RAAS inhibitors are associated with a better chance of surviving of inpatients with Covid-19 without a diagnosis of diabetes mellitus, compared with similar patients who did not require antihypertensive therapy or were treated with other antihypertensives.

Purpose: The effect of renin-angiotensin-aldosterone system (RAAS) inhibitors in combination with COVID-19 and diabetes mellitus (DM) remains unknown. We assessed the risk of death in COVID-19 inpatients based on the presence or absence of DM, arterial hypertension (AH) and the use of RAAS inhibitors or other antihypertensives. Methods: The results of treatment of all adult PCR-confirmed COVID-19 inpatients (n = 1097, women 63.9%) from 02/12/2020 to 07/01/2022 are presented. The presence of DM at the time of admission and the category of antihypertensive drugs during hospital stay were noted. Leaving the hospital due to recovery or death was considered as a treatment outcome. Multivariable logistic regression analysis was used to assess the risk of death. Patients with COVID-19 without AH were considered the reference group. Results: DM was known in 150 of 1,097 patients with COVID-19 (13.7%). Mortality among DM inpatients was higher: 20.0% vs. 12.4% respectively (p=0.014). Male gender, age, fasting plasma glucose (FPG) and antihypertensives were independently associated with the risk of dying in patients without DM. In DM group such independent association was confirmed for FPG and treatment of AH. We found a reduction in the risk of death for COVID-19 inpatients without DM, who received RAAS inhibitors compared with the corresponding risk of normotensive inpatients, who did not receive antihypertensives: OR 0.22 (95% CI 0.07-0.72) adjusted for age, gender and FPG. Conclusion: This result raises a question about the study of RAAS inhibitors effect in patients with Covid-19 without AH.

Actions of Novel Angiotensin Receptor Blocking Drugs, Bisartans, Relevant for COVID-19 Therapy: Biased Agonism at Angiotensin Receptors and the Beneficial Effects of Neprilysin in the Renin Angiotensin System.

Angiotensin receptor blockers (ARBs) used in the treatment of hypertension and potentially in SARS-CoV-2 infection exhibit inverse agonist effects at angiotensin AR1 receptors, suggesting the receptor may have evolved to accommodate naturally occurring angiotensin 'antipeptides'. Screening of the human genome has identified a peptide (EGVYVHPV) encoded by mRNA, complementary to that encoding ANG II itself, which is an inverse agonist. Thus, opposite strands of DNA encode peptides with opposite effects at AR1 receptors. Agonism and inverse agonism at AR1 receptors can be explained by a receptor 'switching' between an activated state invoking receptor dimerization/G protein coupling and an inverse agonist state mediated by an alternative/second messenger that is slow to reverse. Both receptor states appear to be driven by the formation of the ANG II charge-relay system involving TyrOH-His/imidazole-Carboxylate (analogous to serine proteases). In this system, tyrosinate species formed are essential for activating AT1 and AT2 receptors. ANGII is also known to bind to the zinc-coordinated metalloprotease angiotensin converting enzyme 2 (ACE2) used by the COVID-19 virus to enter cells. Here we report in silico results demonstrating the binding of a new class of anionic biphenyl-tetrazole sartans ('Bisartans') to the active site zinc atom of the endopeptidase Neprilysin (NEP) involved in regulating hypertension, by modulating humoral levels of beneficial vasoactive peptides in the RAS such as vasodilator angiotensin (1-7). In vivo and modeling evidence further suggest Bisartans can inhibit ANG II-induced pulmonary edema and may be useful in combatting SARS-CoV-2 infection by inhibiting ACE2-mediated viral entry to cells.

Association of Hypertension with All-Cause Mortality among Hospitalized Patients with COVID-19.

It is unclear to which extent the higher mortality associated with hypertension in the coronavirus disease (COVID-19) is due to its increased prevalence among older patients or to specific mechanisms. Cross-sectional, observational, retrospective multicenter study, analyzing 12226 patients who required hospital admission in 150 Spanish centers included in the nationwide SEMI-COVID-19 Network. We compared the clinical characteristics of survivors versus non-survivors. The mean age of the study population was 67.5 ± 16.1 years, 42.6% were women. Overall, 2630 (21.5%) subjects died. The most common comorbidity was hypertension (50.9%) followed by diabetes (19.1%), and atrial fibrillation (11.2%). Multivariate analysis showed that after adjusting for gender (males, OR: 1.5, p = 0.0001), age tertiles (second and third tertiles, OR: 2.0 and 4.7, p = 0.0001), and Charlson Comorbidity Index scores (second and third tertiles, OR: 4.7 and 8.1, p = 0.0001), hypertension was significantly predictive of all-cause mortality when this comorbidity was treated with angiotensin-converting enzyme inhibitors (ACEIs) (OR: 1.6, p = 0.002) or other than renin-angiotensin-aldosterone blockers (OR: 1.3, p = 0.001) or angiotensin II receptor blockers (ARBs) (OR: 1.2, p = 0.035). The preexisting condition of hypertension had an independent prognostic value for all-cause mortality in patients with COVID-19 who required hospitalization. ARBs showed a lower risk of lethality in hypertensive patients than other antihypertensive drugs.

COVID-19 in a Patient with ß-Thalassemia Major and Severe Pulmonary Arterial Hypertension.

We here report the successful recovery from coronavirus disease-19 (COVID-19) pneumonia in a patient with ß-thalassemia major (ß-TM) and severe pulmonary arterial hypertension (PAH), focusing on the patient's comorbidities, therapeutic course and drug interaction.