4 ms·

This may be relevant: there's a recent (3rd March) hypothesis due to Rami Sommerstein from Department of Infectious Diseases, Bern University Hospital [0] that

This may be relevant: there's a recent (3rd March) hypothesis due to Rami Sommerstein from Department of Infectious Diseases, Bern University Hospital [0] that ACE inhibitors are a potential risk factor for fatal Covid-19 in those patients taking ACE inhibitors for hypertension/diabetes/cardiovascular disease: >The largest Chinese study with 44,672 confirmed cases of Covid-19 shows a high overall case fatality rate (CFR) of 2.3% [2]. Important co-morbidities are hypertension (CFR 6.0%), diabetes (CFR 7.3%), cardiovascular disease (CFR 10.5%) and age >70 (CFR 10.2%) [2]. Similar co-morbidities were noted for the SARS outbreak in 2003. > ... >On the one hand, it has been shown that the Covid-19 agent (also known as SARS-CoV-2), uses the SARS-COV receptor angiotensin converting enzyme (ACE) 2 for entry into target cells [4]. The interface between ACE2 and the viral spike protein SARS-S has been elucidated and the efficiency of ACE2 usage was found to be a key determinant of SARS-CoV transmissibility [4]. > >On the other hand, it could be shown in animal experiments that both the ACE-inhibitor lisinopril and the angiotensin-receptor blocker losartan can significantly increase mRNA expression of cardiac ACE2 (5-fold and 3-fold, respectively) [5]. Further, losartan also significantly increases cardiac ACE2 activity [5]. Edit: thank you philipn for your twitter link. [0] https://www.bmj.com/content/368/bmj.m810/rr-2 https://www.bmj.com/content/368/bmj.m810/rr-2

philipn 7y ago
Please see my twitter account for lots on this. I'm in contact with a bunch of top researchers on this topic (renin-angiotensin system; ACE2/Ang 1-7/Mas axis; ARB usage for viral diseases) and will be posting a summary update soon: https://twitter.com/__philipn__/status/1235756671852589056 https://twitter.com/__philipn__/status/1235756671852589056 It may be the other way around: ACEi/ARB may be protective. HTN without ACEi/ARB would be non-protective, potentially so much so that it skews the group fatality numbers. This is because people with HTN have a different renin-angiotensin system profile: more AT1R, less AT2R, more ACE, potentially less ACE2. This is being looked at now. But the key is that in every study ever done on viral lung disease, etc, AT1R blockade was highly beneficial, and we know that ACE2-knockout basically screws up lungs, makes viral lung disease way worse, etc. Please see my twitter posts. The virus eats up ACE2, downregulating it as it binds. This would have delirious effects. Check out the linked "essential reading" twitter post. Will be posting a summary to my twitter soon.
- deleted 7y ago
  [deleted]
- dpratt71 7y ago
  I'm fairly out of my depth here, but it's somewhat relevant to my personal situation: When this came up for discussion on HN a few days ago, I was initially confused, as some of what I read seemed to suggest that taking e.g. lisinopril could possibly increase the risk of an infection because it seems to increase the expression of ACE2 receptors that are used by the virus to infect cells. On the other hand, some of what I read seemed to suggest that ACE inhibitors (e.g. lisinopril) could have a therapeutic benefit. The virus is going to inactivate a bunch of ACE2 receptors through the course of infection. Since ACE2 receptors inactivate angiotensin, that would leave a lot of active angiotensin floating around, which is potentially very bad. ACE inhibitors would seem to help here because they inhibit the active form of angiotensin from being created in the first place. Now I'm wondering: Is it possible that taking lisinopril could increase the risk of serious infection for those of us not yet infected, but also could reduce the severity of an active infection?
  - frankbeerstein 7y ago
    I agree. There is a +6% increase in COVID-19 mortality for those with hypertension. Assume all were on BP meds. They're cheap, & doctors usually insist. If ACEs or ARBs were protective, it should be more like -6%. Right? Losartan = 400% more ACE2, Lisinopril = 100% more ACE2. Elderly people are usually on BP meds. Diabetics are frequently prescribed Losartan to protect their kidneys. I know. I am a diabetic, and was prescribed it for that reason and also for high BP. As a diabetic over 50 with high BP I have a greater interest than most. Especially since my wife was exposed to coronavirus, is sick, and I am starting to feel unwell. Stopped taking losartan yesterday. Have some tenofovir lying around and might start taking it. It's the only antiviral I was able to get my hands on. Hopefully my chloroquine arrives in the mail soon.
    - Bach-4ever 7y ago
      I read a paper that suggested caffeic acid was the anti-viral component of elderberry extract that was actually inhibiting HCoV-NL63 viral attachment and infection of human lung cells in vitro (Virus Research, 273 (2019)197767). This paper speculated that caffeic acid binds to ACE2 and inhibits viral attachment and infection via this route. Another paper suggested 95% absorption in humans dosed with 500 mg in 200 mL of hot water. A third paper that looked at 2-year study in SD rats suggested pro-carcinogenic properties, but many other papers suggest anti-oxidant/anti-inflammatory/anti-carcinogenic properties. If I start to come down with it, I think I'm going to do a 500 mg caffeic acid dose.
yumraj 7y ago
Could someone explain this in laymen terms please.

philipn 7y ago

Please see my twitter account for lots on this. I'm in contact with a bunch of top researchers on this topic (renin-angiotensin system; ACE2/Ang 1-7/Mas axis; ARB usage for viral diseases) and will be posting a summary update soon: https://twitter.com/__philipn__/status/1235756671852589056 https://twitter.com/__philipn__/status/1235756671852589056 It may be the other way around: ACEi/ARB may be protective. HTN without ACEi/ARB would be non-protective, potentially so much so that it skews the group fatality numbers. This is because people with HTN have a different renin-angiotensin system profile: more AT1R, less AT2R, more ACE, potentially less ACE2. This is being looked at now. But the key is that in every study ever done on viral lung disease, etc, AT1R blockade was highly beneficial, and we know that ACE2-knockout basically screws up lungs, makes viral lung disease way worse, etc. Please see my twitter posts. The virus eats up ACE2, downregulating it as it binds. This would have delirious effects. Check out the linked "essential reading" twitter post. Will be posting a summary to my twitter soon.

deleted 7y ago
[deleted]
dpratt71 7y ago
I'm fairly out of my depth here, but it's somewhat relevant to my personal situation: When this came up for discussion on HN a few days ago, I was initially confused, as some of what I read seemed to suggest that taking e.g. lisinopril could possibly increase the risk of an infection because it seems to increase the expression of ACE2 receptors that are used by the virus to infect cells. On the other hand, some of what I read seemed to suggest that ACE inhibitors (e.g. lisinopril) could have a therapeutic benefit. The virus is going to inactivate a bunch of ACE2 receptors through the course of infection. Since ACE2 receptors inactivate angiotensin, that would leave a lot of active angiotensin floating around, which is potentially very bad. ACE inhibitors would seem to help here because they inhibit the active form of angiotensin from being created in the first place. Now I'm wondering: Is it possible that taking lisinopril could increase the risk of serious infection for those of us not yet infected, but also could reduce the severity of an active infection?
- frankbeerstein 7y ago
  I agree. There is a +6% increase in COVID-19 mortality for those with hypertension. Assume all were on BP meds. They're cheap, & doctors usually insist. If ACEs or ARBs were protective, it should be more like -6%. Right? Losartan = 400% more ACE2, Lisinopril = 100% more ACE2. Elderly people are usually on BP meds. Diabetics are frequently prescribed Losartan to protect their kidneys. I know. I am a diabetic, and was prescribed it for that reason and also for high BP. As a diabetic over 50 with high BP I have a greater interest than most. Especially since my wife was exposed to coronavirus, is sick, and I am starting to feel unwell. Stopped taking losartan yesterday. Have some tenofovir lying around and might start taking it. It's the only antiviral I was able to get my hands on. Hopefully my chloroquine arrives in the mail soon.
  - Bach-4ever 7y ago
    I read a paper that suggested caffeic acid was the anti-viral component of elderberry extract that was actually inhibiting HCoV-NL63 viral attachment and infection of human lung cells in vitro (Virus Research, 273 (2019)197767). This paper speculated that caffeic acid binds to ACE2 and inhibits viral attachment and infection via this route. Another paper suggested 95% absorption in humans dosed with 500 mg in 200 mL of hot water. A third paper that looked at 2-year study in SD rats suggested pro-carcinogenic properties, but many other papers suggest anti-oxidant/anti-inflammatory/anti-carcinogenic properties. If I start to come down with it, I think I'm going to do a 500 mg caffeic acid dose.

yumraj 7y ago

Could someone explain this in laymen terms please.