OT: COVID-19 Presentation from CROI Meeting

[Chin Diesel]

I should somewhat snarkily add that the findings about cardboard viability time undoubtedly make Jeff Bezos and other high-volume online cardboard box delivery businesses breathe a little easier

"breathe a little easier"

Well played.

 

[JustbrewitMan]

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

 

[aburks41]

NPR had an article 10 days ago that the actual death rate in China outside of Wuhan is around 0.4% which is less than 1 death per 100 people. Elderly and at-risk people should take precautions, but the 3-4% death rate number will start to decrease by the end of this

 

[JustbrewitMan]

My two questions are:

If we wipe down a surface with anti bacterial cleaner is the surface really cleaned of the threat? I would assume the surface is like our hands which we should thoroughly wash.

Also if talking to someone and they spray spittle (not unusual) on our face, are we immediately contaminated, if they are? You know the peeps who pronounce certain words with spray.

I was at Pepe's getting a pizza to go, and noticed the staff wiping down menus when collected, even salt and pepper shakers, and who knows what else when customers get up from the table.

1st question: Any commonly-available disinfectant (wipe, spray) should inactivate the virus on a surface. Viruses are very fragile and any detergent/disinfectant should kill them with even very short contact times

2nd question: It's clearly POSSIBLE that the spittle could have the virus in it. There's probably A LOT less than what would hit your face from a deep cough, though. If it were to happen, I'd say it wouldn't hurt to wash your face off with soap to avoid it finding its way into your mouth, nose, etc. Tough to give a highly-definitive answer on this question but I personally would be a lot less worried about the spittle dude versus an uncovered cough dude.

What they're doing at Pepe's sure can't hurt WRT minimizing contact acquisition of the virus. Nice to hear.

I've seen some local breweries announce that they are switching to plastic disposable cups for now to minimize the potential transfer of virus as glasses get passed out from and collected back into the bar. Good idea there too.

 

[upstater]

I remain stunned that months after this virus started spreading, the information on how it is spread is still evolving. The CDC writes that nothing is definitive on its website. The one study about aerosol spread has not been reproduced, whereas you can find a ton of literature in many places saying it is spread by droplets. & Also, research from China suggested that it is not spread through other bodily routes, whereas this new research says that it does spread that way.

 

[upstater]

I'd add that the study on smokers and COVID would explain the very high mortality rate in Italy.

 

[CL82]

My two questions are:

If we wipe down a surface with anti bacterial cleaner is the surface really cleaned of the threat? I would assume the surface is like our hands which we should thoroughly wash.

Also if talking to someone and they spray spittle (not unusual) on our face, are we immediately contaminated, if they are? You know the peeps who pronounce certain words with spray.

I was at Pepe's getting a pizza to go, and noticed the staff wiping down menus when collected, even salt and pepper shakers, and who knows what else when customers get up from the table.

The owner of bagel place I go to explained how he is taking extra precautions "with all the stuff that is going on now" and that from now on "the personal handling the money will not handle food." I'm thinking "Wait, that wasn't already the case? Isn't that food sale hygiene 101? Aw well, they are good bagels and on the way to work."

 

[Caronimo]

I'd like to know if we get it, would we ever get it again? Does our body just need to build the tolerance/immunity like it has done with the common cold virus? Maybe a stupid question but I feel like it wouldn't be nearly as bad the second time around. I'll pass on getting the coronawuhan virus, but just some questions.

 

[NJHusky]

I'd like to know if we get it, would we ever get it again? Does our body just need to build the tolerance/immunity like it has done with the common cold virus? Maybe a stupid question but I feel like it wouldn't be nearly as bad the second time around. I'll pass on getting the coronawuhan virus, but just some questions.

i'm not a dr but was speaking to my physician nephew yesterday and his opinion without clinical data was that he thought it was extremely unlikely but not impossible

 

[Dream Jobbed 2.0]

I'd add that the study on smokers and COVID would explain the very high mortality rate in Italy.

Not sure if you’re joking but that actually makes sense

 

[Edward Sargent]

My two questions are:

If we wipe down a surface with anti bacterial cleaner is the surface really cleaned of the threat? I would assume the surface is like our hands which we should thoroughly wash.

Also if talking to someone and they spray spittle (not unusual) on our face, are we immediately contaminated, if they are? You know the peeps who pronounce certain words with spray.

I was at Pepe's getting a pizza to go, and noticed the staff wiping down menus when collected, even salt and pepper shakers, and who knows what else when customers get up from the table.

The bacteriocide in antibacterial cleaners and soap is for bacteria and is not effective against viruses. The best is to wash your hands with soap and water with a lot more frequency than you are used to. Keep your nails clipped and maybe remove jewelry. Pay special attention to between fingers

 

[superjohn]

I'd add that the study on smokers and COVID would explain the very high mortality rate in Italy.

But Italy smoking rate is less than China. I also believe none of the reporting coming out of China, I have no clue why anyone does.

 

[Edward Sargent]

I've mentioned it in a few posts already, but my job involves doing clinical and translational practice & research in infectious diseases. Although I do not directly perform antiviral research, I am well-adept at reading scientific articles, interpreting them, and applying the info to real-life clinical observations.

With that intro, and since I love my BY peeps, thought I'd drop a few interesting insights related to the evolution of the COVID-19 epidemic. I hope it helps you to understand things more and hope it may decrease some fears/unease you may have at least a little bit about everything:

Spread of COVID-19:

1.) Recently-published data (not fully peer-reviewed yet) provides some suggestive evidence that SARS-CoV-2 (the virus that causes COVID-19 infection) can remain aerosolized *in a controlled research environment* for at least 3 hours. It can survive on plastic and stainless steel surfaces for ~72 hours...BUT there is very, very little viable virus left at that 72h timepoint. It doesn't like cardboard as much...no viable virus detected after 24h.

The researchers note in their discussion that their results are similar to those of the SARS-CoV-1 virus (from the 1st SARS outbreak). The aerosolization test result, combined with preliminary evidence that some patients may shed and transmit the virus while pre-symptomatic or asymptomatic provides some support to the hypothesis that SARS-CoV-2 is capable of causing so-called “super-spreading” events (where one infected person can cause a large number of secondary cases).

Article Link: https://www.medrxiv.org/content/10.1101/2020.03.09.20033217v1.full.pdf

What does this mean practically?

1. While very extreme, the substantial social distancing measures now being implemented are probably a very reasonable idea to slow the spread of COVID-19 (especially since we don't have good ways to treat it/vaccinate). Data from China show that it has worked quite well...since 3/7/2020, the numbers of new reported cases have been less than 50 cases per day compared to a high of 15,000+ cases on 2/13/2020.
2. We can definitely say it aerosolizes similar to the SARS virus, but the 3-hour time was the limit of time evaluated in their experiment. They use a confined, defined volume drum that contains the air they test. This is a much different environment than when someone coughs and expels virus. The more confined and stagnant the air is, the more likely it will stay aerosolized. ALWAYS cover your mouth when you cough, but don't be paranoid about going outside...there's going to be a lot more dispersion and reduction of viral particles outdoors. Don't let the pandemic stop you from doing things like taking a nice walk or hike on a sunny day!

I will likely split this info up into a few separate posts in this thread to reduce the "tldr"-ness of it...

Good article, I read in in NEJM. One point in there is that asymptomatic people such as Rudy Gobert can spread the virus.

 

[ClifSpliffy]

you da man! Ace2 talk in da house! brewit bringin' it!
'Don't let the pandemic stop you from doing things like taking a nice walk or hike on a sunny day!' gold, jerry, gold!

 

[Kitaman]

The bacteriocide in antibacterial cleaners and soap is for bacteria and is not effective against viruses. The best is to wash your hands with soap and water with a lot more frequency than you are used to. Keep your nails clipped and maybe remove jewelry. Pay special attention to between fingers

Understood, but what about surfaces (tables, rails, etc..)? Can those be wiped down to kill the virus that may be on the surface?

You know like restaurants, offices, trains, etc. and you want to decontaminate the surface before touching it. I ask because its real life for me, as my wife has a maddening habit of wiping off tables with her hands, if she sees dirt/particles. Probably COPD but she is my wife.

 

[AZHuskiePop]

I'd add that the study on smokers and COVID would explain the very high mortality rate in Italy.

Italy has a much older population than any country other than Japan 48yrs vs the US 38
Much of Europe is the same way the product of extremely low birth rates.

 

[HuskyBandDad]

My weekend project. Making s cardboard suit.

 

[Rocktheworld]

But Italy smoking rate is less than China. I also believe none of the reporting coming out of China, I have no clue why anyone does.

I hear this, but do you think they would’ve got their basketball league back up and running, as I’ve heard they have, if things weren’t getting better?

 

[auror]

There's not going to be any one factor that leads to higher infection or fatality rates in something as large as a country.

It's going to be a combination of a bunch of things, including:

- Cultural practices
- Medical system quality
- Governmental response
- Frequency of travel and tourism
- Demographics of age, gender, and at risk population including hypertension, etc.
- Potential super spreader event.
- Smoking population
- Possibly climate/humidity levels although this is still being explored.

Italy checks pretty much all the boxes.

 

[auror]

NPR had an article 10 days ago that the actual death rate in China outside of Wuhan is around 0.4% which is less than 1 death per 100 people. Elderly and at-risk people should take precautions, but the 3-4% death rate number will start to decrease by the end of this

We'll see how it plays out, but I'm fairly certain the fatality rate will end up being bimodal based on how well a country's medical system can handle the case load. 0.5-1.5% on one end of the spectrum, 3-4%+ if things the bed.

 

[NH Husky]

Looks like india is being spared. Warmer climate? I wonder

 

[Edward Sargent]

Thanks BrewIt, this is some good information

 

[pj]

Looks like india is being spared. Warmer climate? I wonder

Warmer and more humid probably matters, but it's probably equally a matter of age distribution in the population and which strain they've gotten. There are two strains: Coronavirus: Are there two strains and is one more deadly? -- one of them has fatality rates of 5-15% and was the first to appear in November 2019, the other has fatality rates of 0.1-1% and appeared in December-January. Probably Wuhan and Iran got the severe strain but the less severe strain is dominant in most places now.

Most likely, the first was engineered as a bioweapon and the second was a weakened virus designed to be a vaccine. The authorities are letting the "vaccine" spread around the world, thus the UK government decision to let it spread in the UK, Experts cast doubt on UK plan to allow large amount of population to catch coronavirus for ‘herd immunity’, a policy which would make no sense if it weren't protective against the more severe strain.

 

[superjohn]

I hear this, but do you think they would’ve got their basketball league back up and running, as I’ve heard they have, if things weren’t getting better?

One would think but I trust nothing from them. They're demanding American players to return or they will have lifetime bans, the same time their gov't is saying the American military is responsible for the virus.

The virus has been there for 4 months.
Maybe they've mostly controlled it, they've certainly had a way more ambitious plan than us for containment but I certainly wouldn't want to be ordered back there if I was an American player.

 

[Dream Jobbed 2.0]

Warmer and more humid probably matters, but it's probably equally a matter of age distribution in the population and which strain they've gotten. There are two strains: Coronavirus: Are there two strains and is one more deadly? -- one of them has fatality rates of 5-15% and was the first to appear in November 2019, the other has fatality rates of 0.1-1% and appeared in December-January. Probably Wuhan and Iran got the severe strain but the less severe strain is dominant in most places now.

Most likely, the first was engineered as a bioweapon and the second was a weakened virus designed to be a vaccine. The authorities are letting the "vaccine" spread around the world, thus the UK government decision to let it spread in the UK, Experts cast doubt on UK plan to allow large amount of population to catch coronavirus for ‘herd immunity’, a policy which would make no sense if it weren't protective against the more severe strain.

You had me until the second paragraph