A large number of patients with COVID-19 is expected the coming weeks. Due to the rapid development from a local epidemic in Wuhan China to the current pandemic, clinical care has clearly received highest priority with limited possibilities to further study pathophysiology. However, this may be key to develop strategies for treatment and prevention of unfavorable clinical course. Important aspects such as the role of angiotensin coverting enzyme (ACE)2 in facilitating SARS-CoV-2 cell invasion via binding of a viral spike protein to ACE2 have already been established during an earlier SARS-CoV outbreak with a variant showing large similarity with the current virus, therefore now referred to as SARS-CoV-2. 1-3
Certain drugs have been suggested to influence ACE2 expression, such as ACE inhibitors (inhibiting ACE1), angiotensin II receptor blockers and non-steroid anti-inflammatory drugs (NSAIDs) and therefore some authors suggested that their use might lead to worse outcomes.4 However, this was mainly based on animal studies with conflicting results. 5-7 Clinical data so far did not show a clear correlation but analyses at a large scale are lacking. Use of ACE inhibitors or ARBs could be the common factor explaining that patients with previous cardiovascular disease (CVD, odds ratio (OR) ~25), hypertension and diabetes (both OR ~3) have an increased risk of dying of infection with SARS-CoV-2.8
On the other hand, also an increased risk in these patients due to lower baseline ACE2 might be the explanation, in which case use of ACE inhibitors and ARBS could be protective if any effect on ACE2 is present. (Versmissen et al., submitted; 9). Due to this uncertainty and the well known beneficial effects such as lowering blood pressure and nephroprotective effects, the advice of societies such as the European Society of Cardiology and European Society of Hypertension is to not withdraw these drugs. Also for other drugs, it is currently unknown which might influence the clinical course.
Therefore, we want to study the relationship between use of drugs on clinical outcome of patients with COVID-19. We will focus on ACE inhibitors, ARBs and NSAIDs but more importantly also on other commonly used drugs since the impact of all drugs is unknown.
1. Yan R, Zhang Y, Li Y, Xia L, Guo Y, Zhou Q. Structural basis for the recognition of the SARS-CoV-2 by full-length human ACE2. Science 2020.
2. Zheng YY, Ma YT, Zhang JY, Xie X. COVID-19 and the cardiovascular system. Nat Rev Cardiol 2020.
3. Hoffmann M, Kleine-Weber H, Schroeder S, et al. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell 2020.
4. Fang L, Karakiulakis G, Roth M. Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? Lancet Respir Med 2020.
5. Mendoza-Torres E, Oyarzun A, Mondaca-Ruff D, et al. ACE2 and vasoactive peptides: novel players in cardiovascular/renal remodeling and hypertension. Ther Adv Cardiovasc Dis 2015;9:217-37.
6. Simoes ESAC, Teixeira MM. ACE inhibition, ACE2 and angiotensin-(1-7) axis in kidney and cardiac inflammation and fibrosis. Pharmacol Res 2016;107:154-62.
7. Wang X, Ye Y, Gong H, et al. The effects of different angiotensin II type 1 receptor blockers on the regulation of the ACE-AngII-AT1 and ACE2-Ang(1-7)-Mas axes in pressure overload-induced cardiac remodeling in male mice. J Mol Cell Cardiol 2016;97:180-90.
8. Zhou FY, T.; Du, R.; Fan, G; Liu, Y.; Liu, Z.; Xiang, J.; Wang, Y.; Song, B.; Gu, X.; Guan, L.; Wei, Y.; Li, H.; Wu, X.; Xu, J.; Tu, S.; Zhang, Y.; Chen, H.; Cao, B. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020.
9. Lu N, Yang Y, Wang Y, et al. ACE2 gene polymorphism and essential hypertension: an updated meta-analysis involving 11,051 subjects. Mol Biol Rep 2012;39:6581-9.
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