Tag: long covid treatment

Re: What happens inside a long covid clinic?

Dear Editor

As a patient with severe long covid and myalgic encephalomyelitis (M.E.), I was pleased to see the article ‘What happens in a long covid clinic?’ [1] raising awareness of the scale and impact of long covid and the importance of long covid clinics. According to a recent estimate by Altmann et al, 1 in 10 people who contract COVID-19 will be affected by long covid, whilst the oncoming impact of long covid on health systems, populations and economies will be “so large as to be unfathomable”.[2]

Around 2-14% of patients with long covid develop orthostatic tachycardia six to eight months after COVID infection and as many as 60% show some symptoms of POTS. [3] Yet there remain no agreed guidelines for POTS in long covid, making the early diagnosis and management of the condition in primary care challenging. NICE guidance on long covid only mentions POTS in passing with no information on management.[4] The approach outlined by Espinosa-Gonzalez and colleagues to diagnose and manage POTS in primary care could greatly improve function and health for people with POTS.[5]

While I commend the excellent NHS services highlighted in the feature [1], as a patient with severe long covid I would question how prevalent this integrated medically-led care model is across the country despite it being in the ‘The NHS plan for improving long covid services’.[6] Many patients I speak to in long covid support groups report long waits, only to then be offered basic wellbeing classes or rehabilitation without any active treatment for symptoms.

Access to clinics for the most severely affected is variable with not all services offering remote consultations or home visits. It is imperative that long covid clinics are medically led, inter-disciplinary and able to prescribe medications. Additionally, we need the same standard of care for patients with ME/CFS, who are still waiting for NICE guidance from 2021[7] to be implemented. A recent survey noted there remain significant gaps in provision for patients with ME/CFS.[8]

Previously young fit and healthy patients with severe long covid and ME are being left bed-bound without adequate diagnosis, support, care or treatment as there is no specialty or service that is set up to provide this. I went from climbing mountains and working on-call to unable to stand or feed myself in the space of 8 weeks with long covid – I am still severely affected a year later. Given the multi-system complexity of long covid and ME/CFS it is time for an interdisciplinary patient-centred service for post-viral illnesses that recognises the biological nature of the disease and the unique challenges patients with severe long covid and ME have with safely accessing services given their limited energy available, severe cognitive effects, physical immobility and range of complications across bodily systems.

The Department of Health and Social Care are currently seeking views on the interim delivery plan for ME/CFS care in an online consultation [9], which is relevant to both patient groups and professionals and could lay the groundwork for more comprehensive care of post-viral illnesses in the UK.

Yours sincerely,

Dr Alexis Gilbert BSc MBBS MPH FFPH

Source: MJ 2023;382:p1791 https://www.bmj.com/content/382/bmj.p1791/rr (Full text)

Long COVID: A Chronic Shortage of Blood. Pathophysiology and Treatment Proposal

Abstract:

My hypothesis is that the signs and symptoms of Long COVID can be explained by a shortage of blood in the body and a resulting deficient blood flow through nearly all organs. This shortage arises through damage to the blood-producing organs during the acute phase, while the breakdown of blood continues as normal, after an initial increase.

In order to ensure the perfusion of organs that are directly necessary for survival, the body takes the emergency measure of diverting blood from other organs and tissues. The perfusion of the blood-producing organs is also affected by this distribution measure, which hinders the smooth recovery of the total blood volume. The body is stuck in this vicious circle: a shortage of circulating blood hinders the recovery of blood production. This explains the long duration of Long COVID.

My proposed treatment of Long COVID focuses on the recovery of the correct volume of blood in the body of the right composition by the very careful administration of donor blood products under continuous expert supervision. A trial treatment can be performed in any hospital without much additional preparations, and has a lower associated risk for the patient than analysing the total blood. A diagnosis ex juvantibus, by therapeutic response, is therefore preferable, and will result in the healing process starting earlier.

Indications in blood laboratory values of a shortage of blood are a high serum ferritin due to internal breakdown of blood and values for haematocrit and albumin at reciprocal extremes of the reference ranges due to a stagnation of blood production.

Source: Molenaar, P.A. Long COVID: A Chronic Shortage of Blood. Pathophysiology and Treatment Proposal. Preprints 2023, 2023092109. https://doi.org/10.20944/preprints202309.2109.v1 https://www.preprints.org/manuscript/202309.2109/v1 (Full text available as PDF file)

Complementary and alternative medicine for long COVID: a systematic review of randomized controlled trials

Abstract:

Background: Complementary and alternative medicine (CAM) interventions are growing in popularity as possible treatments for long COVID symptoms. However, comprehensive analysis of current evidence in this setting is still lacking.

Objective: This study aims to review existing published studies on the use of CAM interventions for patients experiencing long COVID through a systematic review.

Design: Systematic review of randomized controlled trials (RCTs).

Methods: A comprehensive electronic literature search was performed in multiple databases and clinical trial registries from September 2019 to January 2023. RCTs evaluating efficacy and safety of CAM for long COVID were included. Methodological quality of each included trial was appraised with the Cochrane ‘risk of bias’ tool. A qualitative analysis was conducted due to heterogeneity of included studies.

Results: A total of 14 RCTs with 1195 participants were included in this review. Study findings demonstrated that CAM interventions could benefit patients with long COVID, especially those suffering from neuropsychiatric disorders, olfactory dysfunction, cognitive impairment, fatigue, breathlessness, and mild-to-moderate lung fibrosis. The main interventions reported were self-administered transcutaneous auricular vagus nerve stimulation, neuro-meditation, dietary supplements, olfactory training, aromatherapy, inspiratory muscle training, concurrent training, and an online breathing and well-being program.

Conclusion: CAM interventions may be effective, safe, and acceptable to patients with symptoms of long COVID. However, the findings from this systematic review should be interpreted with caution due to various methodological limitations. More rigorous trials focused on CAM for long COVID are warranted in the future.

Source: Yang J, Lim KH, Lim KT, Woods JT, Mohabbat AB, Wahner-Roedler DL, Ganesh R, Bauer BA. Complementary and alternative medicine for long COVID: a systematic review of randomized controlled trials. Ther Adv Chronic Dis. 2023 Oct 11;14:20406223231204727. doi: 10.1177/20406223231204727. PMID: 37841213; PMCID: PMC10571674. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10571674/ (Full text)

Vitamin B12 as an epidrug for regulating peripheral blood biomarkers in long COVID-associated visuoconstructive deficit

Abstract:

Approximately four months after recovering from a mild COVID-19 infection, around 25% of individuals developed visuoconstructive deficit (VCD), which was found to be correlated with an increase in peripheral immune markers and alterations in structural and metabolic brain imaging. Recently, it has been demonstrated that supplemental vitamin B12 regulates hyperinflammation during moderate and severe COVID-19 through methyl-dependent epigenetic mechanisms.

Herein, whole peripheral blood cultures were produced using samples obtained from patients with confirmed persistent VCD, and controls without impairment, between 10 and 16 months after mild COVID-19. This experimental model was used to assess the leukocyte expression patterns of 11 biomarkers previously associated with VCD in long COVID and explore the potential of pharmacological B12 in regulating these genes. The results showed that patients with persistent VCD displayed continued upregulation of CCL11 and LIF compared to controls.

It is worth noting that elevated serum levels of CCL11 have been previously linked to age-related neurodegenerative diseases. Notably, the addition of 1 nM of vitamin B12 to blood cultures from individuals with VCD normalized the mRNA levels of CCL11, upregulated the neuroprotective HGF, and, to a lesser extent, downregulated CSF2 and CXCL10. There was an inverse correlation observed between CCL11 mRNA levels and methylation levels of specific cytosines in its promoter region.

These findings underscore the significance of systemic inflammation in persistent VCD associated with long COVID. Moreover, the study provides evidence suggesting that B12, acting as an epidrug, shows promise as a therapeutic approach for addressing this cognitive impairment.

Source: Larissa Cassiano, Jonas Paula, Daniela Rosa et al. Vitamin B12 as an epidrug for regulating peripheral blood biomarkers in long COVID-associated visuoconstructive deficit, 11 October 2023, PREPRINT (Version 1) available at Research Square [https://doi.org/10.21203/rs.3.rs-3158180/v1] https://www.researchsquare.com/article/rs-3158180/v1 (Full text)

Acupuncture as an Additional Method of Rehabilitation Post-COVID-19: a randomized controlled trial

Abstract:

Objectives: The purpose of this study was to evaluate the effectiveness of complex rehabilitation with and without acupuncture in a hospital setting.

Methods: A randomized clinical trial was performed at Rehabilitation center “Kamenskoe Plato” in Almaty, Kazakhstan. 160 patients with Post COVID-19 condition were randomly equally divided into an acupuncture with complex rehabilitation methods and a only complex rehabilitation methods group in the period from March 1, 2022 to July 1, 2022. Either groups was performed for an 10-14 days period. The outcome measures were the Bartel index, the Borg scale, Modified Dyspnea Scale and the 6-minute walking test. Adverse events also were monitored and documented.

Results: We found statistically significant improvement after the rehabilitation course with acupuncture in the all scales. And in the group without acupuncture, only on two scales MDS and Borg scale.

Conclusion: Rehabilitation with acupuncture is possible and effective in patients recovering from post-COVID-19. Our findings may be useful to guide clinicians taking care of patients with post-COVID-19.

Source: Omarova I, Akanova A, Kurmanova A, Kurmanova G, Glushkova N, Seidanova A, Turysbekov K. Acupuncture as an Additional Method of Rehabilitation Post-COVID-19: a randomized controlled trial. J Pharmacopuncture. 2023 Sep 30;26(3):238-246. doi: 10.3831/KPI.2023.26.3.238. PMID: 37799621; PMCID: PMC10547817. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10547817/ (Full text)

Pathophysiology and potential treatment of long COVID: A report of signal index cases and call for targeted research

Abstract:

Objective: Long COVID has afflicted tens of millions globally leaving many previously-healthy persons severely and indefinitely debilitated. The objective here was to report cases of complete, rapid remission of severe forms of long COVID following certain monoclonal antibody (MCA) infusions and review the corresponding pathophysiological implications.

Design: Case histories of the first three index events (among others) are presented. Unaware of others with similar remissions, each subject independently completed personal narratives and standardized surveys regarding demographics/occupation, past history, and the presence and respective severity grading of 33 signs/symptoms associated with long COVID, comparing the presence/severity of those symptoms during the pre-COVID, long-COVID, post-vaccination, and post-MCA phases.

Setting: Patient interviews, e-mails and telephone conversations.

Subjects: Three previously healthy, middle-aged, highly-functioning persons, two women and one man (ages 60, 43, and 63 years respectively) who, post-acute COVID-19 infection, developed chronic, unrelenting fatigue and cognitive impairment along with other severe, disabling symptoms. Each then independently reported incidental and unanticipated complete remissions within days of MCA treatment.

Interventions: The casirivimab/imdevimab cocktail.

Measurements and main results: Irrespective of sex, age, vaccination status, or illness duration (18, 8 and 5 months, respectively), each subject experienced the same complete remission of their persistent disabling disease within a week of MCA infusion. Each rapidly returned to normal health and previous lifestyles/occupations with normalized exercise tolerance, still sustained to date nearly two years later.

Conclusions: These index cases provide compelling clinical signals that MCA infusions may be capable of treating long COVID in certain cases, including those with severe debilitation. While the complete and sustained remissions observed here may only apply to long COVID resulting from pre-Delta variants and the specific MCA infused, the striking rapid and complete remissions observed in these cases also provide mechanistic implications for treating/managing other post-viral chronic conditions and long COVID from other variants.

Key points

  • •Question: Considering that long COVID-19 has been devastating for many millions worldwide, what is the proposed pathophysiology and are there any effective treatments?
  • Findings: Previously-healthy middle-aged persons who had developed persistent debilitating post-acute SARS-CoV-2 sequelae, each experienced complete remission their symptoms within days of receiving a specific monoclonal anti-body infusion despite relative differences in sex, age, vaccination status, and long COVID duration.
  • Meaning: Certain monoclonal antibody infusions may be capable of reversing severe long COVID. Beyond providing an effective potential treatment for long COVID, these findings have mechanistic implications for treating other post-viral chronic conditions, including future long COVID variants.

Source: Kenneth A. Scheppke, Paul E. Pepe, Jonathan Jui, Remle P. Crowe, Eric K. Scheppke, Nancy G. Klimas, Aileen M. Marty. Pathophysiology and potential treatment of long COVID: A report of signal index cases and call for targeted research, The American Journal of Emergency Medicine, 2023. ISSN 0735-6757. https://doi.org/10.1016/j.ajem.2023.09.051. https://www.sciencedirect.com/science/article/abs/pii/S073567572300534X

Adipose-derived, autologous mesenchymal stem cell therapy for patients with post-COVID-19 syndrome: an intermediate-size expanded access program

Abstract:

Background: Evolving mutations of the novel coronavirus continue to fuel up the pandemic. The virus affects the human respiratory system along with other body systems, causing several sequelae in the survivors of the disease, presented as post-COVID-19 syndrome or long-COVID-19. This protocol utilized Hope Biosciences’ autologous, adipose-derived mesenchymal stem cells (HB-adMSCs) to evaluate safety and efficacy of HB-adMSC therapy to improve signs and symptoms associated with post-COVID-19 syndrome.

Methods: Ten eligible subjects with post-COVID-19 syndrome were enrolled in the program for a duration of 40 weeks who received 5 intravenous infusions of 2 × 108 autologous HB-adMSCs each at week 0, 2, 6, 10 and 14 with a follow-up at week 18 and end of the study at week 40. Safety assessments included incidence of adverse and serious adverse events along with the laboratory measures of hematologic, hepatic, and renal function. Efficacy was examined by quality-of-life assessments, fatigue assessments, Visual analog scale (VAS) of symptoms and monitoring of respiration and oxygen saturation rates.

Results: VAS scores and Fatigue Assessment scores (FAS) showed significant improvements post-treatment (P = 0.0039, ES = 0.91) compared to baseline. Respiration rates and oxygen saturation levels that were within the normal range at the baseline remained unchanged at the end of the study (EOS). Paired comparison between baseline and EOS for short-form-36 health survey questionnaire (SF-36) scores also showed improved quality-of-life with significant improvements in individual SF-36 evaluations. Mostly mild AEs were reported during the study period with no incidence of serious AEs. Also, no detrimental effects in laboratory values were seen.

Conclusions: The results of the expanded access program indicated that treatment with autologous HB-adMSCs resulted in significant improvements in the signs and symptoms associated with post-COVID-19 syndrome as assessed by VAS and FAS scores. Additionally, improvements in the patients’ quality-of-life as demonstrated using SF-36 scores that also showed significant improvements in individual scaled scores. Overall, administration of multiple infusions of autologous HB-adMSCs is safe and efficacious for improvements in the quality-of life of patients with post-COVID-19 syndrome.

Trial registration: Clinical trial registration number: NCT04798066. Registered on March 15, 2021. ( https://clinicaltrials.gov/ct2/show/NCT04798066?term=hope+biosciences&cond=Post-COVID-19+Syndrome&draw=2&rank=2 ).

Source: Vij R, Kim H, Park H, Cheng T, Lotfi D, Chang D. Adipose-derived, autologous mesenchymal stem cell therapy for patients with post-COVID-19 syndrome: an intermediate-size expanded access program. Stem Cell Res Ther. 2023 Oct 5;14(1):287. doi: 10.1186/s13287-023-03522-1. PMID: 37798650; PMCID: PMC10557203. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10557203/ (Full text)

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)