The theories that the virus originated in the wild do not to me explain that the epicenter was in the same city with the leading virology lab. Mere coincidence?
A good question, and not a coincidence at all actually--but in the other direction than what people might think.
The biosafety level 4 lab at the Wuhan Institute of Virology was conceived of as a facility that would be able to study zoonotic viruses. It was constructed in Wuhan specifically to be in a large urban area (thus, access and attractiveness for scientific talent) that also happened to be situated near enough to wilder areas to be able to conduct effective field work. This model has worked quite well for producing a much better understanding of bat viruses than we had when SARS-CoV-1 first appeared in the early 2000s. A couple of other considerations were key in the selection of Wuhan as the location--it is neither a major zone for floods or earthquakes that might compromise containment.
Chiefly, though, this was about having a high biosafety lab in a place where it would also be easy to recruit scientists and to do zoonotic virus field work. Of course this also means that Wuhan was a candidate city for the emergence of a virus like SARS-CoV-2 before the BSL4 lab was ever built, too.
All of that said, this doesn't preclude the possibility of this being a natural virus which was collected in the course of that field work and then accidentally released into the public.
What *does* seem to contradict that possibility is epidemiological analysis performed by Michael Worobey, who has shown a timeline of the first cases in Wuhan and demonstrated that they are geographically separated from the WIV, and centered more meaningfully around a particular seafood market which happened to be conducting illicit live animal trade. What Dr. Worobey has demonstrated does not definitively rule out a laboratory accident involving a natural virus, *but* it does create a narrative that better supports a spillover event unrelated to the laboratory.
We don't have a definitive answer here as to the events that led the virus from bats into humans. It looks quite likely that it happened in the seafood market, or as part of that market's operations. It remains possible that it also happened in the course of work with field samples at WIV as well, but this seems *less* likely.
What I can be pretty certain of is that this is a virus that *originated* in the wild, at this point--and everything I've discussed so far is just about how it transitioned from "the wild" to humans. A laboratory leak facilitating the transfer of a naturally-occurring virus to the general population, or a live animal market spillover event both represent the results of humans interacting with wild bats carrying a natural virus. Again, I think the market is most likely here, but I can't rule either possibility out.
What I feel more confident about ruling out is the possibility of intentional design of the virus. The sequence doesn't have any indications of that, it has features that suggest the contrary, and the papers I discussed in today's issue further reinforce the natural origins of the virus itself. I will note again, though, this isn't definitive. It's just a lot of very highly suggestive evidence.
So that leaves us mainly with the question of "How did the virus get from the wild to the city?" And that may be a lot harder to answer any time soon with a high degree of confidence, but the most likely answer from evidence so far is the seafood market. I'm hopeful we will learn more on this, but it may take a while.
There is a pretty rigid definition of "gain of function" research in US granting institution lingo. According to that definition, nothing being done at WIV was gain of function research to the best of my knowledge.
Were they doing experiments where viruses were modified to add functionality? As I understand in some cases they made certain viruses better at infecting mouse cells. Mouse adaptation is a pretty routine virology process.
There is a wider debate on "gain of function" research, however. There are those who would portray it as dangerous modification of viruses, but their argument relies on ignoring both the limited nature of our currently virological knowledge (most gain of function experiments produce a virus that is significantly hampered in other ways beyond the changes that have been introduced) as well as ignoring the vast and powerful nature of the evolutionary machine that exists in the wild. With one mutation per genome, at least, a single virus infection in a single animal does more gain of function experiments than any virologist could do in a lifetime. It also does an even bigger set of loss of function experiments.
To stigmatize gain of function research is to essentially say we want to have a blind spot with regard to what is going on in nature with regard to virus evolution.
This having been said, I do think certain restrictions on gain of function research make sense, and the NIH does have some restrictions on it. Those could perhaps be revamped and keenly specified, but I do not think that gain of function research and the COVID-19 pandemic are connected. At the very least, there is no evidence connecting them. Plenty of speculation about conspiracies to cover up such a connection, but as yet, no evidence of that connection.
As the son of a philosopher and former biology teacher, I have to harp on a nomenclature and taxonomy matter. (There's a weird sentence!)
Referring to "vaccination" in this context, unqualified, can mislead. Vaccination with US-approved vaccines? AstraZeneca? Sputnik 5? Covovax? CORBEVAX? One of the Chinese vaccines? Cuban? Turkey's homegrown entry?
I speculate from your reference to "one-dose" vaccination not being efficacious, and that the results are from the UK, that it might be US-approved mRNA vaccines plus AstraZeneca, but I don't know. So now I'll check.
[checks]
"Being vaccinated was defined as having two doses of the Pfizer-BioNTech, Oxford-AstraZeneca, or Moderna vaccine or one dose of the Janssen vaccine." So that's a very heterogeneous population, then. The link appears to be a very quick review of 8 studies using the UK's NIH dataset. They don't appear to compare between people who received different vaccines--their result is compatible with, say, AstraZeneca being twice as effective in preventing long-term symptoms as Moderna. (Presumably the underlying studies would have caught that, but it isn't discussed in this particular article that I saw.) There's no mention of people given two different vaccines (booster not matching original shots, say), and obviously they haven't studied any of the newly approved vaccines like Covovax.
Something else I noticed: "The review found that vaccine effectiveness against most post-covid symptoms in adults was highest in people over 60 and lowest in those aged 19 to 35." Interesting. Also weird. Is this perhaps because older folks like me would be more likely to have Long COVID in the first place?
When risk factors have been mentioned, female 30-50 and allergy/asthma have been a few of the listed ones. I wonder whether that figures in on where vax is reduction?
And I've been ranting for a while about how I want to see figures on both likelihood in general and post vax of CFS/ME vs lung function vs cardiovascular issues vs dysautonomia vs hair loss, all of which would count under long covid.
thing is, severity of initial symptoms seems to be a big deal with cardiac issues, but I don't remember that coming up in terms of most of the other issues.
The sex-category bias may have to do with an autoimmune dimension of the disease, also. Autoimmune conditions are more common in women. That statement is the tip of a very big iceberg.
Afterthought, and maybe encouraging to you and your bride. You were disappointed that the benefit was only around 50%. This study doesn't cover the boosted. Perhaps folks you like you will do better.
The theories that the virus originated in the wild do not to me explain that the epicenter was in the same city with the leading virology lab. Mere coincidence?
A good question, and not a coincidence at all actually--but in the other direction than what people might think.
The biosafety level 4 lab at the Wuhan Institute of Virology was conceived of as a facility that would be able to study zoonotic viruses. It was constructed in Wuhan specifically to be in a large urban area (thus, access and attractiveness for scientific talent) that also happened to be situated near enough to wilder areas to be able to conduct effective field work. This model has worked quite well for producing a much better understanding of bat viruses than we had when SARS-CoV-1 first appeared in the early 2000s. A couple of other considerations were key in the selection of Wuhan as the location--it is neither a major zone for floods or earthquakes that might compromise containment.
Chiefly, though, this was about having a high biosafety lab in a place where it would also be easy to recruit scientists and to do zoonotic virus field work. Of course this also means that Wuhan was a candidate city for the emergence of a virus like SARS-CoV-2 before the BSL4 lab was ever built, too.
All of that said, this doesn't preclude the possibility of this being a natural virus which was collected in the course of that field work and then accidentally released into the public.
What *does* seem to contradict that possibility is epidemiological analysis performed by Michael Worobey, who has shown a timeline of the first cases in Wuhan and demonstrated that they are geographically separated from the WIV, and centered more meaningfully around a particular seafood market which happened to be conducting illicit live animal trade. What Dr. Worobey has demonstrated does not definitively rule out a laboratory accident involving a natural virus, *but* it does create a narrative that better supports a spillover event unrelated to the laboratory.
We don't have a definitive answer here as to the events that led the virus from bats into humans. It looks quite likely that it happened in the seafood market, or as part of that market's operations. It remains possible that it also happened in the course of work with field samples at WIV as well, but this seems *less* likely.
What I can be pretty certain of is that this is a virus that *originated* in the wild, at this point--and everything I've discussed so far is just about how it transitioned from "the wild" to humans. A laboratory leak facilitating the transfer of a naturally-occurring virus to the general population, or a live animal market spillover event both represent the results of humans interacting with wild bats carrying a natural virus. Again, I think the market is most likely here, but I can't rule either possibility out.
What I feel more confident about ruling out is the possibility of intentional design of the virus. The sequence doesn't have any indications of that, it has features that suggest the contrary, and the papers I discussed in today's issue further reinforce the natural origins of the virus itself. I will note again, though, this isn't definitive. It's just a lot of very highly suggestive evidence.
So that leaves us mainly with the question of "How did the virus get from the wild to the city?" And that may be a lot harder to answer any time soon with a high degree of confidence, but the most likely answer from evidence so far is the seafood market. I'm hopeful we will learn more on this, but it may take a while.
Thank you for that answer. Do we know, as a general matter, if the WVI was engaged in "gain of function" research?
This is a matter of much speculation and debate.
There is a pretty rigid definition of "gain of function" research in US granting institution lingo. According to that definition, nothing being done at WIV was gain of function research to the best of my knowledge.
Were they doing experiments where viruses were modified to add functionality? As I understand in some cases they made certain viruses better at infecting mouse cells. Mouse adaptation is a pretty routine virology process.
There is a wider debate on "gain of function" research, however. There are those who would portray it as dangerous modification of viruses, but their argument relies on ignoring both the limited nature of our currently virological knowledge (most gain of function experiments produce a virus that is significantly hampered in other ways beyond the changes that have been introduced) as well as ignoring the vast and powerful nature of the evolutionary machine that exists in the wild. With one mutation per genome, at least, a single virus infection in a single animal does more gain of function experiments than any virologist could do in a lifetime. It also does an even bigger set of loss of function experiments.
To stigmatize gain of function research is to essentially say we want to have a blind spot with regard to what is going on in nature with regard to virus evolution.
This having been said, I do think certain restrictions on gain of function research make sense, and the NIH does have some restrictions on it. Those could perhaps be revamped and keenly specified, but I do not think that gain of function research and the COVID-19 pandemic are connected. At the very least, there is no evidence connecting them. Plenty of speculation about conspiracies to cover up such a connection, but as yet, no evidence of that connection.
As the son of a philosopher and former biology teacher, I have to harp on a nomenclature and taxonomy matter. (There's a weird sentence!)
Referring to "vaccination" in this context, unqualified, can mislead. Vaccination with US-approved vaccines? AstraZeneca? Sputnik 5? Covovax? CORBEVAX? One of the Chinese vaccines? Cuban? Turkey's homegrown entry?
I speculate from your reference to "one-dose" vaccination not being efficacious, and that the results are from the UK, that it might be US-approved mRNA vaccines plus AstraZeneca, but I don't know. So now I'll check.
[checks]
"Being vaccinated was defined as having two doses of the Pfizer-BioNTech, Oxford-AstraZeneca, or Moderna vaccine or one dose of the Janssen vaccine." So that's a very heterogeneous population, then. The link appears to be a very quick review of 8 studies using the UK's NIH dataset. They don't appear to compare between people who received different vaccines--their result is compatible with, say, AstraZeneca being twice as effective in preventing long-term symptoms as Moderna. (Presumably the underlying studies would have caught that, but it isn't discussed in this particular article that I saw.) There's no mention of people given two different vaccines (booster not matching original shots, say), and obviously they haven't studied any of the newly approved vaccines like Covovax.
Something else I noticed: "The review found that vaccine effectiveness against most post-covid symptoms in adults was highest in people over 60 and lowest in those aged 19 to 35." Interesting. Also weird. Is this perhaps because older folks like me would be more likely to have Long COVID in the first place?
When risk factors have been mentioned, female 30-50 and allergy/asthma have been a few of the listed ones. I wonder whether that figures in on where vax is reduction?
And I've been ranting for a while about how I want to see figures on both likelihood in general and post vax of CFS/ME vs lung function vs cardiovascular issues vs dysautonomia vs hair loss, all of which would count under long covid.
I've definitely seen specific studies in which vax => baseline. Here's a discussion of one preprint: https://mobile.twitter.com/sailorrooscout/status/1483166149110116353
The risk factors for death include being male, so ... maybe we just die before we can get Long COVID?
thing is, severity of initial symptoms seems to be a big deal with cardiac issues, but I don't remember that coming up in terms of most of the other issues.
The sex-category bias may have to do with an autoimmune dimension of the disease, also. Autoimmune conditions are more common in women. That statement is the tip of a very big iceberg.
Afterthought, and maybe encouraging to you and your bride. You were disappointed that the benefit was only around 50%. This study doesn't cover the boosted. Perhaps folks you like you will do better.
Very good point!