The Crosstalk between SARS-CoV-2 Infection and the RAA System in Essential Hypertension-Analyses Using Systems Approach.

Dorota Formanowicz,Piotr Formanowicz,Bartłomiej Szawulak,Kaja Gutowska

doi:10.3390/ijms221910518

Abstract

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), responsible for the coronavirus disease of 2019 (COVID-19) pandemic, has affected and continues to affect millions of people across the world. Patients with essential arterial hypertension and renal complications are at particular risk of the fatal course of this infection. In our study, we have modeled the selected processes in a patient with essential hypertension and chronic kidney disease (CKD) suffering from COVID-19, emphasizing the function of the renin-angiotensin-aldosterone (RAA) system. The model has been built in the language of Petri nets theory. Using the systems approach, we have analyzed how COVID-19 may affect the studied organism, and we have checked whether the administration of selected anti-hypertensive drugs (angiotensin-converting enzyme inhibitors (ACEIs) and/or angiotensin receptor blockers (ARBs)) may impact the severity of the infection. Besides, we have assessed whether these drugs effectively lower blood pressure in the case of SARS-CoV-2 infection affecting essential hypertensive patients. Our research has shown that neither the ACEIs nor the ARBs worsens the course infection. However, when assessing the treatment of hypertension in the active SARS-CoV-2 infection, we have observed that ARBs might not effectively reduce blood pressure; they may even have the slightly opposite effect. On the other hand, we have confirmed the effectiveness of arterial hypertension treatment in patients receiving ACEIs. Moreover, we have found that the simultaneous use of ARBs and ACEIs averages the effects of taking both drugs, thus leading to only a slight decrease in blood pressure. We are a way from suggesting that ARBs in all hypertensive patients with COVID-19 are ineffective, but we have shown that research in this area should still be continued.

Highlights

Since essential hypertension is inherent in the development of cardiovascular diseases and advanced chronic kidney disease (CKD) is associated with an increased risk of severe COVID-19, optimal treatment/management of hypertension can contribute to a better prognosis of the SARSCoV-2 infection
Our systems studies have been mainly focused on analyzing the relationship between taking medications for essential hypertension and the coexistence of COVID-19 disease
We have found that taking antihypertensive medications, such as angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, does not enhance the development of SARS-CoV-2 infection

Summary

Introduction

SARS-CoV-2, responsible for COVID-19, has almost stopped the world [1,2,3,4,5]. For over a year, intensive research has been underway to understand the mechanisms of SARS-CoV-2 action and to find an effective treatment for it. Despite many peoples’ efforts, there is still no efficient antiviral therapy for SARS-CoV-2 infection, which frequently leads to fatal inflammatory responses and acute lung injury. SARS-CoV-2 turns out to be a “cunning criminal,” which binds to the membrane receptor—angiotensin converting enzyme 2 (ACE2)—and enters human cells. The ACE2 is the entry for SARS-CoV2, it plays an important counter-regulatory role in the RAA system, promoting systemic vasodilatory and anti-inflammatory effects [6,7]

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Results

Discussion

Conclusion