Tag: long covid treatment

Post COVID and Apheresis – Where are we Standing?

Abstract:

A continual increase in cases of Long/Post COVID constitutes a medical and socioeconomic challenge to health systems around the globe. While the true extent of this problem cannot yet be fully evaluated, recent data suggest that up to 20% of people with confirmed SARS-CoV-2 suffer from clinically relevant symptoms of Long/Post COVID several weeks to months after the acute phase. The clinical presentation is highly variable with the main symptoms being chronic fatigue, dyspnea, and cognitive symptoms. Extracorporeal apheresis has been suggested to alleviate symptoms of Post/COVID. Thus, numerous patients are currently treated with apheresis.

However, at present there is no data from randomized controlled trials available to confirm the efficacy. Therefore, physicians rely on the experience of practitioners and centers performing this treatment. Here, we summarize clinical experience on extracorporeal apheresis in patients with Post/COVID from centers across Germany.

Source: Steenblock C, Walther R, Tselmin S, Jarzebska N, Voit-Bak K, Toepfner N, Siepmann T, Passauer J, Hugo C, Wintermann G, Julius U, Barbir M, Khan TZ, Puhan MA, Straube R, Hohenstein B, Bornstein SR, Rodionov RN. Post COVID and Apheresis – Where are we Standing? Horm Metab Res. 2022 Nov;54(11):715-720. doi: 10.1055/a-1945-9694. Epub 2022 Sep 16. PMID: 36113501. https://www.thieme-connect.de/products/ejournals/html/10.1055/a-1945-9694 (Full text)

Clinical trials on the pharmacological treatment of long COVID: A systematic review

Abstract:

The postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC), also known as post-acute coronavirus disease 19 (COVID-19) or the long COVID syndrome (long COVID) is an emerging public health concern. A substantial proportion of individuals may remain symptomatic months after initial recovery. An updated review of published and ongoing trials focusing on managing long COVID will help identify gaps and address the unmet needs of patients suffering from this potentially debilitating syndrome.

A comprehensive literature search was conducted on the international databases and clinical trial registries from inception to 31 July 2022. This review included 6 published trials and 54 trial registration records. There is significant heterogeneity in the characterization of long COVID and ascertainment of primary outcomes. Most of the trials are focused on individual symptoms of long COVID or isolated organ dysfunction, classified according to cardiovascular, respiratory and functional capacity, neurological and psychological, fatigue, and olfactory dysfunction.

Most of the interventions are related to the mechanisms causing the individual symptoms. Although the six published trials showed significant improvement in the symptoms or organ dysfunction studied, these initial studies lack internal and external validity limiting the generalizability. This review provides an update of the pharmacological agents that could be used to treat long COVID. Further standardization of the diagnostic criteria, inclusion of participants with concomitant chronic cardiometabolic diseases and standardization of outcomes will be essential in future clinical trials.

Source: Chee YJ, Fan BE, Young BE, Dalan R, Lye DC. Clinical trials on the pharmacological treatment of long COVID: A systematic review. J Med Virol. 2022 Nov 8:e28289. doi: 10.1002/jmv.28289. Epub ahead of print. PMID: 36349400. https://pubmed.ncbi.nlm.nih.gov/36349400/

Transcutaneous Vagus Nerve Stimulation in the Treatment of Long Covid-Chronic Fatigue Syndrome

Abstract:

Many patients do not recover following Covid infection. The resulting illness is called Long Covid. Because there is no agreed upon treatment for this ailment, we decided to do an open label pilot study using non-invasive, transcutaneous stimulation of the auricular branch of the vagus nerve. Inclusion criteria required the patient to fulfill criteria for having chronic fatigue syndrome. Fourteen patients provided evaluable data. Eight of these fulfilled our requirements for treatment success. Since our criterion for a successful study was that at least a third of patients had to show a positive response to treatment, this was a successful pilot that warrants a follow up study that is appropriately sham controlled.

Source: Benjamin H Natelson, Michelle Blate, Tiffany Soto. Transcutaneous Vagus Nerve Stimulation in the Treatment of Long Covid-Chronic Fatigue Syndrome. medRxiv 2022.11.08.22281807; doi: https://doi.org/10.1101/2022.11.08.22281807 https://www.medrxiv.org/content/10.1101/2022.11.08.22281807v1.full-text (Full text)

Co-Ultramicronized Palmitoylethanolamide/Luteolin normalizes GABAB-ergic activity and cortical plasticity in long COVID-19 syndrome

Abstract:

Objective: Transcranial magnetic stimulation (TMS) studies showed that patients with cognitive dysfunction and fatigue after COVID-19 exhibit impaired cortical GABAB-ergic activity, as revealed by reduced long-interval intracortical inhibition (LICI).

Aim of this study was to test the effects of co-ultramicronized palmitoylethanolamide/luteolin (PEA-LUT), an endocannabinoid-like mediator able to enhance GABA-ergic transmission and to reduce neuroinflammation, on LICI.

Methods: Thirty-nine patients (26 females, mean age 49.9 ± 11.4 years, mean time from infection 296.7 ± 112.3 days) suffering from persistent cognitive difficulties and fatigue after mild COVID-19 were randomly assigned to receive either PEA-LUT 700mg + 70mg or PLACEBO, administered orally bid for eight weeks. The day before (PRE) and at the end of the treatment (POST), they underwent TMS protocols to assess LICI. We further evaluate short-latency afferent inhibition (SAI) and long-term potentiation (LTP)-like cortical plasticity.

Results: Patients treated with PEA-LUT but not with PLACEBO showed a significant increase of LICI and LTP-like cortical plasticity. SAI remained unaffected.

Conclusions: Eight weeks of treatment with PEA-LUT restore GABAB activity and cortical plasticity in long Covid patients.

Significance: This study confirms altered physiology of the motor cortex in long Covid and indicates PEA-LUT as a candidate for the treatment of this post-viral condition.

Source: Viviana Versace, Paola Ortelli, Sabrina Dezi, Davide Ferrazzoli, Alessia Alibardi, Ilenia Bonini, Michael Engl, Roberto Maestri, Martina Assogna, Valentina Ajello, Elke Pucks-Faes, Leopold Saltuari, Luca Sebastianelli, Markus Kofler, Giacomo Koch. Co-Ultramicronized Palmitoylethanolamide/Luteolin normalizes GABAB-ergic activity and cortical plasticity in long COVID-19 syndrome. Clinical Neurophysiology, 2022, ISSN 1388-2457, https://doi.org/10.1016/j.clinph.2022.10.017. https://www.sciencedirect.com/science/article/pii/S1388245722009385 (Full text)

 

The role of gut microbiota in etiopathogenesis of long COVID syndrome

To the editor.

COVID-19, a novel infectious disease caused by SARS-CoV-2 first emerged on November 17, 2019 had a high fatality rate and affected millions of people around the world [1]. The involvement of lung gut axis and the identification of viral RNA in feces of infected patients has drawn attention to a possible fecal-oral transmission route of SARS-CoV-2 [2].

Recent research shows a potential connection between long-term COVID-19 and dysbiosis of the gut flora. Long COVID-19 infection or post-acute COVID-19 syndrome is seen after weeks or months after the initial COVID-19 infection is characterized by complications and lingering symptoms such as fatigue, muscle weakness, and sleeplessness. Up to 3 out of 4 individuals report at least one symptom six months after recovering from COVID-19 infection, making it a relatively prevalent condition [3]. Long COVID may develop as a result of a heightened immune response, cell damage, or physiological effects of COVID-19 infection.

The gut microbiome, the billions of bacteria, fungus, and other microbes that live in the digestive tract, has been linked to COVID-19 severity and may possibly have an impact on the healing process, according to a growing body of research [4]. Researchers at the Chinese University of Hong Kong’s Center for Gut Microbiota Research discovered a clue in 2020.

When compared to healthy controls, persons with COVID-19 had unique changes in their gut microbiota, or the population of bacteria that live in their gut [5]. Early reports from Wuhan suggested that 2–10% of COVID-19 patients experienced gastrointestinal (GI) symptoms, such as diarrhoea, however a recent meta-analysis found that up to 20% of patients with COVID-19 had GI symptoms. SARS-CoV-2 virus was found in anal swabs and stool samples in over half of COVID-19 patients, suggesting that the digestive tract could be an extrapulmonary location for virus multiplication and activity [6, 7].

Read the rest of this article HERE.

Source: Kaushik P, Kumari M, Singh NK, Suri A. The role of gut microbiota in etiopathogenesis of long COVID syndrome. Horm Mol Biol Clin Investig. 2022 Nov 1. doi: 10.1515/hmbci-2022-0079. Epub ahead of print. PMID: 36317311. https://www.degruyter.com/document/doi/10.1515/hmbci-2022-0079/html (Full text)

Dysautonomia in Children with Post-Acute Sequelae of Coronavirus 2019 Disease and/or Vaccination

Abstract:

Long-term health problems such as fatigue, palpitations, syncope, and dizziness are well-known in patients after COVID-19 (post-acute sequelae of coronavirus (PASC)). More recently, comparable problems have been noticed after the SARS-CoV-2 vaccination (post-VAC). The pathophysiology of these problems is not well-understood.

Methods: In 38 children and young adults, we tested if these health problems were related to dysautonomia in an active standing test (Group 1: 19 patients after COVID-19; Group 2: 12 patients with a breakthrough infection despite a vaccination; and Group 3: 7 patients after a vaccination without COVID-19). The data were compared with a control group of 47 healthy age-matched patients, as recently published.

Results: All patients had a normal left ventricular function as measured by echocardiography. Significantly elevated diastolic blood pressure in all patient groups indicated a regulatory cardiovascular problem. Compared with the healthy control group, the patient groups showed significantly elevated heart rates whilst lying and standing, with significantly higher heart rate increases. The stress index was significantly enhanced in all patient groups whilst lying and standing. Significantly decreased pNN20 values, mostly whilst standing, indicated a lower vagus activity in all patient groups. The respiratory rates were significantly elevated in Groups 1 and 2.

Conclusion: The uniform increase in the heart rates and stress indices, together with low pNN20 values, indicated dysautonomia in children with health problems after COVID-19 disease and/or vaccination. A total of 8 patients fulfilled the criteria of postural orthostatic tachycardia syndrome and 9 patients of an inappropriate sinus tachycardia, who were successfully treated with omega-3 fatty acid supplementation and pharmacotherapy.

Source: Buchhorn R. Dysautonomia in Children with Post-Acute Sequelae of Coronavirus 2019 Disease and/or Vaccination. Vaccines (Basel). 2022 Oct 9;10(10):1686. doi: 10.3390/vaccines10101686. PMID: 36298551; PMCID: PMC9607162. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9607162/ (Full text)

Nirmatrelvir and the Risk of Post-Acute Sequelae of COVID-19

Abstract:

Long Covid — the disease encompassing the post-acute sequelae of SARS-CoV-2 (PASC) — affects millions of people around the world. Prevention of PASC is an urgent public health priority. In this work, we aimed to examine whether treatment with nirmatrelvir in the acute phase of COVID-19 is associated with reduced risk of post-acute sequelae.

We used the healthcare databases of the US Department of Veterans Affairs to identify users of the health system who had a SARS-CoV-2 positive test between March 01, 2022 and June 30, 2022, were not hospitalized on the day of the positive test, had at least 1 risk factor for progression to severe COVID-19 illness and survived the first 30 days after SARS-CoV-2 diagnosis. We identify those who were treated with oral nirmatrelvir within 5 days after the positive test (n=9217) and those who received no COVID-19 antiviral or antibody treatment during the acute phase of SARS-CoV-2 infection (control group, n= 47,123). Inverse probability weighted survival models were used to estimate the effect of nirmatrelvir (versus control) on a prespecified panel of 12 post-acute COVID-19 outcomes and reported as hazard ratio (HR) and absolute risk reduction (ARR) in percentage at 90 days.

Compared to the control group, treatment with nirmatrelvir was associated with reduced risk of PASC (HR 0.74 95% CI (0.69, 0.81), ARR 2.32 (1.73, 2.91)) including reduced risk of 10 of 12 post-acute sequelae in the cardiovascular system (dysrhythmia and ischemic heart disease), coagulation and hematologic disorders (deep vein thrombosis, and pulmonary embolism), fatigue, liver disease, acute kidney disease, muscle pain, neurocognitive impairment, and shortness of breath. Nirmatrelvir was also associated with reduced risk of post-acute death (HR 0.52 (0.35, 0.77), ARR 0.28 (0.14, 0.41)), and post-acute hospitalization (HR 0.70 (0.61, 0.80), ARR 1.09 (0.72, 1.46)). Nirmatrelvir was associated with reduced risk of PASC in people who were unvaccinated, vaccinated, and boosted, and in people with primary SARS-CoV-2 infection and reinfection.

In sum, our results show that in people with SARS-CoV-2 infection who had at least 1 risk factor for progression to severe COVID-19 illness, treatment with nirmatrelvir within 5 days of a positive SARS-CoV-2 test was associated with reduced risk of PASC regardless of vaccination status and history of prior infection. The totality of findings suggests that treatment with nirmatrelvir during the acute phase of COVID-19 reduces the risk of post-acute adverse health outcomes.

Source: Yan Xie, Taeyoung Choi, Ziyad Al-Aly. Nirmatrelvir and the Risk of Post-Acute Sequelae of COVID-19. medRxiv 2022.11.03.22281783; doi: https://doi.org/10.1101/2022.11.03.22281783 https://www.medrxiv.org/content/10.1101/2022.11.03.22281783v1.full.pdf (Full text)

Long COVID: defining the role of rheumatology in care and research

The global pandemic of COVID-19 has had an impact on the profession of rheumatology from many perspectives, including its effects on our patients with immune-mediated conditions and immunocompromised states, the disruption of care pathways, and beyond. There also are lingering questions about how the next phase of the pandemic will evolve, with the continuing emergence of new viral variants posing a continuing threat to our patients. Beyond these formidable challenges is the uncertainty around the long-term effects of COVID-19—referred to as long COVID among other names—in the rheumatology patient population, and the role of the rheumatology practitioner in care of and research among this population. Given the current global impact of long COVID and our early stages of understanding of the condition, we pose a series of questions for the rheumatology profession, to stimulate reflection and discussion around how to address long COVID.

Read the rest of this article HERE.

Source: Calabrese LH, Calabrese CM. Long COVID: defining the role of rheumatology in care and research. Lancet Rheumatol. 2022 Oct 3. doi: 10.1016/S2665-9913(22)00266-1. Epub ahead of print. PMID: 36211989; PMCID: PMC9529216. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9529216/ (Full text)

Antioxidants and Long Covid

Abstract:

Long Covid has many symptoms that overlap with ME(myalgic encephalomyelitis)/CFS(chronic fatigue syndrome), FM(fibromyalgia), EBV(Epstein-Barr virus), CMV(cytomegalovirus), CIRS (chronic inflammatory response syndrome), MCAS(mast cell activation syndrome), POTS(postural orthostatic tachycardia syndrome), and post viral fatigue syndrome. They all portend a “long haul” with an antioxidant shortfall and elevated Ca:Mg. Oxidative stress is the root cause.

Linkage between TGF(transforming growth factor)-β, IFN(interferon)-γ, the RAS(renin angiotensin system), and the KKS(kallikrein kinin system) is discussed. Technical explanations for the renin aldosterone paradox in POTS, the betrayal of TGF-β, and the commonality of markers for the Warburg effect are offered. The etiology of the common Long Covid symptoms of post exertional malaise, fatigue, and brain fog as well as anosmia, hair loss, and GI symptoms is technically discussed. Ca:Mg is critical to the glutamate/GABA balance. The role of GABA and butyrates from the “good” intestinal bacteria in the gut-brain axis and its correlation with chronic fatigue diseases are explored.

The crosstalk between the ENS(enteric nervous system) and the ANS(autonomic nervous system) and the role of the vagus in both are emphasized. HRV(heart rate variability), the fifth vital sign, points to an expanded gut-brain-heart/lung axis. A suggested approach to all of these – Long Covid, chronic fatigue diseases, post viral fatigue syndrome, and general health – is presented.

Source: Chambers, P. Antioxidants and Long Covid. Preprints 2022, 2022100195 (doi: 10.20944/preprints202210.0195.v1).  https://www.preprints.org/manuscript/202210.0195/v1 (Full text available as PDF file)

Pathophysiology of Post-COVID syndromes: a new perspective

Abstract:

Most COVID-19 patients recovered with low mortality; however, some patients experienced long-term symptoms described as “long-COVID” or “Post-COVID syndrome” (PCS). Patients may have persisting symptoms for weeks after acute SARS-CoV-2 infection, including dyspnea, fatigue, myalgia, insomnia, cognitive and olfactory disorders. These symptoms may last for months in some patients.

PCS may progress in association with the development of mast cell activation syndrome (MCAS), which is a distinct kind of mast cell activation disorder, characterized by hyper-activation of mast cells with inappropriate and excessive release of chemical mediators. COVID-19 survivors, mainly women, and patients with persistent severe fatigue for 10 weeks after recovery with a history of neuropsychiatric disorders are more prone to develop PCS. High D-dimer levels and blood urea nitrogen were observed to be risk factors associated with pulmonary dysfunction in COVID-19 survivors 3 months post-hospital discharge with the development of PCS. PCS has systemic manifestations that resolve with time with no further complications. However, the final outcomes of PCS are chiefly unknown.

Persistence of inflammatory reactions, autoimmune mimicry, and reactivation of pathogens together with host microbiome alterations may contribute to the development of PCS. The deregulated release of inflammatory mediators in MCAS produces extraordinary symptoms in patients with PCS. The development of MCAS during the course of SARS-CoV-2 infection is correlated to COVID-19 severity and the development of PCS. Therefore, MCAS is treated by antihistamines, inhibition of synthesis of mediators, inhibition of mediator release, and inhibition of degranulation of mast cells.

Source: Batiha, G.ES., Al-kuraishy, H.M., Al-Gareeb, A.I. et al. Pathophysiology of Post-COVID syndromes: a new perspective. Virol J 19, 158 (2022). https://doi.org/10.1186/s12985-022-01891-2  https://virologyj.biomedcentral.com/articles/10.1186/s12985-022-01891-2 (Full text)