A review of cytokine-based pathophysiology of Long COVID symptoms

Frontiers in Medicine, Journal Year: 2023, Volume and Issue: 10

Published: March 31, 2023

The Long COVID/Post Acute Sequelae of COVID-19 (PASC) group includes patients with initial mild-to-moderate symptoms during the acute phase illness, in whom recovery is prolonged, or new are developed over months. Here, we propose a description pathophysiology COVID presentation based on inflammatory cytokine cascades and p38 MAP kinase signaling pathways that regulate production. In this model, SARS-CoV-2 viral infection hypothesized to trigger dysregulated peripheral immune system activation subsequent release. Chronic low-grade inflammation leads brain microglia an exaggerated release central cytokines, producing neuroinflammation. Immunothrombosis linked chronic microclot formation decreased tissue perfusion ischemia. Intermittent fatigue, Post Exertional Malaise (PEM), CNS "brain fog," arthralgias, paresthesias, dysautonomia, GI ophthalmic problems can consequently arise as result elevated cytokines. There abundant similarities between myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). DNA polymorphisms viral-induced epigenetic changes gene expression may lead patients, predisposing some develop autoimmunity, which be gateway ME/CFS.

Language: Английский

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The long-term health outcomes, pathophysiological mechanisms and multidisciplinary management of long COVID

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Nov. 1, 2023

Abstract There have been hundreds of millions cases coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome 2 (SARS-CoV-2). With the growing population recovered patients, it crucial to understand long-term consequences and management strategies. Although COVID-19 was initially considered an illness, recent evidence suggests that manifestations including but not limited those cardiovascular, respiratory, neuropsychiatric, gastrointestinal, reproductive, musculoskeletal systems may persist long after phase. These persistent manifestations, also referred as COVID, could impact all patients with across full spectrum illness severity. Herein, we comprehensively review current literature on highlighting its epidemiological understanding, vaccinations, organ-specific sequelae, pathophysiological mechanisms, multidisciplinary In addition, psychological psychosomatic factors underscored. Despite these findings diagnostic therapeutic strategies based previous experience pilot studies remain inadequate, well-designed clinical trials should be prioritized validate existing hypotheses. Thus, propose primary challenges concerning biological knowledge gaps efficient remedies well discuss corresponding recommendations.

Language: Английский

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Interventions for the management of post-COVID-19 condition (long COVID): protocol for a living systematic review and network meta-analysis

BMJ Open, Journal Year: 2025, Volume and Issue: 15(2), P. e086407 - e086407

Published: Feb. 1, 2025

Up to 15% of survivors COVID-19 infection experience long-term health effects, including fatigue, myalgia and impaired cognitive function, termed post-COVID-19 condition or long COVID. Several trials that study the benefits harms various interventions manage COVID have been published hundreds more are planned ongoing. Trustworthy systematic reviews clarify critical promote evidence-based practice. To create maintain a living review network meta-analysis addressing pharmacologic non-pharmacologic for treatment management Eligible will randomise adults with interventions, placebo, sham usual care. We identify eligible studies by searching MEDLINE, EMBASE, CINAHL, PsycINFO, AMED CENTRAL from inception, without language restrictions.Reviewers work independently in duplicate screen search records, collect data trials, trial patient characteristics outcomes interest assess risk bias. Our include patient-reported pain, postexertional malaise, changes education employment status, mental health, dyspnoea, quality life, physical recovery serious adverse events.For each outcome, when possible, we perform frequentist random-effects meta-analysis. When there compelling reasons suspect certain only applicable effective subtype COVID, separate meta-analyses. The Grading Recommendations, Assessment, Development Evaluations (GRADE) approach guide our assessment certainty evidence.We update biannually, on publication seminal trial, new evidence emerges may change clinical This provide comprehensive, trustworthy up-to-date summaries make findings available publicly guideline-producing organisations inform their recommendations. describes protocol uses reports. Therefore, is exempt ethics review. intend deposit all public repository publish iteration online.

Language: Английский

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

Journal of Medical Virology, Journal Year: 2022, Volume and Issue: 95(1)

Published: Nov. 9, 2022

Abstract The postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection (PASC), also known as post‐acute disease 19 (COVID‐19) or the long COVID (long COVID) is an emerging public health concern. A substantial proportion individuals may remain symptomatic months after initial recovery. An updated review published and ongoing trials focusing on managing will help identify gaps address unmet needs patients suffering from this potentially debilitating syndrome. comprehensive literature search was conducted international databases clinical trial registries inception to 31 July 2022. This included 6 54 registration records. There significant heterogeneity in characterization ascertainment primary outcomes. Most are focused individual symptoms isolated organ dysfunction, classified according cardiovascular, functional capacity, neurological psychological, fatigue, olfactory dysfunction. interventions related mechanisms causing symptoms. Although six showed improvement dysfunction studied, these studies lack internal external validity limiting generalizability. provides update pharmacological agents that could be used treat COVID. Further standardization diagnostic criteria, inclusion participants with concomitant chronic cardiometabolic diseases outcomes essential future trials.

Language: Английский

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Interventions for the management of long covid (post-covid condition): living systematic review

BMJ, Journal Year: 2024, Volume and Issue: unknown, P. e081318 - e081318

Published: Nov. 27, 2024

Abstract Objective To compare the effectiveness of interventions for management long covid (post-covid condition). Design Living systematic review. Data sources Medline, Embase, CINAHL, PsycInfo, Allied and Complementary Medicine Database, Cochrane Central Register Controlled Trials from inception to December 2023. Eligibility criteria that randomised adults (≥18 years) with drug or non-drug interventions, placebo sham, usual care. Results 24 trials 3695 patients were eligible. Four (n=708 patients) investigated eight (n=985) physical activity rehabilitation, three (n=314) behavioural, four (n=794) dietary, (n=309) medical devices technologies, one (n=585) a combination exercise mental health rehabilitation. Moderate certainty evidence suggested that, compared care, an online programme cognitive behavioural therapy (CBT) probably reduces fatigue (mean difference −8.4, 95% confidence interval (CI) −13.11 −3.69; Checklist Individual Strength subscale; range 8-56, higher scores indicate greater impairment) improves concentration −5.2, −7.97 −2.43; problems 4-28; impairment). online, supervised, combined rehabilitation leads improvement in overall health, estimated 161 more per 1000 (95% CI 61 292 more) experiencing meaningful recovery, symptoms depression −1.50, −2.41 −0.59; Hospital Anxiety Depression Scale 0-21; impairment), quality life (0.04, 0.00 0.08; Patient-Reported Outcomes Measurement Information System 29+2 Profile; −0.022-1; less intermittent aerobic 3-5 times weekly 4-6 weeks function continuous 3.8, 1.12 6.48; SF-36 component summary score; 0-100; No compelling was found support other including, among others, vortioxetine, leronlimab, probiotics-prebiotics, coenzyme Q10, amygdala insula retraining, L-arginine vitamin C, inspiratory muscle training, transcranial direct current stimulation, hyperbaric oxygen, mobile application providing education on covid. Conclusion suggests CBT improve Systematic review registration Open Science Framework https://osf.io/9h7zm/ . Readers’ note This article is living will be updated reflect emerging evidence. Updates may occur up two years date original publication.

Language: Английский

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Coronavirus disease 2019 (COVID-19) pandemic and autoimmune rheumatic diseases: Outcomes and prospects

Rheumatology Science and Practice, Journal Year: 2024, Volume and Issue: 62(1), P. 32 - 54

Published: Feb. 29, 2024

The pandemic of coronavirus disease 2019 (COVID-19), etiologically related to the SARS-CoV-2 virus (severe acute respiratory syndrome coronavirus-2), has drawn attention new clinical and fundamental problems in immunopathology human diseases associated with virus-induced autoimmunity autoinflammation. provision that “the experience gained rheumatology process studying pathogenetic mechanisms pharmacotherapy immunoinflammatory rheumatic as most common severe forms autoimmune autoinflammatory pathology humans will be demand for deciphering nature pathological processes underlying COVID-19 developing approaches effective pharmacotherapy” was confirmed numerous studies conducted over next 3 years midst pandemic. main focus on a critical analysis data regarding role inflammation, which basis pathogenesis immune-mediated context COVID-19.

Language: Английский

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Alterations in microbiota of patients with COVID‐19: implications for therapeutic interventions

MedComm, Journal Year: 2024, Volume and Issue: 5(4)

Published: March 15, 2024

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recently caused a global pandemic, resulting in more than 702 million people being infected and over 6.9 deaths. Patients with disease (COVID-19) may suffer from diarrhea, sleep disorders, depression, even cognitive impairment, which is associated long COVID during recovery. However, there remains no consensus on effective treatment methods. Studies have found that patients COVID-19 alterations microbiota their metabolites, particularly the gut, be involved regulation of immune responses. Consumption probiotics alleviate discomfort by inflammation oxidative stress. pathophysiological process underlying alleviation COVID-19-related symptoms complications targeting unclear. In current study, we summarize latest research evidence together SARS-CoV-2 vaccine use, focus relationship between use. This work provides probiotic-based interventions improve regulating gut systemic immunity. Probiotics also used as adjuvants to efficacy.

Language: Английский

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Multi-target drugs for the treatment of cognitive impairment and fatigue in post-COVID syndrome: focus on Ginkgo biloba and Rhodiola rosea

Journal of Neural Transmission, Journal Year: 2024, Volume and Issue: 131(3), P. 203 - 212

Published: Feb. 12, 2024

Abstract Cognitive impairment, depression and (mental) fatigue represent the most frequent neuropsychiatric symptoms of post-COVID syndrome. Neuroinflammation, oxidative stress mitochondrial dysfunction have been identified as common pathophysiological mechanisms underlying these symptoms. Attempts to treat post-COVID-associated cognitive impairment with different drugs available for other diseases not yet successful. One probable explanation could be that work by one specific mechanism action only in a broad multi-target way. Therefore, they will address spectrum possibly responsible Notably, nearly all currently under investigation syndrome are rather addressing single target instead several pathomechanisms this condition. Contrary approach, herbal often consist many ingredients pharmacological properties targets. might promising approach treatment symptomatic presentation following SARS-CoV-2 infection. Of drugs, extracts Ginkgo biloba Rhodiola rosea probably best investigated candidates. Their vitro vivo includes anti-oxidative, anti-inflammatory, antidepressant well reducing fatigue. In studies, both showed positive effects on physical mental impaired cognition. Moreover, depressive were also reduced some studies. However, even if results promising, data still preliminary require additional proof further

Language: Английский

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Current landscape of long COVID clinical trials

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 132, P. 111930 - 111930

Published: March 27, 2024

Language: Английский

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Pharmacological evaluation of vitamin D in COVID-19 and long COVID-19: recent studies confirm clinical validation and highlight metformin to improve VDR sensitivity and efficacy

Inflammopharmacology, Journal Year: 2023, Volume and Issue: 32(1), P. 249 - 271

Published: Nov. 13, 2023

Abstract Nearly four years after its first appearance, and having gone from pandemic to endemic, the SARS-CoV-2 remains out of control globally. The purpose this study was evaluate clinical efficacy vitamin D (VD) in COVID-19 long COVID-19, explain discrepancy outcomes highlight potential impact metformin on VD recent articles. Articles January 2022 August 2023 were selected for review. objective achieved by reviewing, analyzing, discussing articles demonstrating (1) mechanism action (2) observational or randomized trials (RCTs) that support not beneficial effects COVID. (3) genetic non-genetic reasons variation VD. collected electronic databases such as PubMed, Scopus, MEDLINE, Google Scholar, Egyptian Knowledge Bank, Science Direct, Cochrane Database Systematic Reviews. Twenty three studies conducted vitro animal models indicated may act through protecting respiratory system antimicrobial peptide cathelicidins, reducing lung inflammation, regulating innate adaptive immune functions up regulation autophagy gene activity. Our review identified 58 met criteria. number publications supporting a activity treating 49 (86%), including 12 meta-analyses. Although total patients included all 14,071,273, role 14,029,411 (99.7%). Collectively, extensive decisive relationship between low levels severity mortality outcomes. Importantly, evidence intervention has demonstrated effectiveness supplements COVID-19. Furthermore, results 4 supported alleviating symptoms disease. However, eight RCTs one meta-analysis contain low-grade against Twenty-five have addressed association VDR DBP polymorphisms treatment failure Impaired signaling underlie variability mechanisms. Interestingly, studies, therapeutic possibly improving AMPK enhancing In conclusion, been significantly strengthened over past 18 months, with several meta-analyses reporting conclusive supplementation highlighting improve sensitivity

Language: Английский

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