SARS-CoV-2 induced HDL dysfunction may affect the host's response to and recovery from COVID-19.

INTRODUCTION: Covid-19 is linked with the development of cardio-metabolic disorders, including dyslipidemia, dysregulation of high-density lipoprotein (HDL), and low-density lipoprotein (LDL). Furthermore, SARS-Co-2 infection is associated with noteworthy changes in lipid profile, which is suggested as a possible biomarker to support the diagnosis and management of Covid-19. METHODS: This paper adopts the literature review method to obtain information about how Covid-19 affects high-risk group patients and may cause severe and critical effects due to the development of acute lung injury and acute respiratory distress syndrome. A narrative and comprehensive review is presented. RESULTS: Reducing HDL in Covid-19 is connected to the disease severity and poor clinical outcomes, suggesting that high HDL serum levels could benefit Covid-19. SARS-CoV-2 binds HDL, and this complex is attached to the co-localized receptors, facilitating viral entry. Therefore, SARS-CoV-2 infection may induce the development of dysfunctional HDL through different mechanisms, including induction of inflammatory and oxidative stress with activation of inflammatory signaling pathways. In turn, the induction of dysfunctional HDL induces the activation of inflammatory signaling pathways and oxidative stress, increasing Covid-19 severity. CONCLUSIONS: Covid-19 is linked with the development of cardio-metabolic disorders, including dyslipidemia in general and dysregulation of high-density lipoprotein and low-density lipoprotein. Therefore, the present study aimed to overview the causal relationship between dysfunctional high-density lipoprotein and Covid-19.

Calprotectin: The Link Between Acute Lung Injury and Gastrointestinal Injury in Covid-19: Ban or Boon.

The pathogenesis of SARS-CoV-2 infection is related to the direct cytopathic effect and associated hyper-inflammation due to exaggerated immune response. Different experimental and clinical studies revealed that many biomarkers could be used to determine the Covid-19 severity, such as Ddimer, procalcitonin, C-reaction protein (CRP), IL-6, and ferritin. Calprotectin (CP) is associated with intestinal inflammation, intestinal injury, and different respiratory diseases such as cystic fibrosis. Thus, CP might be a possible biomarker linking intestinal injury and acute lung injury (ALI) in Covid-19. Therefore, this study aimed to find a potential role of CP regarding GITI and ALI in Covid-19. CP is a complex protein consisting of S100A8 and S100A9, belonging to the Ca+2-binding proteins S100 family abundant in the cytosol of neutrophils and expressed on the monocyte membranes, macrophages, and intestinal epithelial cells. CP is a proinflammatory protein that acts through activation of the receptor for the advanced glycation end product (RAGE) and toll-like receptor 4 (TLR4). CP is a biomarker of neutrophil activation and is released following the turnover of neutrophils. CP could be controversial; it increases airway inflammation or protects lung and airway epithelium from an exaggerated immune response. Therefore, a high level of CP in different respiratory disorders might be protective and compensate against abnormal immune responses. CP level is high in Covid-19 and correlated with Covid-19 severity and oxygen demand due to activation of proinflammatory cytokines and inflammatory signaling pathways. Therefore, CP level is elevated in both ALI and intestinal inflammation so that it could be a potential biomarker that links the respiratory and intestinal injury in Covid-19.

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

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.

Involvement of orexinergic system in psychiatric and neurodegenerative disorders: A scoping review.

Orexin is a neuropeptide secreted from lateral hypothalamus and pre-frontal cortex concerned in the wakefulness and excitement. This study aimed to review the possible neurobiological effect of orexin. A diversity of search strategies was adopted and assumed which included electronic database searches of Medline and PubMed using MeSH terms, keywords, and title words during the search. Orexin plays a vital role in activation of learning, memory acquisition, and consolidation through activation of monoaminergic system, which affect cognitive flexibility and cognitive function. Orexin stimulates adrenocorticotropin and corticosteroid secretions via activation of central corticotropin-releasing hormone. Cerebrospinal fluid (CSF) and serum orexin serum levels are reduced in depression, schizophrenia, and narcolepsy. However, high orexin serum levels are revealed in drug addictions. Regarding neurodegenerative brain diseases, CSF and serum orexin serum levels are reduced Parkinson disease, Alzheimer dementia, Huntington's disease, amyotrphic lateral sclerosis, and multiple sclerosis. Orexin antagonist leads to significant reduction of sympathetic over-activity during withdrawal syndrome. As well, orexin antagonist improves sleep pattern. Orexinergic system is involved in the different psychiatric and neurological disorders; therefore, targeting of this system could be possible novel pathway in the management of these disorders. In addition, measurement of CSF and serum orexin levels might predict the relapse and withdrawal of addict patients.

COVID-19 and Phosphodiesterase Enzyme Type 5 Inhibitors.

COVID-19 pathology is mainly associated to a pulmonary disease which sometimes might result in an uncontrollable storm related to inflammatory diseases which could be fatal. It is well known that phosphodiesterase enzyme type 5 inhibitors (PDE5Is), such as sildenafil, have been successfully developed for the treatment of pulmonary arterial hypertension; interestingly, more recently, it was shown that PDE5Is might be also anti-inflammatory. Therefore, it would be of interest to question about the use of PDE5Is to overcome the COVID-19 storm, as much as PDE5 is mainly present in the lung tissues and vessels.