Statins and Covid-19: The Neglected Front of bidirectional effects

Covid-19 is caused by a novel coronavirus named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 binds angiotensin converting enzyme 2 (ACE2), which is greatly expressed in different tissues including lung alveolar type II cells. Infection with SARS-CoV-2 triggers acute host immune response, inflammatory reactions and cytokine storm leading to acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Different studies reported the pleiotropic effects of statins such as the anti-inflammatory and immune-modulatory effects via modulation of antigen presentation and adhesion of inflammatory molecules since;statins have potential anti-oxidant and redox balance effects that improve endothelial dysfunction and cardiovascular integrity. Objective of the present study is to verify the beneficial and harmful effects of statins in Covid-19. Statins upregulates ACE2 receptors and attenuates the down-regulation effect of SARS-CoV-2 on the ACE2 receptors. Consequently, reduction of ACE2 receptors augment the deleterious effect of angiotensin II (AngII) which causes vasoconstriction and initiation of ALI. On the other hand, statins therapy may increase risk of viral infections such as SARS-CoV-2 via lowering of low density lipoprotein (LDL) since;circulating LDL adhere and inactivates SARS-CoV-2. Statin therapy improves the outcomes of Covid-19 pneumonia through anti-inflammatory, immune-modulation, and in vitro anti-SARS-CoV-2 effects. The antiplatelet and antithrombotic effects may reduce Covid-19 induced-coagulopathy and progression of ARDS.

Pregnancy and risk of vertical transmission in Covid-19

Objectives: The current systematic review was planned to illustrate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections during pregnancy and to explore pregnancy outcomes, vertical and perinatal transmission as well as management of coronavirus disease-2019 (Covid-19) during pregnancy. Methods: The multidisciplinary systematic review was conducted at the Department of Clinical Pharmacology and Therapeutic Medicine, Al-Mustansiriyah University, Bagdad, Iraq. The literature search was conducted in September 2021 and included databases as Medline, PubMed, Scopus, Web of Science, Cochrane Central Register of Controlled Trials and Science Direct databases related to articles on pregnancy and SARS-CoV-2 infections, published between December 2019 and July 2021. Results: Of the 30 articles reviewed, 12(40%) were included. Major reasons for including a small number of studies in systematic review were that majority of the studies had insufficient description of study;analysis was duplicate across various publications, and inadequate explanation of impact of SARA-CoV-2 infection on the pregnancy outcomes. This review included 12 studies based on the assessment and estimation of risk of bias and quality of the eligible studies. Conclusions: Findings revealed that pregnant women were predominantly susceptible to the respiratory viral infection and severe pneumonia due to physiological immune-suppression, immune adaptation and pregnancy-induced changes. The clinical presentation and management of pregnant women with Covid-19 is similar to that of non-pregnant women and there is no strong clinical evidence of vertical transmission. Also, only chloroquine and remdesivir have been found to be effective in the treatment of Covid-19 during pregnancy.

Colchicine in the management of Covid-19: With or lieu of evidence

Coronavirus disease 2019 (Covid-19), leads to global calamitous effects. Covid-19 is caused by a novel coronavirus named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Covid-19 is associated with development of hyper-inflammation and/or cytokine storm that together with high viral load trigger tissue damage and multi-organ failures (MOF). Colchicine (CN) is a lipophilic tricyclic alkaloid used for treatment of gout since ancient time. In Covid-19 era, CN is repurposed for treatment of SARS-CoV-2 infection depending on its anti-inflammatory and broad-spectrum antiviral effects. Therefore, a recent clinical trial recommends use of CN in treating Covid-19 patients. It has been confirmed that inhibition of neutrophil chemotaxis, lysosomal degranulation, and release of pro-inflammatory cytokines is the main mechanism by which CN produces anti-inflammatory effects. CN attenuates generation of free radicals and reactive oxygen species (ROS) with consequent inhibition release of pro-inflammatory cytokines. Different studies illustrate that microtubule network is necessary and important for replication of different viruses including SARS-CoV-2 since;intracellular transport of viral particles is mediated through cytosolic microtubules. Therefore, CN therapy is effective in the management of Covid-19 patients when timely administrated through reduction of tissue damage and hyper-inflammations. Thus, the anti-inflammatory, antiviral, and immunomodulatory properties of CN might be the potential mechanisms of CN therapy against Covid-19. The review concludes that CN is a potent anti-inflammatory agent for the management of Covid-19;it inhibits SARS-CoV-2-induced-acute lung injury(ALI) due to its anti-inflammatory and anti-viral effects.

Anti-histamines and Covid-19: Hype or Hope

Histamine is a biogenic amine distributed extensively in the human cells. Histamine is linked with different inflammatory and allergic disorders through promoting of chemoatractant activity and endothelial changes. Antihistamine drugs are effective in the treatment and prevention of infection of influenza H7N9 through inhibition of viral entry to the host cells. A multiplicity of search strategies including experimental, preclinical and clinical studies were taken on and assumed to review the potential role of H1, H2 or their combination in the management of Coronavirus disease 2019 (Covid-19). Histamine release is associated with early and late pathology of Covid-19 and clinical presentation. Despite the potential effect of famotidine in attenuating the pathogenesis of Covid-19, famotidine has no direct effect on the replication of SARS-CoV-2. However, azelastine (H1receptor blocker) used for allergic rhinitis as nasal spray has potential anti-SARS-CoV-2 activity comparable to that of remdesivir, lopinavir and chloroquine. Azelastine is more effective than other agents that are used in the management of Covid-19 due to significant inhibition of endosomal acidification at respiratory epithelial cells. However, famotidine and cetirizine combination improve clinical outcome and reduce intubation and duration of hospitalization in Covid-19 patients. Taken together, hospitalised Covid-19 patients treated with famotidine only showed more complications as compared with those treated with combination of famotidine and cetirizine. Conclusion: Both H1 and H2 blockade are effective in the management of Covid-19 patients through antiviral and anti-inflammatory properties, which together reduce the risk of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS).

Misfortune and spy story in the neurological manifestations of Covid-19

Covid-19 is associated with different neurological manifestations. About one third of Covid-19 patients have some neurological disorders as paresthesia, headache, cold extremities and disturbances of consciousness, which are more evident in severely affected patients. These neurological manifestations may coexist or precede the onset of respiratory manifestations by about 2-3 weeks. Acute ischaemic stroke (AIS) and associated brain damage may develop due to acute respiratory distress syndrome (ARDS) induced-hypoxia. Prolonged hypoxia in late-stage Covid-19 leads to vasodilatation, intracranial hypertension, brain oedema, and AIS. In view of substantial evidence, this perspective explores the potentially direct or indirect effect of SARS-CoV-2 on the Central Nervous System of patients with COVID-19 pneumonia. The AIS is the end of most Covid-19-induced neurological complications. Covid-19 can lead to various neurological manifestations due to involvement of CNS directly through olfactory neurons or indirectly through induction of cytokine storm.