OT: COVID-19 Presentation from CROI Meeting

[ClifSpliffy]

You guys are the opposite of scientists, you follow social cues rather than logic. And name-call when you can't refute.

I thought we finished this somewhere else here. you remember, dont'cha? ya know, the part aboot the then 1 hour old data from the scots and the genetic results of their infected? you remember phylogenetic clustering, don'tcha? so there's ur refute. but if not, you should know that, as we speak, there is a team 'over there in asia,' (cuz were 'muricans, and we chase every clue to the end) to explore 'the proteins' cuz, even tho all evidence thus far, including cdc, says no mad scientist footprint, we still check it out. and as far as name calling, I too, will simply call u a nut, and leave it at that. or mebbe call u dr. mephesto. if that character ever croaks over at south park, you should audition for the job. and then mebbe tell us how you buy pants with room for 4 butts.
(thread starts out with cutting edge ace2 talk, and now we're at bigfoot. turrible.)

 

[formerlurker]

 

[Hi-Low]

I found this 60 minutes Australia version very illuminating about "wet markets" in Asia and Corona / other viruses emanating from different animal species from different continents mixing in close spaces in markets.

Includes some pretty chilling stuff including a second wave of the virus.
Might be helpful if this was shown on American TV instead of sanitized info.

 

[pj]

What you guys will see is that we have another 3-4 weeks of quarantine-lockdowns to make sure that the lethal version, which is probably what took out the Kirkland Life Care Center residents, is eradicated -- that one has to be absolutely eliminated from the population, which requires ruthless measures everywhere it pops up -- and meanwhile delaying the universal spread of the weakened virus to get us past cold and flu season because the weakened virus will be much less dangerous to the elderly in the summer when they don't have co-morbid respiratory infections, also the medical system will handle it better. In another month or two, if the lethal version has been quarantined, things will calm down, life will go back to normal so that the weakened coronavirus can spread better -- the authorities will want it to spread at that point in order to induce some "herd immunity" before next winter and before the next re-emergence of the lethal virus. Mortality rate in the summer will be 0.1% like a severe flu, versus 1% if it spread in the winter.

Best thing is to prepare, minimize risk of infection now, get yourself as healthy as possible so that when you get the weakened version in a few months, you weather it well.

 

[JustbrewitMan]

@pj I strongly urge you to watch the presentation by Dr. Baric from UNC (not China) on the virology of Coronaviruses. It starts at the 31:00 mark of this video:

Live Webcast : CROI 2020

He Is a world renowned expert on this area. And he dispels pretty much all the claims you are attempting to make and polluting up this thread with.

 

[Chief00]

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)

I think you are on to something. If there wasn’t a good enough reason before to stop smoking , there is now. In China, for whatever cultural reason, a greater % of men are heavy smokers than females. Men over 60 who smoked were much more likely to die than any other group. That group had a 8-10% fatality rate.

 

[pj]

@pj I strongly urge you to watch the presentation by Dr. Baric from UNC (not China) on the virology of Coronaviruses. It starts at the 31:00 mark of this video:

Live Webcast : CROI 2020

He Is a world renowned expert on this area. And he dispels pretty much all the claims you are attempting to make and polluting up this thread with.

It's a good talk. Some key points:
- The slide at 37:00 shows the degrees of genetic similarity you'd expect for zoonotic transmission. The most likely precursor to the 2002 SARS-CoV was WIV-16 in bats with 98% sequence similarity and a civet strain with 99.5% sequence similarity enabling the jump to virulence in humans. Still, even with a close host, it wasn't very infectious in humans and died out quickly. This compares to SARS-CoV-2 having less than 96% sequence similarity to the nearest known animal virus (a virus which is incapable of infecting humans), and no animal in which it has been proven to replicate in.
- The slide at 42:56 presents my point about why SARS-CoV-2 is unlikely to be zoonotic - it is incompatible with what he calls the "Classic Model" of zoonotic transmission in which mutations are needed in the new host to drive virulence. He hypotheses a new model in which bats can now serve as a "Zoonotic Virus Pool" in which they incubate many variations of virus some of which may be able to jump to humans and be infectious immediately. Of course this is the only model which could possibly account for a zoonotic origin of SARS-CoV-2, that's why he proposes it, but as of now there is no evidence for it - SARS-CoV-2 has not been found in bats, nor any virus like it.
- The slide at 50:37 has the phylogenetics, presenting my point about the huge genetic distance from all previously known coronaviruses. He mentions the one reported bat sequence, RaTG13, with 96% nucleotide similarity / 1200 nt different ("quite different" as he says at 51:12).

Again, see the recent Nature article I cited previously summarizing the search for a zoonotic reservoir. Mystery deepens over animal source of coronavirus. The RaTG13 bat virus cannot infect humans, so it is not transmissible. In pangolins the closest virus found has only 92.4% similarity.

So it's a fine talk, but the zoonotic hypothesis is the only origin hypothesis he discusses and he doesn't present any evidence in support of it. So, fine talk, but he doesn't refute any assertion I've made, in fact the evidence he presents supports my assertions.

 

[Letsgohuskies11]

What you guys will see is that we have another 3-4 weeks of quarantine-lockdowns to make sure that the lethal version, which is probably what took out the Kirkland Life Care Center residents, is eradicated -- that one has to be absolutely eliminated from the population, which requires ruthless measures everywhere it pops up -- and meanwhile delaying the universal spread of the weakened virus to get us past cold and flu season because the weakened virus will be much less dangerous to the elderly in the summer when they don't have co-morbid respiratory infections. In another month or so, things will calm down, life will go back to normal so that the weakened coronavirus can spread better -- the authorities will want it to spread at that point in order to induce some "herd immunity" before next winter and before the next re-emergence of the lethal virus. Mortality rate will be 0.1% like a severe flu.

Best thing is to prepare, minimize risk of infection now, get yourself as healthy as possible so that when you get the weakened version in a few months, you weather it well.

the second version of the spanish flu was more deadly than the early version

 

[JustbrewitMan]

Here's a nice recent article chronicling the research done by Dr. Shi Zheng-Li, who has been investigating the role of bats and other mammals for SARS coronavirus infections for the past ~15 years.

Fascinating research. Of course, certain folk on here will argue that since she's from China, everything she's published in high-quality peer-reviewed literature (and corroborated by non-Chinese researchers) over this time should not be believed.

How China's 'Bat Woman' Hunted Down Viruses from SARS to the New Coronavirus

Wuhan-based virologist Shi Zhengli has identified dozens of deadly SARS-like viruses in bat caves, and she warns there are more out there

www.scientificamerican.com

 

[JustbrewitMan]

It's a good talk. Some key points:
- The slide at 37:00 shows the degrees of genetic similarity you'd expect for zoonotic transmission. The most likely precursor to the 2002 SARS-CoV was WIV-16 in bats with 98% sequence similarity and a civet strain with 99.5% sequence similarity enabling the jump to virulence in humans. Still, even with a close host, it wasn't very infectious in humans and died out quickly. This compares to SARS-CoV-2 having less than 96% sequence similarity to the nearest known animal virus (a virus which is incapable of infecting humans), and no animal in which it has been proven to replicate in.

You're overlooking the most important thing to determining the potential ability of any pathogen (including viruses) to cause infection and/or disease across multiple species:

• It's not the overall genetic similarity that is most important (though usually it ends up being quite high due to the way genetic replication works), its the genetic similarity of the regions of the genome (and the proteins, etc. produced by those regions) that are most important for cross-species infectivity. And the SARS-CoV-2 virus is HIGHLY similar in the most important regions of the binding receptor that is needed to cause cell infectivity in bats, humans, and other tested mammals (the ACE2 receptor).

- The slide at 42:56 presents my point about why SARS-CoV-2 is unlikely to be zoonotic - it is incompatible with what he calls the "Classic Model" of zoonotic transmission in which mutations are needed in the new host to drive virulence. He hypotheses a new model in which bats can now serve as a "Zoonotic Virus Pool" in which they incubate many variations of virus some of which may be able to jump to humans and be infectious immediately. Of course this is the only model which could possibly account for a zoonotic origin of SARS-CoV-2, that's why he proposes it, but as of now there is no evidence for it - SARS-CoV-2 has not been found in bats, nor any virus like it.

You're not interpreting this info correctly. The "Classic model" requires multiple random rare mutational events to explain cross-species infections. As implied, this doesn't mean it's NOT POSSIBLE, but based on the available evidence at the time of the classic model development, it fit the data best to explain what people thought happened (bat to civet to human).

A good analogy would be hitting the lottery twice. Has it happened? Yes. Very rarely! But of the people that have hit the lottery, how many have hit the lottery once vs. twice? Probably about 99.99% versus 0.01% (and it's probably even lower than that...). And how many people have played the lottery that haven't won big (99.99%+, most likely). Rare events can indeed happen, but when they appear to start happening more frequently than before, perhaps something has changed in that rare-event system. You should go back and double-check to see if something is different.

His new proposed model makes much more sense given the emergence of all the newer research data that:

• We now know that multiple diverse species of bats are co-mingling in caves together
• Multiple species of coronaviruses are co-mingling together in the same individual bat species
• Coronaviruses are very capable of recombination of genetic material (sharing of bits and pieces of different viruses during replication to form a very genetically-distinct virus compared to the two viruses the material was derived from_...see slide at 33:15 of the presentation

All these findings make it perfectly plausible that, through recombination events, a coronavirus with only 78% overall homology to the original SARS-CoV virus can find its way into humans either directly or through another animal vector. Especially if it picks up a gene that encodes for a viral spike protein that allows it to bind to the ACE2 cell receptors found in human, bat, civet, and mouse cells.

This picture (screenshot from the slide at 52:06) shows this...There are 14 sites on the ACE2 protein that (based on research to date) seem most important for the virus to bind to it. Anywhere you see green means that virus can bind to that site reasonably well. SARS-CoV-2 has 8/14 sites common with the original SARS virus. And as Dr. Baric notes, those differences between SARS-CoV-2 and original SARS actually appear to make it bind BETTER than the original SARS virus to ACE2.

- The slide at 50:37 has the phylogenetics, presenting my point about the huge genetic distance from all previously known coronaviruses. He mentions the one reported bat sequence, RaTG13, with 96% nucleotide similarity / 1200 nt different ("quite different" as he says at 51:12).

Again, see the recent Nature article I cited previously summarizing the search for a zoonotic reservoir. Mystery deepens over animal source of coronavirus. The RaTG13 bat virus cannot infect humans, so it is not transmissible. In pangolins the closest virus found has only 92.4% similarity.

So it's a fine talk, but the zoonotic hypothesis is the only origin hypothesis he discusses and he doesn't present any evidence in support of it. So, fine talk, but he doesn't refute any assertion I've made, in fact the evidence he presents supports my assertions.

See my discussion above, which explains why TOTAL similarity is not as important and similarity of the key virulence genes that the viruses contain.

Best,
JBM

 

[pj]

You're overlooking the most important thing to determining the potential ability of any pathogen (including viruses) to cause infection and/or disease across multiple species:

• It's not the overall genetic similarity that is most important (though usually it ends up being quite high due to the way genetic replication works), its the genetic similarity of the regions of the genome (and the proteins, etc. produced by those regions) that are most important for cross-species infectivity. And the SARS-CoV-2 virus is HIGHLY similar in the most important regions of the binding receptor that is needed to cause cell infectivity in bats, humans, and other tested mammals (the ACE2 receptor).

"The overall sequence 120 similarities between 2019 -nCoV spike and SARS -CoV spike (isolated from human, civet 121 or bat) are around 76% -78% for the whole protein, around 73% -76% for the RBD, and 50%-53% for the RBM (Fig. 3A, 3 B )" Source: https://jvi.asm.org/content/jvi/early/2020/01/23/JVI.00127-20.full.pdf. There is enough similarity to show that SARS-CoV-2 uses ACE2 as its receptor, but not much similarity.

You're not interpreting this info correctly. The "Classic model" requires multiple random rare mutational events to explain cross-species infections. As implied, this doesn't mean it's NOT POSSIBLE, but based on the available evidence at the time of the classic model development, it fit the data best to explain what people thought happened (bat to civet to human).

A good analogy would be hitting the lottery twice. Has it happened? Yes. Very rarely! But of the people that have hit the lottery, how many have hit the lottery once vs. twice? Probably about 99.99% versus 0.01% (and it's probably even lower than that...). And how many people have played the lottery that haven't won big (99.99%+, most likely). Rare events can indeed happen, but when they appear to start happening more frequently than before, perhaps something has changed in that rare-event system. You should go back and double-check to see if something is different.

His new proposed model makes much more sense given the emergence of all the newer research data that:

• We now know that multiple diverse species of bats are co-mingling in caves together
• Multiple species of coronaviruses are co-mingling together in the same individual bat species
• Coronaviruses are very capable of recombination of genetic material (sharing of bits and pieces of different viruses during replication to form a very genetically-distinct virus compared to the two viruses the material was derived from_...see slide at 33:15 of the presentation

All these findings make it perfectly plausible that, through recombination events, a coronavirus with only 78% overall homology to the original SARS-CoV virus can find its way into humans either directly or through another animal vector. Especially if it picks up a gene that encodes for a viral spike protein that allows it to bind to the ACE2 cell receptors found in human, bat, civet, and mouse cells.

At this point, it is just a hypothesis that the bats could be a pool for such a large variety of viruses that one of them might evolve to be a perfect infectious agent in humans. This is very much like the idea of monkeys typing randomly on typewriters and hoping they'll produce Shakespeare: it takes more monkeys than the numbers of atoms in the universe billions of years to have a chance. The chance of SARS-CoV-2 evolving in such a bat pool is hardly "perfectly plausible," it is statistically akin to the monkeys writing Shakespeare. There just aren't enough bats in the world to make a large enough reservoir for this to work.

Meanwhile the classic model, while it does rely on a series of rare events, is known to have happened many times in human history - most pathogens enter humans this way. It will generate pathogens regularly - but not pathogens as super-adapted to humans as SARS-CoV-2. The classic process can and no doubt did generate the 2002 SARS, but it cannot have generated SARS-CoV-2.

Debating whether Dr. Baric's hypothesis is plausible based on statistics is not necessary, because we can go to animals and search for viruses. If the hypothesis that SARS-CoV-2 was one of a diverse pool of randomly varying bat viruses is correct, we'll see a huge range of viruses in bats ranging in genomic similarity from 98% to 100%. In fact, we don't see any closer than 96%. The hypothesis is being disproven by ongoing research.

This picture (screenshot from the slide at 52:06) shows this...There are 14 sites on the ACE2 protein that (based on research to date) seem most important for the virus to bind to it. Anywhere you see green means that virus can bind to that site reasonably well. SARS-CoV-2 has 8/14 sites common with the original SARS virus. And as Dr. Baric notes, those differences between SARS-CoV-2 and original SARS actually appear to make it bind BETTER than the original SARS virus to ACE2.
View attachment 51997



See my discussion above, which explains why TOTAL similarity is not as important and similarity of the key virulence genes that the viruses contain.

Best,
JBM

The fact that SARS-CoV-2 is related to previous SARS (at a low level) does not tell us its origins, because a bioengineer would also begin working from the SARS-CoV sequence. What is key is that the SARS-CoV-2 has improved human binding compared to all those others, but worse animal binding -- yet it did no evolution in humans. There is no natural process that can bring that about (apart from the gazillion monkeys typing hypothesis).

 

[Rocktheworld]

 

[Leebo]

You're really good at typing a lot of words.

 

[alphasigko]

Here's another letter from a doctor I've seen and has been vetter as legit through the interwebs...……….

The coronavirus is here. But fear not.

Mass panic is also here. Fear.

I’m a doctor and an infectious diseases specialist. I’ve been at this for more than 20 years seeing sick patients on a daily basis. I have worked in inner-city hospitals and in the poorest slums of Africa.

HIV-AIDS, Hepatitis, TB, SARS, measles, shingles, whooping cough, diphtheria ... there is little I haven’t been exposed to in my profession. And with the notable exception of SARS, very little has left me feeling vulnerable, overwhelmed or downright scared.

I am not scared of COVID-19. I am concerned about the implications of a novel infectious agent that has spread the world over and continues to find new footholds in different soil. I am rightly concerned for the welfare of those who are elderly, in frail health or disenfranchised who stand to suffer mostly, and disproportionately, at the hands of this new scourge. But I am not scared of COVID-19.

What I am scared about is the loss of reason and wave of fear that has induced the masses of society into a spellbinding spiral of panic, stockpiling obscene quantities of anything that could fill a bomb shelter adequately in a post-apocalyptic world.

I am scared of the N95 masks that are stolen from hospitals and urgent care clinics where they are actually needed for frontline health-care providers and instead are being donned in airports, malls and coffee lounges, perpetuating even more fear and suspicion of others. I am scared that our hospitals will be overwhelmed with anyone who thinks they “probably don’t have it but may as well get checked out no matter what because you just never know ...” and those with heart failure, emphysema, pneumonia and strokes will pay the price for overfilled ER waiting rooms with only so many doctors and nurses to assess.

I am scared that travel restrictions will become so far reaching that weddings will be canceled, graduations missed and family reunions will not materialize. And well, even that big party called the Olympic Games ... that could be kiboshed, too.

Can you even imagine?





I’m scared those same epidemic fears will limit trade, harm partnerships in multiple sectors, business and otherwise, and ultimately culminate in a global recession.

But mostly, I’m scared about what message we are telling our kids when faced with a threat. Instead of reason, rationality, openmindedness and altruism, we are telling them to panic, be fearful, suspicious, reactionary and self-interested.

COVID-19 is nowhere near over. It will be coming to a city, a hospital, a friend, even a family member near you at some point. Expect it. Stop waiting to be surprised further. The fact is the virus itself will not likely do much harm when it arrives. But our own behaviors and “fight for yourself above all else” attitude could prove disastrous.

I implore you all. Temper fear with reason, panic with patience and uncertainty with education. We have an opportunity to learn a great deal about health hygiene and limiting the spread of innumerable transmissible diseases in our society. Let’s meet this challenge together in the best spirit of compassion for others, patience, and above all, an unfailing effort to seek truth, facts and knowledge as opposed to conjecture, speculation and catastrophizing.

Facts, not fear. Clean hands. Open hearts.

Our children will thank us for it.

Dr. Abdu Sharkawy is a doctor and an infectious disease specialist at the University of Toronto in Canada.

THIS is EXACTLY the POINT I have been making in several threads and have been beaten up by numerous fear mongering posters on this site.... The world has lost its sense of reason and balance as evidenced by the cancelation of all sporting events, school years, and other gatherings, plus hoard-buying of anything and everything, even freaking toilet paper. Thankfully this insanity will eventually pass and life will get back to normal, but I am sad for the scars that will be left behind.

 

[Leebo]

THIS is EXACTLY the POINT I have been making in several threads and have been beaten up by numerous fear mongering posters on this site.... The world has lost its sense of reason and balance as evidenced by the cancelation of all sporting events, school years, and other gatherings, plus hoard-buying of anything and everything, even freaking toilet paper. Thankfully this insanity will eventually pass and life will get back to normal, but I am sad for the scars that will be left behind.

Did you read farther into this thread, where the same doctor is advocating reduced travel and avoiding large gatherings now.

 

[alphasigko]

Did you read farther into this thread, where the same doctor is advocating travel restrictions and avoiding large gatherings now.

How much toilet paper did you buy?

 

[Rocktheworld]

THIS is EXACTLY the POINT I have been making in several threads and have been beaten up by numerous fear mongering posters on this site.... The world has lost its sense of reason and balance as evidenced by the cancelation of all sporting events, school years, and other gatherings, plus hoard-buying of anything and everything, even freaking toilet paper. Thankfully this insanity will eventually pass and life will get back to normal, but I am sad for the scars that will be left behind.

The hysterical buying up toilet paper, beans, rice, and medical equipment is indeed insane. But limiting travel and cancelling large events, temporarily, to flatten the curve as we now say, is absolutely necessary; and is not an irrational response to a pandemic. Travel and large gatherings are the exact two things that led this to become a pandemic in the first place, and will only exacerbate it such that hospitals are overrun not just with the people who “might as well get checked out”; but with actual cases.

 

[Leebo]

How much toilet paper did you buy?

I have a normal amount of toiler paper. Also I don't even live in the United States.

 

[Rocktheworld]

How much toilet paper did you buy?

Lol pathetic

 

[ClifSpliffy]

please stop posting pictures of me. I have a little 'problem' with popcorn. so what? im getting help. whattayou perfect?

 

[Chief00]

Here's a nice recent article chronicling the research done by Dr. Shi Zheng-Li, who has been investigating the role of bats and other mammals for SARS coronavirus infections for the past ~15 years.

Fascinating research. Of course, certain folk on here will argue that since she's from China, everything she's published in high-quality peer-reviewed literature (and corroborated by non-Chinese researchers) over this time should not be believed.

How China's 'Bat Woman' Hunted Down Viruses from SARS to the New Coronavirus

Wuhan-based virologist Shi Zhengli has identified dozens of deadly SARS-like viruses in bat caves, and she warns there are more out there

www.scientificamerican.com

Thanks - very informative. Don’t get much scientific research out on The Grind LOL

 

[Stinger92860]

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

I will not trust any data from china, why would anyone believe what the Chinese government is saying.

 

[superjohn]

THIS is EXACTLY the POINT I have been making in several threads and have been beaten up by numerous fear mongering posters on this site.... The world has lost its sense of reason and balance as evidenced by the cancelation of all sporting events, school years, and other gatherings, plus hoard-buying of anything and everything, even freaking toilet paper. Thankfully this insanity will eventually pass and life will get back to normal, but I am sad for the scars that will be left behind.

It's not at all what you've been saying, you got blowback because your posts were absolutely ridiculous.

 

[Stinger92860]

I’ll know who is right in about 4-6 weeks. Until then, I’m playing it safe.

If PJ is right we all die. If his detractors are right, then we all are safe, a good thing. If his detractors are wrong we all die.

Without going bonkers, Plan for the worse, but hope for the best is a solid approach for me.

 

[CL82]

Interesting how we can go years of talking basketball and never really know some other posters are flipping morons, whackos or conspiracy theorist until a pandemic occurs.

Conspiracy Kitty says:
Or are they?