Tag: long covid treatment

Cannabinoids and the Endocannabinoid System in Early SARS-CoV-2 Infection and Long COVID-19—A Scoping Review

Abstract:

Coronavirus disease-19 (COVID-19) is a highly contagious illness caused by the SARS-CoV-2 virus. The clinical presentation of COVID-19 is variable, often including symptoms such as fever, cough, headache, fatigue, and an altered sense of smell and taste. Recently, post-acute “long” COVID-19 has emerged as a concern, with symptoms persisting beyond the acute infection. Vaccinations remain one of the most effective preventative methods against severe COVID-19 outcomes and the development of long-term COVID-19. However, individuals with underlying health conditions may not mount an adequate protective response to COVID-19 vaccines, increasing the likelihood of severe symptoms, hospitalization, and the development of long-term COVID-19 in high-risk populations.
This review explores the potential therapeutic role of cannabinoids in limiting the susceptibility and severity of infection, both pre- and post-SARS-CoV-19 infection. Early in the SARS-CoV-19 infection, cannabinoids have been shown to prevent viral entry, mitigate oxidative stress, and alleviate the associated cytokine storm. Post-SARS-CoV-2 infection, cannabinoids have shown promise in treating symptoms associated with post-acute long COVID-19, including depression, anxiety, post-traumatic stress injury, insomnia, pain, and decreased appetite. While current research primarily focuses on potential treatments for the acute phase of COVID-19, there is a gap in research addressing therapeutics for the early and post-infectious phases. This review highlights the potential for future research to bridge this gap by investigating cannabinoids and the endocannabinoid system as a potential treatment strategy for both early and post-SARS-CoV-19 infection.
Source: Scott C, Hall S, Zhou J, Lehmann C. Cannabinoids and the Endocannabinoid System in Early SARS-CoV-2 Infection and Long COVID-19—A Scoping Review. Journal of Clinical Medicine. 2024; 13(1):227. https://doi.org/10.3390/jcm13010227 https://www.mdpi.com/2077-0383/13/1/227 (Full text)

Analysis of post-COVID symptoms and predisposing factors for chronic post-COVID syndrome

Abstract:

Introduction: While there is sufficient information about acute COVID-19, which can cause a multisystemic and fatal disease, post-COVID syndrome and risk factors for this condition remain poorly known. We aimed to identify postCOVID symptoms and risk factors for chronic post-COVID syndrome through this study.

Materials and methods: This prospective cross-sectional study was conducted on 254 out of 384 COVID-19 patients admitted to our COVID-19 polyclinic between February and April 2021. The patients were questioned with a list of 37 symptoms at the fifth and twelfth weeks after disease onset via phone review, and their acute post-COVID (APC) and chronic post-COVID (CPC) symptoms were recorded. Data on risk factors were collected from the hospital’s medical records system. Associations between symptom count in the CPC phase and age, sex, hospitalization, RT-PCR result, specific radiological findings, comorbidities, and long-term medications were evaluated.

Result: Two hundred twenty-one patients had APC symptoms, and 138 patients had CPC symptoms. While the most common symptom was fatigue at week five, it was hair loss at week 12. Symptoms were observed significantly less in the CPC phase than in the APC phase (Z= -12.301, p= 0.00). Female sex and the presence of specific radiological findings were significantly associated with the occurrence of CPC symptoms (p= 0.03, p= 0.00, respectively). Long-term use of angiotensin-2 receptor blockers (ARBs) was correlated with a low symptom count in the CPC phase (p= 0.00).

Conclusions: Female sex and the presence of specific radiological findings were risk factors for developing CPC. Long-term use of ARBs was associated with a low chronic post-COVID symptom burden. A substantial cluster of multisystemic symptoms was observed in both phases, and this condition highlights the requirement for customized outpatient management that includes long-term follow-up and treatment of COVID-19 patients. Identifying the high-risk patients that will develop persistent symptoms can guide this management.

Source: Abalı H, Demir D, Gül Ş, Şimşek Veske N, Tural Onur S. Analysis of post-COVID symptoms and predisposing factors for chronic post-COVID syndrome. Tuberk Toraks. 2023 Dec;71(4):378-389. English. doi: 10.5578/tt.20239606. PMID: 38152008. https://pubmed.ncbi.nlm.nih.gov/38152008/ (Full text available as PDF file)

Long Covid, the Gut, and Autoimmune Skin Diseases: A Novel Therapeutic Approach

Abstract:

The dermatological manifestations of Long Covid (LC) have languished in the shadows of chronic fatigue and brain fog. Yet they are all linked by gut dysbiosis and the cytokine triad of TNF-α, IL-1β, and IL-6. The gut microbiome common not only to LC, psoriasis, AA, and vitiligo but also to neurodegenerative disease has been recently described. This gut microbiome induces an altered tryptophan metabolism linked to autoimmune disease. SARS CoV2 invades enterochromaffin cells rich in ACE2 receptors and curtails absorption of the essential amino acid tryptophan and subsequent synthesis of serotonin and melatonin.

This review suggests that an etiologic prebiotic (d-mannose)/probiotic (lactobacilli, bifidobacteria)/postbiotic (butyrate) approach to autoimmune skin disease that improves intestinal barrier integrity and that suppresses the triad of TNF-α, IL-6, and IL-1β may enhance or even eliminate the traditional immunotherapy of targeted monoclonal antibodies, Janus kinase inhibitors, and steroids. Health benefits of this approach extend well beyond suppression of autoimmune skin disease.

Source: Chambers, P.W.; Chambers, S.E. Long Covid, the Gut, and Autoimmune Skin Diseases: A Novel Therapeutic Approach. Preprints 2023, 2023121881. https://doi.org/10.20944/preprints202312.1881.v2 https://www.preprints.org/manuscript/202312.1881/v2 (Full text available as PDF file)

Identification of CD8 T-cell dysfunction associated with symptoms in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Long COVID and treatment with a nebulized antioxidant/anti-pathogen agent in a retrospective case series

Highlights:

• Both Long COVID and ME/CFS are characterized by dysfunctional CD8 T-cells with severe deficiencies in their abilities to produce IFNγ and TNFα.

• In a small Long COVID and ME/CFS case series, patients’ immune deficiency and health improve during treatment period with a nebulized antioxidant, anti-pathogen and immune-modulatory pharmacological agent.

• This work provides evidence of a useful biomarker, CD8 T-cell dysfunction reminiscent of T cell exhaustion, that may assist diagnosis and have utility for tracking disease outcome during therapy, including response to a potential new treatment.

Abstract:

Background: Patients with post-acute sequelae of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection (PASC, i.e., Long COVID) have a symptom complex highly analogous to many features of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), suggesting they may share some aspects of pathogenesis in these similar disorders. ME/CFS is a complex disease affecting numerous organ systems and biological processes and is often preceded by an infection-like episode. It is postulated that the chronic manifestations of illness may result from an altered host response to infection or inability to resolve inflammation, as is being reported in Long COVID. The immunopathogenesis of both disorders is still poorly understood. Here, we show data that suggest Long COVID and ME/CFS may be due to an aberrant response to an immunological trigger-like infection, resulting in a dysregulated immune system with CD8 T-cell dysfunction reminiscent of some aspects of T-cell clonal exhaustion, a phenomenon associated with oxidative stress. As there is an urgent need for diagnostic tools and treatment strategies for these two related disabling disorders, here, in a retrospective case series, we have also identified a potential nebulized antioxidant/anti-pathogen treatment that has evidence of a good safety profile. This nebulized agent is comprised of five ingredients previously reported individually to relieve oxidative stress, attenuate NF-κB signaling, and/or to act directly to inhibit pathogens, including viruses. Administration of this treatment by nebulizer results in rapid access of small doses of well-studied antioxidants and agents with anti-pathogen potential to the lungs; components of this nebulized agent are also likely to be distributed systemically, with potential to enter the central nervous system.

Methods and Findings: We conducted an analysis of CD8 T-cell function and severity of symptoms by self-report questionnaires in ME/CFS, Long COVID and healthy controls. We developed a CD8 T-cell functional assay, assessing CD8 T-cell dysfunction by intracellular cytokine staining (ICS) in a group of ME/CFS (n = 12) and Long COVID patients (n = 8), comparing to healthy controls (HC) with similar age and sex (n = 10). Magnet-enriched fresh CD8 T-cells in both patient groups had a significantly diminished capacity to produce both cytokines, IFNγ or TNFα, after PMA stimulation when compared to HC. The symptom severity questionnaire showed similar symptom profiles for the two disorders. Fortuitously, through a retrospective case series, we were able to examine the ICS and questionnaire data of 4 ME/CFS and 4 Long COVID patients in conjunction with their treatment (3–15 months). In parallel with the treatment pursued electively by participants in this retrospective case series, there was an increase in CD8 T-cell IFNγ and TNFα production and a decrease in overall self-reported symptom severity score by 54%. No serious treatment-associated side effects or laboratory anomalies were noted in these patients.

Conclusions: Here, in this small study, we present two observations that appear potentially fundamental to the pathogenesis and treatment of Long COVID and ME/CFS. The first is that both disorders appear to be characterized by dysfunctional CD8 T-cells with severe deficiencies in their abilities to produce IFNγ and TNFα. The second is that in a small retrospective Long COVID and ME/CFS case series, this immune dysfunction and patient health improved in parallel with treatment with an immunomodulatory, antioxidant pharmacological treatment with anticipated anti-pathogen activity. This work provides evidence of the potential utility of a biomarker, CD8 T-cell dysfunction, and suggests the potential for benefit from a new nebulized antioxidant/anti-pathogen treatment. These immune biomarker data may help build capacity for improved diagnosis and tracking of treatment outcomes during clinical trials for both Long COVID and ME/CFS while providing clues to new treatment avenues that suggest potential efficacy for both conditions.

Source: Gil, A., Hoag, G.E., Salerno, J.P., Hornig, M., Klimas, N., Selin, L.K. Identification of CD8 T-cell dysfunction associated with symptoms in myalgic encephalomyelitis/ chronic fatigue syndrome (ME/CFS) and Long COVID and treatment with a nebulized antioxidant/antipathogen agent in a retrospective case series. Brain, Behavior, & Immunity – Health (2024), doi: https://doi.org/10.1016/j.bbih.2023.100720 https://www.sciencedirect.com/science/article/pii/S2666354623001345 (Full text)

Conceptual foundations of acetylcarnitine supplementation in neuropsychiatric long COVID syndrome: a narrative review

Abstract:

Post-acute sequelae of COVID-19 can present as multi-organ pathology, with neuropsychiatric symptoms being the most common symptom complex, characterizing long COVID as a syndrome with a significant disease burden for affected individuals. Several typical symptoms of long COVID, such as fatigue, depressive symptoms and cognitive impairment, are also key features of other psychiatric disorders such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and major depressive disorder (MDD). However, clinically successful treatment strategies are still lacking and are often inspired by treatment options for diseases with similar clinical presentations, such as ME/CFS.

Acetylcarnitine, the shortest metabolite of a class of fatty acid metabolites called acylcarnitines and one of the most abundant blood metabolites in humans can be used as a dietary/nutritional supplement with proven clinical efficacy in the treatment of MDD, ME/CFS and other neuropsychiatric disorders. Basic research in recent decades has established acylcarnitines in general, and acetylcarnitine in particular, as important regulators and indicators of mitochondrial function and other physiological processes such as neuroinflammation and energy production pathways.

In this review, we will compare the clinical basis of neuropsychiatric long COVID with other fatigue-associated diseases. We will also review common molecular disease mechanisms associated with altered acetylcarnitine metabolism and the potential of acetylcarnitine to interfere with these as a therapeutic agent. Finally, we will review the current evidence for acetylcarnitine as a supplement in the treatment of fatigue-associated diseases and propose future research strategies to investigate the potential of acetylcarnitine as a treatment option for long COVID.

Source: Helbing DL, Dommaschk EM, Danyeli LV, Liepinsh E, Refisch A, Sen ZD, Zvejniece L, Rocktäschel T, Stabenow LK, Schiöth HB, Walter M, Dambrova M, Besteher B. Conceptual foundations of acetylcarnitine supplementation in neuropsychiatric long COVID syndrome: a narrative review. Eur Arch Psychiatry Clin Neurosci. 2024 Jan 3. doi: 10.1007/s00406-023-01734-3. Epub ahead of print. PMID: 38172332. https://link.springer.com/article/10.1007/s00406-023-01734-3 (Full text)

Profound Symptom Alleviation in Long-Covid Patients After PAMP-Immunotherapy: Three Case Reports

Abstract:

Background: Long-Covid patients suffer from a range of symptoms with a largely varying degree of severity, including chronic fatigue syndrome (CFS), myalgic encephalomyelitis (ME), post-exertional malaise (PEM), postural orthostatic tachycardia syndrome (POTS), loss of smell and/or taste, cough, shortness of breath, headache, muscle ache, sleep disturbance, cognitive dysfunction, and depression.

Treatment: PAMP-immunotherapy was developed by one of us (UH), inspired by the old fever therapy a century ago, to treat cancer patients. Unintentionally, in three cases of Long-Covid, quick and profound symptom alleviation could be observed after only a few PAMP treatments.

Conclusion: PAMP-immunotherapy might be a treatment option for Long-Covid patients which is surprisingly brief, cheap, and effective.

Source: Raphaela Gaudek, Holger Porath, Uwe Hobohm. (2023). [Case Report] Profound Symptom Alleviation in Long-Covid Patients After PAMP-Immunotherapy: Three Case Reports. Qeios. doi:10.32388/69I32L. https://www.qeios.com/read/69I32L (Full text)

Intravenous immunoglobulin as a potential treatment for long COVID

Abstract:

Introduction: On 31 July 2023, the United States Department of Health and Human Services announced the formation of the Office of Long COVID Research and Practice and the United States National Institutes of Health (NIH) opened enrollment for the therapeutic arm of the RECOVER initiative, a prospective, randomized study to evaluate new treatment options for long coronavirus disease 2019 (long COVID).

Areas covered: One of the first drugs to be studied in this nationwide initiative is intravenous immunoglobulin (IVIG), which will be a treatment option for subjects enrolled in RECOVER-AUTO, a randomized trial to investigate therapeutic strategies for autonomic dysfunction related to long COVID.

Expert opinion: IVIG is a mixture of human antibodies (human immunoglobulin) that has been widely used to treat a variety of diseases, including immune thrombocytopenia purpura, Kawasaki disease, chronic inflammatory demyelinating polyneuropathy, and certain infections such as influenza, human immunodeficiency virus, and measles. However, the role of IVIG in the treatment of post-COVID-19 conditions is uncertain. This manuscript examines what is known about IVIG in the treatment of long COVID and explores how this therapeutic agent may be used in the future to address this condition.

Source: McCarthy MW. Intravenous immunoglobulin as a potential treatment for long COVID. Expert Opin Biol Ther. 2023 Jul-Dec;23(12):1211-1217. doi: 10.1080/14712598.2023.2296569. Epub 2023 Dec 28. PMID: 38100573. https://www.tandfonline.com/doi/full/10.1080/14712598.2023.2296569

Creatine supplementation combined with breathing exercises reduces respiratory discomfort and improves creatine status in patients with long-COVID

Abstract:

Eight long-COVID patients with moderate fatigue that had lasted for ≥3 months were recruited. All patients were allocated in a double-blind parallel-group design to receive either 4 g of creatine per day plus breathing exercises (study group) or breathing exercises only (control group) for 3 months.

Creatine induced a significant increase in tissue total creatine levels for all 14 locations evaluated in the present study (P < 0.05), while its levels significantly dropped in the right frontal gray matter and left parietal mesial gray matter at follow-up in the control group (P < 0.05).

No change in time to exhaustion was demonstrated in the control group (P > 0.05), while the mean time to exhaustion was significantly improved for 54 s in the study group post-administration (P = 0.05).

These preliminary findings suggest that creatine is as an effective adjuvant therapeutic to breathing exercises for tackling the clinical features in long-COVID.

Source: Slankamenac, J; Ranisavljev, M; Todorovic, N; Ostojic, J; Stajer, V; Ostojic, SM. Creatine supplementation combined with breathing exercises reduces respiratory discomfort and improves creatine status in patients with long-COVID. Journal of Postgraduate Medicine ():, December 07, 2023. | DOI: 10.4103/jpgm.jpgm_650_23  https://journals.lww.com/jopm/abstract/9000/creatine_supplementation_combined_with_breathing.99983.aspx (Full text available as PDF file)

Effectiveness of Antiviral Therapy on Long COVID: A Systematic Review and Meta-Analysis

Abstract:

Antiviral treatment reduces the severity and mortality of SARS-CoV-2 infection; however, its effectiveness against long COVID-19 is unclear. This study aimed to evaluate the effectiveness of antiviral drugs in preventing long COVID and related hospitalizations/deaths. Scientific and medical databases were searched from 1 January 2020 to 30 June 2023. We included observational cohort studies comparing individuals receiving early antiviral therapy for COVID-19 and those receiving supportive treatment.
A fixed-effects model was used to merge the effects reported in two or more studies. The risk of post-acute sequelae of COVID-19 (PASC) was combined as an odds ratio (OR). Six studies were selected, including a total of 3,352,235 participants. The occurrence of PASC was 27.5% lower in patients who received antiviral drugs during the early stages of SARS-CoV-2 infection (OR = 0.725; 95% confidence interval [CI] = 0.409–0.747) than in the supportive treatment group. Moreover, the risk of PASC-associated hospitalization and mortality was 29.7% lower in patients receiving early antiviral therapy than in the supportive treatment group (OR = 0.721; 95% CI = 0.697–0.794).
Early antiviral therapy was associated with a reduced risk of PASC and related hospitalization or death. Thus, early antiviral therapy is recommended for at-risk individuals.
Source: Choi YJ, Seo YB, Seo J-W, Lee J, Nham E, Seong H, Yoon JG, Noh JY, Cheong HJ, Kim WJ, et al. Effectiveness of Antiviral Therapy on Long COVID: A Systematic Review and Meta-Analysis. Journal of Clinical Medicine. 2023; 12(23):7375. https://doi.org/10.3390/jcm12237375 https://www.mdpi.com/2077-0383/12/23/7375 (Full text)

A synbiotic preparation (SIM01) for post-acute COVID-19 syndrome in Hong Kong (RECOVERY): a randomised, double-blind, placebo-controlled trial

Abstract:

Background: Post-acute COVID-19 syndrome (PACS) affects over 65 million individuals worldwide but treatment options are scarce. We aimed to assess a synbiotic preparation (SIM01) for the alleviation of PACS symptoms.

Methods: In this randomised, double-blind, placebo-controlled trial at a tertiary referral centre in Hong Kong, patients with PACS according to the US Centers for Disease Control and Prevention criteria were randomly assigned (1:1) by random permuted blocks to receive SIM01 (10 billion colony-forming units in sachets twice daily) or placebo orally for 6 months. Inclusion criterion was the presence of at least one of 14 PACS symptoms for 4 weeks or more after confirmed SARS-CoV-2 infection, including fatigue, memory loss, difficulty in concentration, insomnia, mood disturbance, hair loss, shortness of breath, coughing, inability to exercise, chest pain, muscle pain, joint pain, gastrointestinal upset, or general unwellness. Individuals were excluded if they were immunocompromised, were pregnant or breastfeeding, were unable to receive oral fluids, or if they had received gastrointestinal surgery in the 30 days before randomisation. Participants, care providers, and investigators were masked to group assignment. The primary outcome was alleviation of PACS symptoms by 6 months, assessed by an interviewer-administered 14-item questionnaire in the intention-to-treat population. Forward stepwise multivariable logistical regression was performed to identify predictors of symptom alleviation. The trial is registered with ClinicalTrials.gov, NCT04950803.

Findings: Between June 25, 2021, and Aug 12, 2022, 463 patients were randomly assigned to receive SIM01 (n=232) or placebo (n=231). At 6 months, significantly higher proportions of the SIM01 group had alleviation of fatigue (OR 2·273, 95% CI 1·520-3·397, p=0·0001), memory loss (1·967, 1·271-3·044, p=0·0024), difficulty in concentration (2·644, 1·687-4·143, p<0·0001), gastrointestinal upset (1·995, 1·304-3·051, p=0·0014), and general unwellness (2·360, 1·428-3·900, p=0·0008) compared with the placebo group. Adverse event rates were similar between groups during treatment (SIM01 22 [10%] of 232 vs placebo 25 [11%] of 231; p=0·63). Treatment with SIM01, infection with omicron variants, vaccination before COVID-19, and mild acute COVID-19, were predictors of symptom alleviation (p<0·0036).

Interpretation: Treatment with SIM01 alleviates multiple symptoms of PACS. Our findings have implications on the management of PACS through gut microbiome modulation. Further studies are warranted to explore the beneficial effects of SIM01 in other chronic or post-infection conditions.

Source: Lau RI, Su Q, Lau ISF, Ching JYL, Wong MCS, Lau LHS, Tun HM, Mok CKP, Chau SWH, Tse YK, Cheung CP, Li MKT, Yeung GTY, Cheong PK, Chan FKL, Ng SC. A synbiotic preparation (SIM01) for post-acute COVID-19 syndrome in Hong Kong (RECOVERY): a randomised, double-blind, placebo-controlled trial. Lancet Infect Dis. 2023 Dec 7:S1473-3099(23)00685-0. doi: 10.1016/S1473-3099(23)00685-0. Epub ahead of print. PMID: 38071990. https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(23)00685-0/fulltext (Full text)