Hypertension, a Moving Target in COVID-19

Abstract

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) associates with a considerable high rate of mortality and represents currently the most important concern in global health. The risk of more severe clinical manifestation of COVID-19 is higher in males and steeply raised with age but also increased by the presence of chronic comorbidities. Among the latter, early reports suggested that arterial hypertension associates with higher susceptibility to SARS-CoV-2 infection, more severe course and increased COVID-19–related deaths. Furthermore, experimental studies suggested that key pathophysiological hypertension mechanisms, such as activation of the renin-angiotensin system (RAS), may play a role in COVID-19. In fact, ACE2 (angiotensin-converting-enzyme 2) is the pivotal receptor for SARS-CoV-2 to enter host cells and provides thus a link between COVID-19 and RAS. It was thus anticipated that drugs modulating the RAS including an upregulation of ACE2 may increase the risk for infection with SARS-CoV-2 and poorer outcomes in COVID-19. Since the use of RAS-blockers, ACE inhibitors or angiotensin receptor blockers, represents the backbone of recommended antihypertensive therapy and intense debate about their use in the COVID-19 pandemic has developed. Currently, a direct role of hypertension, independent of age and other comorbidities, as a risk factor for the SARS-COV-2 infection and COVID-19 outcome, particularly death, has not been established. Similarly, both current experimental and clinical studies do not support an unfavorable effect of RAS-blockers or other classes of first line blood pressure lowering drugs in COVID-19. Here, we review available data on the role of hypertension and its management on COVID-19. Conversely, some aspects as to how the COVID-19 affects hypertension management and impacts on future developments are also briefly discussed. COVID-19 has and continues to proof the critical importance of hypertension research to address questions that are important for global health.

Expression Profiles of Plasma IFN Signaling-Related miRNAs (ISR-miRNAs) at the Acute and Recovery Phase of COVID-19

“…Moreover, to understand the questions behind the observed associations, the role of ISR-miRNAs involved in the pathogenesis of COVID-19 should be investigated in both in vivo and in vitro studies. Finally, since the disease progression and antibody response might be in uenced by various risk factors (age, comorbidity disease such as hypertension and diabetes) [32][33][34], the effects of the ISR-miRNAs and interactions of other risk factors on SARS-CoV-2 infection should also be carefully veri ed in the future.…”

Role of the Renin–Angiotensin–Aldosterone and Kinin–Kallikrein Systems in the Cardiovascular Complications of COVID-19 and Long COVID

“…Fortunately, patients with controlled hypertension have shown improved outcomes following SARS-CoV-2 infection in comparison to those with uncontrolled hypertension [ 142 ]. In many cases, the use of ACEi and angiotensin receptor blockers (ARBs) effectively re-establish RAAS homeostasis by reducing Ang II pathophysiological signalling and unsurprisingly, these mechanisms may reduce the progression of severe COVID-19 [ 40 ].…”

“…These hypotheses suggested that ACEi and ARBs could potentiate SARS-CoV-2 infection. This argument was based on evidence of ACEi and ARBs increasing ACE2 expression [ 32 , 142 ]. It has been suggested that an abundance of alveolar ACE2 might facilitate increased SARS-CoV-2 cellular entry and viral replication.…”

“…It has been suggested that an abundance of alveolar ACE2 might facilitate increased SARS-CoV-2 cellular entry and viral replication. This would increase viral load and therefore COVID-19 severity [ 142 , 143 ]. In contrast to this, studies have shown that high levels of ACE2 expressing cells, particularly in children, can mediate protective effects against COVID-19 [ 28 ].…”

“…Interestingly, the study by Pedrosa et al (2021) also showed that treatment with candesartan or captopril could prevent the depletion of ACE2 induced by S protein [32]. Withdrawal of ACEi and ARB treatment can result in a complete reversal of antihypertensive and cardio-protective effects in patients with heart failure and reduced ejection fraction [142,144] and so withdrawal of RAAS is clearly not recommended. A recent meta-analysis in animal models of human disease confirmed that ACE2 overexpression as a consequence of inhibition of the RAAS was rare [145].…”