I'm wondering how we may rule out this worst case scenario.
 Is COVID-19 receiving ADE from other coronaviruses? https://www.sciencedirect.com/science/article/pii/S128645792...
 New blood tests for antibodies could show true scale of coronavirus pandemic https://www.sciencemag.org/news/2020/03/new-blood-tests-anti...
Hard to rule out worst case scenarios, we just have to work with what we have and make hard choices.
This is at least partly why there are no SARS/MERS vaccines. There's a paper I'll try to dig up where 4-8 (can't remember) modified vaccine candidates were tested in multiple animal species, and in each case except one, immunity was conferred but exposure to the virus lead to a dangerous autoimmune response which destroyed lung tissue.
That's why I'm waiting for confirmation of immunity. So far I've only seen increasing numbers of reports of reinfection but that may just be faulty testing.
"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.
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.
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.
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.
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.
> This data suggests a simple and testable hypothesis – there are natural strains of SARS-CoV-2 in the world that have mutated to be non-pathogenic (asymptomatic), but are still infective and will provide immunity to the more pathogenic (deadly) strains.
From the structure of the post it sounded like "this data" referred to Iceland plus the Wuhan study.
If you only meant the Wuhan study then apologies for misunderstanding.
There is also a Singapore study that has identified strains with large gene deletions, but I haven’t yet updated the post to include it .
I’m a lay person here, but it seems a foregone conclusion that viruses experience frequent mutation, and that a novel virus infecting a new host species for the first time is going to see a relative explosion in mutations due to the extreme increase in the number of opportunities for it to occur.
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.
It is not risky to go looking for a naturally attenuated virus. This is the first step that needs to happen.
My suggestion is really one around building trust - it'd help to have others in the same scientific field confirm and/or question the approach.
I almost didn’t read it because the title sounds too generically woowoo, and the domain you are using seemed unprofessional. Then on reading the article, you didn’t give your background, an irrelevant picture of a painting opens the article, and the sidebar of your article topics are all over the shop. Sorry for being so negative: it is much easier to find reasons why something doesn’t feel right, and I’m not a fantastic marketer so I can’t offer you fixes I could predict would help.
It seems like a really good idea (are there others that have suggested it?), but I suspect it needs to be more convincing with a bit of repackaging if you want to push it.
Maybe add comments to those 2 papers with an “elevator pitch” or a request for other relevant info, and link to an improved post, and it should bubble up and find the right people to evaluate it.
Edit: also perhaps get your idea onto the various Covid daily link sites: good ideas should bubble up. Use Twitter to relevant people. Pass the idea to this guy who writes fantastically and has audience: https://medium.com/@tomaspueyo/coronavirus-act-today-or-peop...
Good luck, we need some!
It would probably have the opposite effect. This way it looks like a probably serious scientist wrote an idea that is probably worth considering on his personal website / blog.
If you give the site the "Hacker News treatment", I suspect that it will immediately look like "somebody with funding is trying to sell me on an idea for some reason". This stuff might work for naive consumers, but naive consumers don't matter here. I am sure that this post is already being shared among experts, and they are the ones who need to decide if this idea has merit or not. Throwing marketing bs at them will probably just hurt the cause.
A standard scientific paper will sink without a trace -scientists are just too conservative to take something like this seriously. I hate to say it, but the people who will make something like this a reality are the tech billionaires of this world.
It just seems more practical than hail-mary posting on HN https://news.ycombinator.com/item?id=22810639
If it's mere paperwork, we can solve that with a regular vaccine just as fast. And the regular vaccine would be more likely to be safe, even at an early stage. (Note: I'm a rando, not a medical or biological professional.)
If we're just going to ignore any regulations and bureaucracy for a live virus (like this proposes), we can do the same for a dead virus.
The whole argument about attenuated strains being a possible shortcut seems to be a variation of the "natural medicine" fallacy.
I have some half baked ideas about tradeoffs in infection rate and fatality, but I'm worse than a layman, I'm a layman with an opinion.
I'd sorta thought a virus could be real lethal(like ebola) ore real infectious(like a cold) but it's kinda hard to be both at the same time.
it _seems_ like there's a mapping between getting read (infection rate) and convincing people (fatality).
to be super explicit, is messaging a virus? is there a tradeoff in how the message spreads vs how convincing it is?
You've probably got other things to do, but it seems like there's a parallel there, even if imperfect, that's worth looking at. If you got a minute, I'd love to read your thoughts.
In general the less deadly viruses spread better as dead people are not able to spread the virus around as well as living people. The general trend is for viruses to become less deadly over time, but it can take a long time for this to happen.
That doesn't make any sense, viruses that are more fatal don't spread well because dead people are not good spreaders. Very sick people are also less capable spreaders than someone walking around with a persistent cough. Someone who's convinced would be MORE likely to spread a message.
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 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."
 - https://www.medrxiv.org/content/10.1101/2020.03.10.20033944v...
If I understand correctly, antigens identify the virus by its S proteins. Would we be able to use the same methods <a href='https://www.nature.com/articles/nm.3985'>as in this paper</a> to replace the S protein in a harmless cold-like coronavirus with the S protein of SARS-CoV-2, and would then the resulting immunity defend against SARS-CoV-2?
Send people infected with the harmless version around, after lockdown ends in a month or two, to crowded places?
Would greater virulence be a desirable quality in our reduced strain?
I don’t think we will get to that point. If we collect good data from the natural spread of any attenuated strain then I think the regulatory authorities will allow its use on the basis of this data.
> (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.
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?
There are many teams all over the world that are looking for less deadly (and more deadly!) strains to guide development of therapies. They’re too busy right now to post on message boards or speak to reporters. It’s however extremely unlikely that a less deadly strain will become the therapy, although it could be the basis of a therapy (but I think this too is unlikely).
Can you point me to sources supporting that claim? I searched myself, and what I found says that our knowledge is limited to the polio vaccine:
"Little attention has been given to vaccine transmission, possibly because transmission is rarely measured and largely unknown in humans except for the oral polio vaccine. Whether transmission is indeed rare for other live vaccines, or has merely gone unnoticed, is not clear – polio vaccine transmission is accompanied by evolution to high virulence, creating problems that draw attention to transmission."
From "Transmissible Viral Vaccines", James J. Bull et al., Trends in Microbiology, January 2018. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5777272/
It doesn’t appear that horizontal transfer is absurd, and while I’m not immediately seeing a large body of evidence that it happens all the time, it does seem to be generally accepted that it occurs.
Here’s what I believe to be an informative article on the topic: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3667938/
The polio vaccine actually went to the inactive form to reduce the risk of polio from one of the vaccine strains reverting to wild type and infecting others. It is still less effective at achieving herd immunity than the live version because of the lack of viral spread.
It sorta strains reason to argue that none of these people thought of looking for an attenuated strain.
Isn't the simpler truth just that finding one takes a lot of ground work that's already being done, but hasn't born fruit yet?
My username here is my real name, and I should be easy to find. It’s also my username on Twitter, Keybase, and most other popular platforms.
> If you think you might be that first hop person then please get in contact with me at email@example.com
reply to @ajross:
how would they know someone is asymptomatic? afaik they are mostly testing people who have symptoms , and their contacts (who will have contracted the same , symptomatic strain)
I think in germany they did antibody testing, or PCR of swabs of people who mostly no longer had a live virus infection to sequence. also, it seems the idea has merit; and i havent read about any team looking for this specific method (identify gene deletions and tracing). It certainly doesn't hurt (and doesnt cost much) to try
btw sweden is doing a survey of live infections in stockholm, however i don't think that they sequence the viruses
maybe post about it in reddit on r/covid19, some epidemiologists hang out there for the latest news
The ideal outcome is you find a strain with a deletion and you then test everyone in the area and you find 10,000 more people infected with the strain that have only a mild case and none of these people are in the hospitals. This strain would be very valuable to have.
For reference: I have a family member in virology. He reports that everyone he knows is now working on covid, mostly because if they don't they can't come to work on anything. The biggest problem is finding subjects that will produce a paper of any kind. I really don't think research bandwidth is the issue here.
I guess I have to repeat the question as its converse: is there any evidence that this is not happening? If it isn't, let's figure out the right people to pressure and not just discuss it on HN. And if it is, maybe we should let the experts do their work without pretending to have had their ideas for them?
There was literally a paper published yesterday (or the day before) on a blanket screen done on a population in germany to get some data on the undercount of asymptomatic cases. It was front page news on all the mainstream news sites...
I gotta be honest. This whole discussion has an "amateur hour" vibe. I have a hard time believing that professional academics in a long-established and very competetive field really failed to remember how the measles vaccine worked.
It's not that I think this is a bad idea, just that (1) it's almost certainly someone else's idea already, (2) is therefore probably harder to do than presented and (3) is thus not the magic bullet people are looking for.
To wit: stay the fuck home. Maybe someone will save us. They probably won't. We beat this with isolation or we wait for a vaccine.
Waiting for vaccine is not a good option. This is a situation with only hard choices.
Maybe the feds could allow states to get a waiver from FDA regulations if they want to try things like variolation.
This would still require someone at the federal level to stick their neck out a little, but (I think) a lot less than if they were to propose something like this as a federal policy.
We've got a federal system, let's make some use of it.
The process of finding any useful strain is going generate good data that it is safe anyway.
Natural selection versus bureaucracy!
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.
How about 10 to 50 million ?
I live in Nigeria. Between December and late February, many people in Nigeria and Ghana report experiencing symptoms similar to those that could be caused moderate COVID-19 infection. These included, fever, diarhoea, cough, sore throat, malaise.
Many physicians and scientists I know think it we may have had a mild outbreak of the disease. If so, was this reduced severity due to a mild strain of the virus or to other factors ? It warrants investigation.
Your proposal and the theory underlying it make a lot of sense.
I would really like to be able to dig deeper into this.
Those are also covid symptoms
Nigeria might have more immunocompromised people due to AIDS. But is there any reliable accounting of deaths, much less the reason?
In any case, I wouldn't be surprised if age and lack of accounting is why you don't see a problem in Nigeria.
2. The demographic profile and phylogenetic makeup of Nigeria is similar to Cameroon which has experienced more cases and deaths than Nigeria in both absolute numbers and on a pro-rata basis. This makes some of us believe we are dealing with two different circulating strains in both countries.
3. It definitely is the case that testing is not adequate but a highly susceptible affected population would soon be revealed by the number of symptomatic cases and, (more to the point), deaths. Both indices have remained relatively low
Anosmia is reported in 30%+ of Covid cases. Flu/cold viruses can cause Anosmia but it obviously isn’t common since you don’t hear about it and it isn’t given in lists expected symptoms.
Within a sample of 10 people that have Covid, you have an expected number of people that would have Anosmia.
Beware of false information https://www.nationalgeographic.com/science/2020/04/lost-your... because AFAIK the journalist has incorrect thinking: “flus and colds are a common cause of Anosmia” DOESN’T mean that “Anosmia is a common symptom” (the abstract they reference is poorly written, still poor journalism IMHO).
I would appreciate any references to data showing how uncommon Anosmia is in cold/flu patients (I did look, but didn’t look hard).
Who is going to be the person to recommend deliberately spreading that strain to the world population, knowing that 0.1% of the world, 7 million people, will end up in a hospital and die?
Sure, overall, fewer people might die, but the reality is whichever world leader makes that call has effectively just signed a death warrant for 7 million people. That isn't the way to get re-elected.
One thing is certain and that is unless we go out and look we won’t find anything.
I could quickly put together a team focused on southern Nigeria and Ghana to find through word of mouth, medical records, contact tracing lists and social media, people who have experienced covid-19 symptoms and are likely to have had the disease. My team would also collect samples from people in the worst affected areas who are asymptomatic. In this way, we could collect data and enough samples to isolate a(?the) virus if any.
Do you know any organisations that could provide funding and support for this ?
These are special times. In reality it does not matter if this 0.1% +70yo will die after vaccination since the mortality rates in this age group infected with the wild type are bigger by about two orders of magnitude.
But out of concern to human rights it will make sense not only to exclude any immunocompromised people but also make it voluntary to the groups where mortality rates are at certain level.
Happy to answer questions about the idea, but I am most interested in find collaborators to make it happen ASAP.
No guarantees (they are all swamped). I hope they respond and put you in touch with the right people.
I can confirm that your information got to one of my contacts at the White House. He replied saying he would distribute it to the right people. Your guess is as good as mine as to what happens from there. Even people within the White House have trouble penetrating through various layers due to just how busy everyone is (as well as security, etc.).
I've also done the same for CNN producers.
It'll be interesting to see who responds, if any. My standard advice still holds: Don't hold your breath. Sadly. All of these people are far more interested in ratings than things that matter.
The upside is, you may draw other very interesting conclusions while collecting data for this mission, and be able to "pivot" if you will.
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 .
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.
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.
If you were to start doing this without regulatory approval, the most likely outcomes seems that you’d be arrested . Do you have anything that suggests otherwise?
> 1. We would know it is safe in humans before we began.
The regulatory requirements for “knowing it is safe in humans” are currently quite high. As things stand, I would expect trials to be required. Can you provide any evidence to suggest trials wouldn’t be required?
You want to know how the vaccine effects individuals with pre-existing conditions etc. etc. And, as there’s always some risk, you want to be sure that the vaccine is effective.
> 2. We would know what mutations make the virus less pathogenic.
Large scale sequencing of the virus, in individuals and populations will be interesting. Being able to link this patient outcomes is also interesting. And might help in vaccine development. It would be interesting to have a large dataset of viral sequences from asymptomatic individuals. Can we see clear differences between asymptomatic and symptomatic individuals? This would be an interesting dataset, but I’m not sure that the results would be as clear as “look this deletion exists in a sub-population of asymptomatic individuals”. Would be a cool dataset and an interesting project though. There seems to be a lot of NGS data  available. This might be a suitable starting point for such a project.
> 4. It will be work in poor countries that can’t afford or distribute a conventional vaccine.
If a vaccine is available, then I suspect there will be sufficient international support to make it widely available. Having an active outbreak anywhere in the world would likely be deemed an unacceptable risk, given the potential for further mutation.
As we have seen with the whole HCQ fiasco regulations have a habit of getting lowered once there is data, even poor data. If we contact trace everyone who has been infected with the attenuated strain we will get some good data on the safety of the strain. It might not be 100% safe, and we might have some questions, but that is a discussion we can have once we find the strain.
We need to make some hard choices here between certainty and action. Waiting for certainty is a choice that carries a very high cost.
Both the diagnostic (sequencing or otherwise) and claim that you are vaccinating individuals would seem like they’d require regulatory approval. But I’d be interested in evidence that suggests this is not the case in a modern context.
Overall, it seems like the idea is as dangerous as deploying an untested mRNA vaccine. Because of this, I’d suspect that regulatory or other authorities would get involved.
Otherwise, what is your plan for this attenuated strain? Don't get me wrong, I think large scale sequencing or COVID19 is interesting. But think that attempting to spread a attenuated strain without regulatory approval is probably a very bad idea.
I think it much more likely that the regulatory agency would quickly approve the use of the strain on the basis of the epidemiological data gathered in the process of finding it.
Have you had experience with dealing with said regulatory agencies?
Even if you can’t get the strain it would not be technically very complex to recreate the virus from scratch once you know what deletion you need.
Note: asymptomatic at the time of testing. They may still develop symptoms over time.
While it would be a good idea if the mutated strain was no more dangerous than a common cold coronavirus, we could drive the dangerous strains to extinction without having to infect the vulnerable.
Also the whole thing presumes that immunity is lasting. Some of the data is showing that may not be the case.
Of course the other factor is who is a vulnerable person is a factor of the pathogenicity of the viral strain.
The best way to find a solution is still try to understand how it acts on different types of people and if they have underlying previous conditions what changes it does, this takes time and I believe that’s the reason there isn’t any cure except by chance in a short time.
From what I've seen, it's been published in some news articles and such that there "might be" different strains. Haven't seen anything particularly solid yet.
The issue with covid-19 is that it’s proving to be much harder to understand than other viruses in spite of not mutating like flu virus. Hopefully by more studies we can increase the chances of developing some cure or may be with so many efforts someone discover cure by chance.
The premise of article is actually not novel, it’s the way vaccines are made. Smallpox way of developing vaccine in crude way without scientific understanding was done in the early years, now we have come very far.
This virus is really novel that’s the reason novel corona virus (covid-19). Scientists and research community are frantically searching for a vaccine or treatment plan to manage it. So far there is a very limited understanding. Hope can find some way to treat it, otherwise only solution left is relying on herd immunity.
Even if it doesn’t pan out I think it is worth trying.
Apparently 80% of those tested later get symptoms: https://twitter.com/TonyBurnetti/status/1246258723774963713
If we can find a strain that just makes you feel like you have a cold that you get over in a week or so then that is what we want.
It's pretty confusing when symptoms are below a critical threshold and you don't have a test yet.
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...
German study says in a community linked to an outbreak, there are 14% immune and 2% to be shedding viral DNA.
Austrian study didn't include antibody test (yet).
On top of that, other research indicates some folks might be recovering without developing antibodies at all (they could be clearing the infection with only their innate immune systems). In that case we couldn't be totally sure about the upper bound anytime soon:
The next study that is currently being prepared will include antibody-tests, but it seems logistics and which test to use is not a trivial matter.
We are looking for an attenuated strain and that will be found in people with a mild case. We could sequence all cases, but we would exclude any strain that puts someone in hospital so it is a waste of resources to sequence viruses from people in hospital. From a practical perspective it is better to concentrate on people with only mild cases.
If I pick 1k people with mild cases at random, I will find pretty much any strain that currently is in circulation. How do I know which strain is harmless?
I do describe this in my blog post.
Aka this being one mechanism by which you confirm it is only producing mild illness. There's a limited amount you can find out by asking because nobody knows what strain they had.
If it is a rare strain, how will you know if it's safe? Seems like it would have to be a rare strain with thousands of cases and hospitalizations in that population are extremely rare.
Sampling bias and other confounding factors would be a real problem in this search, at least from a statistical point of view, imo.
I also think finding everyone who has been infected with a strain isn't feasible, at best you are sampling from the population.
politicians aren't stupid, they just play a different game and it looks really dumb from the outside. for them, their moves make sense, they're pros at it.
anyway, you've done very well to find yourself on the top 30 of HN. the smarter press reads this directly. the less smart press reads it a few days later after it spreads through the net via reddits, facebooks, etc. hopefully it's a matter of time a good headline will find its way to pair of eyes in the right place at the right time.
Yes hopefully this thread gets some attention from others.
- 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.
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.
And it would not be free, you still need to collect this strain, replicate it at massive scale and then distribute it.
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.
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.)
Sadly joints tend to work a bit differently from the immune system (with some exceptions).
Also it is a paper from Singapore which should avoid the China negative bias.
Yes. And how would that compare to the various trillions in stimulus to keep a choking world economy afloat, never mind the deaths that could be avoided?
I don't understand posts like this, they say "if we had a good solution, how could we possibly use it?"
One reason I was wondering is that manually administering the virus to people seems more akin to a vaccine in nature.
As I mentioned in my reply to you it will be impossible to stop this strain from being deliberately spread by people on their own.
Actually once a safe strain was identified it would be impossible to stop people spreading it on their own. People would test to make sure they had the safe strain and then invite everyone they knew around for tea and scones.
People will do this on their own once the strain is identified and there is a test for it.
Yes, but this doesn't seem too hard. Just have some infected people spit in a cup, and mix it into large vats of raspberry jam and people can then just spread it on their toast on one morning.
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
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
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.
> 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.
These numbers on the death rate are not mine, but what has been reported in the scientific literature. Probably the best numbers come from South Korea where they have done a pretty good job of tracking down everyone infected. There the fatality rate is around 1.8%.
Even if the true death rate is 0.6% that still means the deaths of nearly 50 million people worldwide.
Infection fatality rate is number of people who die after they are infected. That's one of the most important numbers and it can be estimated. It's different from case fatality rate. Number of people diagnosed with COVID-19 who die.
You started your argument trying to argue based on your understanding of what the infection fatality rate is.
It can be estimated with increasing accuracy.
> There the infection fatality rate is 1.8% and rising as the cases age out and people in the ICUs die.
You continue citing case fatality rate (CFR) numbers and call them infection fatality rate numbers (IFR). Can you please go back to your sources and read what they say. I bet they are case fatality rates. In South Korea one IFR estimates put the number around 0.4 and 0.7%.
Here are some IFR estimates:
1. Estimating the infection fatality rate of COVID 19 in South Korea by using time series correlations https://figshare.com/articles/Estimating_the_infection_fatal...
2. Estimating the infection and case fatality ratio for coronavirus disease (COVID-19) using age-adjusted data from the outbreak on the Diamond Princess cruise ship, February 2020 https://www.eurosurveillance.org/content/10.2807/1560-7917.E...
3. Using early data to estimate the actual infection fatality ratio from COVID-19 in France https://www.medrxiv.org/content/10.1101/2020.03.22.20040915v...
4. Robust Estimation of Infection Fatality Rates during the Early Phase of a Pandemic https://www.medrxiv.org/content/10.1101/2020.04.08.20057729v...
Really it is not important from the perspective of doing something about this pandemic as a huge number of people will die at all estimated levels.
IFR < CFR and IFR estimates go always down over time and never up due to the skewed nature of the data. Antibody tests are coming in already and based on them you get very accurate numbers.
It is worth comparing this to things like SARS. The distribution of SARS symptoms would be pretty narrow - everyone gets really sick. So the variance for SARS is small compared to Covid-19. The same could be observed for influenza or rhinoviruses.
The problem with a "milder" Covid-19 is that it might still have the same massive variance in symtpom severity. It might kill less people, but it would still be morally bankrupt to let it spread. In fact, it might be preferable to not reduce the mean severity, but just decrease the variance so it never gets nasty enough to kill without being immuno-compromised.
If immunity is important to symptom severity, it may manifest as some weird correlation you might find in a cross-sectional study. Maybe gluten intolerance or a history of acid reflux will be a marker that lets you know what your risk of severe disease are.
> In cell culture, DRACO was reported to have broad-spectrum efficacy against many infectious viruses, including dengue flavivirus, Amapari, and Tacaribe arenavirus, Guama bunyavirus, H1N1 influenza, and rhinovirus, and was additionally found effective against influenza in vivo in weanling mice. It was reported to induce rapid apoptosis selectively in virus-infected mammalian cells while leaving uninfected cells unharmed.
They even had a crowdfunding campaign on Indiegogo but as usual, nobody cares about infectious diseases until the pandemic...
Now the crowdfunding seems moved to another page
Bill Gates would like a word.
"However, research on DRACOs has entered the well-known “Valley of Death” in which a lack of funding prevents DRACOs, and many other promising new drugs, from being developed and advancing toward human medical trials. To progress DRACOs research it needs to be demonstrated against clinically relevant viruses (i.e; HSV). To that end an IndieGoGo campaign (http://igg.me/at/EndTheVirus) was started on October 13, 2015."
They don't seem to elaborate on what the hell they mean by the valley of death.
An acquaintance is $600m into a new type of Malaria testing and his funding is slowing, but is frustrated because he feels he is closer then ever. Frankly im amazed he got this far, thats a lot of burn.
Basically funding for drug research is all screwy!
If COVID-19 is human malware, then this is a human software update.
Of course you might find the best strain you can find exists in 100% of asymptomatics and 20% of the dead. That would indicate your strain has some non-zero death rate.
Today we prefer to immunize with a part of the virus structure, which end up doing the same thing.