Tag: long covid treatment

Long COVID endotheliopathy: hypothesized mechanisms and potential therapeutic approaches

Abstract:

SARS-CoV-2–infected individuals may suffer a multi–organ system disorder known as “long COVID” or post-acute sequelae of SARS-CoV-2 infection (PASC). There are no standard treatments, the pathophysiology is unknown, and incidence varies by clinical phenotype.

Acute COVID-19 correlates with biomarkers of systemic inflammation, hypercoagulability, and comorbidities that are less prominent in PASC. Macrovessel thrombosis, a hallmark of acute COVID-19, is less frequent in PASC. Female sex at birth is associated with reduced risk for acute COVID-19 progression, but with increased risk of PASC. Persistent microvascular endotheliopathy associated with cryptic SARS-CoV-2 tissue reservoirs has been implicated in PASC pathology.

Autoantibodies, localized inflammation, and reactivation of latent pathogens may also be involved, potentially leading to microvascular thrombosis, as documented in multiple PASC tissues. Diagnostic assays illuminating possible therapeutic targets are discussed.

Source: Ahamed J, Laurence J. Long COVID endotheliopathy: hypothesized mechanisms and potential therapeutic approaches. J Clin Invest. 2022 Aug 1;132(15):e161167. doi: 10.1172/JCI161167. PMID: 35912863; PMCID: PMC9337829. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9337829/ (Full text)

Use of 1-MNA to Improve Exercise Tolerance and Fatigue in Patients after COVID-19

Abstract:

COVID-19 is not only a short-term infection, as patients (pts) recovering from SARS-CoV-2 infection complain of persisting symptoms, which may lead to chronic fatigue syndrome. There is currently no evidence that nutritional supplements can assist in the recovery of pts with chronic fatigue syndrome. 1-Methylnicotinamide (1-MNA) is an endogenic substance that is produced in the liver when nicotinic acid is metabolized. 1-MNA demonstrates anti-inflammatory and anti-thrombotic properties. Therefore, we investigated whether 1-MNA supplements could improve exercise tolerance and decrease fatigue among patients recovering from SARS-CoV-2.

Methods: The study population was composed of 50 pts who had recovered from symptomatic COVID-19. The selected pts were randomized into two groups: Gr 1 (NO-1-MNA)-without supplementation; Gr 2 (1-MNA) with 1-MNA supplementation. At the beginning of the study (Phase 0), in both groups, a 6-minute walk test (6MWT) was carried out and fatigue assessment was performed using the Fatigue Severity Scale (FSS). Both FSS and 6MWT were repeated after 1 month.

Results: A significant improvement in the mean distance covered in the 6MWT was noted at follow-up in Gr 1-MNA, compared with Gr NO-1-MNA. We also noted that in Gr 1-MNA, the 6MWT distance was significantly higher after 1 month of supplementation with 1-MNA, compared with the beginning of the study (515.18 m in Phase 0 vs. 557.8 m in Phase 1; p = 0.000034). In Gr 1-MNA, significantly more pts improved their distance in the 6MWT (23 out of 25 pts, equal to 92%), by a mean of 47 m, compared with Gr NO-1-MNA (15 of 25 pts, equal to 60%) (p = 0.0061). After one month, significantly more patients in the group without 1-MNA had severe fatigue (FSS ≥ 4) compared with the group with supplementation (Gr 1-MNA = 5 pts (20%) vs. Gr NO-1-MNA = 14pts (56%); p = 0.008).

Conclusions: 1-MNA supplementation significantly improved physical performance in a 6-min walk test and reduced the percentage of patients with severe fatigue after COVID-19. The comprehensive action of 1-MNA, including anti-inflammatory and anticoagulant effects, may be beneficial for the recovery of patients with persistent symptoms of fatigue and low tolerance to exercise after COVID-19.

Source: Chudzik M, Burzyńska M, Kapusta J. Use of 1-MNA to Improve Exercise Tolerance and Fatigue in Patients after COVID-19. Nutrients. 2022 Jul 22;14(15):3004. doi: 10.3390/nu14153004. PMID: 35893858.  https://www.mdpi.com/2072-6643/14/15/3004/htm (Full text)

The Use of Palmitoylethanolamide in the Treatment of Long COVID: A Real-Life Retrospective Cohort Study

Abstract:

COVID-19 can cause symptoms that last weeks or months after the infection has gone, with a significant impairment of quality of life. Palmitoylethanolamide (PEA) is a naturally occurring lipid mediator that has an entourage effect on the endocannabinoid system mitigating the cytokine storm. The aim of this retrospective study is to evaluate the potential efficacy of PEA in the treatment of long COVID.
Patients attending the Neurological Out Clinic of the IRCCS Centro Neurolesi Bonino-Pulejo (Messina, Italy) from August 2020 to September 2021 were screened for potential inclusion in the study. We included only long COVID patients who were treated with PEA 600 mg two times daily for about 3 months. All patients performed the post-COVID-19 Functional Status (PCFS) scale. Thirty-three patients (10 males, 43.5%, mean age 47.8 ± 12.4) were enrolled in the study. Patients were divided into two groups based on hospitalization or home care observation. A substantial difference in the PCFS score between the two groups at baseline and after treatment with PEA were found. We found that smoking was a risk factor with an odds ratio of 8.13 CI 95% [0.233, 1.167]. Our findings encourage the use of PEA as a potentially effective therapy in patients with long COVID.
Source: Raciti L, De Luca R, Raciti G, Arcadi FA, Calabrò RS. The Use of Palmitoylethanolamide in the Treatment of Long COVID: A Real-Life Retrospective Cohort Study. Medical Sciences. 2022; 10(3):37. https://doi.org/10.3390/medsci10030037  https://www.mdpi.com/2076-3271/10/3/37/htm (Full text)

Improvement in Long-COVID Symptoms Using Acupuncture: A Case Study

Abstract:

Background: The long-COVID syndrome (LCS), defined by residual symptoms from acute COVID-19 for <60 days, affects about one-third of all COVID survivors and is an emerging public health challenge. Empirical data about the range of symptoms or the utility of acupuncture alone for the LCS are very limited.

Case: This observational case study of a 46-year-old male with LCS was conducted to preliminarily define the range of symptoms, a Traditional Chinese Medicine (TCM) diagnostic structure, and evaluate the potential utility of prescribed acupuncture for LCS.

Results: The primary TCM diagnostic patterns from this patient’s LCS presentation included Lung Qi and Yin Deficiency, Qi and Blood Stagnation, and Spleen Qi Deficiency with dampness. Acupuncture for this patient was associated with reduced symptoms and signs of LCS.

Conclusion: A preliminary TCM diagnostic structure for LCS was defined. Acupuncture appears to have been helpful for a patient with LCS. Further research is needed to demonstrate the efficacy of acupuncture and/or other TCM modalities for LCS.

Source: Hollifield M, Cocozza K, Calloway T, Lai J, Caicedo B, Carrick K, Alpert R, Hsiao AF. Improvement in Long-COVID Symptoms Using Acupuncture: A Case Study. Med Acupunct. 2022 Jun 1;34(3):172-176. doi: 10.1089/acu.2021.0088. Epub 2022 Jun 16. PMID: 35832108; PMCID: PMC9248334. https://www.liebertpub.com/doi/10.1089/acu.2021.0088 (Full text)

The Role of Acupuncture for Long COVID: Mechanisms and Models

Abstract:

Objective: To establish an evidence-based role for acupuncture as a safe and effective treatment for managing Long COVID in the integrative medical setting.

Background: COVID-19 progresses to a chronic state, termed Long COVID, in about 30% of cases with estimates as high as 40% for prolonged illness. Symptoms are diverse and range over several body systems, including unrelenting fatigue, persistent malaise, chronic pain, and mood changes. Early clinical reports suggest acupuncture can effectively address both symptoms and the underlying causes of Long COVID.

Evidence: Historically, acupuncture is well defined in Traditional Chinese Medicine writings to treat influenza-like febrile illnesses. Contemporary scientific literature and case studies support the value of acupuncture for symptoms associated with acute and chronic respiratory viral infections, such as influenza, including SARS and COVID-19. Recent reports provide early evidence of acupuncture’s effectiveness in managing Long COVID symptoms and may also have disease-modifying benefits.

Conclusion: Acupuncture is a viable adjunctive health care modality as part of a multidisciplinary approach for symptom control and disease management to improve quality of life in Long COVID patients. Since acupuncture may favorably modify the length and outcome of this condition, the model of acupuncture presented in this article warrants broader use in the integrative clinical setting and for further research.

Source: Williams JE, Moramarco J. The Role of Acupuncture for Long COVID: Mechanisms and Models. Med Acupunct. 2022 Jun 1;34(3):159-166. doi: 10.1089/acu.2021.0090. Epub 2022 Jun 16. PMID: 35832109; PMCID: PMC9248327. https://www.liebertpub.com/doi/10.1089/acu.2021.0090 (Full text)

Conceptualizing a Traditional Chinese Medicine and Pathology of Arousal Diagnostic and Pathophysiological Framework for Postacute Sequelae of COVID-19

Abstract:

Introduction: The postacute sequelae of COVID-19 (PASC) is a serious heterogeneous condition that affects a significant minority of those who endured COVID-19. PASC involves multiple body systems and an illness trajectory that has stages now being identified in medical research.

Objective: Traditional Chinese Medicine (TCM) and acupuncture are well suited to conceptualize and treat PASC and other postviral conditions. No description of TCM theory and its relationship with modern medical theory about PASC and its illness trajectory currently exists.

Conclusion: The authors provide an overview of the potential value of TCM for conceptualizing and treating PASC with a few examples and clarify directions for research.

Source: Calloway T, Hsiao AF, Brand M, Lai J, Geise C, Caceido B, Alpert R, Hollifield M. Conceptualizing a Traditional Chinese Medicine and Pathology of Arousal Diagnostic and Pathophysiological Framework for Postacute Sequelae of COVID-19. Med Acupunct. 2022 Jun 1;34(3):167-171. doi: 10.1089/acu.2022.0022. Epub 2022 Jun 16. PMID: 35832113; PMCID: PMC9248333. https://www.liebertpub.com/doi/10.1089/acu.2022.0022 (Full text)

Can aquatic exercises contribute to the improvement of the gait stereotype function in patients with Long COVID outcomes?

Abstract:

A variety of rehabilitation programmes can be offered to Long COVID patients, specifically physical training. Indeed 90% of these patients reports impairments of verticalization, stability and spatial orientation, making difficult exercise in the gym. The aim of our study was to assess the effectiveness and safety of aquatic exercise techniques as part of a comprehensive rehabilitation program for patients with Long COVID.

The first of a two-stage program involved development of aquatic exercises technique, which was evaluated in 12 patients with impaired upright posture control before and after exercising by “Habilect” video gait analysis system. During the second phase, effectiveness and safety of aqua exercises were tested in water pool as part of a comprehensive rehabilitation programme conducted in 23 patients with Long COVID outcomes. Physical examination, 6-minute step test, Euro-QL-5D questionnaire, Borg scale, laser Doppler flowmetry, cardiointervalography, and spirometry were performed before and after the aquatic exercises program.

After the training with aquatic exercises, indices of deviations of the main body axes of the head and the body mass centre ameliorated, as well as direction of body movement vector decreased (p<0.05). This study demonstrated a statistically significant improvement in exercise tolerance in both groups, as measured by the 6-minute step test after rehabilitation. The comparison group averaged 236.7 metres [126; 380] (T=8, p=0.047) after the rehabilitation course and the intervention group averaged 233.71 metres [150; 320] (T=8.0, p=0.047). When tested with the Euro-QL-5D questionnaire, a post-treatment improvement was noted in the comparison group on the anxiety/depression subscale (3 [3;3] (T=0, p=0.043)).

In the intervention group, laser Doppler flowmetry revealed a statistically significant increase in microcirculation (6.36 standard units after rehabilitation) [5.54; 8.17] (T=7.0, p=0.004), and a decrease of oxidative metabolism index of 6.89 standard units. [4.76; 6.96] (T=4.0, p=0.03). No serious adverse events were reported. In conclusion, the developed aquatic exercises technique seems to contribute to recovery of impaired upright posture and motor function, normalizing the walking pattern.

Source: Lobanov AA, Irina A Grishechkina, Andronov SV, Gleb N Barashkov, Andrey I Popov, Anatoliy D Fesyun, Elena P Ivanova, Maccarone MC, Stefano Masiero. Can aquatic exercises contribute to the improvement of the gait stereotype function in patients with Long COVID outcomes? Eur J Transl Myol. 2022 Jul 14. doi: 10.4081/ejtm.2022.10698. Epub ahead of print. PMID: 35833897.  https://pubmed.ncbi.nlm.nih.gov/35833897/ (Full text: Follow link on page)

Local anesthetics as a therapeutic tool for post COVID-19 patients: A case report

Abstract:

Background: Post COVID-19 syndrome (PC-19S) appears to be independent of acute illness severity and humoral response. The involvement of the autonomic nervous system (ANS), expressed by dysautonomia, has been hypothesized as a contributor. Several studies have associated the therapeutic effects of local anesthetics (LA) to their action on the ANS. To the best of our knowledge, this is the first report of therapeutic injections with LA linked to clinical improvement in a patient with PC-19S.

Patient concerns and diagnoses: This was a 54-year-old-man with postCOVID-19 symptoms lasting 14 weeks, including fatigue, breathlessness, diarrhea, muscle pain, and emotional lability.

Interventions and outcome: Injections of 0.5% procaine in the stellate ganglion (SG) and sphenopalatine ganglion (SPG), and in clinically relevant points in the scalp, thorax, and abdomen were performed 3 times over 3 months. The patient reported progressive improvement and was asymptomatic upon completing the treatment. Prescribed medications were discontinued. The 36-Item Short Form Health Survey (SF-36) score showed significant improvement across all SF-36-domains.

Conclusion: Subanesthetic doses of LA injected in clinically relevant points led to rapid and complete symptom resolution in this patient with PC-19S. Targeted LA injections may have therapeutic benefits in PC-19S and in other chronic diseases linked to stress and inflammation.

Source: Vinyes D, Muñoz-Sellart M, Caballero TG. Local anesthetics as a therapeutic tool for post COVID-19 patients: A case report. Medicine (Baltimore). 2022 Jul 15;101(28):e29358. doi: 10.1097/MD.0000000000029358. PMID: 35839020. https://journals.lww.com/md-journal/Fulltext/2022/07150/Local_anesthetics_as_a_therapeutic_tool_for_post.33.aspx (Full text)

Rationale for Nicotinamide Adenine Dinucleotide (NAD+) Metabolome Disruption as a Pathogenic Mechanism of Post-Acute COVID-19 Syndrome

Abstract:

Many acute COVID-19 convalescents experience a persistent sequelae of infection, called post-acute COVID-19 syndrome (PACS). With incidence ranging between 31% and 69%, PACS is becoming increasingly acknowledged as a new disease state in the context of SARS-CoV-2 infection. As SARS-CoV-2 infection can affect several organ systems to varying degrees and durations, the cellular and molecular abnormalities contributing to PACS pathogenesis remain unclear.

Despite our limited understanding of how SARS-CoV-2 infection promotes this persistent disease state, mitochondrial dysfunction has been increasingly recognized as a contributing factor to acute SARS-CoV-2 infection and, more recently, to PACS pathogenesis. The biological mechanisms contributing to this phenomena have not been well established in previous literature; however, in this review, we summarize the evidence that NAD+ metabolome disruption and subsequent mitochondrial dysfunction following SARS-CoV-2 genome integration may contribute to PACS biological pathogenesis.

We also briefly examine the coordinated and complex relationship between increased oxidative stress, inflammation, and mitochondrial dysfunction and speculate as to how SARS-CoV-2-mediated NAD+ depletion may be causing these abnormalities in PACS. As such, we present evidence supporting the therapeutic potential of intravenous administration of NAD+ as a novel treatment intervention for PACS symptom management.

Source: Block T, Kuo J. Rationale for Nicotinamide Adenine Dinucleotide (NAD+) Metabolome Disruption as a Pathogenic Mechanism of Post-Acute COVID-19 Syndrome. Clin Pathol. 2022 Jun 24;15:2632010X221106986. doi: 10.1177/2632010X221106986. PMID: 35769168; PMCID: PMC9234841. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9234841/ (Full text)

Safety and efficacy of low dose naltrexone in a long covid cohort; an interventional pre-post study

Abstract:

Background: Up to 37.7% of patients experience symptoms beyond 12 weeks after infection with SARS-CoV-2. To date care for people with long covid has centred around multidisciplinary rehabilitation, self care and self pacing. No pharmacotherapy has been shown to be beneficial.

Methods: In this single centre interventional pre post study, the safety of Low Dose Naltrexone (LDN) was explored in patients with Post COVID-19 Syndrome (PCS), defined by NICE as patients with ongoing symptoms 12 or more weeks after initial infections with SARS-CoV-2 where alternative explanation for symptoms cannot be found. Patients were recruited through a Post COVID clinic, had a baseline quality of life questionnaire in symmetrical Likert format, were prescribed 2 months (1 mg month one, 2 mg month two) of LDN and repeated the same questionnaire at the end of the second month. Patients were monitored to adverse events.

Findings: In total 52 patients participated of whom 40(76.9%) were female. The median age was 43.5 years(IQR 33.2–49). Healthcare workers represented the largest occupational cohort n = 16(34.8%). The median time from diagnosis of COVID-19 until enrolment was 333 days (IQR 171–396.5). Thirty-eight participants (73.1%) were known to commence LDN, two of whom (5.3%) stopped taking LDN post commencement due to new onset diarrhoea and also described fatigue. In total 36(69.2%) participants completed the questionnaire at the end of the two-month period. Improvement was seen in 6 of 7 parameters measured; recovery from COVID-19, limitation in activities of daily living, energy levels, pain levels, levels of concentration and sleep disturbance (p ≤ 0.001), improvement in mood approached but was not significant (p = 0.054).

Conclusions: LDN is safe in patients with PCS and may improve well-being and reduce symptomatology in this cohort. Randomised control trials are needed to further explore this.

Source: Brendan O’Kelly, Louise Vidal, Tina McHugh, James Woo, Gordana Avramovic, John S. Lambert. Safety and efficacy of low dose naltrexone in a long covid cohort; an interventional pre-post study. Brain, Behavior, & Immunity – Health; Volume 24, October 2022, 100485 https://www.sciencedirect.com/science/article/pii/S2666354622000758  (Full text)