The infectious power of coronaviruses is dependent on cholesterol present in the membranes of their target cells. Indeed, the virus enters the infected cell either by fusion or by endocytosis, in both cases involving cholesterol-enriched membrane microdomains. These membrane domains can be disorganized in-vitro by various cholesterol-altering agents, including statins that inhibit cell cholesterol biosynthesis. As a consequence, numerous cell physiology processes, such as signaling cascades, can be compromised. Also, some examples of anti-bacterial and anti-viral effects of statins have been observed for infectious agents known to be cholesterol dependent. In-vivo , besides their widely-reported hypocholesterolemic effect, statins display various pleiotropic effects mediated, at least partially, by perturbation of membrane microdomains as a consequence of the alteration of endogenous cholesterol synthesis. It should thus be worth considering a high, but clinically well-tolerated, dose of statin to treat Covid-19 patients, in the early phase of infection, to inhibit virus entry into the target cells, in order to control the viral charge and hence avoid severe clinical complications. Based on its efficacy and favorable biodisposition, an option would be considering Atorvastatin, but randomized controlled clinical trials are required to test this hypothesis. This new therapeutic proposal takes benefit from being a drug repurposing, applied to a widely-used drug presenting a high efficiency-to-toxicity ratio. Additionally, this therapeutic strategy avoids any risk of drug resistance by viral mutation since it is host-targeted. Noteworthy, the same pharmacological approach could also be proposed to address different animal coronavirus endemic infections that are responsible for heavy economic losses.

Despite a similar beneficial effect on blood-pressure lowering observed with ACEIs and ARBs, several clinical trials and meta-analyses have reported higher cardiovascular mortality and lower protection against myocardial infarction with ARBs when compared to ACEIs. The European guidelines for the management of coronary syndromes and European guidelines on diabetes recommend using ARBs in patients who are intolerant to ACEIs. We reviewed the main pharmacological differences between ACEIs and ARBs which could provide insights into the differences in the cardiac protection offered by these two drug classes. The effect of ACEIs on the tissue and plasma levels of bradykinin and on nitric oxide production and bioavailability is specific to the mechanism of action of ACEIs; it could account for the different effects of ACEIs and ARBs on endothelial function, atherogenesis and fibrinolysis. Moreover, chronic blockade of AT1 receptors by ARBs induces a significant and permanent increase in plasma angiotensin II and an over-stimulation of its still available receptors. In animal models, AT4 receptors have vasoconstrictive, proliferative and inflammatory effects. Moreover, in models with kidney damage, atherosclerosis, and/or senescence, activation of AT2 receptors could have deleterious fibrotic, vasoconstrictive and hypertrophic effects. seems prudent and reasonable to reserve the use of ARBs for patients who have presented an intolerance to ACE inhibitors.

Objective: Orthostatic hypotension (OH) is a common disease in the elderly, associated with an increased risk of falls and cardiovascular morbi-mortality. Its reproducibility in clinical setting is low. A recent, single-center study has shown the feasibility of home blood pressure monitoring (HBPM) for the detection of OH in subjects older than 65 years referred for a memory complaint, and reported a prevalence of 12% and 42% of HO in the office and ambulatory settings respectively. The prevalence of masked OH detected with HBPM in treated hypertensive elderly subjects is still not known. Design and method: 42 hypertensive patients older than 65 years without office OH were included in 8 specialized hypertension centers. Their treatment has not been changed for at least 1 month. An ambulatory OH was sought according to the following protocol: 3 measurements in sitting position at 1 minute intervals after 5 min of rest, followed by 3 measurements in standing position at 1 minute intervals, every morning and evening for 3 consecutive days, recorded by an automated device with humeral cuff. HBPM was considered valid if more than 4 out of 6 series of measurements were completed. Ambulatory OH was defined as a fall of more than 20mmHg in SBP between one of the 3 measurements in orthostatism compared to the average of the 3 measurements taken while sitting. Results: 100% of HBPM sessions were considered valid. The main characteristics of the patients were: 72 ± 6 years, 39% women, SBP/ DBP: 149 ± 20/82 ± 10 mmHg, 2.4 ± 0.9 antihypertensive drugs, 9.3% history of falls. 20 (47.6%) included patients had a masked OH according to the protocol detailed above, with an average of 2 ± 1.2 episodes and a maximum of 5 episodes. 86% of patients had at least one episode in the morning, and 57% in the evening. In multivariate analysis, no factor identified in the study was significantly associated with the existence of a masked OH. Conclusions: OH detection with HBPM in treated hypertensive elderly subjects is feasible and reveals a significant prevalence of masked OH. Prospective studies are needed to clarify the prognostic value of masked OH.

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