this observational cohort study.

We found that serum CYSC was independently associated with the anti-spike immunoglobulin (S-Ig) serum level (OR: 5.377, 95% CI: 1.822-12.361; p = 0.02), while serum ORM (OR: 9.670 (95% CI: 1.34-9.93; p = 0.025) independently predicted fatigue in patients with long-COVID syndrome, both measured at baseline visit. Additionally, the serum CYSC concentrations measured at the baseline visit showed a positive correlation with the serum SDMA levels. The severity of abdominal and muscle pain indicated by patients at the baseline visit showed a negative correlation with the serum level of L-arginine.

In summary, serum CYSC may indicate subclinical renal impairment, while serum ORM is associated with fatigue in long-COVID syndrome. The potential role of l-arginine in alleviating pain requires further studies.

Source: Zavori L, Molnar T, Varnai R, Kanizsai A, Nagy L, Vadkerti B, Szirmay B, Schwarcz A, Csecsei P. Cystatin-c May Indicate Subclinical Renal Involvement, While Orosomucoid Is Associated with Fatigue in Patients with Long-COVID Syndrome. J Pers Med. 2023 Feb 19;13(2):371. doi: 10.3390/jpm13020371. PMID: 36836605; PMCID: PMC9958557. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9958557/ (Full text)

STIMULATE-ICP: A pragmatic, multi-centre, cluster randomised trial of an integrated care pathway with a nested, Phase III, open label, adaptive platform randomised drug trial in individuals with Long COVID: A structured protocol

Abstract:

Introduction: Long COVID (LC), the persistent symptoms ≥12 weeks following acute COVID-19, presents major threats to individual and public health across countries, affecting over 1.5 million people in the UK alone. Evidence-based interventions are urgently required and an integrated care pathway approach in pragmatic trials, which include investigations, treatments and rehabilitation for LC, could provide scalable and generalisable solutions at pace.

Methods and analysis: This is a pragmatic, multi-centre, cluster-randomised clinical trial of two components of an integrated care pathway (Coverscan™, a multi-organ MRI, and Living with COVID Recovery™, a digitally enabled rehabilitation platform) with a nested, Phase III, open label, platform randomised drug trial in individuals with LC. Cluster randomisation is at level of primary care networks so that integrated care pathway interventions are delivered as “standard of care” in that area. The drug trial randomisation is at individual level and initial arms are rivaroxaban, colchicine, famotidine/loratadine, compared with no drugs, with potential to add in further drug arms. The trial is being carried out in 6-10 LC clinics in the UK and is evaluating the effectiveness of a pathway of care for adults with LC in reducing fatigue and other physical, psychological and functional outcomes at 3 months. The trial also includes an economic evaluation which will be described separately.

Ethics and dissemination: The protocol was reviewed by South Central-Berkshire Research Ethics Committee (reference: 21/SC/0416). All participating sites obtained local approvals prior to recruitment. Coverscan™ has UK certification (UKCA 752965). All participants will provide written consent to take part in the trial. The first participant was recruited in July 2022 and interim/final results will be disseminated in 2023, in a plan co-developed with public and patient representatives. The results will be presented at national and international conferences, published in peer reviewed medical journals, and shared via media (mainstream and social) and patient support organisations.

Trial registration number: ISRCTN10665760.

Source: Forshaw D, Wall EC, Prescott G, Dehbi HM, Green A, Attree E, Hismeh L, Strain WD, Crooks MG, Watkins C, Robson C, Banerjee R, Lorgelly P, Heightman M, Banerjee A; STIMULATE-ICP trial team. STIMULATE-ICP: A pragmatic, multi-centre, cluster randomised trial of an integrated care pathway with a nested, Phase III, open label, adaptive platform randomised drug trial in individuals with Long COVID: A structured protocol. PLoS One. 2023 Feb 15;18(2):e0272472. doi: 10.1371/journal.pone.0272472. PMID: 36791116; PMCID: PMC9931100. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9931100/ (Full text)

Therapeutic Approaches to Dysautonomia in Childhood, with a Special Focus on Long COVID

Abstract:

Background: Dysautonomia seems to be important for the pathophysiology of psychosomatic diseases and, more recently, for long COVID. This concept may explain the clinical symptoms and could help open new therapeutic approaches.
Methods: We compared our data from an analysis of heart rate variability (HRV) in an active standing test in 28 adolescents who had developed an inappropriate sinus tachycardia (IST, n = 13) or postural orthostatic tachycardia syndrome (POTS, n = 15) after contracting COVID-19 disease and/or vaccination with 64 adolescents from our database who developed dysautonomia due to psychosomatic diseases prior to the COVID-19 pandemic. We prove the effects of our treatment: omega-3 fatty acid supplementation (O3-FA, n = 18) in addition to propranolol (low dose, up to 20-20-0 mg, n = 32) or ivabradine 5-5-0 mg (n = 17) on heart rate regulation and heart rate variability (HRV).
Results: The HRV data were not different between the adolescents with SARS-CoV-2-related disorders and the adolescents with dysautonomia prior to the pandemic. The heart rate increases in children with POTS while standing were significantly lower after low-dose propranolol (27.2 ± 17.4 bpm***), ivabradine (23.6 ± 8.12 bpm*), and O-3-FA (25.6 ± 8.4 bpm*). The heart rate in children with IST while lying/standing was significantly lower after propranolol (81.6 ± 10.1 bpm**/101.8 ± 18.8***), ivabradine (84.2 ± 8.4 bpm***/105.4 ± 14.6**), and O-3-FA (88.6 ± 7.9 bpm*/112.1/14.9*).
Conclusions: The HRV data of adolescents with dysautonomia after COVID-19 disease/vaccination are not significantly different from a historical control of adolescents with dysautonomia due to psychosomatic diseases prior to the pandemic. Low-dose propranolol > ivabradine > omega-3 fatty acids significantly decrease elevated heart rates in patients with IST and the heart rate increases in patients with POTS and may be beneficial in these children with dysautonomia.
Source: Buchhorn R. Therapeutic Approaches to Dysautonomia in Childhood, with a Special Focus on Long COVID. Children. 2023; 10(2):316. https://doi.org/10.3390/children10020316 https://www.mdpi.com/2227-9067/10/2/316 (Full text)

Potential of Nano-Antioxidants and Nanomedicine for Recovery from Neurological Disorders Linked to Long COVID Syndrome

Abstract:

Long-term neurological complications, persisting in patients who cannot fully recover several months after severe SARS-CoV-2 coronavirus infection, are referred to as neurological sequelae of the long COVID syndrome. Among the numerous clinical post-acute COVID-19 symptoms, neurological and psychiatric manifestations comprise prolonged fatigue, “brain fog”, memory deficits, headache, ageusia, anosmia, myalgias, cognitive impairments, anxiety, and depression lasting several months.
Considering that neurons are highly vulnerable to inflammatory and oxidative stress damages following the overproduction of reactive oxygen species (ROS), neuroinflammation and oxidative stress have been suggested to dominate the pathophysiological mechanisms of the long COVID syndrome. It is emphasized that mitochondrial dysfunction and oxidative stress damages are crucial for the pathogenesis of neurodegenerative disorders. Importantly, antioxidant therapies have the potential to slow down and prevent disease progression.
However, many antioxidant compounds display low bioavailability, instability, and transport to targeted tissues, limiting their clinical applications. Various nanocarrier types, e.g., liposomes, cubosomes, solid lipid nanoparticles, micelles, dendrimers, carbon-based nanostructures, nanoceria, and other inorganic nanoparticles, can be employed to enhance antioxidant bioavailability.
Here, we highlight the potential of phytochemical antioxidants and other neuroprotective agents (curcumin, quercetin, vitamins C, E and D, melatonin, rosmarinic acid, N-acetylcysteine, and Ginkgo Biloba derivatives) in therapeutic strategies for neuroregeneration. A particular focus is given to the beneficial role of nanoparticle-mediated drug-delivery systems in addressing the challenges of antioxidants for managing and preventing neurological disorders as factors of long COVID sequelae.
Source: Akanchise T, Angelova A. Potential of Nano-Antioxidants and Nanomedicine for Recovery from Neurological Disorders Linked to Long COVID Syndrome. Antioxidants. 2023; 12(2):393. https://doi.org/10.3390/antiox12020393 https://www.mdpi.com/2076-3921/12/2/393 (Full text)

A Prospect to Ameliorate Affective Symptoms and to Enhance Cognition in Long COVID Using Auricular Transcutaneous Vagus Nerve Stimulation

Abstract:

Long COVID, the postviral disorder caused by COVID-19, is expected to become one of the leading causes of disability in Europe. The cognitive consequences of long COVID have been described as “brain fog” and characterized by anxiety and depression, and by cognitive deficits. Long COVID is assumed to be a complex condition arising from multiple causes, including persistent brainstem dysfunction and disrupted vagal signaling.

We recommend the potential application of auricular transcutaneous vagus nerve stimulation (atVNS) as an ADD-ON instrument to compensate for the cognitive decline and to ameliorate affective symptoms caused by long COVID. This technique enhances vagal signaling by directly activating the nuclei in the brainstem, which are hypoactive in long COVID to enhance mood and to promote attention, memory, and cognitive control-factors affected by long COVID.

Considering that atVNS is a non-pharmacological intervention, its ADD-ON to standard pharmaceutical agents will be useful for non-responders, making of this method a suitable tool. Given that atVNS can be employed as an ecological momentary intervention (EMI), we outline the translational advantages of atVNS in the context of accelerating the cognitive and affective recovery from long COVID.

Source: Colzato LS, Elmers J, Beste C, Hommel B. A Prospect to Ameliorate Affective Symptoms and to Enhance Cognition in Long COVID Using Auricular Transcutaneous Vagus Nerve Stimulation. J Clin Med. 2023 Feb 2;12(3):1198. doi: 10.3390/jcm12031198. PMID: 36769845. https://www.mdpi.com/2077-0383/12/3/1198 (Full text)

Long Covid and Neurodegenerative Disease

Abstract:

Brain fog with compromised ability to concentrate has been the most frequent Long Covid (LC) complaint. This is due to an increased TGF beta/IFN gamma with consequently increased bradykinin (BKN), especially in Caucasian females. Brain and lung blood vessels “leak.” This same ratio is increased in Alzheimer’s disease (AD), but decreased in Parkinson’s disease (PD), because CD4+ and CD8+ T cells are differentially affected by the invading associated viruses, e.g., SARS CoV2, HIV, ….

In Covid-19 CD147 receptors on immune cells are critical in generating the increased TGF beta/IFN gamma and those on endothelial cells, platelets, and erythrocytes are critical to the abnormal microvascular blood flow. ACE2 receptors on pneumocytes and enterocytes enable pulmonary and GI entry, initiating gut dysbiosis.

Epigenetics, methylation, magnesium, vitamin D, the B vitamins, and antioxidants suggest that these issues can be surmounted. Biochemical, physiologic, and epidemiologic data are analyzed to answer these questions. An LC model is presented and discussed in the context of the most recent research. Suggestions to avoid these and other worrisome concerns are included. Other topics discussed include estrogen, the gut microbiome, type 2 diabetes (T2D), and homocysteine.

Source: Chambers, P. Long Covid and Neurodegenerative Disease. Preprints 2023, 2023020027 (doi: 10.20944/preprints202302.0027.v1) https://www.preprints.org/manuscript/202302.0027/v1 (Full text available as PDF file)

 

Compounding for the Treatment of COVID-19 and Long COVID, Part 1: Terminology, Mutations, and Variants

Abstract:

COVID-19 (coronavirus disease 2019), which is caused by the positive-stranded ribonucleic acid virus SARS-CoV-2 (acute respiratory syndrome coronavirus 2), is an extremely contagious airborne illness of pandemic proportions. In the modern era, few diseases other than COVID-19 have produced such severe, prolific, and protean short-term adverse effects and long-term sequelae. In addition, few other pandemics have exhibited a trajectory of morbidity and mortality so affected by social, economic, and political factors as well as individual personal perceptions and beliefs.

Vaccines for the prevention of SARS-CoV-2 infection and treatments for COVID-19 mitigate associated morbidity and mortality, but an increasing array of variants presents challenges to therapeutic effectiveness. As a result, afflicted patients often require customized treatments that address the severity of their infection, the manifestations of disease they exhibit, and their individual pharmacogenomic profile. In such cases, a compounded preparation may offer needed support for recovery.

This article, which is the first in a series on compounding for COVID-19 and long COVID (i.e., the long- term sequelae of SARS-CoV-2 infection), provides information about pertinent viral terminology and a brief overview of SARS-CoV-2 mutations and variants of note. Two formulations for customized compounds that may prove effective in treating the acute and/or long-term effects of COVID-19 when commercial therapies have failed are also provided.

Source: Riepl M. Compounding for the Treatment of COVID-19 and Long COVID, Part 1: Terminology, Mutations, and Variants. Int J Pharm Compd. 2023 Jan-Feb;27(1):12-21. PMID: 36720058. https://pubmed.ncbi.nlm.nih.gov/36720058/

Long-term high-dose immunoglobulin successfully treats Long COVID patients with pulmonary, neurologic, and cardiologic symptoms

Abstract:

Introduction: Long COVID is the overarching name for a wide variety of disorders that may follow the diagnosis of acute SARS-COVID-19 infection and persist for weeks to many months. Nearly every organ system may be affected.

Methods: We report nine patients suffering with Long COVID for 101 to 547 days. All exhibited significant perturbations of their immune systems, but only one was known to be immunodeficient prior to the studies directed at evaluating them for possible treatment. Neurological and cardiac symptoms were most common. Based on this data and other evidence suggesting autoimmune reactivity, we planned to treat them for 3 months with long-term high-dose immunoglobulin therapy. If there was evidence of benefit at 3 months, the regimen was continued.

Results: The patients’ ages ranged from 34 to 79 years—with five male and four female patients, respectively. All nine patients exhibited significant immune perturbations prior to treatment. One patient declined this treatment, and insurance support was not approved for two others. The other six have been treated, and all have had a significant to remarkable clinical benefit.

Conclusion: Long-term high-dose immunoglobulin therapy is an effective therapeutic option for treating patients with Long COVID.

Source: Thompson JS, Thornton AC, Ainger T and Garvy BA (2023) Long-term high-dose immunoglobulin successfully treats Long COVID patients with pulmonary, neurologic, and cardiologic symptoms. Front. Immunol. 13:1033651. doi: 10.3389/fimmu.2022.1033651 https://www.frontiersin.org/articles/10.3389/fimmu.2022.1033651/full (Full text)

Hyperbaric oxygen therapy for long COVID (HOT-LoCO), an interim safety report from a randomised controlled trial

Abstract:

Background: With ~ 50 million individuals suffering from post-COVID condition (PCC), low health related quality of life (HRQoL) is a vast problem. Common symptoms of PCC, that persists 3 months from the onset of COVID-19 are fatigue, shortness of breath and cognitive dysfunction. No effective treatment options have been widely adopted in clinical practice. Hyperbaric oxygen (HBO2) is a candidate drug.

Methods: The objective of this interim analysis is to describe our cohort and evaluate the safety of HBO2 for post covid condition. In an ongoing randomised, placebo-controlled, double blind, clinical trial, 20 previously healthy subjects with PCC were assigned to HBO2 or placebo. Primary endpoints are physical domains in RAND-36; Physical functioning (PF) and Role Physical (RP) at 13 weeks. Secondary endpoints include objective physical tests. Safety endpoints are occurrence, frequency, and seriousness of Adverse Events (AEs). An independent data safety monitoring board (DSMB) reviewed unblinded data. The trial complies with Good Clinical Practice. Safety endpoints are evaluated descriptively. Comparisons against norm data was done using t-test.

Results: Twenty subjects were randomised, they had very low HRQoL compared to norm data. Mean (SD) PF 31.75 (19.55) (95% Confidence interval; 22.60-40.90) vs 83.5 (23.9) p < 0.001 in Rand-36 PF and mean 0.00 (0.00) in RP. Very low physical performance compared to norm data. 6MWT 442 (180) (95% CI 358-525) vs 662 (18) meters p < 0.001. 31 AEs occurred in 60% of subjects. In 20 AEs, there were at least a possible relationship with the study drug, most commonly cough and chest pain/discomfort.

Conclusions: An (unexpectedly) high frequency of AEs was observed but the DSMB assessed HBO2 to have a favourable safety profile. Our data may help other researchers in designing trials.

Trial Registration ClinicalTrials.gov: NCT04842448. Registered 13 April 2021, https://clinicaltrials.gov/ct2/show/NCT04842448 . EudraCT: 2021-000764-30. Registered 21 May 2021, https://www.clinicaltrialsregister.eu/ctr-search/trial/2021-000764-30/SE.

Source: Kjellberg A, Hassler A, Boström E, El Gharbi S, Al-Ezerjawi S, Kowalski J, Rodriguez-Wallberg KA, Bruchfeld J, Ståhlberg M, Nygren-Bonnier M, Runold M, Lindholm P. Hyperbaric oxygen therapy for long COVID (HOT-LoCO), an interim safety report from a randomised controlled trial. BMC Infect Dis. 2023 Jan 20;23(1):33. doi: 10.1186/s12879-023-08002-8. PMID: 36670365; PMCID: PMC9854077. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9854077/ (Full text)

Long COVID: Is There a Role for Antidepressants?

Abstract:

Two years into this historic pandemic, the scientific and healthcare communities continue to learn a great deal regarding COVID-19. The most urgent and immediate focus has been on vaccine development for disease prevention/mitigation and on identification of effective therapeutic interventions for acute phase of illness. However, attention is increasingly being placed on formulating treatment strategies for individuals who are post-COVID-19 and experiencing a syndrome of persistent symptoms that is being referred to as long COVID.

One strategy is to repurpose drugs which have been approved for other conditions and subsequently assess their safety and efficacy when applied to COVID-19. In this light, antidepressant medications have garnered attention amidst evidence supporting anti-inflammatory and anti-viral properties.

In this article, we present purported anti-inflammatory mechanisms of antidepressants, review studies appearing in the literature to date regarding antidepressants and acute COVID-19, and discuss the utility of antidepressants as a potential therapeutic resource for long COVID.

Source: Rivas-Vázquez R, Carrazana EJ, Blais MA, Rey GJ, RivasVázquez E, Quintana AA. Long COVID: Is There a Role for Antidepressants? Neurol Curr Res. 2022;2(3):1019. https://www.medtextpublications.com/open-access/long-covid-is-there-a-role-for-antidepressants-1249.pdf (Full text)