The potential role of neopterin in Covid-19: a new perspective

Al-Niemi³

et al. 2022

Inflammation

Self Cite

SARS-CoV-2 by the direct cytopathic effect or indirectly through the propagation of pro-inflammatory cytokines could cause endothelial dysfunction (ED) and oxidative stress (OS). It has been reported that OS is triggered by various types of viral infections, including SARS-CoV-2. Into the bargain, allopurinol is regarded as a potent antioxidant that acts through inhibition of xanthine oxidase (XO), which is an essential enzyme of purine metabolism. Herein, the present study aimed to find the potential protective effects of allopurinol on the biomarkers of OS and ED in patients with severe Covid-19. This single-center cohort study recruited 39 patients with mild-moderate Covid-19 compared with 41 patients with severe Covid-19. Nineteen patients with severe Covid-19 were on the allopurinol treatment because of underlying chronic gout 3 years ago compared with 22 Covid-19 patients not on this treatment. The recruited patients were allocated into three groups: group I, mild-moderate Covid-19 on the standard therapy ( n = 39); group II, severe Covid-19 patients on the standard therapy only ( n = 22); and group III, severe Covid-19 patients on the standard therapy plus allopurinol ( n = 19). The duration of the study was 3 weeks from the time of hospitalization till the time of recovery. In addition, inflammatory biomarkers (D-dimer, LDH, ferritin, CRP, procalcitonin), neutrophil–lymphocyte ratio (NLR), endothelin-1 (ET-1), uric acid and oxidative stress index (OSI), CT scan score, and clinical score were evaluated at the time of admission and discharge regarding the effect of allopurinol treatment adds to the standard treatment of Covid-19. Allopurinol plus standard treatment reduced LDH, ferritin, CRP, procalcitonin, and ET-1 serum level significantly ( P < 0.05) compared with Covid-19 patients on standard treatment. Besides, neutrophil (%), lymphocyte (%), and neutrophil–lymphocyte ratio (NLR) were reduced in patients with severe Covid-19 on standard treatment plus allopurinol compared with Covid-19 patients on standard treatment alone ( P < 0.01). OSI was higher in patients with severe Covid-19 than mild-moderate Covid-19 patients ( P = 0.00001) at admission. At the time of discharge, the oxidative status of Covid-19 patients was significantly improved compared with that at admission ( P = 0.01). In conclusion, Covid-19 severity is linked with high OS and inflammatory reaction with ED development. High uric acid in patients with severe Covid-19 is correlated with high OS and inflammatory biomarkers. Allopurinol with standard treatment in patients with severe Covid-19 reduced oxidative and inflammatory disorders with significant amelioration of ED and clinical outcomes.

Section: Discussionmentioning

confidence: 99%

The Prospective Effect of Allopurinol on the Oxidative Stress Index and Endothelial Dysfunction in Covid-19

Al-Niemi³

et al. 2022

Inflammation

Self Cite

“…High NLR is correlated with underlying inflammatory reactions and is an independent risk factor for Covid-19 severity [30] . In SARS-CoV-2 infection, different chemokines and cytokines that act as NTs attractants are elevated primarily in patients with severe Covid-19, suggesting the possible role of the NTs against SARS-CoV-2 [31] . It has been reported that the lungs autopsies of patients with Covid-19 have high NTs infiltrations characterized by neutrophilic mucositis, acute capillaritis, and fibrin deposition with neutrophilic extravasations into the air space [8] .…”

Section: Introductionmentioning

confidence: 99%

Neutrophil Extracellular Traps (NETs) and Covid-19: A new frontiers for therapeutic modality

International Immunopharmacology

Al-Hussaniy³

et al. 2022

Self Cite

136

Coronavirus disease 2019 (Covid-19) is a worldwide infectious disease caused by severe acute respiratory coronavirus 2 (SARS-CoV-2) . In severe SARS-CoV-2 infection, there are severe inflammatory reactions due to neutrophil recruitments and infiltration in the different organs with the formation of neutrophil extracellular traps (NETs), which involved various complications of SARS-CoV-2 infection . Therefore, the objective of the present review was to explore the potential role of NETs in the pathogenesis of SARS-CoV-2 infection and to identify the targeting drugs against NETs in Covid-19 patients. Different enzyme types are involved in the formation of NETs, such as neutrophil elastase (NE), which degrades nuclear protein and release histones, peptidyl arginine deiminase type 4 (PADA4), which releases chromosomal DNA and gasdermin D, which creates pores in the NTs cell membrane that facilitating expulsion of NT contents. Despite of the beneficial effects of NETs in controlling of invading pathogens, sustained formations of NETs during respiratory viral infections are associated with collateral tissue injury. Excessive development of NETs in SARS-CoV-2 infection is linked with the development of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) due to creation of the NETs-IL-1β loop. Also, aberrant NTs activation alone or through NETs formation may augment SARS-CoV-2-induced cytokine storm (CS) and macrophage activation syndrome (MAS) in patients with severe Covid-19. Furthermore, NETs formation in SARS-CoV-2 infection is associated with immuno-thrombosis and the development of ALI/ARDS. Therefore, anti-NETs therapy of natural or synthetic sources may mitigate SARS-CoV-2 infection-induced exaggerated immune response, hyperinflammation, immuno-thrombosis, and other complications.

“…Likewise, Keidar et al ( 2005 ) illustrated that aldosterone antagonist eplerenone improves cardiac contractility through augmentation expression of ACE2, which increase the protective Ang1-7 and reduces harmful AngII (Keidar et al 2005 ). These findings may explain the protective role of ACEIs and ARBs against SARS-CoV-2 infection-induced acute cardiac injury through overexpression of cardiac ACE2 (Al-kuraishy et al 2021d ). Moreover, in HF, chymase activity is increased, leading to elevation of AngII and reduction of Ang 1-7.…”

Section: Covid-19 and Risk Of Heart Failurementioning

confidence: 99%

Covid-19 and development of heart failure: mystery and truth

Onohuean

Naunyn-Schmiedeberg's Arch Pharmacol

et al. 2021

Self Cite

Coronavirus disease 2019 (Covid-19) is a novel worldwide pandemic caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). During Covid-19 pandemic, socioeconomic deprivation, social isolation, and reduced physical activities may induce heart failure (HF), destabilization, and cause more complications. HF appears as a potential hazard due to SARS-CoV-2 infection, chiefly in elderly patients with underlying comorbidities. In reality, the expression of cardiac ACE2 is implicated as a target point for SARS-CoV-2-induced acute cardiac injury. In SARS-CoV-2 infection, like other febrile illnesses, high blood viscosity, exaggerated pro-inflammatory response, multisystem inflammatory syndrome, and endothelial dysfunction-induced coagulation disorders may increase risk of HF development. Hypoxic respiratory failure, as in pulmonary edema, severe acute lung injury (ALI), and acute respiratory distress syndrome (ARDS) may affect heart hemodynamic stability due to the development of pulmonary hypertension. Indeed, Covid-19-induced HF could be through the development of cytokine storm, characterized by high proliferation pro-inflammatory cytokines. In cytokine storm-mediated cardiac dysfunction, there is a positive correlation between levels of pro-inflammatory cytokine and myocarditis-induced acute cardiac injury biomarkers. Therefore, Covid-19-induced HF is more complex and related from a molecular background in releasing pro-inflammatory cytokines to the neuro-metabolic derangements that together affect cardiomyocyte functions and development of HF. Anti-heart failure medications, mainly digoxin and carvedilol, have potent anti-SARS-CoV-2 and anti-inflammatory properties that may mitigate Covid-19 severity and development of HF. In conclusion, SARS-CoV-2 infection may lead to the development of HF due to direct acute cardiac injury or through the development of cytokine storms, which depress cardiomyocyte function and cardiac contractility. Anti-heart failure drugs, mainly digoxin and carvedilol, may attenuate severity of HF by reducing the infectivity of SARS-CoV-2 and prevent the development of cytokine storms in severely affected Covid-19 patients.