COVID‐19 and renin angiotensin aldosterone system: Pathogenesis and therapy

Abstract

Aims The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) binds to the ACE2 component of the renin‐angiotensin aldosterone system (RAAS) and infects the human cells. The aims of the present review were to look at the role and alteration of the RAAS components in SARS‐CoV‐2 infection, therapeutic approaches, and clinical trials in this field. Methods We surveyed the literature (PubMed, Web of Science, and Scopus) till August 18, 2021, and 59 published papers regarding the components of the RAAS and their role and alterations in SARS‐CoV‐2 infection along with various COVID‐19 therapies based on the RASS components were included in the study. Results ACE inhibitors, angiotensin receptor blockers, and mineralocorticoid receptor inhibitors are agents that significantly enhance the ACE2 and Ang‐(1‐7) levels, which can be suggestive for their role as therapeutics against SARS‐CoV‐2 infection. Beta‐adrenergic blockers, which negatively regulate renin release from juxtaglomerular cells, and vitamin D, as a regulator of the RAAS and renin expression, are proposed therapeutics in the treatment of COVID‐19. Some antihyperglycemic agents could be potentially protective against COVID‐19‐induced lung injury. Also, the inhibition of the Janus kinase/signal transducer and activator of the transcription pathway as a potential treatment for COVID‐19 has been suggested. Finally, resveratrol, an antioxidant that can suppress Ang II, has been suggested as an adjunct to other therapies. Conclusion Regarding the suggested potential therapies for COVID‐19, there are many clinical trials whose results might change the treatment strategies of SARS‐CoV‐2 infection. So, the results of well‐organized clinical trials on the efficacy and safety of the mentioned agents in the treatment of COVID‐19 will be useful in the management and therapy of the disease.

The comparison of the mortality rates of plasmapheresis/hemoperfusion therapy with current treatment among Covid-19 patients

“…Cytokine storm is one of the most important events in COVID-19, which could lead to multi-organ failure, ARDS, and eventually death. It is believed that strategies to remove the pro-inflammatory mediators from the circulation, including TPE and HP, could prevent disease progression and decrease mortality [ 17 ]. Studies on the effectiveness of TPE and HP in COVID-19 patients are scarce [ 18 ].…”

Vitamin D and estrogen steroid hormones and their immunogenetic roles in Infectious respiratory (TB and COVID-19) diseases

“…Thus, when RAAS dysregulation occurs, the classical axis presents excessive activity when compared to the alternative axis. Generally, individuals with systemic arterial hypertension, heart failure or other comorbidity use medications such as ACE inhibitors (iACE) and angiotensin receptor blockers (ARBs), which promote higher ACE2 production ( de Kloet et al ., 2010 ; Babajani et al ., 2021 ). ACE is the gateway to SARS-CoV-2 through its S protein, competing with Ang-II blocking ACE2 activity, promoting vasoconstriction and endothelial dysfunction.…”

“…VD 3 acts inhibiting the expression of ACE and stimulating the alternative axis activity, while negatively regulating the classical axis ( Babajani et al ., 2021 ). Even if there is greater expression of ACE2, this hormone reduces the entry and replication of viruses, including SARS-CoV-2 , through previously mentioned mechanisms.…”

Does Oxidative Stress Management Help Alleviation of COVID-19 Symptoms in Patients Experiencing Diabetes?

“…Another clinical trial showed no effect of a flavonoid against placebo over a 12-week combined treatment of isoquercetin (225 mg once daily) and sodium nitrite (40 mg twice daily) in CKD patients (n = 35 per group) [111]. Noticeably, an antioxidant such as resveratrol (a stilbenoid compound) caused suppression of angiotensin-2 that may be used as an adjunct therapy to COVID-19 [112,113]. It seems that not all antioxidants are effective in preventing oxidative stress.…”