Tag: long covid treatment

Aromatherapy blend of thyme, orange, clove bud, and frankincense boosts energy levels in post-COVID-19 female patients: A randomized, double-blinded, placebo controlled clinical trial

Abstract:

Background: A large proportion of individuals who have recovered from an acute COVID-19 infection continue to experience symptoms months later. Post-acute COVID-19 (long-haul COVID-19) can range from serious complications to quality of life symptoms such as fatigue or insomnia. The purpose of this study was to evaluate the potential for inhalation of essential oils to improve energy levels among otherwise healthy female survivors of acute COVID-19 who experience a lack of energy more than five months after recovery. This study was conducted in the United States in late 2021.

Method: This was a randomized double blind, placebo controlled trial to evaluate the potential for inhalation of Longevity™, a proprietary essential oil blend manufactured by Young Living Essential Oils (Lehi, Utah, USA), on energy levels among female survivors of COVID-19 who continue to experience fatigue more than 5 months recovery from the acute infection. Forty women were randomized to two groups: intervention and placebo. Both groups inhaled the assigned product twice daily for fourteen consecutive days. Fatigue scores were measured using the Multidimensional Fatigue Symptom Inventory (MFSI). Secondary outcomes included scores on each of the MFSI’s ten subscales.

Results: Individuals who inhaled the essential oil blend for 2 weeks had significantly lower fatigue scores after controlling for baseline scores, employment status, BMI, olfactory function, and time since diagnosis, with a large effect size (F (1,39) = 6.15, p = .020, partial eta squared = 0.198). Subscale analysis identified subscales of vigor, as well as global, behavioral, general, and mental fatigue as benefiting from the intervention. This study provides evidence that a proprietary aromatherapy blend can significantly improve energy levels among women who are experiencing fatigue after recovering from COVID-19.

Source: Hawkins J, Hires C, Keenan L, Dunne E. Aromatherapy blend of thyme, orange, clove bud, and frankincense boosts energy levels in post-COVID-19 female patients: A randomized, double-blinded, placebo controlled clinical trial. Complement Ther Med. 2022 Aug;67:102823. doi: 10.1016/j.ctim.2022.102823. Epub 2022 Mar 25. PMID: 35341944; PMCID: PMC8949693. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8949693/ (Full text)

Case Report: Therapeutic and immunomodulatory effects of plasmapheresis in long-haul COVID

Abstract:

Many patients with COVID-19 experience a range of debilitating symptoms months after being infected, a syndrome termed long-haul COVID. A 68-year-old male presented with lung opacity, fatigue, physical and cognitive weaknesses, loss of smell and lymphocytopenia. After rounds of therapeutic plasma exchange (TPE), the patient returned to normal activities and work. Mechanistically in the patient’s peripheral blood mononuclear cells (PBMCs), markers of inflammatory macrophages diminished and markers of lymphocytes, including natural killer (NK) cells and cytotoxic CD8 T-cells, increased. Circulating inflammatory proteins diminished, while positive regulators of tissue repair increased. This case study suggests that TPE has the capacity to treat long-haul COVID.

Source: Kiprov DD, Herskowitz A, Kim D, Lieb M, Liu C, Watanabe E, Hoffman JC, Rohe R, Conboy MJ, Conboy IM. Case Report: Therapeutic and immunomodulatory effects of plasmapheresis in long-haul COVID. F1000Res. 2021 Nov 24;10:1189. doi: 10.12688/f1000research.74534.2. PMID: 35464182; PMCID: PMC9021669. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9021669/ (Full text)

Epipharyngeal Abrasive Therapy Down-regulates the Expression of SARS-CoV-2 Entry Factors ACE2 and TMPRSS2

Abstract:

COVID-19 often causes sequelae after initial recovery, referred to collectively as long COVID. Long COVID is considered to be caused by the persistence of chronic inflammation after acute COVID-19 infection. We found that all long COVID patients had residual inflammation in the epipharynx, an important site of coronavirus replication, and some long COVID symptoms are similar to those associated with chronic epipharyngitis. Epipharyngeal abrasive therapy (EAT) is a treatment for chronic epipharyngitis in Japan that involves applying zinc chloride as an anti-inflammatory agent to the epipharyngeal mucosa.
In this study, we evaluated the efficacy of EAT for the treatment of long COVID. The subjects in this study were 58 patients with long COVID who were treated with EAT in the outpatient department once a week for one month (mean age = 38.4 ± 12.9 years). The intensities of fatigue, headache, and attention disorder, which are reported as frequent symptoms of long COVID, were assessed before and after EAT using the visual analog scale (VAS). EAT reduced inflammation in the epipharynx and significantly improved the intensity of fatigue, headache, and attention disorder, which may be related to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). These results suggest that EAT has potential as a novel method for long COVID treatment.
Source: Imai K, Yamano T, Nishi S, Nishi R, Nishi T, Tanaka H, Tsunoda T, Yoshimoto S, Tanaka A, Hiromatsu K, Shirasawa S, Nakagawa T, Nishi K. Epipharyngeal Abrasive Therapy (EAT) Has Potential as a Novel Method for Long COVID Treatment. Viruses. 2022; 14(5):907. https://doi.org/10.3390/v14050907  (Full text)

Long COVID: systemic inflammation and obesity as therapeutic targets

Management of the post-COVID-19 condition—often referred to as long COVID—is a challenge for health-care professionals because of the heterogeneity and complexity of its clinical manifestations and the probable need for multidisciplinary management approaches. Identification and understanding of modifiable determinants associated with manifestations of long COVID would help in the adaptation of treatment pathways for particular phenotypes. In The Lancet Respiratory Medicine, the PHOSP-COVID Collaborative Group report the latest results from the UK-based, multicentre, prospective Post-hospitalisation COVID-19 (PHOSP-COVID) study, in which the investigators identified systemic inflammation and obesity as factors that might be associated with long COVID, representing potentially treatable traits in people with more severe post-COVID-19 symptoms.

In the current report, the PHOSP-COVID Collaborative Group found increased levels of several biomarkers related to systemic inflammation and lung damage in individuals with more severe physical and mental health impairments 1 year after hospital discharge. The presence of increased levels of systemic inflammatory biomarkers (eg, cytokines) in individuals with severe acute COVID-19 has been reported previously. Moreover, the use of anti-inflammatory agents such as corticosteroids or interleukin-6 (IL-6)-blocking agents has been found to be associated with positive outcomes in patients hospitalised with acute COVID-19.

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Source: Florencio LL, Fernández-de-Las-Peñas C. Long COVID: systemic inflammation and obesity as therapeutic targets. Lancet Respir Med. 2022 Apr 22:S2213-2600(22)00159-X. doi: 10.1016/S2213-2600(22)00159-X. Epub ahead of print. PMID: 35472305; PMCID: PMC9034853. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9034853/ (Full text)

Comments to “Fluvoxamine and long COVID-19: a new role for sigma-1 receptor (S1R) agonists” by Khani and Entezari-Maleki

To the Editor:

The coronavirus disease 2019 (COVID-19) pandemic causes short-term and long-term health problems in survivors after infection of SARS-CoV-2 (severe acute respiratory syndrome-coronavirus-2). A recent systematic review using 57 studies with 250,351 survivors of COVID-19 shows that the median proportion of COVID-19 survivors experiencing at least 1 PASC (post-acute sequelae of COVID-19) was 54% at 1 month (short-term), 55% at 2–5 months (intermediate-term), and 54% at 6 or more months (long-term) [1]. The most common sequelae involved neurologic symptoms (i.e., headaches, memory deficits, difficulty concentrating, cognitive impairment), psychiatric symptoms (i.e., depression, anxiety, sleep disorders), pulmonary abnormalities (i.e., dyspnea, cough, increased oxygen requirement, pulmonary diffusion abnormalities, chest imaging abnormalities), and functional mobility impairment (i.e., impairment in general functioning, mobility decline, reduced exercise tolerance). However, there are no therapeutic drugs for long-term symptoms in survivors of COVID-19.

The precise mechanisms underlying SARS-CoV-2 induced long-term detrimental effects remain unclear. Infection of SARS-CoV-2 can damage endothelial cells leading to inflammation, thrombi and brain damage. SARS-CoV-2-associated systemic inflammation leads to decreased monoamines and neurotrophic factors, and microglial activation in the brain, resulting in long-term neurological and psychiatric symptoms in COVID-19 survivors [2]. A retrospective study of Wuhan University (Wuhan, China) reported that patients with Epstein-Barr virus (EBV)/SARS-CoV-2 coinfection have about 3-fold risk of having a fever symptom than patients with SARS-CoV-2 infection alone, and that levels of C-reactive protein and aspartate aminotransferase in patients with EBV/SARS-CoV-2 coinfection were higher than those in patients with SARS-CoV-2 infection alone [3]. This report suggests that EBV reactivation may be associated with the severity of clinical symptoms after SARS-CoV-2 infection.

Interestingly, approximately 67% of patients (20/30) with long-term sequelae of COVID-19 were positive for EBV reactivation based on positive titers for EBV early antigen-diffuse IgG or EBV viral capsid antigen IgM [4]. Thus, EBV reactivation may play a role in long-term symptoms in COVID-19 survivors although further study using a large sample size is needed. The authors suggest that most of long-lasting symptoms in COVID-19 survivors following the recovery from SARS-CoV-2 infection might not be directly affected by the virus but probably result from SARS-CoV-2-associated inflammation and EBV reactivation [4].

In the issue, Khani and Entezari-Maleki proposed that fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), may be a new therapeutic drug for long-term consequences of COVID-19 survivors [5]. Fluvoxamine has been demonstrated to prevent clinical deterioration in early-stage subjects with COVID-19 [6]. In addition of serotonin transporter inhibition, sigma-1 receptor chaperone in the endoplasmic reticulum (ER) and acid sphingomyelinase might play a role in the mechanisms of beneficial action of fluvoxamine for patients with SARS-CoV-2 infection [6,7,8]. It is also reported that sigma-1 receptor agonists such as fluvoxamine could produce potent anti-inflammatory actions by the prevention of inositol requiring enzyme 1α (IRE1) and X-box binding protein-1 (XBP-1) pathway [9]. Collectively, it is likely that sigma-1 receptor agonists such as fluvoxamine could produce potent anti-inflammatory effects through sigma-1 receptor/IRE1/XBP-1 pathway in the ER [6,7,8,9].

Among the SSRIs, fluvoxamine was the most potent at sigma-1 receptor in the brain [6,7,8]. Given the link between EBV reactivation and XBP-1 [10], it is possible that the potent sigma-1 receptor agonist fluvoxamine may have beneficial effects for long-term consequences in COVID-19 survivors through sigma-1 receptor/IRE1/XBP-1 pathway [4]. Therefore, it is of great interest to examine whether fluvoxamine can improve long-term sequelae in COVID-19 survivors.

Source: Hashimoto Y, Suzuki T, Hashimoto K. Comments to “Fluvoxamine and long COVID-19: a new role for sigma-1 receptor (S1R) agonists” by Khani and Entezari-Maleki. Mol Psychiatry. 2022 Apr 6:1–2. doi: 10.1038/s41380-022-01546-2. Epub ahead of print. PMID: 35388183; PMCID: PMC8985059. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8985059/ (Full text)

Long COVID and long chain fatty acids (LCFAs): Psychoneuroimmunity implication of omega-3 LCFAs in delayed consequences of COVID-19

Abstract:

The global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the lasting pandemic of coronavirus disease 2019 (COVID-19) and the post-acute phase sequelae of heterogeneous negative impacts in multiple systems known as the “long COVID.” The mechanisms of neuropsychiatric complications of long COVID are multifactorial, including long-term tissue damages from direct CNS viral involvement, unresolved systemic inflammation and oxidative stress, maladaptation of the renin-angiotensin-aldosterone system and coagulation system, dysregulated immunity, the dysfunction of neurotransmitters and hypothalamus–pituitaryadrenal (HPA) axis, and the psychosocial stress imposed by societal changes in response to this pandemic. The strength of safety, well-acceptance, and accumulating scientific evidence has now afforded nutritional medicine a place in the mainstream of neuropsychiatric intervention and prophylaxis.

Long chain omega-3 polyunsaturated fatty acids (omega-3 or n-3 PUFAs) might have favorable effects on immunity, inflammation, oxidative stress and psychoneuroimmunity at different stages of SARS-CoV-2 infection. Omega-3 PUFAs, particularly EPA, have shown effects in treating mood and neurocognitive disorders by reducing pro-inflammatory cytokines, altering the HPA axis, and modulating neurotransmission via lipid rafts. In addition, omega-3 PUFAs and their metabolites, including specialized pro-resolvin mediators, accelerate the process of cleansing chronic inflammation and restoring tissue homeostasis, and therefore offer a promising strategy for Long COVID. In this article, we explore in a systematic review the putative molecular mechanisms by which omega-3 PUFAs and their metabolites counteract the negative effects of long COVID on the brain, behavior, and immunity.

Source: Yang CP, Chang CM, Yang CC, Pariante CM, Su KP. Long COVID and long chain fatty acids (LCFAs): Psychoneuroimmunity implication of omega-3 LCFAs in delayed consequences of COVID-19. Brain Behav Immun. 2022 Apr 4;103:19-27. doi: 10.1016/j.bbi.2022.04.001. Epub ahead of print. PMID: 35390469; PMCID: PMC8977215. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8977215/ (Full text)

Reducing fatigue-related symptoms in Long COVID-19: a preliminary report of a lymphatic drainage intervention

Abstract:

In the early days of the first global wave of the COVID-19 pandemic, the potential for a postviral syndrome to manifest following COVID-19 infection was first recognized. Here, we present an analysis of a case series of the first 20 patients’ data collected in clinical practice to evaluate the potential of a possible alternative treatment for Long COVID.

Methods: Face-to-face treatment sessions with Perrin technique practitioners occurred weekly involving effleurage/other manual articulatory techniques. The individuals being treated also undertook daily self-massage along with gentle mobility exercises. Patients recorded symptom severity using the self-report 54-item profile of fatigue-related states (PFRS) before and after treatment.

Results: The mean age of male patients was 41.8 years (range, 29-53 years), and for female patients, 39.3 years (range, 28-50 years). None of the participants had a prior diagnosis of chronic fatigue syndrome, and all were new attendees to the clinics at the time of initial assessment. The average number of treatment sessions was 9.7 in men and 9.4 in women. The reduction in PFRS scores was 45% in men and 52% in women. The highest subscale scores on average were for fatigue, with the lowest for somatic symptoms. All subscale scores showed, on average, a similar reduction of approximately 50% postintervention, with the reduction in score relating to a decrease in the severity of symptoms.

Conclusion: Our findings suggest that a specific manual lymphatic drainage intervention may help to reduce fatigue symptoms related to Long COVID. Perhaps preventing acute symptoms through early intervention.

Source: H Heald A, Perrin R, Walther A, Stedman M, Hann M, Mukherjee A, Riste L. Reducing fatigue-related symptoms in Long COVID-19: a preliminary report of a lymphatic drainage intervention. Cardiovasc Endocrinol Metab. 2022 Apr 12;11(2):e0261. doi: 10.1097/XCE.0000000000000261. PMID: 35441129; PMCID: PMC9010124. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9010124/ (Full text)

Dietary Recommendations for Post-COVID-19 Syndrome

Abstract:

At the beginning of the coronavirus disease (COVID-19) pandemic, global efforts focused on containing the spread of the virus and avoiding contagion. Currently, it is evident that health professionals should deal with the overall health status of COVID-19 survivors. Indeed, novel findings have identified post-COVID-19 syndrome, which is characterized by malnutrition, loss of fat-free mass, and low-grade inflammation. In addition, the recovery might be complicated by persistent functional impairment (i.e., fatigue and muscle weakness, dysphagia, appetite loss, and taste/smell alterations) as well as psychological distress.

Therefore, the appropriate evaluation of nutritional status (assessment of dietary intake, anthropometrics, and body composition) is one of the pillars in the management of these patients. On the other hand, personalized dietary recommendations represent the best strategy to ensure recovery. Therefore, this review aimed to collect available evidence on the role of nutrients and their supplementation in post-COVID-19 syndrome to provide a practical guideline to nutritionists to tailor dietary interventions for patients recovering from COVID-19 infections.

Source: Barrea L, Grant WB, Frias-Toral E, Vetrani C, Verde L, de Alteriis G, Docimo A, Savastano S, Colao A, Muscogiuri G. Dietary Recommendations for Post-COVID-19 Syndrome. Nutrients. 2022 Mar 20;14(6):1305. doi: 10.3390/nu14061305. PMID: 35334962; PMCID: PMC8954128. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8954128/(Full text)

Efficacy of Adaptogens in Patients with Long COVID-19: A Randomized, Quadruple-Blind, Placebo-Controlled Trial

Abstract:

Currently, no effective treatment of comorbid complications or COVID-19 long-haulers during convalescence is known. This randomized, quadruple-blind, placebo-controlled trial aimed to assess the efficacy of adaptogens on the recovery of patients with Long COVID symptoms. One hundred patients with confirmed positive SARS-CoV-2 test, discharged from COVID Hotel isolation, Intensive Care Unit (ICU), or Online Clinics, and who experienced at least three of nine Long COVID symptoms (fatigue, headache, respiratory insufficiency, cognitive performance, mood disorders, loss of smell, taste, and hair, sweatiness, cough, pain in joints, muscles, and chest) in the 30 days before randomization were included in the study of the efficacy of Chisan®/ADAPT-232 (a fixed combination of adaptogens Rhodiola, Eleutherococcus, and Schisandra) supplementation for two weeks.

Chisan® decreased the duration of fatigue and pain for one and two days, respectively, in 50% of patients. The number of patients with lack of fatigue and pain symptoms was significantly less in the Chisan® treatment group than in the placebo group on Days 9 (39% vs. 57%, pain relief, p = 0.0019) and 11 (28% vs. 43%, relief of fatigue, * p = 0.0157). Significant relief of severity of all Long COVID symptoms over the time of treatment and the follow-up period was observed in both groups of patients, notably decreasing the level of anxiety and depression from mild and moderate to normal, as well as increasing cognitive performance in patients in the d2 test for attention and increasing their physical activity and workout (daily walk time).

However, the significant difference between placebo and Chisan® treatment was observed only with a workout (daily walk time) and relieving respiratory insufficiency (cough). A clinical assessment of blood markers of the inflammatory response (C-reactive protein) and blood coagulation (D-dimer) did not reveal any significant difference over time between treatment groups except significantly lower IL-6 in the Chisan® treatment group. Furthermore, a significant difference between the placebo and Chisan® treatment was observed for creatinine: Chisan® significantly decreased blood creatinine compared to the placebo, suggesting prevention of renal failure progression in Long COVID. In this study, we, for the first time, demonstrate that adaptogens can increase physical performance in Long COVID and reduce the duration of fatigue and chronic pain. It also suggests that Chisan®/ADAPT-232 might be useful for preventing the progression of renal failure associated with increasing creatinine.

Source: Karosanidze I, Kiladze U, Kirtadze N, Giorgadze M, Amashukeli N, Parulava N, Iluridze N, Kikabidze N, Gudavadze N, Gelashvili L, Koberidze V, Gigashvili E, Jajanidze N, Latsabidze N, Mamageishvili N, Shengelia R, Hovhannisyan A, Panossian A. Efficacy of Adaptogens in Patients with Long COVID-19: A Randomized, Quadruple-Blind, Placebo-Controlled Trial. Pharmaceuticals (Basel). 2022 Mar 11;15(3):345. doi: 10.3390/ph15030345. PMID: 35337143; PMCID: PMC8953947. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8953947/ (Full text)

Registered clinical trials investigating treatment of long COVID: a scoping review and recommendations for research

Abstract:

Background: A considerable proportion of individuals report persistent, debilitating and disparate symptoms despite resolution of acute COVID-19 infection (i.e. long COVID). Numerous registered clinical trials investigating treatment of long COVID are expected to be completed in 2021–2022. The aim of this review is to provide a scope of the candidate treatments for long COVID. A synthesis of ongoing long COVID clinical trials can inform methodologic approaches for future studies and identify key research vistas.

Methods: Scoping searches were conducted on multiple national and international clinical trial registries. Interventional trials testing treatments for long COVID were selected. The search timeline was from database inception to 28 July 2021.

Results: This scoping review included 59 clinical trial registration records from 22 countries with a total projected enrolment of 6718. Considerable heterogeneity was exhibited amongst component records with respect to the characterization of long COVID (i.e. name, symptoms- including frequency, intensity, trajectory and duration- mode of ascertainment, and definition of acute phase). In addition, the majority of proposed interventions were non-pharmacological and either targeted multiple long COVID symptoms simultaneously, or focussed on treatment of respiratory/pulmonary sequelae. Multiple interventions targeted inflammation, as well as tissue oxygenation and cellular recovery, and several interventions were repurposed from analogous conditions.

Conclusions: The results of this scoping review investigating ongoing clinical trials testing candidate treatments for long COVID suggest that a greater degree of definitional stringency and homogeneity is needed insofar as the characterization of long COVID and inclusion/exclusion criteria.

Source: Ceban F, Leber A, Jawad MY, Yu M, Lui LMW, Subramaniapillai M, Di Vincenzo JD, Gill H, Rodrigues NB, Cao B, Lee Y, Lin K, Mansur RB, Ho R, Burke MJ, Rosenblat JD, McIntyre RS. Registered clinical trials investigating treatment of long COVID: a scoping review and recommendations for research. Infect Dis (Lond). 2022 Mar 14:1-11. doi: 10.1080/23744235.2022.2043560. Epub ahead of print. PMID: 35282780; PMCID: PMC8935463. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8935463/ (Full text)