I'm not qualified to assess the risk, but if the there's indeed ADE (antibody dependent enhancement),[1][2] people once infected with a milder strain may suffer from more severe symptom from the deadlier strains, thus killing more people in the end.
I'm wondering how we may rule out this worst case scenario.
Article [1] is dated Feb 12, and contains the sentence:
"Instead, it [SARS-CoV-2] appears to be no more concerning than the influenza virus." The citation for this claim is an article in Canada's National Post.
I posted and deleted a few comments. I don't know what to make of this and it's getting controversial. If it could be helpful, I'd love to improve it. I just don't know where it fits in ongoing discussions by prominent researchers on analysis of strains and types.
Three things that jump out at me:
a) You'll get more credibility from having a thorough lit review than from listing credentials. Linking to magazine articles from journalists on genetic variations, when there's academic research to cite, is a little bewildering.
b) You don't identify something harmless by just testing asymptomatics. This is counterintuitive, but a great example of the Wason selection task:
You would probably want to survey the rate of variants in asymptomatics in a certain community, then compare that with the rate of variants in fatal cases in the same community to look for significant differences (and be fully prepared not to find any significant differences beyond chance, a real and likely possibility).
c) I'm still not sure what the author is specifically recommending we do next. Researchers are looking for functional variants, we don't have one to distribute yet, so we should do more sequencing. Ok, great. From what populations? How many geographic areas? Where do we get the samples? There are bottlenecks in sample collection, how do we overcome those? Given (b), how can we get more samples from fatal cases, to compare virulence to those in the general population? Task overloaded hospitals to send us additional samples from dying patients? Is there another way we can get this info?
I don't want to dismiss this out of hand, this might be a good area for additional focused research. I do think there are some key unanswered questions though, and currently a worrying disconnect with the current state of research on variants.
EDIT: Daniel, I know you're going through the comments here, and some of them have gotten pretty harsh, sorry for that. I genuinely hope you're on to something, and are able to continue to refine the post into a more robust and specific proposal using all this feedback, despite the tenor of some of the comments. That's really the best case for all of us, so good luck.
Just woke up (I am in Australia). I expect some harsh comments as the idea is controversial. To your specific points.
a) The post was intended for a lay audience, not other scientists directly. The reason I didn’t write a scientific paper on this is it would sink without a trace as most scientists and doctors are too conservative. It is quite a radical idea and while scientifically sound, it will take mavericks outside of science to see this done. For better or worse it will take the efforts of someone like on of the tech billionaires to push this forward.
b) If I had to choose one aspect that gets most commonly confused by people who read the idea it would be the reason for searching only mild/asymptomatic cases. This is purely an efficiency issue. In an ideal world we would sequence the strains in all cases, look to see if we can find mutants with deletions, and then see what was the clinical outcome of those infected with that strain. If we find that all cases of a particular mutant are mild/asymptomatic then we would have our candidate.
Because we live in a constrained world where it is not possible to sequence all cases, where should we first look? Since we are looking for a mutant that only causes mild/asymptomatic cases we can exclude patients with serious symptoms as a first pass. Once we find a candidate strain that has the right sort of mutation we can then sequence all cases in the local area, both serious and mild to get the full clinical picture. This will make the search much more efficient.
c) I am recommending that we put b) into action and get on with specifically looking for an attenuated (only causes mild disease) strain ASAP. If we find one then we can discuss what to do next, but the first step is to get started.
The good news is this can be done quickly and relatively cheaply provide we have the will and the support of someone with the clout to make it happen. It won’t be easy, but it can be done.
> b) You don't identify something harmless by just testing asymptomatics.
True, but I think you are missing part of Daniel's proposal. You don't "just" check for unique variations of the virus in asymptomatic carriers, you also check the sequence for major deletions: We would ideally be looking for a virus strain with a large(ish) deletion in an essential viral gene. This sort of mutation is easy to spot in the SARS-CoV-2 genome data, and because the genetic information has been removed, it makes the virus very unlikely to be able to mutate back into a dangerous strain. Ideally, the strain identified will have infected a number of other people in the local area too so we can know it is safe.
So while you do want to verify that the sequence is not also present in "serious" cases, you are prescreening by a factor that theoretically should correlate to severity. Whether you "need" to do additional testing depends on your assessment of base risk. If you assume that almost everyone is going to be infected with a powerful strain if you do nothing, doing your testing in live cases with a strain you suspect is mild might still be justified. Ideally (as quoted from Daniel) this "testing" might be mostly satisfied by just monitoring those already infected by the original carrier(s) with the same mild strain.
How does the Iceland data suggest the hypotheses that 1) an attenuated strain exists in the wild and 2) it provides immunity to the worse strain? It's asserted in the post, but I don't see it. It seems likely to me their experience isn't any different from any other country's, and they're just testing more.
The idea in the post is obviously a good one if it can be done, it's just that it seems like a generic idea that should be considered for any viral pandemic, which makes me wonder why it's not already an approach people are working on.
As for why people aren’t working on this idea I don’t know. Maybe someone is and they will send me an email and I can update my post. I would certainly be extremely happy with this outcome.
Can you provide peer / concept review from virologists?
A few items of feedback:
- You could use a title that includes a distinct word to identify your proposed solution: "Using accentuated COVID-19 strains as a (possible) solution". This helps people to communicate and refer to the idea concisely.
- The top three paragraphs may be known to your target audience; consider allowing the reader to get straight to your point.
- It took me a while (certainly to the Q&A section) to grasp that attenuated virus strains are different from dangerous ones. Explaining this (perhaps in a brief sentence, then repeated and elaborated in a more detailed paragraph) near the top may also help.
- Further references (especially peer review from respected authors) may help gain traction. Decision makers can be -- sensibly -- risk averse in global crises like these.
I am a virologist - well I have published many papers in this area. I have a PhD in molecular microbiology and have been a tenured professor (I now work in the biotech sector). This is not intended to be a scientific paper, but a layman’s summary of the idea so non-technical people can understand the idea.
It is not risky to go looking for a naturally attenuated virus. This is the first step that needs to happen.
While you do not recommend ZJ01 due to the potential for it to mutate back into the original strain, isn't it also quite dangerous?
That would likely remain a primary concern for many - we musn't cause large scale harm intentionally. And if we don't know what effects a strain has, it makes it ethically difficult to distribute.
From the ZJ01 Medrxiv[1] page you link to:
"We found, in our 788 confirmed COVID-19 patients, the decreased rate of severe/critical type, increased liver/kidney damage and prolonged period of nuclear acid positivity during virus dissemination, when compared with Wuhan."
I hear the phrase "peer review" thrown around so much it's reaching semantic satiation. I get that it's the way respected science gets done, but it's also the laziest possible critique because you're literally asking for someone else to think about it for you.
A naturally attenuated strain would still be regulated. In the US, 21 USC §321(g):
> (1) The term "drug" means… (B) articles intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease in man or other animals;
CBER would be the responsible center for the FDA. Other countries have analogous regulations.
Could you come to market with a naturally attenuated strain? Yes. Would it take less time? Not really, because you don’t get to do an “end run around the regulations” as you put it in another comment. The logistics of making sure it works and then setting up the supply chain and quality systems are what take the most time. There are no shortcuts in medicine.
There are plenty of shortcuts in medicine. Think how you would stop this strain from being spread by individuals once it was identified. This strain will spread no matter what the FDA says.
Personally I think the regulatory authorities would rapid approve it based on the epidemiology data collected in the process of finding the strain. The FDA has already shown that it can move faster than its usual glacial pace given sufficient motivation.
The much more important question is when are we going to start seriously looking for such a strain?
Robin Hanson has been covering variolation: http://www.overcomingbias.com/2020/04/variolation-test-desig... and part of the issue is that the FDA is poorly equipped and set up to respond to a pandemic. One obvious solution is to cut through the bureaucracy and make emergency exceptions, but no one with political power in the US seems to know this, or understand it.
Alternatively, if this approach actually works, all the countries in the world that can appropriately adapt their regulations will survive, and the ones that choose not to won't.
Virus can be asymptomatic for a number of reasons. Host factors, such as age, (speculation) history of the previous coronavirus but not covid-19 infections, etc.
Going after covid-19 genomes in a group of asymptomatic and symptomatic 70+ years old with sampling from different regions/countries may give us better data.
Finding a mutated strain which never gives symptoms in old people from diverse locations, diet, health status etc. is the holy grail of this approach.
I just sent your article to my contacts at the White House, Department of Defense, DARPA and a couple of other acronym agencies. I sent this to Director level people (or just under) at those agencies.
No guarantees (they are all swamped). I hope they respond and put you in touch with the right people.
I totally missed it from the article but how is he going to tell the deadly strain from the less deadly one? I mean I understand how they can tell the difference between the two strains. But how to tell that some particular strain is less deadly? To the best of my understanding the only way to get there is to sequence the virus from statistically significant number (~10^5 ??) of carriers including the significant proportion of those with asymptomatic cases. Not realistic IMHO.
Not to mention relying on each person's account of the severity of the symptoms, and coding that into a dataset that corresponds to the sequencing results. You need a LOT of asymptomatic people with the strain in order to draw any strong conclusions.
The upside is, you may draw other very interesting conclusions while collecting data for this mission, and be able to "pivot" if you will.
This is all described in the post. I have updated it to make it a little clearer (based on feedback). If you missed it the first time around you might get it now.
You make this statement: "The most important thing to note is that such a virus would not be a vaccine from a regulatory perspective."
Can you provide any evidence to back up this statement? If you were to start intentionally infecting people with a (naturally) attenuated strain claiming that it will confer immunity I suspect authorities would request you get regulatory approval.
If you're approach does require regulatory approval. What advantage does your approach have over those currently in developement? Some of them are just bits of the virus (mRNA that codes for the spike protein) packaged with a delivery mechanism [1].
It's a plausible approach, that has been tested in animal studies. There are a number of other, similarly plausible vaccines entering human trials.
It is however deemed to be too high risk to just start giving the vaccine to large numbers of people. So the vaccine will have to go through (an accelerated) trial process. It will then likely be given to at risk groups (health care professionals), before becoming widely available. Most experts expect this to take at least 16 months (which would be a world record).
Your approach would have the same issues as are present with any other vaccine.
If regulatory authorities are willing to skip trials for your approach, then the same should apply to other vaccines under development.
You are looking at this from the wrong perspective. If people start spreading this attenuated strain around on their own what are the regulatory agencies going to do?
Even if you wanted to go down the regulatory pathway for some reason it still has a number of advantages over other approaches.
1. We would know it is safe in humans before we began.
2. We would know what mutations make the virus less pathogenic.
3. Once used it would drive the pathogenic strains to extinction.
4. It will be work in poor countries that can’t afford or distribute a conventional vaccine.
5. It will infect and protect those that are not deliberately infected through contact with others.
I like your idea a lot. It seems that a 12 nucleotide insertion mutation is responsible for a lot of the Covid-19 virulence. If such a large mutation is possible, how would we prevent your loss of function asymptomatic strain from reverting its mutation in the wild? How big of a mutation are you envisioning? Is it impossible for it to be reverted in the wild or just unlikely?
I think 12 nucleotides is too small, I would be happier with something north of 30. There have already been strains identified with a deletion of 382 bases [0].
Yes this is true. For the purpose of my idea it doesn’t matter if the person is asymptomatic or they just have a mild case. What is important is the strain identified doesn’t put people in hospital.
I don't know if all [corona]viruses move this way but it seems covid illness evolution goes in waves. high symptoms, 2 days ok, high symptoms, 2 days ok, ... repeat a few cycles
It's pretty confusing when symptoms are below a critical threshold and you don't have a test yet.
The results of a study in austria with 1500 randomly selected citizens have just been published, just 5 have been found to be currently infected with SARS-CoV2.
The conclusion is that the prevalence of asymptomatic cases is about 0,32%, CL95 is 0,12-0,76%.
Stupid question: if you only search people with mild or even asymptomatic cases, how does that even tell you something about the virus? Should you not also search in (many) severe cases for the candidate, to exclude it from the list of dangerous virii?
I see two problems with this approach, both political / social:
- No one will want to be the one "deploying" the attenuated strain in a human and then be responsible for some unforeseen death (even if it's just 1 in a billion). Utilitarianism is not widespread nor socially accepted. Even less so in politicians, who are quite risk averse.
- There is no lobby supporting it. There's no $$ to be made and the "vaccine" is basically free.
No one will want to be the one "deploying" the attenuated strain in a human and then be responsible for some unforeseen death (even if it's just 1 in a billion). Utilitarianism is not widespread nor socially accepted. Even less so in politicians, who are quite risk averse.
I would give them more credit, especially in a situation where the status quo includes so many deaths. I was impressed with how readily most states licensed self-driving vehicles, knowing that there would certainly be deaths. Their rationality here likely came from seeing tens of thousands of people dying on the roads each year.
Lets solve this issues once we find the right attenuated strain. Personally I think these sort of social problems will be overcome once we compare with the alternative of sitting around waiting for a vaccine.
I am not an expert, so I apologize if these are a dumb questions, but here goes:
1) Wouldn't natural selection result in a milder strain crowding out a more deadly strain? After shelter in place lifts, people with a mild strain will be more likely to go out and spread the virus whereas people with the deadly strain will be more likely to stay home sick.
2) Is there any consensus on whether we become immune to COVID after getting it (e.g. if we get a mild strain will we really be immune to a deadly one)? I've heard different opinions and I'm wondering what the leading hypothesis is at the moment.
This reminds me of a story 20 years ago when Pittsburgh Steelers (American football) announcer Myron Cope ran into head coach Bill Cowher...
Myron said, "I see that Lee Flowers is playing today after a high ankle sprain 2 weeks ago. But I thought that high ankle sprains took 4 weeks to heal. What gives?"
Coach Cowher replied, "4 weeks is true, Myron, for the first high ankle sprain. But if you recall, Lee had a high ankle sprain on the same foot last year. And since subsequent high ankle sprains only take 2 weeks to heal, he's ready to play."
Myron paused and asked, "Then why don't you just take the whole team out in February and sprain all their ankles?"
(We laughed 20 years ago. Nobody's laughing today.)
This reminds me of the old joke that, because the possibility of there being two bombs on a plane is infinitesimally small, you should always bring your own bomb with you.
I understand the metaphor you’re using, but for the sake of clarity I feel compelled to explain that there is a big difference: ankle-spraining significantly increases in likelihood with each subsequent instance. So “spraining ‘em all” even once would literally result in long-term degradation and increased frequency of injury. They would take less to heal, but would also get injured so often that the aggregated result would be worse than before.
Sadly joints tend to work a bit differently from the immune system (with some exceptions).
This is exactly the sort of strain we want to be looking for all though we want a strain that doesn’t come from hospitalised patients. This deletion is still too pathogenic for our needs, but it does prove these deletion strains are out there. If we look we will find.
How would you allow the harmless strain to spread without also spreading the deadly strain? If you relax or reverse social distancing, wouldn't the deadly strain also have a chance to spread widely again? It seems like you'd need to manually administer this strain to millions of people, or have very carefully administered 'contagion parties' where everyone is pre-screened for the deadly strain, while everyone else keeps social distancing.
I don't think the mutations are the reason for asymptomatic cases. Coronaviruses mutate very slowly.
More likely, viral load, immune system strength, overall age and the genetics of the person infected are what determines if the infection is fought off before any symptoms are shown
2. Regla-Nava, J. A. et al. Severe acute respiratory syndrome coronaviruses with mutations in the E protein are attenuated and promising vaccine candidates. J. Virol. 89, 3870–3887 (2015). https://www.ncbi.nlm.nih.gov/pubmed/25609816/
Authors idea of spreading the attenuated virus is based on the idea that if the immediate COVID-19 disease can be avoided, increasing viral load in population is smaller risk. I think that's the weak point. If the vaccine is developed and the virus establishes itself in the population, the number of people getting infected will be lower overall and less people will get severe disease due to natural immunity + vaccine.
ps.
> appears to be killing between 1% to 3.5% of the people it infects
Author is confusing case fatality rate (CFR) with infection fatality rate (IFR). Infection fatality ratio seems to be something like 0.6% according to recent estimates. IFR estimates seem to go down over time.
[+] [-] dongping|6 years ago|reply
I'm wondering how we may rule out this worst case scenario.
[1] Is COVID-19 receiving ADE from other coronaviruses? https://www.sciencedirect.com/science/article/pii/S128645792...
[2] New blood tests for antibodies could show true scale of coronavirus pandemic https://www.sciencemag.org/news/2020/03/new-blood-tests-anti...
[+] [-] danieltillett|6 years ago|reply
Hard to rule out worst case scenarios, we just have to work with what we have and make hard choices.
[+] [-] nolta|6 years ago|reply
"Instead, it [SARS-CoV-2] appears to be no more concerning than the influenza virus." The citation for this claim is an article in Canada's National Post.
[+] [-] brownbat|6 years ago|reply
Three things that jump out at me:
a) You'll get more credibility from having a thorough lit review than from listing credentials. Linking to magazine articles from journalists on genetic variations, when there's academic research to cite, is a little bewildering.
b) You don't identify something harmless by just testing asymptomatics. This is counterintuitive, but a great example of the Wason selection task:
https://en.wikipedia.org/wiki/Wason_selection_task
You would probably want to survey the rate of variants in asymptomatics in a certain community, then compare that with the rate of variants in fatal cases in the same community to look for significant differences (and be fully prepared not to find any significant differences beyond chance, a real and likely possibility).
c) I'm still not sure what the author is specifically recommending we do next. Researchers are looking for functional variants, we don't have one to distribute yet, so we should do more sequencing. Ok, great. From what populations? How many geographic areas? Where do we get the samples? There are bottlenecks in sample collection, how do we overcome those? Given (b), how can we get more samples from fatal cases, to compare virulence to those in the general population? Task overloaded hospitals to send us additional samples from dying patients? Is there another way we can get this info?
I don't want to dismiss this out of hand, this might be a good area for additional focused research. I do think there are some key unanswered questions though, and currently a worrying disconnect with the current state of research on variants.
EDIT: Daniel, I know you're going through the comments here, and some of them have gotten pretty harsh, sorry for that. I genuinely hope you're on to something, and are able to continue to refine the post into a more robust and specific proposal using all this feedback, despite the tenor of some of the comments. That's really the best case for all of us, so good luck.
[+] [-] danieltillett|6 years ago|reply
a) The post was intended for a lay audience, not other scientists directly. The reason I didn’t write a scientific paper on this is it would sink without a trace as most scientists and doctors are too conservative. It is quite a radical idea and while scientifically sound, it will take mavericks outside of science to see this done. For better or worse it will take the efforts of someone like on of the tech billionaires to push this forward.
b) If I had to choose one aspect that gets most commonly confused by people who read the idea it would be the reason for searching only mild/asymptomatic cases. This is purely an efficiency issue. In an ideal world we would sequence the strains in all cases, look to see if we can find mutants with deletions, and then see what was the clinical outcome of those infected with that strain. If we find that all cases of a particular mutant are mild/asymptomatic then we would have our candidate.
Because we live in a constrained world where it is not possible to sequence all cases, where should we first look? Since we are looking for a mutant that only causes mild/asymptomatic cases we can exclude patients with serious symptoms as a first pass. Once we find a candidate strain that has the right sort of mutation we can then sequence all cases in the local area, both serious and mild to get the full clinical picture. This will make the search much more efficient.
c) I am recommending that we put b) into action and get on with specifically looking for an attenuated (only causes mild disease) strain ASAP. If we find one then we can discuss what to do next, but the first step is to get started.
The good news is this can be done quickly and relatively cheaply provide we have the will and the support of someone with the clout to make it happen. It won’t be easy, but it can be done.
[+] [-] nkurz|6 years ago|reply
True, but I think you are missing part of Daniel's proposal. You don't "just" check for unique variations of the virus in asymptomatic carriers, you also check the sequence for major deletions: We would ideally be looking for a virus strain with a large(ish) deletion in an essential viral gene. This sort of mutation is easy to spot in the SARS-CoV-2 genome data, and because the genetic information has been removed, it makes the virus very unlikely to be able to mutate back into a dangerous strain. Ideally, the strain identified will have infected a number of other people in the local area too so we can know it is safe.
So while you do want to verify that the sequence is not also present in "serious" cases, you are prescreening by a factor that theoretically should correlate to severity. Whether you "need" to do additional testing depends on your assessment of base risk. If you assume that almost everyone is going to be infected with a powerful strain if you do nothing, doing your testing in live cases with a strain you suspect is mild might still be justified. Ideally (as quoted from Daniel) this "testing" might be mostly satisfied by just monitoring those already infected by the original carrier(s) with the same mild strain.
[+] [-] ubercow13|6 years ago|reply
[+] [-] losvedir|6 years ago|reply
The idea in the post is obviously a good one if it can be done, it's just that it seems like a generic idea that should be considered for any viral pandemic, which makes me wonder why it's not already an approach people are working on.
[+] [-] danieltillett|6 years ago|reply
As for why people aren’t working on this idea I don’t know. Maybe someone is and they will send me an email and I can update my post. I would certainly be extremely happy with this outcome.
[+] [-] jka|6 years ago|reply
Can you provide peer / concept review from virologists?
A few items of feedback:
- You could use a title that includes a distinct word to identify your proposed solution: "Using accentuated COVID-19 strains as a (possible) solution". This helps people to communicate and refer to the idea concisely.
- The top three paragraphs may be known to your target audience; consider allowing the reader to get straight to your point.
- It took me a while (certainly to the Q&A section) to grasp that attenuated virus strains are different from dangerous ones. Explaining this (perhaps in a brief sentence, then repeated and elaborated in a more detailed paragraph) near the top may also help.
- Further references (especially peer review from respected authors) may help gain traction. Decision makers can be -- sensibly -- risk averse in global crises like these.
Good luck!
[+] [-] danieltillett|6 years ago|reply
It is not risky to go looking for a naturally attenuated virus. This is the first step that needs to happen.
[+] [-] jka|6 years ago|reply
While you do not recommend ZJ01 due to the potential for it to mutate back into the original strain, isn't it also quite dangerous?
That would likely remain a primary concern for many - we musn't cause large scale harm intentionally. And if we don't know what effects a strain has, it makes it ethically difficult to distribute.
From the ZJ01 Medrxiv[1] page you link to:
"We found, in our 788 confirmed COVID-19 patients, the decreased rate of severe/critical type, increased liver/kidney damage and prolonged period of nuclear acid positivity during virus dissemination, when compared with Wuhan."
[1] - https://www.medrxiv.org/content/10.1101/2020.03.10.20033944v...
[+] [-] Igelau|6 years ago|reply
[+] [-] IdoRA|6 years ago|reply
> (1) The term "drug" means… (B) articles intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease in man or other animals;
CBER would be the responsible center for the FDA. Other countries have analogous regulations.
Could you come to market with a naturally attenuated strain? Yes. Would it take less time? Not really, because you don’t get to do an “end run around the regulations” as you put it in another comment. The logistics of making sure it works and then setting up the supply chain and quality systems are what take the most time. There are no shortcuts in medicine.
[+] [-] danieltillett|6 years ago|reply
Personally I think the regulatory authorities would rapid approve it based on the epidemiology data collected in the process of finding the strain. The FDA has already shown that it can move faster than its usual glacial pace given sufficient motivation.
The much more important question is when are we going to start seriously looking for such a strain?
[+] [-] jseliger|6 years ago|reply
[+] [-] buboard|6 years ago|reply
[+] [-] exikyut|6 years ago|reply
Natural selection versus bureaucracy!
[+] [-] elmolino89|6 years ago|reply
Going after covid-19 genomes in a group of asymptomatic and symptomatic 70+ years old with sampling from different regions/countries may give us better data.
Finding a mutated strain which never gives symptoms in old people from diverse locations, diet, health status etc. is the holy grail of this approach.
[+] [-] danieltillett|6 years ago|reply
Happy to answer questions about the idea, but I am most interested in find collaborators to make it happen ASAP.
[+] [-] robomartin|6 years ago|reply
No guarantees (they are all swamped). I hope they respond and put you in touch with the right people.
[+] [-] mkl|6 years ago|reply
[+] [-] grey-area|6 years ago|reply
https://crowdfightcovid19.org/
[+] [-] Glavnokoman|6 years ago|reply
[+] [-] joncrane|6 years ago|reply
The upside is, you may draw other very interesting conclusions while collecting data for this mission, and be able to "pivot" if you will.
[+] [-] danieltillett|6 years ago|reply
[+] [-] new299|6 years ago|reply
Can you provide any evidence to back up this statement? If you were to start intentionally infecting people with a (naturally) attenuated strain claiming that it will confer immunity I suspect authorities would request you get regulatory approval.
If you're approach does require regulatory approval. What advantage does your approach have over those currently in developement? Some of them are just bits of the virus (mRNA that codes for the spike protein) packaged with a delivery mechanism [1].
It's a plausible approach, that has been tested in animal studies. There are a number of other, similarly plausible vaccines entering human trials.
It is however deemed to be too high risk to just start giving the vaccine to large numbers of people. So the vaccine will have to go through (an accelerated) trial process. It will then likely be given to at risk groups (health care professionals), before becoming widely available. Most experts expect this to take at least 16 months (which would be a world record).
Your approach would have the same issues as are present with any other vaccine.
If regulatory authorities are willing to skip trials for your approach, then the same should apply to other vaccines under development.
[1] https://www.modernatx.com/modernas-work-potential-vaccine-ag...
[+] [-] danieltillett|6 years ago|reply
Even if you wanted to go down the regulatory pathway for some reason it still has a number of advantages over other approaches.
1. We would know it is safe in humans before we began.
2. We would know what mutations make the virus less pathogenic.
3. Once used it would drive the pathogenic strains to extinction.
4. It will be work in poor countries that can’t afford or distribute a conventional vaccine.
5. It will infect and protect those that are not deliberately infected through contact with others.
[+] [-] JohnJamesRambo|6 years ago|reply
https://www.nature.com/articles/s41591-020-0820-9
[+] [-] danieltillett|6 years ago|reply
0. https://www.biorxiv.org/content/10.1101/2020.03.11.987222v1....
[+] [-] ziga|6 years ago|reply
Note: asymptomatic at the time of testing. They may still develop symptoms over time.
https://www.icelandreview.com/sci-tech/is-icelands-coronavir...
https://twitter.com/cmyeaton/status/1246196001775460358
[+] [-] danieltillett|6 years ago|reply
[+] [-] raverbashing|6 years ago|reply
Apparently 80% of those tested later get symptoms: https://twitter.com/TonyBurnetti/status/1246258723774963713
[+] [-] agumonkey|6 years ago|reply
It's pretty confusing when symptoms are below a critical threshold and you don't have a test yet.
[+] [-] moopling|6 years ago|reply
[+] [-] rmu09|6 years ago|reply
The conclusion is that the prevalence of asymptomatic cases is about 0,32%, CL95 is 0,12-0,76%.
Link (in german): https://www.sora.at/nc/news-presse/news/news-einzelansicht/n...
[+] [-] choeger|6 years ago|reply
[+] [-] dmichulke|6 years ago|reply
- No one will want to be the one "deploying" the attenuated strain in a human and then be responsible for some unforeseen death (even if it's just 1 in a billion). Utilitarianism is not widespread nor socially accepted. Even less so in politicians, who are quite risk averse.
- There is no lobby supporting it. There's no $$ to be made and the "vaccine" is basically free.
[+] [-] FriedPickles|6 years ago|reply
I would give them more credit, especially in a situation where the status quo includes so many deaths. I was impressed with how readily most states licensed self-driving vehicles, knowing that there would certainly be deaths. Their rationality here likely came from seeing tens of thousands of people dying on the roads each year.
[+] [-] danieltillett|6 years ago|reply
[+] [-] chaseadam17|6 years ago|reply
1) Wouldn't natural selection result in a milder strain crowding out a more deadly strain? After shelter in place lifts, people with a mild strain will be more likely to go out and spread the virus whereas people with the deadly strain will be more likely to stay home sick.
2) Is there any consensus on whether we become immune to COVID after getting it (e.g. if we get a mild strain will we really be immune to a deadly one)? I've heard different opinions and I'm wondering what the leading hypothesis is at the moment.
Thanks!
[+] [-] bob33212|6 years ago|reply
[+] [-] edw519|6 years ago|reply
Myron said, "I see that Lee Flowers is playing today after a high ankle sprain 2 weeks ago. But I thought that high ankle sprains took 4 weeks to heal. What gives?"
Coach Cowher replied, "4 weeks is true, Myron, for the first high ankle sprain. But if you recall, Lee had a high ankle sprain on the same foot last year. And since subsequent high ankle sprains only take 2 weeks to heal, he's ready to play."
Myron paused and asked, "Then why don't you just take the whole team out in February and sprain all their ankles?"
(We laughed 20 years ago. Nobody's laughing today.)
[+] [-] pjc50|6 years ago|reply
[+] [-] toyg|6 years ago|reply
Sadly joints tend to work a bit differently from the immune system (with some exceptions).
[+] [-] robocat|6 years ago|reply
Also it is a paper from Singapore which should avoid the China negative bias.
[+] [-] danieltillett|6 years ago|reply
[+] [-] ubercow13|6 years ago|reply
[+] [-] user_50123890|6 years ago|reply
More likely, viral load, immune system strength, overall age and the genetics of the person infected are what determines if the infection is fought off before any symptoms are shown
[+] [-] nabla9|6 years ago|reply
Developing attenuated-virus vaccines is by screening serially propagated SARS-CoV-2 for reduced pathogenity has also been suggested already.
1. The outbreak of SARS-CoV-2 pneumonia calls for viral vaccines https://www.nature.com/articles/s41541-020-0170-0
2. Regla-Nava, J. A. et al. Severe acute respiratory syndrome coronaviruses with mutations in the E protein are attenuated and promising vaccine candidates. J. Virol. 89, 3870–3887 (2015). https://www.ncbi.nlm.nih.gov/pubmed/25609816/
Authors idea of spreading the attenuated virus is based on the idea that if the immediate COVID-19 disease can be avoided, increasing viral load in population is smaller risk. I think that's the weak point. If the vaccine is developed and the virus establishes itself in the population, the number of people getting infected will be lower overall and less people will get severe disease due to natural immunity + vaccine.
ps.
> appears to be killing between 1% to 3.5% of the people it infects
Author is confusing case fatality rate (CFR) with infection fatality rate (IFR). Infection fatality ratio seems to be something like 0.6% according to recent estimates. IFR estimates seem to go down over time.