Potential harmful effects of discontinuing ACE-inhibitors and ARBs in COVID-19 patients

Abstract

The discovery that SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) binds to the angiotensin converting enzyme (ACE)-2, which is highly expressed in the lower airways, explained why SARS-CoV-2 causes acute respiratory distress syndrome (ARDS) and respiratory failure. After this, the news spread that ACEis and ARBs would be harmful in SARS-CoV-2-infected subjects.To the contrary compelling evidence exists that the ACE-1/angiotensin (Ang) II/ATR-1 pathway is involved in SARS-CoV-2-induced ARDS, while the ACE-2/Ang (1-7)/ATR2/MasR pathway counteracts the harmful actions of AngII in the lung. A reduced ACE-1/ACE-2 ratio is, in fact, a feature of ARDS that can be rescued by human recombinant ACE-2 and Ang (1-7) administration, thus preventing SARS-CoV-2-induced damages to the lung. Based on the current clinical evidence treatment with ACE-inhibitors I (ACEis) or angiotensin receptor blockers (ARBs) continues to provide cardiovascular and renal protection in patients diagnosed with COVID-19. Discontinuing these medications may therefore potentially be harmful in this patients population. COVID19 PandemicsThe pandemic proportions of Covid-19 (Coronavirus Disease 2019) from the SARS (Severe Acute Respiratory Syndrome) Coronavirus 2 (CoV-2) infecting a million and killing 47,266 people worldwide as of April 2, has fueled enormous interest in the mechanisms whereby this new coronavirus causes acute respiratory distress syndrome (ARDS) and multiorgan failure. The estimated 79% infection rate from undocumented cases in Covid-19 patients (Li et al., 2020), and the high lethality of the infections, along with its enormous socio-economic impact, emphasise the importance of fully understanding these mechanisms for developing effective treatment strategies.Early in 2020 reports of the full RNA sequence of the SARS-CoV-2 virus highlighted remarkable similarities with the SARS-CoV virus, which was responsible of an outbreak that killed 774 people in 2003(Xu et al., 2020. As the processes whereby the SARS-CoV virus infects the lung cells were already dissected (Kuba et al., 2005), and it was held that SARS-CoV-2 uses identical mechanisms, these discoveries allowed an unprecedented acceleration of knowledge.

Diabetes mellitus is associated with increased mortality and severity of disease in COVID-19 pneumonia – A systematic review, meta-analysis, and meta-regression

“…[37,39,40] This enzyme acts by counteracting the inflammatory actions of angiotensin II, lowering the concentration of pro-inflammatory cytokine interleukin (IL)-6, increasing the anti-inflammatory, and increasing the antioxidant action of angiotensin 1-7, escalating the levels of surfactant protein D and promoting vasodilation. [41] The novel coronavirus responsible for COVID-19 is expected to act similary to Severe Acute Respiratory Syndrome (SARS-CoV). Both utilize ACE2 to bind and gain entry to the host pneumocytes.…”

Hypertension is associated with increased mortality and severity of disease in COVID-19 pneumonia: A systematic review, meta-analysis and meta-regression

“…40,41 Thus, the presence of ACE2 neutralizes the inflammatory effects of angiotensin II, reduces the levels of proinflammatory cytokine interleukin-6, enhances the anti-inflammatory and antioxidant roles of angiotensin 1-7, increases the concentration of alveolar surfactant protein D and triggers vasodilation. 42,43 It is likely that novel coronavirus responsible for COVID-19 worked through a similar pathway as the coronavirus that caused SARS-CoV, where they use ACE2 on the surfaces of epithelial cells as a receptor to attach and enter the host pneumocytes. [40][41][42] Viral surface spike (S) protein of COVID-19 binds to ACE2 receptor following the spike protein activation by transmembrane protease serine 2 (TMPRSS2).…”

COVID-19: Coronavirus replication, pathogenesis, and therapeutic strategies

“…The fi nding that ACE2 is a primary SARS-CoV-2 receptor has further led to extensive discussion of dysregulation of the renin-angiotensin system, which regulates blood pressure and electrolyte balance. [33][34][35] Conversion of angiotensin I to angiotensin II by angiotensinconverting enzyme (ACE) activates pathways During coevolution with their hosts, viruses have learned to counteract the interferon antiviral response on June 9, 2020. For personal use only.…”

“…Nevertheless, current recommendations are to continue treatment. 34,35 The complexity of the renin-angiotensin system will require more extensive retrospective analysis of larger and ethnically diverse patient groups.…”