4 ms·

Seems like it should be really straightforward to determine if this hypothesis is right by measuring bradykinin levels in Covid patients versus non-Covid patien

Seems like it should be really straightforward to determine if this hypothesis is right by measuring bradykinin levels in Covid patients versus non-Covid patients. One thing that I think strongly suggests that this hypothesis is wrong is that there is no strong relation between ACE-inhibitors and Covid mortality. Indeed, most of the studies that I've seen suggest that ACE-inhibitors have a somewhat protective effect whereas ARBs actually seem to have a minor detrimental effect [1]. So for the article to claim that covid behaves pharmacologically like ACE-inhibitors seems wrong at face value. [1] https://www.nejm.org/doi/full/10.1056/NEJMoa2007621 https://www.nejm.org/doi/full/10.1056/NEJMoa2007621

DoofusOfDeath 6y ago
> One thing that I think strongly suggests that this hypothesis is wrong is that there is no strong relation between ACE-inhibitors and Covid mortality. Perhaps you can clear up something for me. We've all heard how obesity and hypertension are risk factors for covid morbidity. But I could never get a clarification regarding treated vs. untreated hypertension. AFAIK, many obese people take ACE inhibitors to treat hypertension. If we divide obese people into three groups: (a) untreated, (b) treated with ACE inhibitors, and (c) treated with other medications, how do their covid moribity rates compare?
- Enginerrrd 6y ago
  I had this same question early on and I recall reading somewhere that treated hypertension reduced risk. Ostensibly, even if that was from a credible source, it may not mean much though.
  - woeirua 6y ago
    The problem is that the relationship between hypertension, antihypertensives, and Covid is going to be very nuanced and difficult to ascertain without large patient populations to study. One of the very unique aspects of the Covid pandemic is that the NPIs seem to be very effective at damping the spread, so much so that the pool of patients to study keeps moving from region to region every 60 days or so.
    - DoofusOfDeath 6y ago
      What does "NPI" mean in this context?
      - altcognito 6y ago
        Non-pharmaceutical interventions, such as distancing and mask wearing.
    - r00fus 6y ago
      > so much so that the pool of patients to study keeps moving from region to region every 60 days or so. How does NPI/mask effectiveness impact the study moving regions?
      - pas 6y ago
        (Not OP, not an expert either.) By the time you design a study, recruit a pool and wait for some of them to get covid, not enough get it for the study to have enough statistical power.
- woeirua 6y ago
  The answer to treated vs untreated hypertension right now is that we simply do not know. What we do know is that treated hypertensive patients don't appear to have significantly worse outcomes. This article does a great job outlining the current state of the knowledge on the subject of Covid/hypertension as well as some clinical trials that should be posting results early next year [1]. I haven't seen any studies that try and tease apart all of the complex relationships amongst various comorbidities, but I think we have seen pretty conclusively that obesity is a very significant risk factor. [1]https://www.acc.org/latest-in-cardiology/articles/2020/07/06/08/15/covid-19-and-hypertension https://www.acc.org/latest-in-cardiology/articles/2020/07/06...
  - deleted 6y ago
    [deleted]
michaelhoffman 6y ago
The cited article has been retracted. (I know this because I have the PubPeer extension installed which puts a big red warning by it.)
- stonogo 6y ago
  The retraction is linked on the right sidebar under Related Articles: https://www.nejm.org/doi/full/10.1056/NEJMc2021225?query=recirc_curatedRelated_article https://www.nejm.org/doi/full/10.1056/NEJMc2021225?query=rec...
- Crye 6y ago
  It shows for me too and I don't have the PubPeer add on
  - toxicFork 6y ago
    The addon makes it show on the HN comments page
- woeirua 6y ago
  My apologies. I missed it earlier. Here is another article that looks to be in good standing that comes to similar conclusions about ACE-I vs ARBs [2]. [2] https://www.nejm.org/doi/full/10.1056/NEJMoa2008975 https://www.nejm.org/doi/full/10.1056/NEJMoa2008975
sradman 6y ago
ACE and ACE2 [1] work in tandem: > ACE2 counters the activity of the related angiotensin-converting enzyme (ACE) by reducing the amount of angiotensin-II and increasing Ang(1-7) The cell/tissue tropism of SARS-CoV-2 must logically have some effect on the function of the renin–angiotensin system (RAS). What is frustrating is that these questions remain unanswered. [1] https://en.wikipedia.org/wiki/Angiotensin-converting_enzyme_2 https://en.wikipedia.org/wiki/Angiotensin-converting_enzyme_... [2] https://en.wikipedia.org/wiki/Pulmonary_alveolus#Type_II_cells https://en.wikipedia.org/wiki/Pulmonary_alveolus#Type_II_cel...

DoofusOfDeath 6y ago

> One thing that I think strongly suggests that this hypothesis is wrong is that there is no strong relation between ACE-inhibitors and Covid mortality. Perhaps you can clear up something for me. We've all heard how obesity and hypertension are risk factors for covid morbidity. But I could never get a clarification regarding treated vs. untreated hypertension. AFAIK, many obese people take ACE inhibitors to treat hypertension. If we divide obese people into three groups: (a) untreated, (b) treated with ACE inhibitors, and (c) treated with other medications, how do their covid moribity rates compare?

Enginerrrd 6y ago
I had this same question early on and I recall reading somewhere that treated hypertension reduced risk. Ostensibly, even if that was from a credible source, it may not mean much though.
- woeirua 6y ago
  The problem is that the relationship between hypertension, antihypertensives, and Covid is going to be very nuanced and difficult to ascertain without large patient populations to study. One of the very unique aspects of the Covid pandemic is that the NPIs seem to be very effective at damping the spread, so much so that the pool of patients to study keeps moving from region to region every 60 days or so.
  - DoofusOfDeath 6y ago
    What does "NPI" mean in this context?
    - altcognito 6y ago
      Non-pharmaceutical interventions, such as distancing and mask wearing.
  - r00fus 6y ago
    > so much so that the pool of patients to study keeps moving from region to region every 60 days or so. How does NPI/mask effectiveness impact the study moving regions?
    - pas 6y ago
      (Not OP, not an expert either.) By the time you design a study, recruit a pool and wait for some of them to get covid, not enough get it for the study to have enough statistical power.
woeirua 6y ago
The answer to treated vs untreated hypertension right now is that we simply do not know. What we do know is that treated hypertensive patients don't appear to have significantly worse outcomes. This article does a great job outlining the current state of the knowledge on the subject of Covid/hypertension as well as some clinical trials that should be posting results early next year [1]. I haven't seen any studies that try and tease apart all of the complex relationships amongst various comorbidities, but I think we have seen pretty conclusively that obesity is a very significant risk factor. [1]https://www.acc.org/latest-in-cardiology/articles/2020/07/06/08/15/covid-19-and-hypertension https://www.acc.org/latest-in-cardiology/articles/2020/07/06...
- deleted 6y ago
  [deleted]

michaelhoffman 6y ago

The cited article has been retracted. (I know this because I have the PubPeer extension installed which puts a big red warning by it.)

stonogo 6y ago
The retraction is linked on the right sidebar under Related Articles: https://www.nejm.org/doi/full/10.1056/NEJMc2021225?query=recirc_curatedRelated_article https://www.nejm.org/doi/full/10.1056/NEJMc2021225?query=rec...
Crye 6y ago
It shows for me too and I don't have the PubPeer add on
- toxicFork 6y ago
  The addon makes it show on the HN comments page
woeirua 6y ago
My apologies. I missed it earlier. Here is another article that looks to be in good standing that comes to similar conclusions about ACE-I vs ARBs [2]. [2] https://www.nejm.org/doi/full/10.1056/NEJMoa2008975 https://www.nejm.org/doi/full/10.1056/NEJMoa2008975

sradman 6y ago

ACE and ACE2 [1] work in tandem: > ACE2 counters the activity of the related angiotensin-converting enzyme (ACE) by reducing the amount of angiotensin-II and increasing Ang(1-7) The cell/tissue tropism of SARS-CoV-2 must logically have some effect on the function of the renin–angiotensin system (RAS). What is frustrating is that these questions remain unanswered. [1] https://en.wikipedia.org/wiki/Angiotensin-converting_enzyme_2 https://en.wikipedia.org/wiki/Angiotensin-converting_enzyme_... [2] https://en.wikipedia.org/wiki/Pulmonary_alveolus#Type_II_cells https://en.wikipedia.org/wiki/Pulmonary_alveolus#Type_II_cel...