OT: COVID-19 Presentation from CROI Meeting

[Dream Jobbed 2.0]

Read a report that 10s of 1000s of CT residents will contract the virus. Seems pretty wild if only 80,000 Chinese caught it and it’s very dwindled there.
No way both those stats are right.
Regardless, STAY HOME.

 

[Leebo]

Read a report that 10s of 1000s of CT residents will contract the virus. Seems pretty wild if only 80,000 Chinese caught it and it’s very dwindled there.
No way both those stats are right.
Regardless, STAY HOME.

It's not hard to see why they could be different if you saw what China implemented to stop the spread. We're just not going to do that kind of thing until much later, if at all.

 

[Letsgohuskies11]

Mistakes have been and will be made. Our government needs to fix any issues quickly as they arrive when possible. I get the sense that some people want our government agencies to fail.

want? they already have failed

 

[Letsgohuskies11]

Read a report that 10s of 1000s of CT residents will contract the virus. Seems pretty wild if only 80,000 Chinese caught it and it’s very dwindled there.
No way both those stats are right.
Regardless, STAY HOME.

Have you not seen or heard what they did in China? They literally went through draconian measures to stop the virus. I drove to the store today in Queens and tons of people are in bars and restaurants right next to each other. We havent a clue.

 

[superjohn]

Mistakes have been and will be made. Our government needs to fix any issues quickly as they arrive when possible. I get the sense that some people want our government agencies to fail.

Yep, that's it.

We all want people to get sick, die, and have have permanent lung damage. We all want our money wiped out.

What we want and should expect is to be told the truth, to not minimize, to be much more prepared, to be given a coherent message.

We haven't gotten any of that.

 

[HuskyHawk]

Part #2:

Potentially more vulnerable / more at-risk populations:


There is very convincing evidence that the original SARS virus (SARS-CoV-1) and the current SARS-CoV-2 virus causing COVID-19 infection bind to a receptor protein found on the surface of human cells. The receptor protein is called Angiotensin Converting Enzyme 2 (ACE2).

ACE2 is expressed on certain cells in our body. Some of them include: many different cell types found in our respiratory tract and lungs, heart, kidneys, intestines, etc.

Some recently-published articles (links at the bottom of this post) indicate some fascinating things about ACE2-producing cells:


-From a study of lung cell cultures (derived from lung transplant donor lungs):

Single-cell RNA expression profiling of ACE2, the putative receptor of Wuhan 2019-nCov

A novel coronavirus (2019-nCov) was identified in Wuhan, Hubei Province, China in December of 2019. This new coronavirus has resulted in thousands of cases of lethal disease in China, with additional patients being identified in a rapidly growing number internationally. 2019-nCov was reported to...

www.biorxiv.org

-ACE2 gene expression (indirect measure of the receptor production) seems to be concentrated in a relatively small fraction of lung cells. Specifically, the majority of cells are type-II alveolar cells (AT2 cells). These cells also seem to produce certain enzymes/factors that the virus needs to replicate optimally
-There may be differences in the expression of ACE2 based on sex (Males > Females). There was on average, about 4x more cells expressing ACE2 in the 2 male donor samples versus the 6 female donor samples
-There may be differences in expression of ACE2 based on race. There was ~5x more ACE2 expression in the donor sample from an Asian male as compared to the donor samples from "white and african american" donor samples. These are small samples sizes though...take with grains of salt.

This is an evolving research area though...here's a research report that provides some supportive evidence to the research above:

Comparative genetic analysis of the novel coronavirus (2019-nCoV/SARS-CoV-2) receptor ACE2 in different populations - Cell Discovery

www.nature.com

And here's one that did not observe significant differences based on race or sex or age (>60 vs. <60):

Tobacco-Use Disparity in Gene Expression of ACE2, the Receptor of 2019-nCov

In current severe global emergency situation of 2019-nCov outbreak, it is imperative to identify vulnerable and susceptible groups for effective protection and care. Recently, studies found that 2019-nCov and SARS-nCov share the same receptor, ACE2. In this study, we analyzed four large-scale...

www.preprints.org

But, these researchers DID observe a significantly higher ACE2 gene expression in smokers' samples versus non-smokers' samples.

Much of the variation in results can be related to different research methods (single-cell analysis versus multiple-cell/combined different cell analysis).

But, there's some interesting findings that relate to emerging trends as the pandemic evolves:

The geographic variation / variation by country in severity of illness, transmittability, etc. is very likely to at least be influenced to some extent by:

• Variations in genetics that modulate ACE2 expression / function
• Variations in ACE2 expression/function induced by smoking and other external/concomitant factors

Interestingly enough, the reportedly higher risk/higher severity illness a/w hypertension is likely related in some way to ACE2 alterations in poorly-controlled/active hypertension. It will be interesting to see with further analysis if "well managed hypertension" presents less (or equal) risk than "poorly managed" hypertension.


What would I advise a patient/friend/family member as the COVID epidemic progresses???

• STOP SMOKING (probably vaping too) as soon as possible
• Continue to take your meds for treating any heart disease/hypertension. Start taking them regularly if you're notoriously poorly-adherent to those medications.

(edits to make bulletpoints, bolding...no significant content chages)

Other Links to relevant articles:

Single-cell RNA expression profiling of ACE2, the putative receptor of Wuhan 2019-nCov

A novel coronavirus (2019-nCov) was identified in Wuhan, Hubei Province, China in December of 2019. This new coronavirus has resulted in thousands of cases of lethal disease in China, with additional patients being identified in a rapidly growing number internationally. 2019-nCov was reported to...

www.biorxiv.org

Comparative genetic analysis of the novel coronavirus (2019-nCoV/SARS-CoV-2) receptor ACE2 in different populations - Cell Discovery

www.nature.com

Quantitative mRNA expression profiling of ACE 2, a novel homologue of angiotensin converting enzyme - PubMed

ACE 2, a novel homologue of angiotensin converting enzyme, has recently been identified. This study used QRT-PCR to quantitatively map the transcriptional expression profile of ACE 2 (and the two isoforms of ACE) in 72 human tissues. While confirming that ACE 2 expression is high in renal and...

www.ncbi.nlm.nih.gov

Organ distribution of severe acute respiratory syndrome (SARS) associated coronavirus (SARS-CoV) in SARS patients: implications for pathogenesis and virus transmission pathways - PubMed

We previously identified the major pathological changes in the respiratory and immune systems of patients who died of severe acute respiratory syndrome (SARS) but gained little information on the organ distribution of SARS-associated coronavirus (SARS-CoV). In the present study, we used a murine...

www.ncbi.nlm.nih.gov

Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis - PubMed

Severe acute respiratory syndrome (SARS) is an acute infectious disease that spreads mainly via the respiratory route. A distinct coronavirus (SARS-CoV) has been identified as the aetiological agent of SARS. Recently, a metallopeptidase named angiotensin-converting enzyme 2 (ACE2) has been...

www.ncbi.nlm.nih.gov

Animal Origins of the Severe Acute Respiratory Syndrome Coronavirus: Insight from ACE2-S-Protein Interactions

www.ncbi.nlm.nih.gov

Interestingly my wife noted last night that China and Italy both have a relatively high rate of smokers. China more than Italy. Also, kids tend not to smoke and fewer young adults smoke. So if there is a connection you’d see old smokers being most heavily impacted.

 

[superjohn]

Have you not seen or heard what they did in China? They literally went through draconian measures to stop the virus. I drove to the store today in Queens and tons of people are in bars and restaurants right next to each other. We havent a clue.

I went to the gym yesterday hoping it would be empty and it was the same amount of people on a typical Saturday, if not more. I left and drove around the neighborhood some and there were huge groups of young people hitting the bars. Not as many as usual but I'm guessing no parade and the awful weather had more to do with it than the virus.

 

[superjohn]

Interestingly my wife noted last night that China and Italy both have a relatively high rate of smokers. China more than Italy. Also, kids tend not to smoke and fewer young adults smoke. So if there is a connection you’d see old smokers being most heavily impacted.

We also have a fatter more diabetic population than them.

 

[phillionaire]

Are you suggesting that the Johns Hopkins numbers which come from the states is not truthful? Let me ask, do you think this is serious or a hoax?

This is serious, I think the government has been downplaying how serious it is for over a month and now it's out of control.

 

[JustbrewitMan]

Excellent overview of the implications of the ACE2 receptor involvement in COVID-19 infections and how it impacts other vital organ health/disease (heart, kidneys, etc.) released today (3/16). I'm watching it now and may add commentary soon.

 

[NJHusky]

I would also add info from Dr. Peter Attia...He's a great thought leader on health.

Peter Attia Covid Info

 

[tdrink]

Hey pj,

Similar evolution towards less-virulent strains has occurred with many human-infecting viruses including influenzae, and the original SARS virus (Strains in the few cases post 2002-3 were much less virulent). I think that there's evidence that this is already happening again naturally.

In perusing bioRxiv.org this AM, there are a couple new non-peer-reviewed articles that, through skimming the abstracts, are suggesting this in some strains within and outside of China. Haven't read them completely though.

There's also another non-peer-reviewed article I'm going to dive into later that seems to show that through protein structure modeling, that the SARS-CoV-1 and SARS-CoV-2 viruses, though only showing 72.8% sequence identity of receptor-binding domains, had 97% structural similarity of those areas.

https://www.biorxiv.org/content/10.1101/2020.03.10.986398v1.full.pdf

Agree that we all may interpret things quite differently in as shortly as 2-4 weeks as new data furiously emerges.

I'm a little worried and fascinated about some of the new VERY PRELIMINARY suggestive concerns for relationships between people with higher-ACE2 states (hypertension, poorly-controlled diabetes, possibly obesity, as well as people receiving various cardiovascular/kidney disease with ACE inhibitors and/or Angiotensin Receptor Blockers (ARBs) and more severe COVID-19 infections / higher mortality

It's a bit too early to say whether people should stop taking these medications yet / switch to some other class of antihypertensive medication (so people, PLEASE PLEASE don't do this on your own!) in the face of the COVID-19 pandemic...but its something to watch closely.

Have you seen any more on correlation between hypertension drugs and COVID-19 morbidity?

When I did some internet sleuthing I found an article that suggests that ARB's May be useful in blocking the virus from binding to receptor sites.

Full disclosure: I am looking this up because I manage hypertension with Losartan.

Angiotensin receptor blockers as tentative SARS-CoV-2 therapeutics. - PubMed - NCBI

 

[pj]

Have you seen any more on correlation between hypertension drugs and COVID-19 morbidity?

When I did some internet sleuthing I found an article that suggests that ARB's May be useful in blocking the virus from binding to receptor sites.

Full disclosure: I am looking this up because I manage hypertension with Losartan.

Angiotensin receptor blockers as tentative SARS-CoV-2 therapeutics. - PubMed - NCBI

Here's a scientist's comment on Losartan for coronavirus:

AT1R blocker losartan is being tested based on a proposal that it will upregulate the SARS-CoV-2 receptor ACE2,
preventing loss of ACE2 function which may be protective against the acute respiratory distress syndrome that is one cause of death by SARS and COVID-19 (Pubmed 32129518) (www.startribune.com/university-of-minnesota-to-testthree-drugs-for-covid-patients/568766632/)
– This only deals with lung injury secondary to viral replication, not the virus itself.
– This comes from an old hypothesis (2005) that SARS lethality was due to downregulation of ACE2
(www.nature.com/articles/nrd1830) whose validity I’m not too confident about, since it was based on injecting massive amounts of viruses into mice (who are pretty different from humans in their cardiovascular regulation).
– Others have suggested that upregulating the receptor for the virus with losartan might increase susceptibility to the initial infection; this probably doesn’t matter either because a virus particle isn’t going to care if the cell it’s sitting on has 100 or 300 receptor molecules when it’s stuck on the surface and has time to swim around
(www.thelancet.com/journals/lanres/article/PIIS2213-2600(20)30116-8/fulltext).
– I think it’s better to concentrate on specific antiviral medications and not worry about the complex ACE2/AT1R pathway.

 

[Rocktheworld]

No, people can transmit the virus while asymptomatic.

Wearing a mask in public would be helpful. Really, there ought to be masks distributed to everyone, and everyone ought to wear them. We ought to manufacture billions of them.

Yeah we should snap our fingers and make billions of masks that aren't even shown to be effective. Screw the healthcare workers who actually need them. The lone "benefit" of wearing a mask is that it'll limit you from inadvertently touching your mouth with your hands. That's it.

 

[Stinger92860]

Read a report that 10s of 1000s of CT residents will contract the virus. Seems pretty wild if only 80,000 Chinese caught it and it’s very dwindled there.
No way both those stats are right.
Regardless, STAY HOME.

China is not being truthful

 

[Stinger92860]

Yeah we should snap our fingers and make billions of masks that aren't even shown to be effective. Screw the healthcare workers who actually need them. The lone "benefit" of wearing a mask is that it'll limit you from inadvertently touching your mouth with your hands. That's it.

The CNO at Stamford hospital told her nurses on Sunday not to use them and they are not effective. I believe she is stupid.

 

[Rocktheworld]

The CNO at Stamford hospital told her nurses on Sunday not to use them and they are not effective.

Probably in favor of an N-95.

I believe she is stupid.

Probably not.

 

[Stinger92860]

want? they already have failed

So when do you die, i’ll send flowers.

 

[Stinger92860]

Probably in favor of an N-95.


Probably not.

You are wrong. A group of doctors reported her. She was is favor on NOT using the N-95’s because they are going through a lot.

EDIT: when the nurses walk due to safety concerns you can go help her.

 

[Letsgohuskies11]

So when do you die, i’ll send flowers.

You're right, they are all doing a fantastic job.

 

[Stinger92860]

You're right, they are all doing a fantastic job.

According to you Fait Accompli, you have given up and all is lost. Sorry, but I don’t agree.

 

[Rocktheworld]

You are wrong. A group of doctors reported her. She was is favor on NOT using the N-95’s because they are going through a lot.

EDIT: when the nurses walk due to safety concerns you can go help her.

If you've got a link, I'll stand corrected. Scary stuff. So you're saying she was telling her nurses to go in to COVID rooms with no face barrier?

Then yeah that is beyond insane and she should be exiled from the medical field forever

 

[Letsgohuskies11]

According to you Fait Accompli, you have given up and all is lost. Sorry, but I don’t agree.

Never said all is lost, I said they've already failed, which they have. Testing and preparation are way behind where it should of been. That's a failure, there is no work in progress here, you either have planned ahead or your doing damage control.

 

[pj]

Yeah we should snap our fingers and make billions of masks that aren't even shown to be effective. Screw the healthcare workers who actually need them. The lone "benefit" of wearing a mask is that it'll limit you from inadvertently touching your mouth with your hands. That's it.

Your usual idiocy. First, picking up virus from a surface and then touching your mouth is the primary way this virus is transmitted. So if that were the lone benefit of a mask, it would be a great boon. But second, masks also stop aerosol transmission which is significant and even dominant in crowded environments. Masks are very effective. N95 masks bring the probability of transmission down 99.9%. If everyone wore them, R0 would go down from 3-5 to 0.03. The virus would die out in short order. Instead of hundreds of millions infected and millions dead, we would have a few thousand deaths.

Then you object to making billions of masks because that would screw healthcare workers by depriving them of masks. Hard to be dumber than this. Making more masks gets more masks to healthcare workers, not fewer.

It costs about ten cents to make a mask. If you use a mask a day, that's $36.50 per person per year. For $36 we would save countless lives and disability. The only thing standing in the way is manufacturing capacity. And nitwits like you who object to simple, inexpensive, and effective means to combat infectious disease.

 

[Rocktheworld]

Your usual idiocy. First, picking up virus from a surface and then touching your mouth is the primary way this virus is transmitted. So if that were the lone benefit of a mask, it would be a great boon. But second, masks also stop aerosol transmission which is significant and even dominant in crowded environments. Masks are very effective. N95 masks bring the probability of transmission down 99.9%. If everyone wore them, R0 would go down from 3-5 to 0.03. The virus would die out in short order. Instead of hundreds of millions infected and millions dead, we would have a few thousand deaths.

Then you object to making billions of masks because that would screw healthcare workers by depriving them of masks. Hard to be dumber than this. Making more masks gets more masks to healthcare workers, not fewer.

It costs about ten cents to make a mask. If you use a mask a day, that's $36.50 per person per year. For $36 we would save countless lives and disability. The only thing standing in the way is manufacturing capacity. And nitwits like you who object to simple, inexpensive, and effective means to combat infectious disease.

Listen son you’ve been undressed several times ITT you’re not as smart or informed as you think you are, sad as that is given your claims to your background

Yes touching a surface then your face is a major way by which the virus is transmitted. Simple awareness will do a mask’s job in that regard; hence, not worth the production.

you implied directing masks to the public, which would necessarily divert resources from healthcare workers for a measure that is minimally beneficial as long as people adhere to general hygiene practices. Wasteful at best. the masks provide trivial relief. You should know better.