Tag: long covid treatment

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.

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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)

A new clinical challenge: Supporting patients coping with the long-term effects of COVID-19

Abstract:

Mental Health Practitioners (MHPs) have a unique opportunity to provide resources and support to those suffering from Long COVID (LC), the post infectious illness that often follows an acute SARS-CoV-2 infection. In working with these individuals, MHPs can learn from the experiences of patients with another post-infectious disease known as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). ME/CFS was once thought to be a psychologically mediated disorder caused by deconditioning and the fear of exertion following a precipitating event such as a viral infection. Research now shows that LC and ME/CFS are biomedical, multisystem, complex physiologic diseases. This article provides a framework to MHPs for the treatment of LC patients using knowledge derived from three decades of research on ME/CFS.

Source: Neal C. Goldberg, Sabrina Poirier, Allison Kanas, Lisa McCorkell, Carrie Anna McGinn, Yochai Re’em, Kathi Kuehnel, Nina Muirhead, Tahlia Ruschioni, Susan Taylor-Brown & Leonard A. Jason (2022) A new clinical challenge: supporting patients coping with the long-term effects of COVID-19, Fatigue: Biomedicine, Health & Behavior, DOI: 10.1080/21641846.2022.2128576 (Full text)

Social Media Mining of Long-COVID Self-Medication Reported by Reddit Users: Feasibility Study to Support Drug Repurposing

Background: Since the beginning of the COVID-19 pandemic, over 480 million people have been infected and more than 6 million people have died from COVID-19 worldwide. In some patients with acute COVID-19, symptoms manifest over a longer period, which is also called “long-COVID.” Unmet medical needs related to long-COVID are high, since there are no treatments approved. Patients experiment with various medications and supplements hoping to alleviate their suffering. They often share their experiences on social media.

Objective: The aim of this study was to explore the feasibility of social media mining methods to extract important compounds from the perspective of patients. The goal is to provide an overview of different medication strategies and important agents mentioned in Reddit users’ self-reports to support hypothesis generation for drug repurposing, by incorporating patients’ experiences.

Methods:We used named-entity recognition to extract substances representing medications or supplements used to treat long-COVID from almost 70,000 posts on the “/r/covidlonghaulers” subreddit. We analyzed substances by frequency, co-occurrences, and network analysis to identify important substances and substance clusters.

Results: The named-entity recognition algorithm achieved an F1 score of 0.67. A total of 28,447 substance entities and 5789 word co-occurrence pairs were extracted. “Histamine antagonists,” “famotidine,” “magnesium,” “vitamins,” and “steroids” were the most frequently mentioned substances. Network analysis revealed three clusters of substances, indicating certain medication patterns.

Conclusions: This feasibility study indicates that network analysis can be used to characterize the medication strategies discussed in social media. Comparison with existing literature shows that this approach identifies substances that are promising candidates for drug repurposing, such as antihistamines, steroids, or antidepressants. In the context of a pandemic, the proposed method could be used to support drug repurposing hypothesis development by prioritizing substances that are important to users.

Source: Koss J, Bohnet-Joschko S. Social Media Mining of Long-COVID Self-Medication Reported by Reddit Users: Feasibility Study to Support Drug Repurposing. JMIR Form Res. 2022 Oct 3;6(10):e39582. doi: 10.2196/39582. PMID: 36007131; PMCID: PMC9531770. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9531770/ (Full text)

Long-COVID Syndrome and the Cardiovascular System: A Review of Neurocardiologic Effects on Multiple Systems

Abstract:

Purpose of review: Long-COVID syndrome is a multi-organ disorder that persists beyond 12 weeks post-acute SARS-CoV-2 infection (COVID-19). Here, we provide a definition for this syndrome and discuss neuro-cardiology involvement due to the effects of (1) angiotensin-converting enzyme 2 receptors (the entry points for the virus), (2) inflammation, and (3) oxidative stress (the resultant effects of the virus).

Recent findings: These effects may produce a spectrum of cardio-neuro effects (e.g., myocardial injury, primary arrhythmia, and cardiac symptoms due to autonomic dysfunction) which may affect all systems of the body. We discuss the symptoms and suggest therapies that target the underlying autonomic dysfunction to relieve the symptoms rather than merely treating symptoms. In addition to treating the autonomic dysfunction, the therapy also treats chronic inflammation and oxidative stress. Together with a full noninvasive cardiac workup, a full assessment of the autonomic nervous system, specifying parasympathetic and sympathetic (P&S) activity, both at rest and in response to challenges, is recommended. Cardiac symptoms must be treated directly. Cardiac treatment is often facilitated by treating the P&S dysfunction. Cardiac symptoms of dyspnea, chest pain, and palpitations, for example, need to be assessed objectively to differentiate cardiac from neural (autonomic) etiology. Long-term myocardial injury commonly involves P&S dysfunction. P&S assessment usually connects symptoms of Long-COVID to the documented autonomic dysfunction(s).

Source: DePace NL, Colombo J. Long-COVID Syndrome and the Cardiovascular System: A Review of Neurocardiologic Effects on Multiple Systems. Curr Cardiol Rep. 2022 Sep 30:1–16. doi: 10.1007/s11886-022-01786-2. Epub ahead of print. PMID: 36178611; PMCID: PMC9524329.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9524329/ (Full text)

Gut Microbiota Dynamics in Relation to Long-COVID-19 Syndrome: Role of Probiotics to Combat Psychiatric Complications

Abstract:

Increasing numbers of patients who recover from COVID-19 report lasting symptoms, such as fatigue, muscle weakness, dementia, and insomnia, known collectively as post-acute COVID syndrome or long COVID. These lasting symptoms have been examined in different studies and found to influence multiple organs, sometimes resulting in life-threating conditions.
In this review, these symptoms are discussed in connection to the COVID-19 and long-COVID-19 immune changes, highlighting oral and psychiatric health, as this work focuses on the gut microbiota’s link to long-COVID-19 manifestations in the liver, heart, kidney, brain, and spleen. A model of this is presented to show the biological and clinical implications of gut microbiota in SARS-CoV-2 infection and how they could possibly affect the therapeutic aspects of the disease. Probiotics can support the body’s systems in fighting viral infections. This review focuses on current knowledge about the use of probiotics as adjuvant therapies for COVID-19 patients that might help to prevent long-COVID-19 complications.
Source: Alenazy MF, Aljohar HI, Alruwaili AR, Daghestani MH, Alonazi MA, Labban RS, El-Ansary AK, Balto HA. Gut Microbiota Dynamics in Relation to Long-COVID-19 Syndrome: Role of Probiotics to Combat Psychiatric Complications. Metabolites. 2022; 12(10):912. https://doi.org/10.3390/metabo12100912 (Full text)

Neurogenesis is disrupted in human hippocampal progenitor cells upon exposure to serum samples from hospitalized COVID-19 patients with neurological symptoms

Abstract:

Coronavirus disease 2019 (COVID-19), represents an enormous new threat to our healthcare system and particularly to the health of older adults. Although the respiratory symptoms of COVID-19 are well recognized, the neurological manifestations, and their underlying cellular and molecular mechanisms, have not been extensively studied yet. Our study is the first one to test the direct effect of serum from hospitalised COVID-19 patients on human hippocampal neurogenesis using a unique in vitro experimental assay with human hippocampal progenitor cells (HPC0A07/03 C). We identify the different molecular pathways activated by serum from COVID-19 patients with and without neurological symptoms (i.e., delirium), and their effects on neuronal proliferation, neurogenesis, and apoptosis.

We collected serum sample twice, at time of hospital admission and approximately 5 days after hospitalization. We found that treatment with serum samples from COVID-19 patients with delirium (n = 18) decreased cell proliferation and neurogenesis, and increases apoptosis, when compared with serum samples of sex- and age-matched COVID-19 patients without delirium (n = 18). This effect was due to a higher concentration of interleukin 6 (IL6) in serum samples of patients with delirium (mean ± SD: 229.9 ± 79.1 pg/ml, vs. 32.5 ± 9.5 pg/ml in patients without delirium).

Indeed, treatment of cells with an antibody against IL6 prevented the decreased cell proliferation and neurogenesis and the increased apoptosis. Moreover, increased concentration of IL6 in serum samples from delirium patients stimulated the hippocampal cells to produce IL12 and IL13, and treatment with an antibody against IL12 or IL13 also prevented the decreased cell proliferation and neurogenesis, and the increased apoptosis. Interestingly, treatment with the compounds commonly administered to acute COVID-19 patients (the Janus kinase inhibitors, baricitinib, ruxolitinib and tofacitinib) were able to restore normal cell viability, proliferation and neurogenesis by targeting the effects of IL12 and IL13.

Overall, our results show that serum from COVID-19 patients with delirium can negatively affect hippocampal-dependent neurogenic processes, and that this effect is mediated by IL6-induced production of the downstream inflammatory cytokines IL12 and IL13, which are ultimately responsible for the detrimental cellular outcomes.

Source: Borsini, A., Merrick, B., Edgeworth, J. et al. Neurogenesis is disrupted in human hippocampal progenitor cells upon exposure to serum samples from hospitalized COVID-19 patients with neurological symptoms. Mol Psychiatry (2022). https://doi.org/10.1038/s41380-022-01741-1  (Full text)

Lactoferrin as Possible Treatment for Chronic Gastrointestinal Symptoms in Children with Long COVID: Case Series and Literature Review

Abstract:

Long COVID is an emergent, heterogeneous, and multisystemic condition with an increasingly important impact also on the pediatric population. Among long COVID symptoms, patients can experience chronic gastrointestinal symptoms such as abdominal pain, constipation, diarrhea, vomiting, nausea, and dysphagia.
Although there is no standard, agreed, and optimal diagnostic approach or treatment of long COVID in children, recently compounds containing multiple micronutrients and lactoferrin have been proposed as a possible treatment strategy, due to the long-standing experience gained from other gastrointestinal conditions. In particular, lactoferrin is a pleiotropic glycoprotein with antioxidant, anti-inflammatory, antithrombotic, and immunomodulatory activities. Moreover, it seems to have several physiological functions to protect the gastrointestinal tract.
In this regard, we described the resolution of symptoms after the start of therapy with high doses of oral lactoferrin in two patients referred to our post-COVID pediatric unit due to chronic gastrointestinal symptoms after SARS-CoV-2 infection.
Source: Morello R, De Rose C, Cardinali S, Valentini P, Buonsenso D. Lactoferrin as Possible Treatment for Chronic Gastrointestinal Symptoms in Children with Long COVID: Case Series and Literature Review. Children. 2022; 9(10):1446. https://doi.org/10.3390/children9101446 (Full text)

Epipharyngeal Abrasive Therapy (EAT) Reduces the mRNA Expression of Major Proinflammatory Cytokine IL-6 in Chronic Epipharyngitis

Abstract:

The epipharynx, located behind the nasal cavity, is responsible for upper respiratory tract immunity; however, it is also the site of frequent acute and chronic inflammation. Previous reports have suggested that chronic epipharyngitis is involved not only in local symptoms such as cough and postnasal drip, but also in systemic inflammatory diseases such as IgA nephropathy and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Long COVID.

Epipharyngeal Abrasive Therapy (EAT), which is an effective treatment for chronic epipharyngitis in Japan, is reported to be effective for these intractable diseases. The sedation of chronic epipharyngitis by EAT induces suppression of the inflammatory cytokines and improves systemic symptoms, which is considered to be one of the mechanisms, but there is no report that has proved this hypothesis. The purpose of this study was to clarify the anti-inflammatory effect of EAT histologically.

The study subjects were 8 patients who were not treated with EAT and 11 patients who were treated with EAT for chronic epipharyngitis for 1 month or more. For immunohistochemical assessment, the expression pattern of IL-6 mRNA, which plays a central role in the human cytokine network, was analyzed using in situ hybridization. The expression of IL-6 in the EAT-treated group was significantly lower than those in the EAT nontreated group (p = 0.0015). In addition, EAT suppressed the expression of tumor necrosis factor alpha (TNFα), a crucial proinflammatory cytokine. As a result, continuous EAT suppressed submucosal cell aggregation and reduced inflammatory cytokines. Thus, EAT may contribute to the improvement of systemic inflammatory diseases through the suppression of IL-6 expression.

Source: Nishi K, Yoshimoto S, Nishi S, Nishi T, Nishi R, Tanaka T, Tsunoda T, Imai K, Tanaka H, Hotta O, Tanaka A, Hiromatsu K, Shirasawa S, Nakagawa T, Yamano T. Epipharyngeal Abrasive Therapy (EAT) Reduces the mRNA Expression of Major Proinflammatory Cytokine IL-6 in Chronic Epipharyngitis. Int J Mol Sci. 2022 Aug 16;23(16):9205. doi: 10.3390/ijms23169205. PMID: 36012469; PMCID: PMC9409341. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9409341/ (Full text)