key: cord-263123-5y8cc5eb authors: Bian, Jingwei; Zhao, Rongsheng; Zhai, Suodi; Li, Zijian title: Anti-RAS drugs and SARS-CoV-2 infection date: 2020-04-28 journal: Acta Pharm Sin B DOI: 10.1016/j.apsb.2020.04.013 sha: doc_id: 263123 cord_uid: 5y8cc5eb • There is no enough evidence to indicate that ACEIs and ARBs result in ACE2 upregulation. • The level of ACE2 expression is not completely related with the risk of COVID-19 infection. • There is currently no evidence that ACEI/ARB increase risk for COVID-19 infection from clinical trials. • It is not recommended that COVID-19 patients with hypertension or normal hypertensive patients at risk for exposure to stop using ACEI/ARB or change to other antihypertensive drugs. To the Editor: Corona virus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly throughout the world. It has already posed a great threat to global public health security. Angiotensin-converting enzyme 2 (ACE2) has been identified as the major receptor of SARS-CoV-2. In addition, ACE2 is well-known as a counter-regulator of the renin-angiotensin system (RAS) and plays a key role in cardiovascular disease, especially Here, we present a completely different perspective on the relationship between SARS-CoV-2 infection and ACEI/ARB drugs. Firstly, there is no sufficient evidence to support that ACEIs and ARBs can upregulate the protein expression level of ACE2. Indeed, some studies have shown that the mRNA level of ACE2 can be increased by both ACEIs and ARBs, such as lisinopril (ACEI) and losartan (ARB) 3 . However, as we know, the change of protein levels is not always consistent with the mRNA levels, sometimes even in the opposite direction. So far, it is still inconclusive whether ACEIs and ARBs would increase ACE2 expression at the protein level. For example, ramipril (ACEI) was found to decrease ACE2 protein expression 4 . Besides, no changes in ACE2 protein expression was observed after the treatment of olmesartan (ARB) 5 . Therefore, there is no adequate evidence to support that ACEIs/ARBs increase the risk of the SARS-CoV-2 infection by up-regulating ACE2 protein level. reported that ACE2 expression is higher in ileum than that in lung, but the ileum is not at higher risk of SARS-CoV-2 infection than the lung, suggesting other complicated mechanisms might be involved in virus infection. The possible mechanisms include other receptors, co-receptors or some unknown regulatory mechanism. Recently, angiotensin II type 2 receptor (AT2R), a G-protein coupled receptor, has been identified as one of the receptors for SARS-CoV-2, as well as the transmembrane glycoprotein CD147 6, 7 . In addition, liver/lymph node-specific and dendritic In summary, there is currently no clear evidence indicating that anti-RAS drugs (ACEIs and ARBs) increase the risk of SARS-CoV-2 infection, as well as target organ injury. There is still no need to recommend the discontinuation of ACEIs/ARBs for hypertensive patients with or at high risk of SARS-CoV-2 infection, or the change to other antihypertensive drugs. Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? Hypothesis: angiotensin-converting enzyme inhibitors and angiotensin receptor blockers may increase the risk of severe COVID-19 Effect of angiotensin-converting enzyme inhibition and angiotensin II receptor blockers on cardiac angiotensin-converting enzyme 2 Combination renin-angiotensin system blockade and angiotensin-converting enzyme 2 in experimental myocardial infarction: implications for future therapeutic directions Increased expression of angiotensin converting enzyme 2 in conjunction with reduction of neointima by angiotensin II type 1 receptor blockade AGTR2, one possible novel key gene for the entry of 2019-nCoV into human cells SARS-CoV-2 invades host cells via a novel route: CD147-spike protein. bioRxiv preprint 2020 CD209L (L-SIGN) is a receptor for severe acute respiratory syndrome coronavirus pH-dependent entry of severe acute respiratory syndrome coronavirus is mediated by the spike glycoprotein and enhanced by dendritic cell transfer through DC-SIGN Risk of pneumonia associated with use of angiotensin converting enzyme inhibitors and angiotensin receptor blockers: systematic review and meta-analysis There is currently no evidence that ACEI/ARB increase risk for COVID-19 infection from clinical trials It is not recommended that COVID-19 patients with hypertension or normal hypertensive patients at risk for exposure to stop using ACEI/ARB or change to other antihypertensive drugs The authors acknowledge funding support from the National Natural Science Foundation of China All authors researched data for the article and discussed its content. Jingwei Bian wrote the manuscript. Rongsheng Zhao and Suodi Zhai discussed the content of manuscript and provided some advice. Zijian Li designed this manuscript, reviewed and edited it before submission. The authors declare no conflicts of interest.