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.
Thanks. This is the problem I have run into which is all the right people are so busy at the moment that they don’t have time to look at something like this from someone like me.
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 just forwarded your information and article to the producers for the top shows at Fox News. Let's see if they move on it and get in touch.
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.
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.
The best would be to find a mutation that cannot jump from human to human .
Otherwise it could be dangerous if it mutates again to a more dangerous virus, even if not the original coronavirus (as you said we choose a mutation with a deletion).
No. A major part of the value would be the host to host transmission as it would get herd immunity into those people not directly given the virus. Only a transmissible virus strain can drive the pathogenic strains to extinction too.
Large deletion mutations don’t back mutate in practice.
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.
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.
It looks like you need to find someone who can help make your post feel more professional - perhaps Ask HN for help or just directly email one of the clued up people here that are open to cold emails (patio11?).
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...
The site is my personal blog. I thought about writing a more technical level paper, but what I wanted to accomplish is to get this idea in front of a non-scientific audience who can think outside the box (like many of those on HN).
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.
The tech billionaires of this world will not fund anything based on a layman's explanation. They want to fund ideas based on reliable research. The Gates Foundation is staffed with tons of specialists for this reason.
I think that if you really believe your idea has some merit, you should still write a paper. After that you can blog about it for any audience out there and maybe write a follow-up. You're a professional, you know how it works.
I most likely will write such a paper, but the first thing is to get those that can make this happen interested. They are not going to be reading a scientific paper.
> It looks like you need to find someone who can help make your post feel more professional - perhaps Ask HN for help or just directly email one of the clued up people here that are open to cold emails (patio11?).
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.
This seems like a pretty good idea (good enough that certainly there must already be people working on it) so it seems like if you could find and contact them, maybe you could contribute to their efforts?
Well I hope other are working on it, but I haven’t found much evidence of this so far. HN has a pretty diverse audience including a lot of scientists like me.
It would probably be helpful to mention that at the start or end of the post. Clear, non-inflated credentials/background with links.
(I sometimes see this in italics at the top)
Sort of a weird ask, but as a real, no shit, virologist, what do you think about changing your messaging to make content more accessible to lazy readers?
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.
Viruses don’t really care about thing like death rate, they just care about how effectively they are spread from person to person (viruses don’t really care about anything, but I am describing how they appear to act if they had a mind).
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.
Spread rate would also need to stay in a certain range for a virus to stick around. Spread too fast and there won't be a second wave. The herd immunity effect gives this system some self-balancing properties, but there's surely a tipping point where even that won't help a speeding virus to survive.
> is there a tradeoff in how the message spreads vs how convincing it is?
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.
This is an attenuated live vaccine, though. So the risks are similar or worse than just doing a real, engineered vaccine.
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.)
The proposal is to intentionally apply a live virus to people, so absolutely there are bureaucratic barriers to this (and for good reason). There is no a priori reason why this should have less red tape than a dead virus.
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 reason why this should be able to advance faster than a normal vaccine approach is that we will have epidemiological data that it is safe in humans. Sure it would be nice to have double blinded placebo controlled data, but good epidemiology data is still data on which a regulatory decision could be made. In the current circumstances I think this will satisfy the regulators.
It would only be logical to require a "vaccine-strain" that has the capability for uncontrolled spread to go through much more stringent trials and paperwork than one that is limited by distribution.
The whole argument about attenuated strains being a possible shortcut seems to be a variation of the "natural medicine" fallacy.
Except the experiment has been done for us already by nature. We are not doing the experiment, just observing what has already happened. Sure you would not be able to make a strain of unknown attenuation in the lab and spread it around (this would be very dangerous), but you can use the data that nature has provided us. I am proposing we go and collect that data.
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."
This just rules our using ZJ01. There are other attenuated strains out there that will have deletion mutations that can’t mutate back. We need to go find them.
Sorry if it's a stupid question, but hypothetically, would we be able to engineer rather than find a harmless strain of coronavirus with the spike protein of SARS-CoV-2?
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?
This is not a stupid question. Yes we could engineer such a strain, the problem would be testing it given we would not be able to predict how dangerous it was.
Well if the regulatory agencies decided that they weren’t going to act then I suspect there would be a grass roots level spread of the strain anyway. This would be the worst way to use such a strain, but I don’t think it would be possible to stop this happening.
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.
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.
Agreed that the risk:reward ratio here would be worth it. This sounds super promising. That being said, how is it known that having had the mutated strain provides immunity to the dangerous strain?
It probably won't be known at first, but we're talking a timescale of months to work out things like that. Things could be back to normal by the end of the year if we start now-ish. That is not blind hope either, it's just simple math.
The reason why it would provide immunity is all the structural proteins would be the same. To our immune system it would look like the same virus as the pathogenic strains.
This is not really anything unusual and is exactly how viral live vaccines work. The vaccine for live polio and measles work exactly this way.
They know which parts of the RNA express the spike protein that our antibodies recognise. If the spike protein is not affected, then the virus should still be good for training our immune system to respond to.
I'm glad people are realizing that all this social distancing is merely a pause button on the virus. Once we press play on society, exponential growth will happen again and we will have effectively rolled back the clock until we reach herd immunity through things like the OP's suggestion.
At least this next time we'll hopefully have more PPE.
A country without other options might be more interested in the idea? I imagine that many first world countries would be too worried about the potential liabilities.
On second thoughts perhaps the idea wouldn’t work in countries that don’t have an effective lockdown. Could the infection wave of a less dangerous genotype overtake the number of infections of the more dangerous genotype before the population has been mostly infected already?
Yes if we act soon as we can spread the less dangerous version faster than the normal human-to-human spread of the dangerous version. For example if we were to send a postcard infected with the less dangerous version to 10 million people it would get out ahead of the dangerous version spreading normally.
good luck, we could have completely eliminated HIV by now but corporate profits are more important than that so the vast majority of the population who has the virus doesn't get the medication they need to not transmit it.
I'd much rather live in a world where everyone is required to wear masks all the time than live in a world where we are all told to stay home all the time.
I believe it's also well established that any measures taken to slow the spread of a new virus will always result in fewer total deaths, in that sense quarantining is much more effective than just being a pause button.
"where everyone is required to wear masks all the time"
And this is what bothers me with such laws. No it does not make sense to wear masks all the time. (even assumed only outside) When I am running alone in the forest I do not need a mask. While driving a car alone, or with a partner, I do not need a mask. So the law should be, wearing masks all the time in populated public spaces.
"I believe it's also well established that any measures taken to slow the spread of a new virus will always result in fewer total deaths"
And this is only true if you look only isolated at the virus and do not take into account the various big side effects of a lockdown. Because you will get deaths from: suicide, domestic violence, other diseases, because staying home is not really good for the immune system and general health. Also this only takes into account the rich world. In india staying home is also required, but this is a really serious death risk, if your home is a metal barrack in the slums, with no AC, meaning you just get cooked. Before you starve to death, because you have no income anymore.
"fewer total deaths"
Yes, but not fewer total infections. You save lives by spreading out the infections over time, reducing strain on the healthcare system.
This is a false dichotomy. Masks or gloves as worn by ordinary people are nowhere near effective enough to mean lockdowns could end. They're very effective in clinical settings with proper ppe head to toe and procedures for taking them off outside the dirty ward, but there's no way most people can stick to those, nor keep their houses/shops clean enough.
I believe it's also well established that any measures taken to slow the spread of a new virus will always result in fewer total deaths
In the sense that they prevent a healthcare system being overwhelmed yes, in any other sense no, they are very much just a pause button for the spread of the virus, not a cure.
We wouldn't insist that people 'stop breathing' to prevent the spread of coromaviris. It's only somewhat different to insist that we all stop living and working.
Masks and gloves, plus generally keeping 6ft apart and routinely testing and contact tracing/quarantining infected individuals... what's the effective rate there? 95%? The modern medical establishment would move heaven and Earth, and incur thousands of dollars per person to get that last 5%. Most of us routinely ignore them in this regard, with respect to our own personal health, as we live our daily lives.
There just isn't a lot of evidence for the case that the choice is shutting the economic or killing millions.
Yes, although reality seems to be disagreeing with the models more and more. You have countries in southeast Asia with community transmission but no lockdown, and countries in Europe with the military enforcing a strict lockdown, and the latter are far worse off in terms of hospital admissions and deaths per capita than the former.
> I'd much rather live in a world where everyone is required to wear masks all the time
A properly fitting mask is uncomfortable. It hurts your nose, it hurts your ears. If you wear spectacles they fog up. People don't tolerate them, and so they fiddle with the mask, taking it off and putting it back, or dropping it under their chin.
Here's what happens when you wear a mask for a couple of shifts at work.
(I am not a professional, so what I write below might be wrong)
Having more time to develop a vaccine or effective treatments is essential, it doesn't have to be herd immunity. Plus in countries where covid19 rate is low enough, social distancing can be helpful for finding and isolating clusters to suppress the epidemic.
Of course, there are two ways out of this, herd or vaccine. The above is a variation of herd that may result in less deaths.
The real problem is that waiting until a vaccine is just not even remotely realistic for so many reasons that it's not even funny. We could end up causing more indirect deaths with social isolation than we could possibly imagine, worst case being a huge collapse in the economy results in a large regional or global conflict.
"How did it end?
The most popular theory of how the plague ended is through the implementation of quarantines. The uninfected would typically remain in their homes and only leave when it was necessary, while those who could afford to do so would leave the more densely populated areas and live in greater isolation.
Improvements in personal hygiene are also thought to have begun to take place during the pandemic, alongside the practice of cremations rather than burials due to the sheer number of bodies."
Indeed, CDC's numbers for March indicate that social isolation is reducing non-ncovid-19 deaths by twice as much as sars-cov-2 is adding them. That's short term, so not what GP was talking about, but very significant numbers nonetheless.
How many suicides? Guys losing their businesses that they put everything into. Can't even go fishing without their fellow man ratting them out to Big Brother.
It's not a pause button, it's a playback speed button that slows down the contamination.
Remember #FlattenTheCurve.
What is true is that it would take waaaay longer to reach herd immunity this way.
Another thing that people usually get wrong is the her immunity concept: from what I understand, it doesn't mean we ALL need to be infected. We just need to be enough, so the virus can't spread anymore.
Isn't this why there is a 1918-related flu outbreak every generation and why bubonic plauge used to recurved every generation because there aren't immune?
What about people born after that point? As immune people die over time from other causes, and as people are born without immunity, the percent of the population with immunity from having had it falls.
I think the idea is that once there is herd immunity, the virus has no way to propagate and ends up disappearing w/o vectors. However, that would require global immunity.
Statistically a disease reaches herd immunity if everyone except 1 / R0 are infected.
For a disease with R0 of 3 (such as covid) this would be 66%. To explain: If two out of three are immune then a disease which usually infects three people will run out of steam.
The whole idea of herd immunity in this context is fucking nonsense. No self-respecting epidemiologist would even bring it up this early into a pandemic.
Herd immunity is the last resort for the immunocompromised or unvaccinated, not the foundation for public health policy.
At that R0 herd immunity will be probably achieved when at least 70% of the population is infected. So it’s not all, but we are still speaking of about 5.5 billion people globally...
The point of social distancing is to bring the number of cases down to a point where other measures are possible, such as test-and-trace. Social distancing is step 1, not the whole process.
This isn't really correct, and the proof is that most of east asia is relaxing restrictions right now without experiencing another exponential outbreak.
Testing, tracing and quarantine of infected people does work. It requires a bunch of infrastructure that we don't have yet (and in many places still aren't building, which is beyond frustrating). It also requires that the baseline level of the outbreak be small enough that you can catch most of the cases, which thus requires the continued lockdowns until we get back to that level. But it does work.
Interesting, I wonder if this could explain to some extend different death ratios that are currently blamed on hospital capacity, age etc. - in other words, what if Italy has spread of more danerous mutation kind and Japan has spread of less dangerous one.
The global sequencing effort makes this reasonably straightforward to study. While the prevalance of different strains does vary geographically, new international tranmission events occur so frequently that most places have a handful of circulating strains already [0]
> The reason why is immunity to respiratory viruses (like corona) doesn’t last long – 6 months to 2 years.
I haven’t read anything like this before. It seems like you’re extrapolating from the flu vaccine, which doesn’t last because the flu mutates too quickly. Coronavirus mutate much slower and the thought is that we’ll likely only need one vaccine. Have we actually found any less deadly strains? My understanding is that there have been mutations, but all are small and as far as we can tell superficial. You would likely need to create such a mutation and then you’re back in vaccine trial territories, except dozens of labs that are experts on this have a head start.
We we have found less deadly strains (I link to one paper in the post that found one - still too deadly) and we have found strains with large (and small) deletions. What we haven’t done is go specifically looking for strains with exactly the properties we want (yet at least).
There is no need to create any viral mutants in the lab (and all the difficulties this will involve), just use what is already out there in the community. We just need to go and look for them.
> If humans do develop immunity, how long does it last?
> That’s another big unknown. Immunity is short-lived for the coronaviruses that cause common colds; even people who have high levels of antibodies against these viruses can still become infected, says Stanley Perlman, a coronavirologist at the University of Iowa in Iowa City.
> The evidence is more equivocal for the two other coronaviruses that have triggered epidemics: those that cause severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). Perlman says his team has found that after people recover from MERS, their antibodies against the virus drop precipitously. He also says that his team has gathered data — not yet published — showing that SARS antibodies are still present in the body 15 years after infection. But it’s not clear whether this immune response is enough to prevent reinfection. “We don’t have good evidence of long-lasting immunity, but we also don’t have really good data from both SARS and MERS,” Perlman adds.
I invited danieltillett to repost https://news.ycombinator.com/item?id=22798626. My reason is to build up a body of community reactions to the idea, that can serve as a basis for deciding whether to promote it further. I don't know Bill Gates, but I do know some people inside YC who are hard at work on this problem, and maybe they know someone who knows someone, etc.
If it's just a repetition of the previous thread, I'm sorry. Repetition isn't good and that wasn't my intention.
That's a bit uncomfortable because I thought it deserved the flag, but knowing that this has been mod-reviewed means that flagging probably doesn't serve a constructive purpose.
Isn't this just one of many ways to produce a vaccine, so won't it need the same long term trials for safety and effectiveness that any type of vaccine needs? Reducing this this time somehow is what I think is needed.
Do you mean this "virus would not be a vaccine from a regulatory perspective"? In that case it is just another vaccine approach, but one that you alledge falls outside the current regulations. Do you think the regulations need to change due to the emergency?
It's extremely important because it's a question a lot of people are going to be asking. You'll need a good answer as to why this approach should not be subject to similar regulations as vaccines otherwise this will go nowhere.
Because the attenuate virus we are looking for would be one that can spread naturally. Of course humans might choose to help it along once it is found by say hanging out with an infected person. Lots of options here
I'm a layman to this topic but it makes total sense that we should be pursuing this approach. At some point, it needs an influential person to back it and help remove the red tape. I think it could be done though. Probably just needs money first to find the right mutation and that would be the lure for an influential person.
Something else to think about: This post implies that this solution would be implemented in some thoughtful and publicly-known way. We should consider the possibility that some organization (government or otherwise) could do this regardless of whether society accepts this as a solution. It's possible that this is already in the process of being implemented right now. Maybe better to ask for forgiveness than permission...
> One thing is certain with the current situation is we need to take some risks if we are going to solve it quickly.
Looking for quick answers in a crisis is really risky. There is a natural push to try to get things back to normal as soon as possible, but developing an attenuated vaccine (even with a potential strain already in existence), takes a lot of time and testing.
I certainly agree that we should be trying to sequence every variation we can find in the wild, but even if everything works just right, it will take a lot of time. I haven’t followed enough of the reports, but how many strains have been identified thus far?
Another issue is that even just getting the reagents to collect and passage the virus is difficult as they are all needed for clinical testing. So working with live (even attenuated) virus is very difficult at the moment. But this highlights a reason why it is so critical to study these topics when we aren’t in crisis mode. Much of the current vaccine work has been adapted from earlier SARS-CoV research.
But this approach of finding a weakened strain (or generating one), is a good idea to be attempted in parallel. (I’m sure that someone is trying to passage the virus though a different host to attenuate it as we speak). The first step is to try and sequence as much as we can from the wild, but this has its own logistical difficulties. Hopefully there is a research study going on that is trying to collect as many samples as possible now, so that we can sequence later when things have calmed a bit (because there is likely going to be a second round).
I don’t intend to sound so negative on this. I largely agree that this is one avenue that needs to be studied. And from your background, I know you understand these risks/concerns. I worry about the larger public though. My main concern is that this concept can be very risky, especially with an already scared public looking for quick answers. Seriously, the last thing we need is people intentionally trying to get infected in the hope of getting a less lethal strain. This isn’t a cowpox scenario. I guess my hesitation comes down to me not liking the idea of taking too many risks for the sake of doing it quick. That’s been known to come back and bite people.
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.
Technically they don’t provided we can get the herd immunity up to a decent level in the rest of the population.
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.
Very difficult to get herd immunity up to a decent enough level without putting the vulnerable portion of the population in great danger though. Most countries are approaching something like 0.1% or 0.2% of the population having been infected. Herd immunity requires 70% - 80% immunity. About 350x - 800x more than what's happened already.
Also the whole thing presumes that immunity is lasting. Some of the data is showing that may not be the case.
The level of herd immunity needed is related to the R0 which is a function of behaviour. This is a really complex topic to discuss, but it is only one we can have once an attenuated strain is found.
Of course the other factor is who is a vulnerable person is a factor of the pathogenicity of the viral strain.
Well this is what many countries and scientists are already doing. It’s just not working as virus is unpredictable and it might infect some but not others.
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.
Are they already doing that? Is there somewhere I can find the statistics broken out by strain? Or even a list of identifiers of the known strains?
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.
Covid-19 is not mutating like other viruses, but it acts differently on different people, and very problematic for people with pre-existing conditions. Also in some cases again not proven it also infected heart muscles, now it’s not clear yet that it’s due to pneumonia or covid-19. In China they tried plasma from recovered patients and that also didn’t yield very good results. Also in some studies they find a correlation between BCG vaccine and low mortality (again not proven).
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.
Well it’s not mutating the virus they found in initial cases is still the same as the one at present in Patients in Europe and USA.
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.
The premise of using an attenuated virus as a vaccine is not novel, but the idea of using genome sequencing to find an attenuated strain and showing through epidemiology that it is safe does seem to be novel.
Even if it doesn’t pan out I think it is worth trying.
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.
I want to argue that the flaw in this is with the ability to find any strain that consistently causes only minor symptoms. If you infect a whole group of people with Covid-19 then we would see a distribution of severity from no symptoms to lethal. This broad spectrum is really just it's statistical variance (whatever the underlying distribution really looks like).
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.
Yes. Or just variations in our immune systems. Immune systems are incredibly complex systems. It is difficult to overstate just how complex and varied they are. And they differ between individuals to an amazing extent.
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.
> We found, in our 788 confirmed COVID-19 patients, the decreased rate of severe/critical type, increased liver/kidney damage and a prolonged period of nuclear acid positivity, when compared with Wuhan.
So how are we gonna deal this increased liver damage then, if we are actually gonna use this less pathogenic branch of the virus as a quasi-vaccine?
Is there way to reengineer this virus so that it would be less kidney/liver damaging?
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
And anyways, the harsh lockdowns currently implemented are basically forcing the virus to evolve into being asymptomatic.
Currently, anyone with even mild flu-like symptoms stays home
My understanding (not an expert) is that there is a difference depending how much of an initial dose of the virus you get. If it is very small then your immune system has more time to respond before the virus replicates to dangerously large numbers, whereas if your initial dose is large then you are starting with a large number of virus particles that replicate too fast for your immune system to respond.
Yes, that is the discussion I have heard, that healthcare workers without proper PPE get larger doses than those with the right gear and are more likely to fall ill. Same effect applies to the average person in public when exposed to an infected person who may not be showing systems - even imperfect PPE reduces their initial dose and increases their odds of having a less severe infection.
It is deemed to have an RNA repair mechanism. This is suggested by analogy with other coronaviruses [1,2] and the length of its RNA of ~30k nucleotides while the upper limit for RNA without repair mechanism seems to be 10k [3]. The german wikipedia cites [4] which I found nicer to read.
In theory the idea would work. People being cooperative enough is where I'm skeptical. I assume anyone in the high risk group would volunteer to receive the less-dangerous strain and when the incentive of lowering risk of death is obvious. I speculate young people wouldn't volunteer unless they have a health issue placing them in the high risk group.
>I speculate young people wouldn't volunteer unless they have a health issue placing them in the high risk group.
I suspect lots of young people would happily volunteer if it meant their life could return to normal. Heck, I'd bet even for the current strain, with a ~0.1% risk of death for young people, quite a few people would volunteer to get it if it meant they could get out of lockdown.
I'm not disagreeing with that opinion. I just haven't observed young adults taking the lockdown seriously.
I personally work from home (as one of the privileged few being a programmer) and when I do go outside I take social distancing serious. My health in general isn't great although I'm not old (early 30s) and which is why I don't leave my apartment much anymore. I live in a college area and young adults are still going over to each others apartments and without practicing social distancing when going out to buy groceries. I'm in Quebec for context. I've heard it isn't much different in the USA.
Maybe the (possible) solution could work without young people on board.
>I live in a college area and young adults are still going over to each others apartments and without practicing social distancing when going out to buy groceries.
That's my point: the young adults don't want to comply with the social distancing, so if someone said "hey, if you let me infect you with this virus that has a 1/50,000 chance of killing you, you can no longer get/transmit the more dangerous strain so you don't have to social distance any more", a lot would take the offer.
The whole approach requires young people to not take the lockdown seriously. They will be the people who spread around the less dangerous strain of the virus.
That doesn't matter. The reason why everything is closed is hospital capacity. That impacts everybody. If you had a car accident you may not get all the help you need.
14% of people may need hospitalisation and you want to focus your efforts on that group. There is almost no young people there.
Would anyone have a choice? Surely once a few people are infected it will start spreading on its own. Even if people who are infected were instructed to isolate there will be a certain level of non-compliance, particularly at scale.
It seems the reason the vaccine will take so long (12-18months) to develop is because it needs to be tested for long-term safety which takes a trial with long-term monitoring. As this is essentially a sort of (active) vaccine, how do you propose ensuring it's long-term safety? It seems you'd run into essentially the same problem as with developing the vaccine.
It seems to me that the whole article describes to me an alternative way to find a vaccine . Maybe someone can enlighten me: aren't there vaccines that are simply rather harmless mutations/relatives of the virus but trigger the same immune reaction?
By doing an end run around the regulations. Actually even if you were to follow all the vaccine regulations by choice this would still be faster as it would have already been tested in human. Nature has run the trials for us.
I don't see the point of this. Nature has most certainly not established the long-term effects of this virus, seeing as it has only been spreading in humans for a short while.
Skirting the regulations is pointless, because the important thing is the intent of the regulations. If it were just a problem with the regulations, we could also just change the regulations and give the untested vaccine.
Plus, if you want to argue from a pure legal background, this approach would probably still run into trouble, as in most countries it would be highly illegal to infect people on purpose.
If we wait for the long term we will all get infected and we will all be broke. We need to think differently.
I am not arguing that we should infect people on purpose. If people chose to become infected on their own by hanging out with those infected with an attenuated strain then that is a very different legal question.
Personally I think the result would be the regulatory agency would just rush the use through based on the epidemiology data gathered in the search for the attenuated strain.
Well, in principle it does sound like a possibly "vaccine", but without the long-term testing I still don't see how we can be sure we have found this attenuated strain. Personally, I am youngish (30s) and healthy, so I would probably fall into the core group of those that "should" be infected. But given the choice, I don't think I'd do it, because even now, three months after this virus became big, there is still huge uncertainty about its lethality (even among young people), the number of severe cases (possibly causing long-term long tissue), and how this virus behaves in the long-term: how long would immunity even last? [seems unclear now]. There were also reports from China, and now South Korea, about possible reinfections or reactivations. Under these circumstances, I'd rather pass and keep to social distancing/masks etc. until a better solution comes along or the safety of an attenuated strain has actually been proven through a large scale, controlled trial.
Here's what I have trouble reconciling: You say that this attenuated virus would spread automatically -- just like a virus -- and yet no one would be infected on purpose, only if people "chose to become infected on their own by hanging out with those infected with an attenuated strain".
How much agency do I have in whether I get infected or not? It seems strange to me if it depends on the genetic makeup of the virus.
If you were to deliberately go and hangout with someone you know is infected with the attenuated strain then a lot, if you catch it because your neighbour did this then none.
This discussion is really a distraction as I don’t think a “grass roots” spread would be the way any such strain would be spread. I think the regulatory agencies would look at the data collected from the natural spread and use this to approve the strain for use.
Any back of envelope math on how much this "search" will cost? Does it require someone with Bill Gates sized bank account or are you mentioning him because you know he is specifically active in this area of philanthropy/very influential?
Yes. Less than a million dollars - I actually can afford to pay the whole thing myself. The only reason to get someone like Bill Gates involved it to get access to the samples and the required political capital to make it happen.
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?
There are no stupid questions, just stupid politicians.
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.
But honestly, if you only look into people with mild cases, how do you know the virus causes these mildness?
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?
You don’t, but what you are looking for is a virus with a largish deletion in an essential gene. You then go and look for anyone in contact with this person and check them and then expand out to the whole local area. If everyone infected with this strain has a mild illness they you have hit the jackpot.
I think GP's point was that if you have a candidate it would also make sense to use sequences from the hospitalised to try and confirm your strain didn't put them there.
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.
You really want to find every single person who has been infected with the mutant strain and find out how sick they got. If you find a mutant that infected 10,000 people and didn’t cause any serious illness then you have a pretty good idea it safe.
I think the point is that you have to sequence people in the hospital as well, otherwise you won't know if that particular strain is safe or not.
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.
You actually want to screen all people in the local area for the strain that may have it. If all the people have had a mild case and none of them are in hospital then you have something special.
Ah, so you first check for a candidate and then check a (somewhat random) group of people infected with that candidate for severity. That sounds sensible. Thanks for updating a stranger from the internet!
> There are no stupid questions, just stupid politicians.
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.
Considering that we are now in a shutdown, and assuming that most symptomatic people do get tested and isolate themselves, doesnt that mean there is pressure for asymptomatic strains to evolve and keep spreading faster in the population anyway? they would be more likely to exist in the early epidemics, specifically south korea which aggressively quarantines people, but does not impose lockdowns, letting the asymptomatic spread
There is really no selection pressure on the current dangerous strain right now. If it was killing 50-60% of people infected then yes the selection pressure would be there, but at a death rate of 1.5%-2% there basically is very little selection pressure on the timescales we are interested in.
It doesn’t really matter to us today if this virus eventually becomes less dangerous in the next 500 years. We need to speed things up a little.
That's already baked in to human responses to suspected COVID-19 though, and a chance mutation to a less lethal strain would be unlikely to change human responses to an outbreak in a way which benefited the virus' ability to spread.
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.
You probably won't find that... You might find a strain where 99.9% of people get a mild case.
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.
I think we can do better than 0.1% death rate. In principle there is no reason we can’t find a strain that is no more dangerous than the coronaviruses that cause the common cold.
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 ?
0.1% would be great. That's the mortality of the regular flu and we have ramped up the hospitals to cope already so the 0.1% severe cases would be better handled. That would be much better than we manage the flu. It would also make it actually possible to take risk groups and isolate only those for a longer time without crashing the economy. It would be the opposite of the flu where vaccination is focused on risk groups.
Agreed. But for the heard immunity one does not have to go and vaccinate/expose to an attenuated strain of virus the whole population. Even getting a majority of say under 50yo immunized should have a big effect.
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.
>What we really want is a strain that has infected a whole lot of people and all of them have had a mild case
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.
1. Age is not the main factor at play here.
While the median age is lower than Italy's there are still a lot of elderly people in Nigeria. On an age and population adjusted basis, Nigeria has nowhere near the number of cases and deaths as Italy.
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
If you are part of a cluster of a viral infection and you suspect Covid, then look for Anosmia as a symptom.
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).
I've been thinking about this a few days ago when I went into the wikipedia rabbit hole about vaccinations and inoculation.
A few questions:
- How about the dengue fever scenario? (Immunity to less pathogenic strain can cause more severe reaction with a different strain). Can we asses the risk somehow?
> Apart from the time it will take to develop, trial, and mass produce a vaccine (12-18 months), it is unlikely that any vaccine will be practicable. The reason why is immunity to respiratory viruses (like corona) doesn’t last long – 6 months to 2 years
Is there any proof that this is the case with this virus?
Is is possible to do the infection outside the human body?
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[ 40.3 ms ] story [ 469 ms ] threadHappy to answer questions about the idea, but I am most interested in find collaborators to make it happen ASAP.
https://crowdfightcovid19.org/
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.
Also it is a paper from Singapore which should avoid the China negative bias.
Otherwise it could be dangerous if it mutates again to a more dangerous virus, even if not the original coronavirus (as you said we choose a mutation with a deletion).
Large deletion mutations don’t back mutate in practice.
- 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.
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!
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!
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 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.
It just seems more practical than hail-mary posting on HN https://news.ycombinator.com/item?id=22810639
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.
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.
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...
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.
This is not really anything unusual and is exactly how viral live vaccines work. The vaccine for live polio and measles work exactly this way.
At least this next time we'll hopefully have more PPE.
I believe it's also well established that any measures taken to slow the spread of a new virus will always result in fewer total deaths, in that sense quarantining is much more effective than just being a pause button.
And this is what bothers me with such laws. No it does not make sense to wear masks all the time. (even assumed only outside) When I am running alone in the forest I do not need a mask. While driving a car alone, or with a partner, I do not need a mask. So the law should be, wearing masks all the time in populated public spaces.
"I believe it's also well established that any measures taken to slow the spread of a new virus will always result in fewer total deaths"
And this is only true if you look only isolated at the virus and do not take into account the various big side effects of a lockdown. Because you will get deaths from: suicide, domestic violence, other diseases, because staying home is not really good for the immune system and general health. Also this only takes into account the rich world. In india staying home is also required, but this is a really serious death risk, if your home is a metal barrack in the slums, with no AC, meaning you just get cooked. Before you starve to death, because you have no income anymore.
I believe it's also well established that any measures taken to slow the spread of a new virus will always result in fewer total deaths
In the sense that they prevent a healthcare system being overwhelmed yes, in any other sense no, they are very much just a pause button for the spread of the virus, not a cure.
Masks and gloves, plus generally keeping 6ft apart and routinely testing and contact tracing/quarantining infected individuals... what's the effective rate there? 95%? The modern medical establishment would move heaven and Earth, and incur thousands of dollars per person to get that last 5%. Most of us routinely ignore them in this regard, with respect to our own personal health, as we live our daily lives.
There just isn't a lot of evidence for the case that the choice is shutting the economic or killing millions.
Which is why we have models, no?
My understanding is it takes 1 - 3 weeks to see the effect of a lockdown?
A properly fitting mask is uncomfortable. It hurts your nose, it hurts your ears. If you wear spectacles they fog up. People don't tolerate them, and so they fiddle with the mask, taking it off and putting it back, or dropping it under their chin.
Here's what happens when you wear a mask for a couple of shifts at work.
https://twitter.com/gabbyjackson95x/status/12479391789623255...
https://twitter.com/george_kerris/status/1241821041107906560
https://twitter.com/LeaBasra/status/1246467174589517825
https://twitter.com/CorneliaLG/status/1247309904106393608
https://twitter.com/paigeleigh95/status/1247509440405876738
https://twitter.com/gsmarri/status/1241845315587715073
https://twitter.com/molliemariaa/status/1246285482130059267
https://twitter.com/freyja_woolston/status/12472261992120115...
https://twitter.com/johnnynash69/status/1248278245914693639
https://twitter.com/TJGrundy/status/1247771125553065986
https://twitter.com/rosenorth_/status/1247235204957208577
https://twitter.com/erikalouxx/status/1245240263947227136
https://twitter.com/ilkahannah/status/1248395954102759431
https://twitter.com/LeanneThornex/status/1247587759025504256
https://twitter.com/drccr74/status/1247601616548769798
https://twitter.com/lauraworwa/status/1246469150735826944
Having more time to develop a vaccine or effective treatments is essential, it doesn't have to be herd immunity. Plus in countries where covid19 rate is low enough, social distancing can be helpful for finding and isolating clusters to suppress the epidemic.
The real problem is that waiting until a vaccine is just not even remotely realistic for so many reasons that it's not even funny. We could end up causing more indirect deaths with social isolation than we could possibly imagine, worst case being a huge collapse in the economy results in a large regional or global conflict.
Are there any examples of humanity developing herd immunity without a vaccine?
"How did it end? The most popular theory of how the plague ended is through the implementation of quarantines. The uninfected would typically remain in their homes and only leave when it was necessary, while those who could afford to do so would leave the more densely populated areas and live in greater isolation.
Improvements in personal hygiene are also thought to have begun to take place during the pandemic, alongside the practice of cremations rather than burials due to the sheer number of bodies."
Remember #FlattenTheCurve.
What is true is that it would take waaaay longer to reach herd immunity this way.
Another thing that people usually get wrong is the her immunity concept: from what I understand, it doesn't mean we ALL need to be infected. We just need to be enough, so the virus can't spread anymore.
Also, we never "solved" the plauge, but it died down a lot before antibiotics were even a thing.
Non-vaccine acquired herd immunity is temporary.
For a disease with R0 of 3 (such as covid) this would be 66%. To explain: If two out of three are immune then a disease which usually infects three people will run out of steam.
Herd immunity is the last resort for the immunocompromised or unvaccinated, not the foundation for public health policy.
Testing, tracing and quarantine of infected people does work. It requires a bunch of infrastructure that we don't have yet (and in many places still aren't building, which is beyond frustrating). It also requires that the baseline level of the outbreak be small enough that you can catch most of the cases, which thus requires the continued lockdowns until we get back to that level. But it does work.
[0] https://nextstrain.org/ncov/europe
See links here: https://news.ycombinator.com/item?id=22799096
> The reason why is immunity to respiratory viruses (like corona) doesn’t last long – 6 months to 2 years.
I haven’t read anything like this before. It seems like you’re extrapolating from the flu vaccine, which doesn’t last because the flu mutates too quickly. Coronavirus mutate much slower and the thought is that we’ll likely only need one vaccine. Have we actually found any less deadly strains? My understanding is that there have been mutations, but all are small and as far as we can tell superficial. You would likely need to create such a mutation and then you’re back in vaccine trial territories, except dozens of labs that are experts on this have a head start.
There is no need to create any viral mutants in the lab (and all the difficulties this will involve), just use what is already out there in the community. We just need to go and look for them.
> If humans do develop immunity, how long does it last?
> That’s another big unknown. Immunity is short-lived for the coronaviruses that cause common colds; even people who have high levels of antibodies against these viruses can still become infected, says Stanley Perlman, a coronavirologist at the University of Iowa in Iowa City.
> The evidence is more equivocal for the two other coronaviruses that have triggered epidemics: those that cause severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). Perlman says his team has found that after people recover from MERS, their antibodies against the virus drop precipitously. He also says that his team has gathered data — not yet published — showing that SARS antibodies are still present in the body 15 years after infection. But it’s not clear whether this immune response is enough to prevent reinfection. “We don’t have good evidence of long-lasting immunity, but we also don’t have really good data from both SARS and MERS,” Perlman adds.
If it's just a repetition of the previous thread, I'm sorry. Repetition isn't good and that wasn't my intention.
I'm wary of adding bookkeeping facilities for that reason generally.
If COVID-19 is human malware, then this is a human software update.
More seriously there is nothing for the FDA to regulate here. It is a natural virus spreading in a natural way.
> One thing is certain with the current situation is we need to take some risks if we are going to solve it quickly.
Looking for quick answers in a crisis is really risky. There is a natural push to try to get things back to normal as soon as possible, but developing an attenuated vaccine (even with a potential strain already in existence), takes a lot of time and testing.
I certainly agree that we should be trying to sequence every variation we can find in the wild, but even if everything works just right, it will take a lot of time. I haven’t followed enough of the reports, but how many strains have been identified thus far?
Another issue is that even just getting the reagents to collect and passage the virus is difficult as they are all needed for clinical testing. So working with live (even attenuated) virus is very difficult at the moment. But this highlights a reason why it is so critical to study these topics when we aren’t in crisis mode. Much of the current vaccine work has been adapted from earlier SARS-CoV research.
But this approach of finding a weakened strain (or generating one), is a good idea to be attempted in parallel. (I’m sure that someone is trying to passage the virus though a different host to attenuate it as we speak). The first step is to try and sequence as much as we can from the wild, but this has its own logistical difficulties. Hopefully there is a research study going on that is trying to collect as many samples as possible now, so that we can sequence later when things have calmed a bit (because there is likely going to be a second round).
I don’t intend to sound so negative on this. I largely agree that this is one avenue that needs to be studied. And from your background, I know you understand these risks/concerns. I worry about the larger public though. My main concern is that this concept can be very risky, especially with an already scared public looking for quick answers. Seriously, the last thing we need is people intentionally trying to get infected in the hope of getting a less lethal strain. This isn’t a cowpox scenario. I guess my hesitation comes down to me not liking the idea of taking too many risks for the sake of doing it quick. That’s been known to come back and bite people.
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
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.
https://www.straitstimes.com/asia/east-asia/mystery-of-long-...
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.
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.
https://www.medrxiv.org/content/10.1101/2020.03.28.20036715v...
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.
So how are we gonna deal this increased liver damage then, if we are actually gonna use this less pathogenic branch of the virus as a quasi-vaccine?
Is there way to reengineer this virus so that it would be less kidney/liver damaging?
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
[1] https://en.wikipedia.org/wiki/Coronavirus#Replication [2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4984655/ [3] https://de.wikipedia.org/wiki/Coronaviridae#Genom [4] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3127101/
I suspect lots of young people would happily volunteer if it meant their life could return to normal. Heck, I'd bet even for the current strain, with a ~0.1% risk of death for young people, quite a few people would volunteer to get it if it meant they could get out of lockdown.
I personally work from home (as one of the privileged few being a programmer) and when I do go outside I take social distancing serious. My health in general isn't great although I'm not old (early 30s) and which is why I don't leave my apartment much anymore. I live in a college area and young adults are still going over to each others apartments and without practicing social distancing when going out to buy groceries. I'm in Quebec for context. I've heard it isn't much different in the USA.
Maybe the (possible) solution could work without young people on board.
That's my point: the young adults don't want to comply with the social distancing, so if someone said "hey, if you let me infect you with this virus that has a 1/50,000 chance of killing you, you can no longer get/transmit the more dangerous strain so you don't have to social distance any more", a lot would take the offer.
That doesn't matter. The reason why everything is closed is hospital capacity. That impacts everybody. If you had a car accident you may not get all the help you need.
14% of people may need hospitalisation and you want to focus your efforts on that group. There is almost no young people there.
https://en.m.wikipedia.org/wiki/Attenuated_vaccine
Skirting the regulations is pointless, because the important thing is the intent of the regulations. If it were just a problem with the regulations, we could also just change the regulations and give the untested vaccine.
Plus, if you want to argue from a pure legal background, this approach would probably still run into trouble, as in most countries it would be highly illegal to infect people on purpose.
I am not arguing that we should infect people on purpose. If people chose to become infected on their own by hanging out with those infected with an attenuated strain then that is a very different legal question.
Personally I think the result would be the regulatory agency would just rush the use through based on the epidemiology data gathered in the search for the attenuated strain.
How much agency do I have in whether I get infected or not? It seems strange to me if it depends on the genetic makeup of the virus.
This discussion is really a distraction as I don’t think a “grass roots” spread would be the way any such strain would be spread. I think the regulatory agencies would look at the data collected from the natural spread and use this to approve the strain for use.
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.
It doesn’t really matter to us today if this virus eventually becomes less dangerous in the next 500 years. We need to speed things up a little.
it isnt killing, but it's isolating them, preventing its spread
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.
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.
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.
Source: https://en.m.wikipedia.org/wiki/List_of_countries_by_median_...
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.
https://www1.racgp.org.au/newsgp/clinical/push-to-include-an...
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).
A few questions:
- How about the dengue fever scenario? (Immunity to less pathogenic strain can cause more severe reaction with a different strain). Can we asses the risk somehow?
> Apart from the time it will take to develop, trial, and mass produce a vaccine (12-18 months), it is unlikely that any vaccine will be practicable. The reason why is immunity to respiratory viruses (like corona) doesn’t last long – 6 months to 2 years
Is there any proof that this is the case with this virus?
Is is possible to do the infection outside the human body?