[AF] Coronavirus e IECA

José Ramón García Soláns jrgarcia en uninet.edu
Vie Mar 13 11:49:33 CET 2020

Me contesto parcialmente yo; recien publicado en Lancet respiratory (Lancet Respir Med 2020, Published Online, March 11, 2020,  https://doi.org/10.1016/PII)

Spoiler: "no hemos encontrado ninguna evidencia que sugiera que el uso de IECA incremente la actividad o expresión de ACE2" (por si TL;DR)

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. Notably, the most frequent comorbidities reported in these three studies of patients with COVID-19 are often treated with angiotensinconverting enzyme (ACE) inhibitors; however, treatment was not assessed in either study. 
Human pathogenic coronaviruses (severe acute respiratory syndrome coronavirus [SARS-CoV] and SARSCoV-2) bind to their target cells through angiotensin-converting enzyme 2 (ACE2), which is expressed by epithelial cells of the lung, intestine, kidney, and blood vessels.4 The expression of ACE2 is substantially increased in patients with type 1 or type 2 diabetes, who are treated with ACE inhibitors and angiotensin II type-I receptor blockers (ARBs).4 Hypertension is also treated with ACE inhibitors and ARBs, which results in an upregulation of ACE2.5 ACE2 can also be increased by thiazolidinediones and ibuprofen. These data suggest that ACE2 expression is increased
in diabetes and treatment with ACE inhibitors and ARBs increases ACE2 expression. Consequently, the increased expression of ACE2 would facilitate infection with COVID-19. We therefore hypothesise that diabetes and hypertension treatment with ACE2-stimulating drugs increases the risk of developing severe and fatal COVID-19.
If this hypothesis were to be confirmed, it could lead to a conflict regarding treatment because ACE2 reduces inflammation and has been suggested as a potential new therapy for inflammatory lung diseases, cancer, diabetes, and hypertension. A further
aspect that should be investigated is the genetic predisposition for an increased risk of SARS-CoV-2 infection, which might be due to ACE2 polymorphisms that have been
linked to diabetes mellitus, cerebral stroke, and hypertension, specifically in Asian populations. Summarising this information, the sensitivity of an individual might result from a combination of both therapy and ACE2 polymorphism. We suggest that patients with cardiac diseases, hypertension, or diabetes, who are treated with ACE2-
increasing drugs, are at higher risk for severe COVID-19 infection and, therefore, should be monitored for ACE2-modulating medications, such as ACE inhibitors or ARBs. Based on a PubMed search on Feb 28, 2020, we did not find any evidence to suggest
that antihypertensive calcium channel blockers increased ACE2 expression or activity, therefore these could be a suitable alternative treatment in these patients.
We declare no competing interests.
Lei Fang, George Karakiulakis,
*Michael Roth
michael.roth en usb.ch
Pulmonary Cell Research and Pneumology,
Department of Biomedicine and Internal Medicine,
University Hospital Basel, CH-4031 Basel,
Switzerland (LF, MR); and Department of
Pharmacology, School of Medicine, Aristotle
University of Thessaloniki, Thessaloniki, Greece (GK)
1 Yang X, Yu Y, Xu J, et al. Clinical course and
outcomes of critically ill patients with
SARS-CoV-2 pneumonia in Wuhan, China:
a single-centered, retrospective, observational
study. Lancet Respir Med 2020; published
online Feb 24. https://doi.org/10.1016/S2213-
2 Guan W, Ni Z, Hu Y, et al. Clinical characteristics
of coronavirus disease 2019 in China.
N Engl J Med 2020; published online Feb 28.
3 Zhang JJ, Dong X, Cao YY, et al. Clinical
characteristics of 140 patients infected by
SARS-CoV-2 in Wuhan, China. Allergy 2020;
published online Feb 19. DOI:10.1111/
4 Wan Y, Shang J, Graham R, Baric RS, Li F.
Receptor recognition by novel coronavirus from
Wuhan: An analysis based on decade-long
structural studies of SARS. J Virology 2020;
published online Jan 29. DOI:10.1128/
5 Li XC, Zhang J, Zhuo JL. The vasoprotective
axes of the renin-angiotensin system:
physiological relevance and therapeutic
implications in cardiovascular, hypertensive

Salu2: Jose Ramon

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