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The Coronavirus Conundrum: ACE2 and Hypertension Edition
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There are no clinical data to support that being on an ACEi or ARB increases a risk, nor does the basic science discussed above support a clear association. So more ACE2 might even be good. ???? We don’t know if there is an association between ACEi/ARB and COVID19. There is even a clinical trial being planned to *start* losartan in patients with COVID19. The actual decision for an individual patient should be an individualized one, based on the specific needs, benefits, and hemodynamics. We do hope more data become available in the coming days to allow us to make more informed choices.. What in the world is the link between ACE2 and coronavirus?.......The clinical impact of this study remains uncertain, but this study could provide another mechanism by which ACE inhibition or ARBs could prevent COVID-19 viral entry.......A correspondence in The Lancet suggested the use of a AP2-associated protein kinase 1 inhibitor (regulator of endocytosis)/ janus kinase inhibitor called baricitinib could reduce viral entry.
Thus hypertension does seem to be a common comorbidity, even more so than diabetes - but these are all data from China, and one brief report from Italy (latter with much higher hypertension rate) so one should be careful before generalization. It is also not clear how hypertension was coded - we can speculate that it might be based on use of hypertension medications rather than actual BP measurement. Without better adjusted or stratified data, it is hard to say what this represents.
Can ARB/ACEi use (Less Ang II and potentially increased ACE2) actually be beneficial in coronavirus and other viral pneumonias?....
dedicated area with focus on hypertension and ACE2.
What does this all mean?
We have more questions than answers right now. It is unclear whether or not continuing or stopping ARBs or ACEi’s is warranted in COVID19. However, it is clear that ACE2 and TMPRSS2 are important targets for therapy. Then link between hypertension is very much confounded by age. If you have more to add please let us know.
Current known clinical trials examining RAS blockade in COVID19
Recombinant human ACE2; pilot RCT with 24 patients (as of 3/17 withdrawn)
Losartan RCT in COVID-19; University of Minnesota:
• Outpatient NCT04311177
• Inpatient NCT04312009
Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection?
March 11, 2020
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 colleagues were cerebrovascular diseases (22%) and diabetes (22%). Another study 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, 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 angiotensin-converting enzyme (ACE) inhibitors; however, treatment was not assessed in either study.
Human pathogenic coronaviruses (severe acute respiratory syndrome coronavirus [SARS-CoV] and SARS-CoV-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. 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). Hypertension is also treated with ACE inhibitors and ARBs, which results in an upregulation of ACE2.
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.

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