Antihypertensive drugs and risk of COVID-19?
Authors: Kevin Bryan Lo, Peter A McCullough, Janani Rangaswami
Journal: The Lancet Respiratory Medicine (2020)

Lei Fang and colleagues1Fang L Karakiulakis G Roth M Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection?.Lancet Respir Med. 2020; (published online March 11.)https://doi.org/10.1016/S2213-2600(20)30116-8Summary Full Text Full Text PDF Scopus (2084) Google Scholar postulate that because severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to the angiotensin-converting enzyme 2 (ACE2) receptor to facilitate host cell entry,2Ferrario CM Jessup J Chappell MC et al.Effect of angiotensin-converting enzyme inhibition and angiotensin II receptor blockers on cardiac angiotensin-converting enzyme 2.Circulation. 2005; 111: 2605-2610Crossref PubMed Scopus (1278) Google Scholar, 3Hoffmann M Kleine-Weber H Krueger N Mueller MA Drosten C Pöhlmann S The novel coronavirus 2019 (2019-nCoV) uses the SARS-coronavirus receptor ACE2 and the cellular protease TMPRSS2 for entry into target cells.https://www.biorxiv.org/content/10.1101/2020.01.31.929042v1Date: Jan 31, 2020Date accessed: March 23, 2020Google Scholar disease severity and mortality of coronavirus disease 2019 (COVID-19) might be increased in patients taking angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) during the COVID-19 pandemic, because the ACE2 receptor might be upregulated with use of ACEIs and ARBs. Although it is true that many patients with severe COVID-19 have hypertension and diabetes, as reported by Guan and colleagues in a study of more than 1000 patients,4Guan W Ni Z Hu Y et al.Clinical characteristics of coronavirus disease 2019 in China.N Engl J Med. 2020; (published online Feb 28.)DOI:10.1056/NEJMoa2002032Crossref Google Scholar in that study other factors were also notably unevenly distributed among groups, including age, sex, smoking status (eg, current smoker), and chronic pulmonary disease. Even though patients with diabetes and hypertension frequently use ACEIs and ARBs, many confounders must be accounted for when interpreting findings of observational studies.5Jepsen P Johnsen SP Gillman MW Sørensen HT Interpretation of observational studies.Heart. 2004; 90: 956-960Crossref PubMed Scopus (188) Google Scholar In another study looking at risk factors for mortality among patients with COVID-19,6Zhou F Yu T Du R et al.Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study.Lancet. 2020; (published online March 11.)https://doi.org/10.1016/S0140-6736(20)30566-3Summary Full Text Full Text PDF Scopus (18738) Google Scholar despite hypertension and diabetes being identified as the most frequently associated comorbidities, after multivariate regression the association between these disorders and COVID-19 mortality was no longer significant. In theory, use of ACEIs and ARBs over time would result in an upregulation of ACE2 receptors. In children and young adults, ACE2 receptors are present at a much higher density in lung tissue than in older individuals. Thus, the condition in people taking ACEIs and ARBs emulates that in young people. It is possible that having more ACE2 receptors provides a reserve against target-mediated destruction by SARS-CoV-2.7Gurwitz D Angiotensin receptor blockers as tentative SARS-CoV-2 therapeutics.Drug Dev Res. 2020; (published online March 4.)DOI:10.1002/ddr.21656Crossref PubMed Scopus (610) Google Scholar ACE2 functions to produce the heptapeptide angiotensin (1-7), which has favourable effects on the pulmonary endothelium and might provide resilience from development of pulmonary failure in COVID-19.7Gurwitz D Angiotensin receptor blockers as tentative SARS-CoV-2 therapeutics.Drug Dev Res. 2020; (published online March 4.)DOI:10.1002/ddr.21656Crossref PubMed Scopus (610) Google Scholar We caution against indiscriminate discontinuation of ACEIs and ARBs in patients who rely on these drugs for treatment of heart failure and who, additionally, might benefit from the postulated positive effects during overwhelming infection with SARS-CoV-2. Discontinuation of ACEIs or ARBs is associated with readmission to hospital and mortality among patients with heart failure.8Oliveros E Oni ET Shahzad A et al.Benefits and risks of continuing angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists, and mineralocorticoid receptor antagonists during hospitalizations for acute heart failure.Cardiorenal Med. 2020; 10: 69-84Crossref PubMed Scopus (21) Google Scholar A surge of admissions to hospital for heart failure because of indiscriminate cessation of these important agents could overload already burdened health-care systems with vulnerable patients and cause diagnostic problems in view of the range of symptoms shared between acute heart failure and COVID-19, such as cough and shortness of breath. The quick developing nature of the COVID-19 pandemic, and uncertainty around best practice, calls for caution when putting forward hypotheses that suggest a change in drugs. More evidence is needed before any clinical decisions are made. Related links•The latest guidance from WHO on ibuprofen and COVID-19 (dated: 19.03.2020)•Statement from Prof Michael Roth on how to interpret the original letter •The latest guidance from WHO on ibuprofen and COVID-19 (dated: 19.03.2020)•Statement from Prof Michael Roth on how to interpret the original letter We declare no competing interests. Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection?The most distinctive comorbidities of 32 non-survivors from a group of 52 intensive care unit patients with novel coronavirus disease 2019 (COVID-19) in the study by Xiaobo Yang and colleagues1 were cerebrovascular diseases (22%) and diabetes (22%). Another study2 included 1099 patients with confirmed COVID-19, of whom 173 had severe disease with comorbidities of hypertension (23·7%), diabetes mellitus (16·2%), coronary heart diseases (5·8%), and cerebrovascular disease (2·3%). In a third study,3 of 140 patients who were admitted to hospital with COVID-19, 30% had hypertension and 12% had diabetes. Full-Text PDF Antihypertensive drugs and risk of COVID-19?Lei Fang and colleagues1 suggest that clinicians should consider withholding angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) because of a potential increased risk of worse clinical outcomes in patients with coronavirus disease 2019 (COVID-19), and they suggest calcium channel blockers as an alternative. The hypothesis behind this suggestion is that the entry point for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the ACE2 receptor and that ACEIs and ARBs have the potential to upregulate ACE2. Full-Text PDF Antihypertensive drugs and risk of COVID-19?Lei Fang and colleagues1 extrapolated results from a molecular study of coronaviruses, which showed that this group of viruses uses angiotensin-converting enzyme 2 (ACE2) to target cells on the epithelium of the lungs, intestine, kidneys, and blood vessels.2 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), would probably share these properties. Full-Text PDF Antihypertensive drugs and risk of COVID-19? – Authors' replyWe thank Joshua Brown, Kevin Lo and colleagues, and Christopher Tignanelli and colleagues for their responses to our Correspondence1, and we welcome the opportunity to reply. Full-Text PDF