Pathophysiology of Post-COVID syndromes: a new perspective

Virology Journal, Год журнала: 2022, Номер 19(1)

Опубликована: Окт. 9, 2022

Most COVID-19 patients recovered with low mortality; however, some experienced long-term symptoms described as "long-COVID" or "Post-COVID syndrome" (PCS). Patients may have persisting for weeks after acute SARS-CoV-2 infection, including dyspnea, fatigue, myalgia, insomnia, cognitive and olfactory disorders. These last months in patients. PCS progress association the development of mast cell activation syndrome (MCAS), which is a distinct kind disorder, characterized by hyper-activation cells inappropriate excessive release chemical mediators. survivors, mainly women, persistent severe fatigue 10 recovery history neuropsychiatric disorders are more prone to develop PCS. High D-dimer levels blood urea nitrogen were observed be risk factors associated pulmonary dysfunction survivors 3 post-hospital discharge has systemic manifestations that resolve time no further complications. However, final outcomes chiefly unknown. Persistence inflammatory reactions, autoimmune mimicry, reactivation pathogens together host microbiome alterations contribute The deregulated mediators MCAS produces extraordinary during course infection correlated severity Therefore, treated antihistamines, inhibition synthesis mediators, mediator release, degranulation cells.

Язык: Английский

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The interacting physiology of COVID‐19 and the renin‐angiotensin‐aldosterone system: Key agents for treatment

Pharmacology Research & Perspectives, Год журнала: 2022, Номер 10(1)

Опубликована: Фев. 1, 2022

Abstract SARS‐CoV‐2 interacting with its receptor, angiotensin‐converting enzyme 2 (ACE2), turns the host response to viral infection into a dysregulated uncontrolled inflammatory response. This is because ACE2 limits production of peptide angiotensin II (Ang II) and SARS‐CoV‐2, through destruction ACE2, allows Ang II. Recovery from trauma requires activation both tissue injury whole‐body maintain perfusion. Tissue circulating renin‐angiotensin systems (RASs) play an essential role in actions II, mediated via AT 1 receptor. Both arms renin aldosterone system's (RAAS) need be regulated. The effects steroid hormone, aldosterone, on fluid electrolyte homeostasis circulation are controlled by elaborate feedback networks that respond alterations composition volume fluids within circulatory system. however, mainly metabolism conversion Ang‐(1‐7) ACE2. has contrary II‐AT R effects. Thus, results loss control pro‐inflammatory destruction. Therefore, it responsible for pathogenesis COVID‐19.

Язык: Английский

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Role of the renin-angiotensin system in the development of COVID-19-associated neurological manifestations

Frontiers in Cellular Neuroscience, Год журнала: 2022, Номер 16

Опубликована: Сен. 16, 2022

SARS-CoV-2 causes COVID-19, which has claimed millions of lives. This virus can infect various cells and tissues, including the brain, for numerous neurological symptoms have been reported, ranging from mild non-life-threatening (e.g., headaches, anosmia, dysgeusia, disorientation) to severe life-threatening meningitis, ischemic stroke, cerebral thrombosis). The cellular receptor is angiotensin-converting enzyme 2 (ACE2), an that belongs renin-angiotensin system (RAS). RAS endocrine classically associated with regulating blood pressure fluid electrolyte balance; however, it also involved in promoting inflammation, proliferation, fibrogenesis, lipogenesis. Two pathways constitute counter-balancing effects, key its regulation. first axis (classical) composed (ACE), angiotensin (Ang) II, type 1 (AT1R) as main effector, -when activated- increases production aldosterone antidiuretic hormone, sympathetic nervous tone, pressure, vasoconstriction, fibrosis, reactive oxygen species (ROS) production. Both systemic local classical RAS’ within brain are cognitive impairment, cell death, inflammation. second (non-classical or alternative) includes ACE2, converts Ang II Ang-(1–7), a peptide molecule activates Mas (MasR) charge opposing II/AT1R actions. Thus, alternative enhances cognition, synaptic remodeling, survival, signal transmission, antioxidant/anti-inflammatory mechanisms brain. In physiological state, both axes remain balanced. However, some factors dysregulate arms. binding ACE2 internalization degradation this enzyme, reducing activity, disrupting balance RAS, partially explain appearance COVID-19. Therefore, review aims analyze role development effects due infection. Moreover, we will discuss RAS-molecular targets could be used therapeutic purposes treat short long-term COVID-19-related sequelae.

Язык: Английский

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Repurposing methylene blue in the management of COVID-19: Mechanistic aspects and clinical investigations

Biomedicine & Pharmacotherapy, Год журнала: 2021, Номер 142, С. 112023 - 112023

Опубликована: Авг. 10, 2021

The severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is the most recent coronaviruses, which has infected humans, and caused disease COVID-19. World Health Organization declared COVID-19 as a pandemic in March 2020. SARS-CoV-2 enters human hosts majorly via tract, affecting lungs first. In few critical cases, infection progresses to failure of system known distress syndrome may be further associated with multi-organ vasoplegic shock. Currently, treatment involves use antiviral anti-cytokine drugs. However, both drugs have low efficacy because they cannot inhibit production free radicals cytokines at same time. Recently, some researchers reported methylene blue (MB) management. MB been used since long time therapeutic agent, approved by US FDA for other diseases. additional advantage its cost. safe drug when dose < mg/kg. this review, applicability mechanistic aspects explored compiled. clinical studies explained great detail. Thus, potential management examined.

Язык: Английский

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A Review of the Potential Roles of Antioxidant and Anti-Inflammatory Pharmacological Approaches for the Management of Mild-to-Moderate Symptomatic COVID-19

Medical Science Monitor, Год журнала: 2022, Номер 28

Опубликована: Фев. 28, 2022

In the past 2 years, coronavirus disease 2019 (COVID-19) pandemic has driven investigational studies and controlled clinical trials on antiviral treatments vaccines that have undergone regulatory approval. Now severe acute respiratory syndrome (SARS-CoV-2) its variants may become endemic over time, there remains a need to identify drugs treat symptoms of COVID-19 prevent progression toward cases, hospitalization, death. Understanding molecular mechanisms SARS-CoV-2 infection is extremely important for development effective therapies against COVID-19. This review outlines key pathways involved in host response discusses potential role antioxidant anti-inflammatory pharmacological approaches management early mild-to-moderate COVID-19, using examples combined indomethacin, low-dose aspirin, omeprazole, hesperidin, quercetin, vitamin C. The targets these substances are described here their possible synergism counteracting replication from upper airways blood, avoiding vascular complications cytokine bradykinin storms.

Язык: Английский

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Between two storms, vasoactive peptides or bradykinin underlie severity of COVID‐19?

Physiological Reports, Год журнала: 2021, Номер 9(5)

Опубликована: Март 1, 2021

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to be a world-wide pandemic with overwhelming socioeconomic impact. Since inflammation is one of the major causes COVID-19 complications, associated molecular mechanisms have been focus many studies better understand this and develop improved treatments for patients contracting SARS-CoV-2. Among these, strong emphasis has placed on pro-inflammatory cytokines, associating severity so-called "cytokine storm." More recently, peptide bradykinin, its dysregulated signaling or "bradykinin storm," emerged as primary mechanism explain COVID-19-related complications. Unfortunately, important development may not fully capture main players that underlie severity. To end, in focused review, several lines evidence are provided suggest addition two closely related vasoactive peptides, substance P neurotensin, also likely drive microvascular permeability inflammation, responsible pathology. Furthermore, based published experimental observations, it postulated ACE neprilysin, peptidase neurolysin (Nln) contribute accumulation progression disease. In conclusion, proposed "vasoactive storm" simultaneous inhibition all three peptidergic systems could therapeutically more advantageous rather than modulation any single alone.

Язык: Английский

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The des-Arg9-bradykinin/B1R axis: Hepatic damage in COVID-19

Frontiers in Physiology, Год журнала: 2022, Номер 13

Опубликована: Дек. 19, 2022

Patients infected by the SARS-CoV-2 virus are commonly diagnosed with threatening liver conditions associated drug-induced therapies and systemic viral action. RNA-Seq data from cells in bronchoalveolar lavage fluid COVID-19 patients have pointed out dysregulation of kallikrein-kinin renin-angiotensin systems as a possible mechanism that triggers multi-organ damage away leading site infection. Therefore, we measured plasma concentration biologically active peptides system, bradykinin des-Arg 9 -bradykinin, expression its proinflammatory axis, 1 receptor (B1R). We -bradykinin 20 virologically confirmed using liquid chromatography-tandem mass spectrometry-based methodology. The B1R was evaluated immunohistochemistry post-mortem specimens 27 individuals. found significantly higher blood level lower compared to healthy, uninfected control group. also observed increased levels hepatic tissues under all injuries analyzed (liver congestion, portal vein dilation, steatosis, ischemic necrosis). Our indicate -bradykinin/B1R is acute dysfunction induced infection pathogenesis COVID-19.

Язык: Английский

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Structures of the SARS-CoV-2 spike glycoprotein and applications for novel drug development

Frontiers in Pharmacology, Год журнала: 2022, Номер 13

Опубликована: Авг. 9, 2022

COVID-19 caused by SARS-CoV-2 has raised a health crisis worldwide. The high morbidity and mortality associated with the lack of effective drugs or vaccines for emphasize urgent need standard treatment prophylaxis COVID-19. receptor-binding domain (RBD) glycosylated spike protein (S protein) is capable binding to human angiotensin-converting enzyme 2 (hACE2) initiating membrane fusion virus entry. Hence, it rational inhibit RBD activity S blocking interaction hACE2, which makes potential target designing developing antiviral agents. In this study, molecular features are highlighted, such as structures, functions, interactions ACE2. Additionally, computational tools developed provided, example, algorithms, databases, relevant programs. Finally, recent advances in novel development antivirals against summarized, including screening natural products, drug repurposing design. This study expected provide insights efficient discovery promising candidates contribute broad-spectrum anti-coronavirus fight SARS-CoV-2.

Язык: Английский

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The role of Substance P in the defense line of the respiratory tract and neurological manifestations post COVID-19 infection

Frontiers in Neurology, Год журнала: 2023, Номер 14

Опубликована: Март 6, 2023

Substance P (SP) has been a great interest for scientists due to its unique properties and involvement in various physiological pathological phenomenon. It took almost century the current understanding of this peptide so far. Its role brain gut were initially discussed later on it was widely studied observed cardiovascular system, asthma, traumatic injury, immune response, vasodilation, behavior, inflammation, arthritis, cancer, airway hyper responsiveness respiratory disorders. Involvement SP sudden perinatal death COVID-19 also which shed light vital rhythm regulation initiation cytokine storming COVID-19. This article will provide comprehensive overview researches done understand basic functions different processes cell association with diseases. describes historical scientific journey from discovery until today, including future perspectives.

Язык: Английский

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Bradykinin-target therapies in SARS-CoV-2 infection: current evidence and perspectives

Naunyn-Schmiedeberg s Archives of Pharmacology, Год журнала: 2022, Номер 395(3), С. 275 - 283

Опубликована: Янв. 28, 2022

Язык: Английский

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