COVID-19 Coronavirus Containment Efforts

[bob012345]

Sweden has a population of 10 million. Norway has 5 million, Finland has 6 million, Denmark has has 6 million. I don't know why you brought up total population, but clearly these countries are closer in population than e.g. Germany with 80 million or France with 70 million?
If you think Scandinavian countries are so similar to Western Europe (and no matter where you look, they are not) you would have to explain why they all had death tolls so much lower than most of Western Europe. Well, all except Sweden.

Sweden hasn't done so bad and it's a false comparison to assume the Scandinavian countries must be compared as a unit. The WHO now says Sweden is a model for reopening economies.

 

[mfb]

I don't say Sweden has done bad, but its deaths were much higher than for all its neighbors. All the neighbors kept the disease at a much lower level.

 

[PAllen]

Sweden has a population of 10 million. Norway has 5 million, Finland has 6 million, Denmark has has 6 million. I don't know why you brought up total population, but clearly these countries are closer in population than e.g. Germany with 80 million or France with 70 million?
If you think Scandinavian countries are so similar to Western Europe (and no matter where you look, they are not) you would have to explain why they all had death tolls so much lower than most of Western Europe. Well, all except Sweden.

Also, as I noted earlier, Denmark has six times higher population density than Sweden (with similar population) and has a land connection to Western Europe, all of which would suggest much worse results than Sweden. Instead, they have done much better.

 

[OmCheeto]

Anyone have a guess how Denmark ended up with a worse deaths/million (X/M) ratio than Hubei?

Belgium thru Denmark are the top 15 X/M nations, minus San Marino(1214), Andorra(636), and Luxembourg(168), as their populations strike me more as town/cityish.

 

[wukunlin]

Anyone have a guess how Denmark ended up with a worse deaths/million (X/M) ratio than Hubei?

View attachment 263028
Belgium thru Denmark are the top 15 X/M nations, minus San Marino(1214), Andorra(636), and Luxembourg(168), as their populations strike me more as town/cityish.

Just a wild guess. I took a quick look and saw around 40% of Hubei's population are registered in rural areas. The only contacts they have with people outside their local clusters of villages are either people who come into buy their fresh produce, or their children who work in cities. The former were on holiday during the outbreak because it was near spring break, the latter couldn't come home due to the lock down.

 

[Rive]

...ended up...

What bothers me the most regarding the/an ongoing pandemic is the usage of 'ended'.
I would reserve that word for later use - it is just not fair and not useful to apply it now.

 

[PeroK]

Sweden has a population of 10 million. Norway has 5 million, Finland has 6 million, Denmark has has 6 million. I don't know why you brought up total population, but clearly these countries are closer in population than e.g. Germany with 80 million or France with 70 million?
If you think Scandinavian countries are so similar to Western Europe (and no matter where you look, they are not) you would have to explain why they all had death tolls so much lower than most of Western Europe. Well, all except Sweden.

In some ways all these countries have too low a population to be statistically significant. The virus breaks out exponentially in certain areas. A country the size of Denmark can get "lucky" and practically avoid the virus, whereas another small country like Belgium can get "unlucky" and be disproportionately hit. In the larger countries like Italy, Spain and France the data tends to even out. You'll find regions in these countries as badly hit as Belgium and other regions who, like Denmark, have low numbers.

That would be, IMO, a significant part of the reason why Denmark has 95 deaths per million and Belgium 784. If there had been an early major outbreak in Copenhagen rather than Brussels it could have been the other way round.

The virus is not evenly spread across western Europe. There are other countries with low death rates:

Portugal (adjacent to Spain) has 121 per million; Spain has 593.
Austria only 70 per million; whereas Switzerland has 218.

There is a massive spread in numbers, especially across the smaller countries and that points to the randomness of uncontrolled outbreaks.

 

[atyy]

The Trinity of COVID-19: Immunity, Inflammation and Intervention | Assoc Prof Paul MacAry (Part 2)

Lecture by Paul MacAry, an immunologist at the National University of Singapore. The part from 6:15 to the end gives an introduction to vaccines in general, and an overview of current vaccine efforts. He says it may be possible for a vaccine will become available in early 2021 for emergency use or similar protocols, given the number of ongoing efforts and coordination among governments and the WHO.

 

[Vanadium 50]

A country the size of Denmark can get "lucky" and practically avoid the virus, whereas another small country like Belgium can get "unlucky" and be disproportionately hit.

Look at Liechtenstein and the neighboring Swiss canton of Graubunden. Things are an order of magnitude worse in Graubunden. The difference used to be even more evident, but then Liechtenstein got a case.

 

[russ_watters]

In some ways all these countries have too low a population to be statistically significant. The virus breaks out exponentially in certain areas. A country the size of Denmark can get "lucky" and practically avoid the virus, whereas another small country like Belgium can get "unlucky" and be disproportionately hit. In the larger countries like Italy, Spain and France the data tends to even out.

I'd say the first bit slightly differently or even amplify: it's the larger sample sizes that show the smoothest exponential curves. But for "certain areas" the starting point is often one of explosive clusters. At that choir practice in Washington, one person infected a probable 52 others in a single event. If the average reproduction rate is 2.2 and the average time is 5 days, that's 3.5 weeks (5 generations) of growth from a single event. Or put another way, instead of starting with 1 case and 3.5 weeks later having 53, you now have 1,200. That kind of explosive growth early in the pandemic in some places likely had a huge impact on the outcome for smaller areas that happened to be unlucky enough to have them; especially to have them early.

 

[david2]

some hopeful news

Moderna Announces Positive Interim Phase 1 Data for its mRNA Vaccine

https://modernatx.gcs-web.com/news-...ositive-interim-phase-1-data-its-mrna-vaccine

 

[Astronuc]

Coronavirus: Baby develops life-threatening inflammatory condition 'while her twin escapes unscathed'
https://www.yahoo.com/lifestyle/coronavirus-covid1-kawasaki-disease-inflammation-092538403.html

A mother of identical twins has revealed how one suffered a life-threatening illness after overcoming the coronavirus, while the other is thought to have escaped unscathed.

Hannah Godwin, 35, noticed her five-month-old daughter Leia had a rash and fever while lying next to her “healthy and happy” sister Thea.

NHS doctors have been told to look out for signs of “multi-system inflammation” after intensive care units in London saw eight children with unusual symptoms, some of whom tested positive for the coronavirus.

Leia has spent the past three weeks in hospital, . . . . Although Leia is no longer in critical care, doctors have warned she has a long road to recovery.

Even without COVID-19 respiratory distress, the inflammation presents yet another challenge.

 

[bob012345]

Is it just me or is anyone else alarmed by so called gain-of-function research on dangerous viruses? This is the practice of taking a virus, such as the bird flu and making it more transmittable to humans for the purpose of researching cures and vaccines in the event that virus ever naturally mutates and gets into the human population. I mentioned bird flu because that was debated and defended by prominent scientists a decade ago with references below.

https://osp.od.nih.gov/biotechnology/gain-of-function-research/

https://www.washingtonpost.com/opin...worth-taking/2011/12/30/gIQAM9sNRP_story.html

https://www.bbc.com/news/world-us-canada-16279365

https://www.sciencemag.org/news/201...iments-make-bird-flu-more-risky-poised-resume

Relevant to the current crisis is the fact that NIH funded and NIAID administered gain-of-function research at the Wuhan Institute of Virology and elsewhere using SARS-CoV-2. Basically, we paid them to make it much easier to transmit to humans for research purposes. Here is the NIH funding for EcoHealth Alliance, the organization that funnels NIH money to labs around the world.

https://projectreporter.nih.gov/reporter_SearchResults.cfm?icde=50081038

Notice this statement from the sixth project title down;

2

R01

AI110964

06

Speaking of SARSr-CoVs,;

"We will use S protein sequence data, infectious clone technology, in vitro and in vivo infection experiments and analysis of receptor binding to test the hypothesis that % divergence thresholds in S protein sequences predict spillover potential."

Note that I made no claims that this research was the cause of the pandemic. But representatives of 122 nations just demanded that the actual source of the virus be vigorously investigated.

 

[mfb]

Note that I made no claims that this research was the cause of the pandemic.

Good, because that claim would be foolish.

But representatives of 122 nations just demanded that the actual source of the virus be vigorously investigated.

Why put this completely unrelated point next to the other one?

 

[atyy]

Moderna Announces Positive Interim Phase 1 Data for its mRNA Vaccine

Interesting. I hadn't been very hopeful for the RNA/DNA vaccines as they need the body to produce the antigen from the RNA, whereas other vaccine contain the antigen. Also, none to date have been approved for any other use in people, although they have veterinary use. However, these are generally thought to be very likely to be safe.

 

[Jarvis323]

Is it just me or is anyone else alarmed by so called gain-of-function research on dangerous viruses? This is the practice of taking a virus, such as the bird flu and making it more transmittable to humans for the purpose of researching cures and vaccines in the event that virus ever naturally mutates and gets into the human population. I mentioned bird flu because that was debated and defended by prominent scientists a decade ago with references below.

https://osp.od.nih.gov/biotechnology/gain-of-function-research/

https://www.washingtonpost.com/opin...worth-taking/2011/12/30/gIQAM9sNRP_story.html

https://www.bbc.com/news/world-us-canada-16279365

https://www.sciencemag.org/news/201...iments-make-bird-flu-more-risky-poised-resume

Relevant to the current crisis is the fact that NIH funded and NIAID administered gain-of-function research at the Wuhan Institute of Virology and elsewhere using SARS-CoV-2. Basically, we paid them to make it much easier to transmit to humans for research purposes. Here is the NIH funding for EcoHealth Alliance, the organization that funnels NIH money to labs around the world.

https://projectreporter.nih.gov/reporter_SearchResults.cfm?icde=50081038

Notice this statement from the sixth project title down;

2

R01

AI110964

06

Speaking of SARSr-CoVs,;

"We will use S protein sequence data, infectious clone technology, in vitro and in vivo infection experiments and analysis of receptor binding to test the hypothesis that % divergence thresholds in S protein sequences predict spillover potential."

Note that I made no claims that this research was the cause of the pandemic. But representatives of 122 nations just demanded that the actual source of the virus be vigorously investigated.

Here is a good video on the topic. Two leading experts give presentations: the first, Marc Lipsitch (Harvard), makes the case against gain of function research, and the second, Derek Smith (Cambridge), makes the case for it.



Regardless if gain of function research at WIV contributed to the outbreak of sars-cov-2, the current pandemic has at least put this topic into public view. I think it's a very important topic that needs to be more widely discussed.

I agree with Marc Lipsitch, that it's not worth the risks. People are not reliable enough to trust with manipulating, creating, and testing dangerous viruses. It seems pretty clear that scientists don't fully understand the risks, but a worst case event/accident can be catastrophic (similar or much worse than what is happening now). Basically, a single screw up at a lab could result in millions of deaths, and bring a new deadly viruse into the world that may never go away. People are constantly screwing everything up.

 

[kadiot]

What is the medical definition of "Second Wave"?

 

[kadiot]

To truly learn from this pandemic, we must understand why pandemics occur? And how can we prevent a recurrence?

 

[bob012345]

Good, because that claim would be foolish.Why put this completely unrelated point next to the other one?

While it would be foolish at this point to make such an absolute claim, it would not be foolish to consider that possibility. Let's put this in physics terms. Gain-of-function research farmed out to labs in countries not yet up to level 4 CDC standards is like making nuclear weapons at an insecure facility in Turkey. There is a decent chance a few might go missing. And even in level 4 U.S. labs it's risky. The upside is you might learn something that might be relevant if nature produced a crossover with a sufficiently similar genetic code at some point in the future. The downside is a global pandemic with hundreds of thousands of deaths plunging the world economy into deep depression.

Let's consider the coincidence here. The whole point of doing gain-of-function research is to accelerate nature that might take eons to do the same thing. So, Peter Daszak through EcoHealth Alliance decides to push to do that. Then suddenly, out of the blue, and in a similar timeframe, a pandemic emerges with an incredible ability to be transmittable to humans, even a weird 14 day incubation period where its highly contagious well before symptoms even appear if ever. And yet we are told the possibility of that virus escaping from a lab is impossible and that it must have been a purely natural occurrence. Can you imagine the fallout if it was concluded that the pandemic was caused by the accidental release of a virus after gain-of-function experiments paid for the the NIH? Interestingly, the experts telling us that have a vested interest in not being seen as being in any way responsible for the pandemic. We may be looking at the Chinese version of Chernobyl with the U.S. implicated too.

I included that disclaimer because I can't prove that scenario happened but I'm certainly suspicious that is one possibility and it's entirely related to the demand by the U.N. representatives to find out what really happened.

 

[PeroK]

So, Peter Daszak through EcoHealth Alliance decides to push to do that. Then suddenly, out of the blue, and in a similar timeframe, a pandemic emerges with an incredible ability to be transmittable to humans, even a weird 14 day incubation period where its highly contagious well before symptoms even appear if ever. And yet we are told the possibility of that virus escaping from a lab is impossible and that it must have been a purely natural occurrence.

Following your hypothesis that this started in Peter Daszak's lab, why did the outbreak begin in Wuhan?

 

[bob012345]

Following your hypothesis that this started in Peter Daszak's lab, why did the outbreak begin in Wuhan?

Dr. Peter Daszak heads the EcoHealth Alliance as president which is a organization dedicated to "prevent pandemics" and that includes funding labs studying bat viruses and includes gain-of-function experiments. They received grants from NIH administered through NIAID (Dr. Fauci) and channeled the money to various labs including Wuhan. Daszak doesn't personally do the research in his own lab. He receives grants and funds research. Dr. Fauci is a supporter of gain-of-function research.

https://www.ecohealthalliance.org

Here is the mission statement;

"EcoHealth Alliance is an international nonprofit dedicated to a 'One Health' approach to protecting the health of people, animals and the environment from emerging infectious diseases. The organization formed with the merger of two highly respected organizations, Wildlife Trust and the Consortium for Conservation Medicine. The urgent concern for wildlife conservation and the overall health of our planet has led EcoHealth Alliance to become an environmental science and public health leader working to prevent pandemics in global hotspot regions across the globe and to promote conservation."

It may very well turn out that EcoHealth Alliance are among the heros in all this mess but when people promote potentially risky research with deadly viruses we shouldn't just give them a pass without even being allowed to legitimately ask questions.

 

[PeroK]

Dr. Peter Daszak heads the EcoHealth Alliance as president which is a organization dedicated to "prevent pandemics" and that includes funding labs studying bat viruses and includes gain-of-function experiments. They received grants from NIH administered through NIAID (Dr. Fauci) and channeled the money to various labs including Wuhan.

I don't imagine anyone outside the Chinese Communist Party has much influence on what goes on in a lab in Wuhan.

 

[bob012345]

I don't imagine anyone outside the Chinese Communist Party has much influence on what goes on in a lab in Wuhan.

As I understand it, EcoHealth Alliance gave the Wuhan lab $600k for the purpose of doing experiments on bat viruses including gain-of-function experiments. Free money from the U.S. to do experiments they wanted to do anyway. I find it interesting that the money doesn't come directly from NIH but through an intermediary non-profit. Perhaps that gives the NIH some deniability if outside labs don't follow strict protocols? Obviously, the CCP approved of the work but then when Wuhan scientists started speaking out about the virus breaking out into the human population (whether naturally or by accident), they were silenced.

 

[PeroK]

As I understand it, EcoHealth Alliance gave the Wuhan lab $600k for the purpose of doing experiments on bat viruses including gain-of-function experiments. Free money from the U.S. to do experiments they wanted to do anyway. I find it interesting that the money doesn't come directly from NIH but through an intermediary non-profit. Perhaps that gives the NIH some deniability if outside labs don't follow strict protocols? Obviously, the CCP approved of the work but then when Wuhan scientists started speaking out about the virus breaking out into the human population (whether naturally or by accident), they were silenced.

I found this:

https://www.ft.com/content/255a3524-0459-4724-a92a-58268ab627e2

 

[nsaspook]

FINDINGS FROM INVESTIGATION AND ANALYSIS OF RE-POSITIVE CASES

○ Based on active monitoring, epidemiological investigation, and laboratory testing of re-positive cases and their contacts, no evidence was found that indicated infectivity of re-positive cases.

- Of the 447 re-positive cases as of 15 May, epidemiological investigation was conducted on 285 cases and laboratory analysis on 108 cases. (*473 as of 18 May)

- From monitoring of 790 contacts of the 285 re-positive cases, no case was found that was newly infected solely from contact with re-positive cases during re-positive period.

- Virus isolation in cell culture of respiratory samples of 108 re-positive cases, all result was negative (i.e. virus not isolated).

- Of the 23 re-positive cases from which the first and the second serum samples were obtained, 96% were positive for neutralizing antibodies.

https://www.cdc.go.kr/board/board.es?mid=a30402000000&bid=0030

 

[bob012345]

I found this:

https://www.ft.com/content/255a3524-0459-4724-a92a-58268ab627e2

It has several denials of the possibility the virus came from the Wuhan lab. Why are they so certain this early? Statements such as this;

"Edward Holmes, an Australian virologist who helped map and share the genetic sequence of the virus, said there was “no evidence” that Sars-Cov-2, the virus that causes Covid-19 in humans, originated in a Wuhan laboratory."

I'm glad the "no evidence" was in quotes because I've seen the logic explained as because the sequence that makes it very effective could not be predicted a priori by computer, it must have been natural. But there are other ways of putting enhancements into the virus without artificial engineering such as using gene editing techniques with naturally occurring sequences. In other words, those claiming "no evidence" may well be parsing subtle distinctions about what is considered natural and what is considered man made that the public wouldn't appreciate.

Also, "no evidence" doesn't mean it didn't happen. It means one doesn't have the evidence at hand to prove it happened. It's far too early to know.

Fauci says he is “very, very strongly leaning toward this could not have been artificially or deliberately manipulated”. He would have to say that or admit he funded research that led to the pandemic.

The article seems to imply the Sars-Cov-2 wasn't even at the Wuhan lab.

This Livescience article also makes that claim but discusses a scenario at the end that researchers may have unknowingly had sars-cov-2 or a precursor virus in the lab samples and even enhanced it by genetic selection as a byproduct of other work. It ends with an appropriate measure of uncertainty.

https://www.livescience.com/coronavirus-wuhan-lab-complicated-origins.html

But then there is this;

WIV was not immune to those concerns. In 2018, after scientist diplomats from the U.S. embassy in Beijing visited the WIV, they were so concerned by the lack of safety and management at the lab that the diplomats sent two official warnings back to the U.S. One of the official cables, obtained by The Washington Post, suggested that the lab's work on bat coronaviruses with the potential for human transmission could risk causing a new SARS-like pandemic, Post columnist Josh Rogin wrote.

 

[mfb]

Let's consider the coincidence here.

Said the lottery winner to argue that something else must have played a role.
If you look hard enough you'll always find coincidences somewhere. Omit everything that doesn't fit, add some misinformation that was shared online, brew everything together, and you get a completely wrong conclusion.

Can we get back to containment efforts (the topic of this thread)?

One more case in Iceland on Tuesday, a week after the previous case.

 

[bob012345]

Said the lottery winner to argue that something else must have played a role.
If you look hard enough you'll always find coincidences somewhere. Omit everything that doesn't fit, add some misinformation that was shared online, brew everything together, and you get a completely wrong conclusion.

Can we get back to containment efforts (the topic of this thread)?

One more case in Iceland on Tuesday, a week after the previous case.

Perhaps I should have started a new thread but I wasn't sure if there would be enough interest.

Here's my take on containment. Stop federal funding of dangerous experiments that could possibly lead to catastrophic pandemics and ban outright all gain-of-function experiments. Take a flamethrower to the bat caves and wet markets where this virus came from.

 

[Ygggdrasil]

Speaking of SARSr-CoVs,;

"We will use S protein sequence data, infectious clone technology, in vitro and in vivo infection experiments and analysis of receptor binding to test the hypothesis that % divergence thresholds in S protein sequences predict spillover potential."

The experiments proposed in this grant would likely not pose the risk of releasing a new pandemic strain of coronavirus. Speaking as someone who has worked in labs that study RNA viruses, there are ways to perform these studies in a safe manner. To study how mutations in the spike protein affect cell entry, scientists create something called a pseudotyped virus. This is essentially taking the spike protein from the coronaviruses that you'd like to study, and putting it on the outside of what is essentially a harmless virus shell. Typically, researchers use lentiviral vectors, which are derived from HIV. These viruses have been extensively modified to prevent them from being able to reproduce, so once the virus enters the cell, it cannot make new copies of itself (see the Addgene link above for more details). This technology is routinely used in many biomedical research labs to introduce foreign genes into cells. These types of experiments using pseudotyped viruses have been done with SARS-CoV-2 spike protein in many published studies (for example, studying which antibodies are able to bind the SARS-CoV-2 spike protein to prevent viral entry). So, this one sentence does not necessarily mean that the researchers were engaged in dangerous gain of function experiments.

Newsweek, however, does report that gain of function studies on bat coronaviruses did occur at the Wuhan Institute of Virology. They write:

The Institute began a program of gain-of-function research into bat coronaviruses in 2015. That involved taking selected strains and seeking to increase the ability of those viruses to transmit from one person to another. The gain-of-function research went hand-in-hand with the surveillance project. As scientists identified new classes of bat viruses that have the ability to infect human cells, that raised the question of what changes would have to arise in nature to make that virus transmissible in humans, which would pose a pandemic threat.

In 2015, the Wuhan lab performed a gain of function experiment using cut-and-paste genetic engineering, in which scientists take a natural virus and directly make substitutions in its RNA coding to make it more transmissible. They took a piece of the original SARS virus and inserted a snippet from a SARS-like bat coronavirus, resulting in a virus that is capable of infecting human cells. A natural virus altered with these methods would be easily flagged in a genetic analysis, like a contemporary addition to an old Victorian house.

The article seems to be referring to this 2015 publication in Nature Medicine. As the Newsweek article notes, genetic analysis of the viral RNA would easily spot a virus generated through such gain of function studies, and the SARS-CoV-2 RNA sequence does not show signs of being manipulated in these ways.

The Newsweek article discusses the possibility that the virus could have evolved through passaging of the virus in laboratory conditions, which could adapt a bat virus to be more transmissible in human cells. Again, genetic analysis of the viral RNA has identified various genetic features of the virus that enable its transmissibility in humans. One feature are a set of mutations in the receptor binding domain of the spike protein that help the spike protein bind to the human ACE2 receptor more strongly. These mutations are similar to mutations found in a Pangolin coronavirus, so these mutations were likely introduced naturally into the progenitor bat Coronavirus through recombination. The other feature is a polybasic furin cleavage site within the spike protein, which is not found in other related coronaviruses. It is certainly possible for such sites to evolve naturally, as many other viruses have evolved furin sites in their extracellular proteins (including the MERS coronavirus), though the exact origins of the SARS-CoV-2 furin site remains unknown. While evolution of furin cleavage sites has been observed in laboratory passage of influenza virus, the SARS-CoV-2 sequence has other features (such as the introduction of a glycosylation site) that would not be expected to be selected for during passage in cultured cells, which would disfavor the laboratory passage hypothesis over a natural origin.

While the exact origins of the virus aren't known (and may never be known), most of the existing evidence supports a natural origin over an accidental release hypothesis. Indeed, we know of many new viruses that have jumped from animals to humans (e.g. HIV, ebola, swine flu, avian flu, Zika virus), including two new coronaviruses that have emerged within the past two decades (the original SARS and MERS). Ultimately, extraordinary claims require extraordinary evidence. While we can't disprove the hypothesis that the virus escaped from a lab, I have not seen any compelling evidence to favor the laboratory escape hypothesis over a natural, zoonotic origin of the virus.

 

[Jarvis323]

The experiments proposed in this grant would likely not pose the risk of releasing a new pandemic strain of coronavirus. Speaking as someone who has worked in labs that study RNA viruses, there are ways to perform these studies in a safe manner. To study how mutations in the spike protein affect cell entry, scientists create something called a pseudotyped virus. This is essentially taking the spike protein from the coronaviruses that you'd like to study, and putting it on the outside of what is essentially a harmless virus shell. Typically, researchers use lentiviral vectors, which are derived from HIV. These viruses have been extensively modified to prevent them from being able to reproduce, so once the virus enters the cell, it cannot make new copies of itself (see the Addgene link above for more details). This technology is routinely used in many biomedical research labs to introduce foreign genes into cells. These types of experiments using pseudotyped viruses have been done with SARS-CoV-2 spike protein in many published studies (for example, studying which antibodies are able to bind the SARS-CoV-2 spike protein to prevent viral entry). So, this one sentence does not necessarily mean that the researchers were engaged in dangerous gain of function experiments.

Newsweek, however, does report that gain of function studies on bat coronaviruses did occur at the Wuhan Institute of Virology. They write:The article seems to be referring to this 2015 publication in Nature Medicine. As the Newsweek article notes, genetic analysis of the viral RNA would easily spot a virus generated through such gain of function studies, and the SARS-CoV-2 RNA sequence does not show signs of being manipulated in these ways.

The Newsweek article discusses the possibility that the virus could have evolved through passaging of the virus in laboratory conditions, which could adapt a bat virus to be more transmissible in human cells. Again, genetic analysis of the viral RNA has identified various genetic features of the virus that enable its transmissibility in humans. One feature are a set of mutations in the receptor binding domain of the spike protein that help the spike protein bind to the human ACE2 receptor more strongly. These mutations are similar to mutations found in a Pangolin coronavirus, so these mutations were likely introduced naturally into the progenitor bat Coronavirus through recombination. The other feature is a polybasic furin cleavage site within the spike protein, which is not found in other related coronaviruses. It is certainly possible for such sites to evolve naturally, as many other viruses have evolved furin sites in their extracellular proteins (including the MERS coronavirus), though the exact origins of the SARS-CoV-2 furin site remains unknown. While evolution of furin cleavage sites has been observed in laboratory passage of influenza virus, the SARS-CoV-2 sequence has other features (such as the introduction of a glycosylation site) that would not be expected to be selected for during passage in cultured cells, which would disfavor the laboratory passage hypothesis over a natural origin.

While the exact origins of the virus aren't known (and may never be known), most of the existing evidence supports a natural origin over an accidental release hypothesis. Indeed, we know of many new viruses that have jumped from animals to humans (e.g. HIV, ebola, swine flu, avian flu, Zika virus), including two new coronaviruses that have emerged within the past two decades (the original SARS and MERS). Ultimately, extraordinary claims require extraordinary evidence. While we can't disprove the hypothesis that the virus escaped from a lab, I have not seen any compelling evidence to favor the laboratory escape hypothesis over a natural, zoonotic origin of the virus.

The only exception I take is the implication that a laboratory accident and a natural zoonotic origin are necessarily independent.

Is the glycosylation site also evidence against origins that include in-vivo serial passage or knowledge gained through such experiments?

If sars-cov-2 is unlikely to have arisen through gain of function research, would that be evidence that gain of function research on bat coronaviruses is fruitless?

 

[DennisN]

I just heard about this brand new paper which is bang on topic:

Haushofer, Metcalf, "Which interventions work best in a pandemic?" (Science, 21 May 2020)
http://science.sciencemag.org/content/early/2020/05/20/science.abb6144
A PDF is here.

Abstract:

The only approaches currently available to reduce transmission of the novel Coronavirus severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2) are behavioral: handwashing, cough and sneeze etiquette, and above all, social distancing. Policy-makers have a variety of tools to enable these “nonpharmaceutical interventions” (NPIs), ranging from simple encouragement and recommendations to full-on regulation and sanctions. However, these interventions are often used without rigorous empirical evidence: They make sense in theory, and mathematical models can be used to predict their likely impact (1, 2), but with different policies being tried in different places—often in complicated combinations and without systematic, built-in evaluation—we cannot confidently attribute any given reduction in transmission to a specific policy.

Because many of these interventions differ from each other in terms of their economic and psychological cost—ranging from very inexpensive, in the case of interventions based on behavioral economics and psychology, to extremely costly, in the case of school and business closures—it is crucial to identify the interventions that most reduce transmission at the lowest economic and psychological cost. Randomized controlled trials (RCTs) are one of several methods that can be used for this purpose but surprisingly have received little attention in the current pandemic, despite a long history in epidemiology and social science. We describe how RCTs for NPIs can be practically and ethically implemented in a pandemic, how compartmental models from infectious disease epidemiology can be used to minimize measurement requirements, and how to control for spillover effects and harness their benefits.

 

[Vanadium 50]

I was kind of hoping they'd answer that question rather than pose it.

 

[bob012345]

The experiments proposed in this grant would likely not pose the risk of releasing a new pandemic strain of coronavirus. Speaking as someone who has worked in labs that study RNA viruses, there are ways to perform these studies in a safe manner. To study how mutations in the spike protein affect cell entry, scientists create something called a pseudotyped virus. This is essentially taking the spike protein from the coronaviruses that you'd like to study, and putting it on the outside of what is essentially a harmless virus shell. Typically, researchers use lentiviral vectors, which are derived from HIV. These viruses have been extensively modified to prevent them from being able to reproduce, so once the virus enters the cell, it cannot make new copies of itself (see the Addgene link above for more details). This technology is routinely used in many biomedical research labs to introduce foreign genes into cells. These types of experiments using pseudotyped viruses have been done with SARS-CoV-2 spike protein in many published studies (for example, studying which antibodies are able to bind the SARS-CoV-2 spike protein to prevent viral entry). So, this one sentence does not necessarily mean that the researchers were engaged in dangerous gain of function experiments.

Newsweek, however, does report that gain of function studies on bat coronaviruses did occur at the Wuhan Institute of Virology. They write:The article seems to be referring to this 2015 publication in Nature Medicine. As the Newsweek article notes, genetic analysis of the viral RNA would easily spot a virus generated through such gain of function studies, and the SARS-CoV-2 RNA sequence does not show signs of being manipulated in these ways.

The Newsweek article discusses the possibility that the virus could have evolved through passaging of the virus in laboratory conditions, which could adapt a bat virus to be more transmissible in human cells. Again, genetic analysis of the viral RNA has identified various genetic features of the virus that enable its transmissibility in humans. One feature are a set of mutations in the receptor binding domain of the spike protein that help the spike protein bind to the human ACE2 receptor more strongly. These mutations are similar to mutations found in a Pangolin coronavirus, so these mutations were likely introduced naturally into the progenitor bat Coronavirus through recombination. The other feature is a polybasic furin cleavage site within the spike protein, which is not found in other related coronaviruses. It is certainly possible for such sites to evolve naturally, as many other viruses have evolved furin sites in their extracellular proteins (including the MERS coronavirus), though the exact origins of the SARS-CoV-2 furin site remains unknown. While evolution of furin cleavage sites has been observed in laboratory passage of influenza virus, the SARS-CoV-2 sequence has other features (such as the introduction of a glycosylation site) that would not be expected to be selected for during passage in cultured cells, which would disfavor the laboratory passage hypothesis over a natural origin.

While the exact origins of the virus aren't known (and may never be known), most of the existing evidence supports a natural origin over an accidental release hypothesis. Indeed, we know of many new viruses that have jumped from animals to humans (e.g. HIV, ebola, swine flu, avian flu, Zika virus), including two new coronaviruses that have emerged within the past two decades (the original SARS and MERS). Ultimately, extraordinary claims require extraordinary evidence. While we can't disprove the hypothesis that the virus escaped from a lab, I have not seen any compelling evidence to favor the laboratory escape hypothesis over a natural, zoonotic origin of the virus.

Thanks for the informative answer. If it were just me maybe you would have a case but if it's so 'safe' why were the experts like Fauci and others agonizing over whether to do it or not?

"Ultimately, extraordinary claims require extraordinary evidence. "

I strongly disagree. Escaping from a lab known to have safety issues and known to have done dangerous experiments with deadly viruses is definitely NOT the extraordinary claim here! Asserting near total confidence in a unknown natural pathway in spite of all the issues with WVI and gain-of-function research and the Chinese authorities, THAT is the extraordinary claim.

"genetic analysis of the viral RNA would easily spot a virus generated through such gain of function studies,"

There are assumptions in that. Newsweek pointed out there are possible ways it can be modified without being so obvious or even know by the researchers doing it.

"most of the existing evidence supports a natural origin over an accidental release hypothesis."

Accidental release doesn't have to mean it was modified in any way.

Whenever people are involved, bad things can easily happen regardless of safety protocols. Also, I understand there is a very strong motive to "defend science" and if the accident hypothesis turns out be true, that will set back the field immensely. So, I'm going to be skeptical of the rush to clear WVI and gain-of-function research.

 

[Keith_McClary]

This was on CBC "The Current" today:

MG: Let's talk briefly about timelines. You've been involved with vaccines for decades. How long on average does it take to get one to market?

ROB VAN EXAN: Normal timeline is about 15 years. The range is anywhere from 10 to 30. And I would also point out that there's many diseases for which we've been trying to develop a vaccine for many decades and have been unsuccessful.

MG: When you hear politicians and some manufacturers say we're looking at 12 to 18 months, what goes through your mind?

ROB VAN EXAN: I'm highly sceptical of it for a number of reasons. It's, I mean, there's two things in our favour is that there are a lot of vaccines for this disease in the pipeline. One hundred and some. But you also have to realize that out of all of those vaccines, there's only really eight different platforms or eight different technologies. And all of those vaccines are being developed, pretty much all of them using a single antigen for the COVID-19 virus. The spike protein antigen. And so that the this sort of minimizes all of the benefit of that. The normal probability of a vaccine being successful is about 10 percent. So with all these vaccines, yes, we will get something. But how quickly is a question? The first number might fail. Part of this is due to the fact that we know next to nothing about this virus, it's new.

MG: The other part of it is about the scale and how many we would need. I was reading something last night suggesting that just about everybody on the planet is in some way susceptible to this. So you would need, at the very least, what? Eight billion doses maybe people need a couple of different shots. You need sixteen million doses. How long does something like that take to manufacture?

ROB VAN EXAN: Well, I'm looking I'm looking at the manufacturers themselves and saying, what is your manufacturing capacity? The highest I've seen is about a billion doses a year. So you would be looking I mean, if it's a one dose vaccine and there's only one of them, it's eight years till everybody gets a shot.

 

[bob012345]

This was on CBC "The Current" today:

I believe it's possible to make 1 billion doses a month globally if they wanted to. They just have to engineer the process and ramp it up to a capacity many times normal. As a simple comparison, 77% of U.S. adults take vitamins so that's on the order of 150 million doses a day. So 8 billion doses is about 50 days production. Of course a vaccine is likely more complicated but maybe it won't be.

I'm old enough to remember getting the polio vaccine as a child. Long lines at the public High School. The vaccine was given in a sugar cube.