Comparison of Infection Risks and Clinical Outcomes in Patients with and Without SARS-CoV-2 Lung Infection Under Renin-angiotensin-aldosterone System Blockade: Systematic Review and Meta-analysis

Overview

Journal Br J Clin Pharmacol

Specialty Pharmacology

Date 2020 Nov 20

PMID 33217033

Citations 20

Authors

Chang Chu

Shufei Zeng

Ahmed A Hasan

Carl-Friedrich Hocher

Bernhard K Kramer

Berthold Hocher

Affiliations

Soon will be listed here.

Abstract

Aims: Angiotensin-converting enzyme-2 (ACE2) is the receptor for SARS-CoV-2. Animal studies suggest that renin-angiotensin-aldosterone system (RAAS) blockers might increase the expression of ACE2 and potentially increase the risk of SARS-CoV-2 infection.

Methods And Results: The effect of ACE inhibitor (ACEI) treatment on the pneumonia incidence in non-COVID-19 patients (25 studies, 330 780 patients) was associated with a 26% reduction of pneumonia risk (odds ratio [OR]: 0.74, P < .001). Pneumonia-related death cases in ACEI-treated non-COVID-19 patients were reduced by 27% (OR: 0.73, P = .004). However, angiotensin II receptor blockers (ARB) treatment (10 studies, 275 621 non-COVID-19 patients) did not alter pneumonia risk in patients. Pneumonia-related death cases in ARB-treated non-COVID-19 patients was analysed only in 1 study and was significantly reduced (OR, 0.47; 95% confidence interval, 0.30 to 0.72). Results from 11 studies (8.4 million patients) showed that the risk of getting infected with the SARS-CoV-2 virus was reduced by 13% (OR: 0.87, P = .014) in patients treated with ACEI, whereas analysis from 10 studies (8.4 million patients) treated with ARBs showed no effect (OR, 0.92, P = .354). Results from 34 studies in 67 644 COVID-19 patients showed that RAAS blockade reduces all-cause mortality by 24% (OR = 0.76, P = .04).

Conclusion: ACEIs reduce the risk of getting infected with the SARS-CoV-2 virus. Blocking the RAAS may decrease all-cause mortality in COVID-19 patients. ACEIs also reduce the risk of non-COVID pneumonia. All-cause mortality due to non-COVID pneumonia is reduced by ACEI and potentially by ARBs.

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References

Hendrickson C, Matthay M . Viral pathogens and acute lung injury: investigations inspired by the SARS epidemic and the 2009 H1N1 influenza pandemic. Semin Respir Crit Care Med. 2013; 34(4):475-86. PMC: 4045622. DOI: 10.1055/s-0033-1351122. View

Mortensen E, Coley C, Singer D, Marrie T, Obrosky D, Kapoor W . Causes of death for patients with community-acquired pneumonia: results from the Pneumonia Patient Outcomes Research Team cohort study. Arch Intern Med. 2002; 162(9):1059-64. DOI: 10.1001/archinte.162.9.1059. View

Mehta N, Kalra A, Nowacki A, Anjewierden S, Han Z, Bhat P . Association of Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers With Testing Positive for Coronavirus Disease 2019 (COVID-19). JAMA Cardiol. 2020; 5(9):1020-1026. PMC: 7201375. DOI: 10.1001/jamacardio.2020.1855. View

Felice C, Nardin C, Di Tanna G, Grossi U, Bernardi E, Scaldaferri L . Use of RAAS Inhibitors and Risk of Clinical Deterioration in COVID-19: Results From an Italian Cohort of 133 Hypertensives. Am J Hypertens. 2020; 33(10):944-948. PMC: 7314218. DOI: 10.1093/ajh/hpaa096. View

Senkal N, Meral R, Medetalibeyoglu A, Konyaoglu H, Kose M, Tukek T . Association between chronic ACE inhibitor exposure and decreased odds of severe disease in patients with COVID-19. Anatol J Cardiol. 2020; 24(1):21-29. PMC: 7414823. DOI: 10.14744/AnatolJCardiol.2020.57431. View

Wrapp D, Wang N, Corbett K, Goldsmith J, Hsieh C, Abiona O . Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science. 2020; 367(6483):1260-1263. PMC: 7164637. DOI: 10.1126/science.abb2507. View

. The Case-Crossover Design: A Method for Studying Transient Effects on the Risk of Acute Events. Am J Epidemiol. 2018; 185(11):1174-1183. DOI: 10.1093/aje/kwx105. View

Burrell L, Risvanis J, Kubota E, Dean R, Macdonald P, Lu S . Myocardial infarction increases ACE2 expression in rat and humans. Eur Heart J. 2005; 26(4):369-75. DOI: 10.1093/eurheartj/ehi114. View

Henry C, Zaizafoun M, Stock E, Ghamande S, Arroliga A, White H . Impact of angiotensin-converting enzyme inhibitors and statins on viral pneumonia. Proc (Bayl Univ Med Cent). 2019; 31(4):419-423. PMC: 6414001. DOI: 10.1080/08998280.2018.1499293. View

10.

Li Y, Zeng Z, Li Y, Huang W, Zhou M, Zhang X . Angiotensin-converting enzyme inhibition attenuates lipopolysaccharide-induced lung injury by regulating the balance between angiotensin-converting enzyme and angiotensin-converting enzyme 2 and inhibiting mitogen-activated protein kinase activation. Shock. 2015; 43(4):395-404. DOI: 10.1097/SHK.0000000000000302. View

11.

Arai T, Sekizawa K, Ohrui T, Fujiwara H, Yoshimi N, Matsuoka H . ACE inhibitors and protection against pneumonia in elderly patients with stroke. Neurology. 2005; 64(3):573-4. DOI: 10.1212/01.WNL.0000150897.14961.0F. View

12.

Gao C, Cai Y, Zhang K, Zhou L, Zhang Y, Zhang X . Association of hypertension and antihypertensive treatment with COVID-19 mortality: a retrospective observational study. Eur Heart J. 2020; 41(22):2058-2066. PMC: 7314067. DOI: 10.1093/eurheartj/ehaa433. View

13.

de Abajo F, Rodriguez-Martin S, Lerma V, Mejia-Abril G, Aguilar M, Garcia-Luque A . Use of renin-angiotensin-aldosterone system inhibitors and risk of COVID-19 requiring admission to hospital: a case-population study. Lancet. 2020; 395(10238):1705-1714. PMC: 7255214. DOI: 10.1016/S0140-6736(20)31030-8. View

14.

Shah S, McArthur E, Farag A, Nartey M, Fleet J, Knoll G . Risk of hospitalization for community acquired pneumonia with renin-angiotensin blockade in elderly patients: a population-based study. PLoS One. 2014; 9(10):e110165. PMC: 4212901. DOI: 10.1371/journal.pone.0110165. View

15.

Chen L, Li X, Chen M, Feng Y, Xiong C . The ACE2 expression in human heart indicates new potential mechanism of heart injury among patients infected with SARS-CoV-2. Cardiovasc Res. 2020; 116(6):1097-1100. PMC: 7184507. DOI: 10.1093/cvr/cvaa078. View

16.

Hoesch R, Lin E, Young M, Gottesman R, Altaweel L, Nyquist P . Acute lung injury in critical neurological illness. Crit Care Med. 2011; 40(2):587-93. DOI: 10.1097/CCM.0b013e3182329617. View

17.

Chen C, Wang F, Chen P, Jiang J, Cui G, Zhou N . Mortality and Pre-Hospitalization use of Renin-Angiotensin System Inhibitors in Hypertensive COVID-19 Patients. J Am Heart Assoc. 2020; 9(21):e017736. PMC: 7763411. DOI: 10.1161/JAHA.120.017736. View

18.

Tsukagoshi H, Ishioka T, Noda M, Kozawa K, Kimura H . Molecular epidemiology of respiratory viruses in virus-induced asthma. Front Microbiol. 2013; 4:278. PMC: 3771312. DOI: 10.3389/fmicb.2013.00278. View

19.

Noris M, Benigni A, Remuzzi G . The case of complement activation in COVID-19 multiorgan impact. Kidney Int. 2020; 98(2):314-322. PMC: 7246017. DOI: 10.1016/j.kint.2020.05.013. View

20.

De Spiegeleer A, Bronselaer A, Teo J, Byttebier G, De Tre G, Belmans L . The Effects of ARBs, ACEis, and Statins on Clinical Outcomes of COVID-19 Infection Among Nursing Home Residents. J Am Med Dir Assoc. 2020; 21(7):909-914.e2. PMC: 7294267. DOI: 10.1016/j.jamda.2020.06.018. View