Direct evidence for T-cell immunity as a factor behind Covid-19 heterogeneity
science.sciencemag.org
science.sciencemag.org
> Based on these data, it is plausible to hypothesize that pre-existing cross-reactive HCoV CD4+ T cell memory in some donors could be a contributing factor to variations in COVID-19 patient disease outcomes, but this is at present highly speculative
Also I recommend to read this: https://www.theatlantic.com/health/archive/2020/08/covid-19-...
> we designed a peptide pool encompassing peptides homologous to CD4-R30 epitopes, derived from HCoV-229E, HCoV-NL63, HCoV-OC43, HCoV-HKU1 and several other HCoVs (see Methods), for a total of 129 HCoV homologs (HCoV-R129; table S2). Similarly, we synthesized a pool that encompassed peptides homologous to the SARS-CoV-2 CD4-S31 epitope pool, consisting of potential epitopes derived from other HCoVs, for a total of 124 HCoV homologs (HCoV-S124; table S3).
The "speculation" disclaimer, IMHO, is based on the assumption that the designed peptide pools invoke responses similar to their viral homologs. I have no issue with the "direct evidence" heading as this research makes an important step in demonstrating cross-reactivity.
Teasing out the degree of protection this cross-reactivity provides in real-world populations is a much harder problem.
[1] https://science.sciencemag.org/content/early/2020/08/04/scie...
Could we just start deliberately spreading these weaker cold viruses then?
For everyone else, we should have a vaccine in the next 2-3 months.
Altho if they required testing of the culture to ensure no mutation that would slow things down
If you can let people actually catch the virus, then can't you avoid a lot of the vaccine production by letting people spread it to each other?
AstraZenica also to provide 300 million doses starting in October. https://www.hhs.gov/about/news/2020/05/21/trump-administrati...
The problem with the whole anti-anti-vaxxer thing is that any nuance gets lost. I’ve been called an antivaxxer (on the internet) for stating that I don’t want to take a poorly tested vaccine candidate.
Personally I am not afraid of SARS-CoV-2, for someone in my risk category the risk of bad outcomes is vanishingly low. Whereas a rushed out novel vaccine - which by definition cannot be tested for long term effects - is much more risky, personally.
BTW, because both the mortality and unproven (and imo nonexistent) “long term impacts” of COVID-19 are so dramatically overblown, the threshold for “this vaccine is safe” will be very loose IMO. Especially simce you can argue that the societal benefit of the vaccine means it’s worth more risk than the risk of COVID infection.
Fortunately, most of the US is practically begging for a vaccine and will take it as soon as available, so at least we’ll have great data. (Provided negative reactions aren’t suppressed as censored the way legitimate scientific papers have been)
> The problem with the whole anti-anti-vaxxer thing is that any nuance gets lost. I’ve been called an antivaxxer (on the internet) for stating that I don’t want to take a poorly tested vaccine candidate.
> Personally I am not afraid of SARS-CoV-2, for someone in my risk category the risk of bad outcomes is vanishingly low. Whereas a rushed out novel vaccine - which by definition cannot be tested for long term effects - is much more risky, personally.
> BTW, because both the mortality and unproven (and imo nonexistent) “long term impacts” of COVID-19 are so dramatically overblown, the threshold for “this vaccine is safe” will be very loose IMO. Especially simce you can argue that the societal benefit of the vaccine means it’s worth more risk than the risk of COVID infection.
It's statements like this and the one above why you get called an antivaxxer i suspect. Both the mortality rate and the long term impacts of COVID19 are both real and have not been overblown, there is a lot of evidence out there, but you just need to talk to any medical professional who has worked in the hospitals that treated patients to hear how bad this virus is. But it sounds like you have made up your mind already even though you say they are unproven (which they are not) , so you I guess you're making this assessments based on idiology not evidence.
The mortality rate for healthy people is incredibly low.
For example Singapore has had ~54,000 cases with a death count of only 27 since it was mostly young healthy people who got it.
Likewise there has been basically no excess deaths in many European countries for <65 years olds.
This is not at all how the media is treating covid.
So what? If you're alive now, if you survived the initial wave of the virus, the risk to you, now, of getting the virus is much less than it was back in March.
And if you're trying to figure out if the risk of the vaccine is worth it to you later this year, you have to weigh it against the risk of dying from covid-19 at that point in time, not what the risk of dying from it was back in March.
Was it very very high in the <65 not obese, not diabetic group?
We know it is dangerous to the old and some cities did a horrendous job of looking after their elderly.
You are just picking and choosing random data points to make very broad statements.
Check the number of deaths by age group at EuroMOMO: https://euromomo.eu/graphs-and-maps
The total number of covid-19 dead that were younger than 45 in the countries that EuroMOMO covers is in the low thousands, while the total number of covid-19 dead is in the low hundreds of thousands. That's two magnitudes lower risk compared to the general lethality.
Every individual has to do their own risk analysis, and see if they belong to any of the risk groups for covid-19, because that changes the individual equation.
Is the data random? Would it really cluster like that across countries?
I don’t think your statement makes a lot of sense.
If you're a healthy adult, your risk of dying or being affected by any long-term effects of the virus is about two magnitudes less than the risk for people who are 70+ or have any of the comorbidities.
I am a healthy adult, I am neither obese nor a diabetic, I don't smoke, I don't belong to any of the risk groups. For me, the risk of dying of covid-19 is in the ballpark of 1:100000, and decreasing, because we're getting better and better at treating the disease. If I catch the virus, I am overwhelmingly likely to suffer as much as I would of a common cold.
Those are the numbers that any vaccine has to beat in order for me to consider getting it. Provably beat. I'd rather wait until you and a couple of million people have had the vaccine before even thinking about getting it, thank you very much.
It's strangely difficult to get up-to-date information about hospitalisation rates but early estimates from the Chinese data suggest it's 4.25% for people in their 40s[0].
If you get hospitalised (or even if you don't) you have a significant chance of long-term health problems.
I don't know if that estimate has come down since we've not had to rely on filtered China data but a 1-in-20 chance of hospitalisation seems worrying enough for individuals and a huge problem for society if you let the virus get out of control.
> or being affected by any long-term effects of the virus is about two magnitudes less than the risk for people who are 70+
What data are you basing this on?
[0] https://www.thelancet.com/journals/laninf/article/PIIS1473-3...
Here's data for Sweden:
https://experience.arcgis.com/experience/09f821667ce64bf7be6...
Total number of confirmed cases for people in their 40's: 13687. Of those, 282 ended up in the ICU, and 44 ended up dead.
Since the number of actual cases is higher than the confirmed cases, the 2% hospitalization rate the above numbers result in is an upper bound.
And since the number of actual cases is probably at least a magnitude higher than the confirmed cases, the hospitalization rate for people in their 40's is probably somewhere around 0.2%. That's 1-in-500, not 1-in-20.
Note that these numbers completely ignore risk factors. There's also this page with data about risk factors for patients in Sweden: https://www.svt.se/datajournalistik/corona-i-intensivvarden/
Scroll down to "riskgrupper", and you can see that for men between 40 and 59, 22% were diabetic, 31% suffered high blood pressure, and 11% had some kind of chronic lung disease, for example.
So if you don't belong to any of these risk groups, the risk of you suffering long-term health problems from the virus is even lower than 1-in-500.
I can't understand the language (Swedish, presumably), but the ICU percentage is not the hospitalisation rate. Rather more people than need ICU are being hospitalised.
If 2% are needing ICU treatment, 4.6% needing oxygen in hospital sounds plausible if not an underestimate.
> And since the number of actual cases is probably at least a magnitude higher than the confirmed cases
That (probably) isn't true, or at least is not confirmed. I would expect most symptomatic cases to be tested now, and estimates of asymptomatic cases vary but seem to hover around 40%.
> So if you don't belong to any of these risk groups
Being male is also a risk group. If you're a man, most stats look worse compared to women at a ratio of about 2-1.
True, but being in an ICU in Sweden also doesn't mean you're necessarily hooked up to a ventilator. You'll be hooked up to the machine that goes bing, and you'll probably be hooked up to oxygen. It's a pretty iffy proxy measurement for the amount of people who will suffer long-term health effects, but it's probably in the same ballpark. And we haven't quantified the severity of those health effects. For some it means getting winded more easily for up to a year after being sick, and for others it means having to amputate a limb because you developed a blood clot while in a ventilator coma. One of these is not like the other.
>> And since the number of actual cases is probably at least a magnitude higher than the confirmed cases
> That (probably) isn't true, or at least is not confirmed. I would expect most symptomatic cases to be tested now
Ok, doing the numbers for July for Sweden which is when testing finally reached acceptable levels:
10487 new confirmed cases.
62 new ICU patients.
Assuming the age distribution is the same as for the full period, people in their 40's make up 16.7% of the cases and 11.2% of the ICU patients. That's 1751 cases and 7 of the ICU patients, which results in a hospitalization rate of 0.4%.
That's a lot closer to my estimates than yours.
> Being male is also a risk group. If you're a man, most stats look worse compared to women at a ratio of about 2-1.
Fair enough, and it's actually 3-1 for Sweden. Still, that doesn't bring the number anywhere near 1-in-20. 1-in-100, tops.
On the contrary, those talking of "lifelong complications" and "long haulers" are ideologically motivated. I have looked at the actual research, as well as thought deeply from a more theoretical standpoint, and have found the risks to be entirely overblown, particularly with respect to my risk category.
You throw IMO around like it matters what your opinion is to the rest of the world. I'll take empirical evidence, known post-virus complications, and scientific research over you opinion any day.
There are all kinds of horror stories one can imagine from a new type of vaccine like the Moderna one, but enough humans won't need it to balance out the risk of those that do.
There's no good answer. We either vaccinate or we let millions of people suffer and die. It's not a good choice...but it's one we have to make.
I'm moderately high risk and if all goes well with the trials and there are no significant mutations that the vaccine can't address, I'll be first in line.
I think in all of this, the number one fear is a mutation like the 1918 flu. It went from killing very young and very old to killing everyone. From a V to a W. Covid-19 is mostly a hook pointing at the very old. Let's hope it stays that way.
Do you have data to support these two claims?
Edit: I am not sure why I have been downvoted for requesting support data regarding two quite strong claims. Someone, even if it's not the downvoter, care to explain?
https://www.reuters.com/article/us-astrazeneca-results-vacci...
This is a unique situation where we as a company simply cannot take the risk if in ... four years the vaccine is showing side effects
I suppose you will call me an anti-vaxxer but why would a company want to avoid liability if its products were safe? Note that they will gladly take all the profits.
Since I don't have a crystal ball to see 4 years into the future, when this executive predicts the negative side effects will emerge, presumably based on experience with other vaccines, no. By all means, volunteer to be amongst the first to test it, and be sure to let HN know.
Perhaps you could provide some data on how normal it is for companies to disclaim liability before a product is even launched?
The fact is that you don’t have any evidence that the vaccine doesn’t have side effects four years out and that’s precisely the point the OP is trying to make.
No, he's the one making claims without supporting data or evidence.
He said, textually:
(About the virus) "for someone in my risk category the risk of bad outcomes is vanishingly low"
(About the vaccine) "Whereas a rushed out novel vaccine - which by definition cannot be tested for long term effects - is much more risky, personally"
You can tell he's passing opinions as facts the moment he feels guilty and adds "personally".
The fact that we don't know if there could be long term side effects with the vaccine doesn't mean it is not a calculated risk. The fact that we haven't waited for 4 years doesn't mean the scientists behind it do not fully understand how the vaccine works and what are the potential risks. It's not a blind gamble.
That's why I think it is important, if you're in for a serious discussion and not for anti-vaxxer histrionic propaganda, to make sure we support wild claims with strong evidence.
Maybe tons of people if not the majority don’t care or would happily take the vaccine - let them!
But it seems far too short-sighted to discount all the people that wouldn’t want to take an incredibly quickly developed vaccine (with debated and unproven benefit - does it provide immunity? how long?) for a disease that seems mild for most people.
This is much less clear cut than you’re letting on, while being obstinate about data which we don’t have.
The accelerated testing should still make them safe enough to administer to the risk groups where the risk of catching the virus is higher than the risk of the vaccine.
You don’t put sick 80yo people into early trials, even these accelerated ones.
Even before the "at risk" population gets the vaccine, nurses and doctors (who will be treating the at-risk population) need to first be immunized... otherwise the nurses/doctors risk spreading the virus to the at-risk population.
Fauci was very careful to say that this isn't any decision he will make on the matter. But it is extremely likely that nurses / doctors will get the first dose of vaccines.
Even so, the logistics I think will add another extra year (at least for the "Western" countries, which I'm pretty sure will forget about the "equality for all humans" mantra and will scramble to get first in line). For the roughly 3.4-5 billion people that we need to vaccinate in order to begin to get herd immunity I honestly think we're looking at a 3-5 year timeframe (at least).
This is a naive question, but to my knowledge there has never been a widely successful and safe vaccine developed for a coronavirus, am I wrong? People have been talking vaccine, but I've always thought that coronavirus, i.e. common cold family, has been nearly impossible to nail down with a vaccine.
You seem a lot more confident so I must be in the wrong here.
..and Immune Enhancement Syndrome one of the serious consequences of the SARS1 and MERS vaccines that never made it past their trials.
There are a lot of factors to immunity beyond antibodies. Traditional vaccines are either close viruses in the animal world (horsepox for smallpox) or heat treated inactivated virus (flu). We know they produce anitbodies, but there are hundreds of other parts of our immune system (complement system, inane, etc.) that might interact and form memory as well.
Vaccines come out of bad places; from eras where hundreds if not thousands of people were going blind, dying or getting paralyzed by disease. It was easier to just test things on people back then too, and a lot of them died (Chinese were inoculating people with actual smallpox 300 years before Jenner discovered making a vaccine from Cowpox/horsepox).
In the 1970s, the Swing Flu vaccine was a disaster. Sure millions of people got the vaccine and were fine, but 3,000 people developed Guillain-Barre syndrome. Some still have trouble walking or smiling (see the 60 Minutes documentary from that era)
Vaccines need a lot of testing. I do not understand why we're trusting the man who gave us Windows 95 to lead the Gates/Gavi alliance responsible for giving us a "safe" vaccine in less than a year. That's insane.
On a similar note: when a vaccine gets developed, does it make more sense to vaccinate those age groups (on the grounds that it will protect the most vulnerables) or to vaccinate everybody else (on the grounds that the vaccines may not be 100% safe and thus it may be safer for those age groups to benefit from the herd immunity)?
Vaccine deployment won't eradicate the virus immediately, so the most at-risk populations will likely need to be personally vaccinated before they can safely stop social distancing.
If mild common cold can make you immune to covid19, delibirate infections may be a much more efficient way to achieve herd immunity than a propiatary vaccine.
Of course this is all hand waving, but the point is we shouldn't automatically think that a man made vaccine is a much better solution.
Ah yes, we surely shouldn't automatically about anything. We should use reason and data.
The more money is at stake the greater force is applied. The last few years have proven what a devastating effect it had on our ability to discuss and think reasonably about anything.
Let's say you have a 5% chance of dying from COVID-19, a 10% chance of contracting it, but only a 0.05% chance of dying from some harmless coronavirus that would reduce your chance of dying from COVID-19 by half. It would be irrational not to deliberately contract the harmless coronavirus.
The problem is just that we don't know all these variables, especially for a given individual.
Being together with other humans is always a health risk if you want to look at it like that. While it might be incredible stupid to not take the lesser risk, you cannot force people to be rational.
I'm still a little scared by the Moderna vaccine because the mechanism for RNA vaccines is so new, and this one's being rushed out. Give a choice between that an a month of common colds, I'd take the colds.
I'd say that there's a 70% chance that there's millions of doses available for North America by late January of a >50% efficacy vaccine with a high production rate from that point.
There are so many different vaccine efforts now, and so many of them producing at risk. Some will work. It's just a question of how high the efficacy is and the duration of protection.
> ..and Immune Enhancement Syndrome one of the serious consequences of the SARS1 and MERS vaccines that never made it past their trials.
A lot of us were worried about antibody dependent enhancement. But we've had basically no evidence that this is a significant concern: successful treatment with convalescent plasma, successful challenge tests with vaccines in animal models, successful monoclonal antibody therapies in animal tests, etc, all point the other way.
> Sure millions of people got the vaccine and were fine, but 3,000 people developed Guillain-Barre syndrome.
And this wasn't a good trade, because the vaccine probably saved a lot fewer than 3,000 lives. But at this point, you'd save a whole lot of lives even with a vaccine that bad. (And we're not going quite that quick that time around and we have somewhat better tools to prevent bad outcomes).
> I do not understand why we're trusting the man who gave us Windows 95 to lead the Gates/Gavi alliance responsible for giving us a "safe" vaccine in less than a year.
??? Now you've gone completely off the rails. Gavi's primary role is as a purchaser of vaccines and not in development. The couple dozen vaccine development efforts worldwide are what we can expect to yield a vaccine.
Yeah, good last resort, not first.
Sure, the Oxford vaccine uses an adenovirus that is not present in humans outside Africa, but when they try to make a second vaccine, based on the same adenovirus, people who took the COVID-19 vaccine might not be protected.
So while not tested, mRNA might be a much better bet for the future, because we will be able to develop vaccines much faster and not have to search for a new virus vector each time a new vaccine is developed.
It looks like the side effects from mRNA vaccines are bigger than a typical vaccination. It's starting to look like mRNA vaccines may not be the vaccine you'd want in the long term based on this alone. The question is, do they create high severity side effects that preclude using them in the short term? We're about to learn...
There's a lot of other efforts; adenovirus vectors, attenuated efforts, non-replicating virus efforts. Of course, the adenovirus vectors are of concern because if immunity wears off, you can't necessarily give someone a booster a couple years later.
Both Gavi and the Gates Foundation are intended to create "healthy markets" for vaccines. Gates didn't design Windows 95 either; he was a business and marketing guy promoting it. It's not the development that's the issue, it's the fact that these alliances are profit motivated and vaccines have been a loosing bet for years due to the incredibly amount of research funding needed to bring one to market.
Their motives for rushing a vaccine to market right now are not altruistic. They want to prove they can bring vaccines for novel viruses to the market quickly. It could work, but it could also be a disaster. The fact that this is an 'emergency' allows them to avoid a lot of regulations, and even liability if the trials end up making people sick or killing them.
> Edward Jenner, FRS FRCPE[1] (17 May 1749 – 26 January 1823) was an English physician and scientist who was the pioneer of smallpox vaccine, the world's first vaccine.[2][3]
(Unfortunately, since common cold research is a lot less big, glamourous and high-profile than Covid-19, I don't think we know a huge amount for sure about the other human coronaviruses - and what we do know isn't exactly front-page headline news.)
edit to remove the phrases: "pandemic" & "new normal"
While the solution has not yet been identified 100%, we should be looking at everything. That is just good problem solving.
I'd expect geography to be a significant factor based on how viruses propagate on Earth
I'm wondering in cities with high volume airports saw it back in Jan/Feb here in the states.
This study provides direct evidence that the “novel factor” is not as important as was previously thought. Maybe no-one has cleared a virus exactly like this one before (we can’t be sure), but it is looking more and more like many people have pre-existing immune responses that can clear this one.
> Suppression/eradication is the only way forward.
You may end up being right, but to me this is sounding less and less like a scientific conclusion, and more and more like a religious creed.
The way to say is ..."the only way we can count on" is eradication. Sure, keep working on the other approaches but relying on them is foolish.
And eradication is literally impossible. It just shows how little these people know. It’s a zoonotic virus with abundant animal reservoirs, a high reproduction rate and pre-symptomatic spread. Even with a vaccine it fails the zoonotic requirement.
It’s endemic and here to stay. Anyone paying attention has known that from the start. I’ve personally been saying this for months and I’m just a deterministic algorithm operating on fixed-length groups of bits called blocks.
True, another spillover from animal reservoirs is likely, either this virus or a similar one. Early warning with prompt response will be needed to control another outbreak. Immediately shutting down all international air travel would be a first action. Imagine if the next spillover is with a virus that is deadly as SARS-1 but as transmissible as SARS-2.
This isn't quite true, but even if I accept that as true, you haven't addressed the problem that this is a zoonotic virus. There are abundant animal reservoirs that will never go away.
> Imagine if the next spillover is with a virus that is deadly as SARS-1 but as transmissible as SARS-2.
I used to say exactly that, until realizing that a virus as deadly as SARS-1 will never spread as well as SARS-2. Granted, if this hypothetical virus had SARS-1 lethality with SARS-2 incubation period, it would do a lot "better" than SARS-2.
Anyway, having thought deeply about this - and I'm sure you will strongly disagree here - even a SARS-1 danger virus with SARS-2 spread, I would be against (a) obviously eradication since I've already discussed why eradication is impossible, but more importantly: (b) I'm against trying to contain highly infectious respiratory viruses period.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7095063/
As for what that means for eradication:
See https://en.wikipedia.org/wiki/Eradication_of_infectious_dise...
> The targeted organism must not have a non-human reservoir (or, in the case of animal diseases, the infection reservoir must be an easily identifiable species, as in the case of rinderpest), and/or amplify in the environment. This implies that sufficient information on the life cycle and transmission dynamics is available at the time an eradication initiative is programmed.
^ This is why we can never eradicate it. There's a couple of other requirements. For example we could eventually pass this check:
> An efficient and practical intervention (such as a vaccine or antibiotic) must be available to interrupt transmission of the infective agent.
At its heart is the understanding that controlling the virus is the single most important thing right now - that this is a total war. This policy can only work, however, in societies with effective governance and a strong social fabric.
You misspelled “belief”.
Similarly, but less strongly, exposure to other human CoVs produces t cell cross reactivity.
The “suppression/eradication” is just dogma. BTW eradicating SARS-2 is impossible. It’s zoonotic in origin. Viruses with abundant animal reservoirs can never be feasibly eradicated. Please do some reading on this it’s basic stuff.
OC43 has like a 9% nursing home fatality rate tho (which is kind of a hint that SARS-2 isn’t too special as far as mortality is concerned)
Anyway if you have kids you have probably already been exposed to one of these CoVs at some point. The TL;DR is the more you do real life stuff the more likely you are to have exposure. Add it to the long list of externalities due to lockdown. Natural spread of pathogens is a good thing and not to be feared.
1. Populations may naturally have a head start towards herd immunity from COVID. 2. Sweden could be really close in that regard; their current super low daily mortality and declining cases may point towards herd immunity.
they are presently doing about as well as all their immediate neighbors for per-capita deaths: https://ourworldindata.org/coronavirus-data-explorer?zoomToS...
Reference: https://ourworldindata.org/coronavirus-data-explorer?zoomToS... (graph basically looks identical between per capita or raw, pick your poison).
I'm not sure how you make a meaningful statistical difference between them at this point when the numbers are approaching rounding errors.
It’s hard to measure behavior but nothing suggests people have less contact now than in March (more contact is more likely, but on the other hand it’s now more contact outdoors compared to spring).
It doesn't mean that they're hitting herd immunity in an "everything back to normal world". But it's still good news
Have they announced anything about when they're planning to ease restrictions?
There isn’t much talk about easing but I suspect the visitor restrictions on elderly homes might be lifted as soon as possibly since 6 months without being able to visit is a long time. Also the 50 person event restriction is being reviewed. It’s a bit inconsistent to allow 100 people in a restaurant or bus but not 51 people in Sweden’s largest football stadium that seats 50k...
Spectators for kids sportS outdoors also becomes allowed I hope. Having parents watch a children’s game outdoors, for example.
General easing of the last restrictions would be e.g allowing full stadiums for sports and concerts but that is not going to happen this year. The authorities recommend working from home for the rest of the year so that gives some indication about other restrictions. Travel recommendations are easing now but obviously change quickly.
I don't think Sweden got to 10% infection in the pop. at the moment (avg. for Spain is 5% and 15% on the heaviest hit cities)
(Not to mention this whole t-cell story is being used by negationists and "skeptics" to deny the actual mortality of the virus)
I also doubt Sweden has 10% infection (As measured by serological tests) but most larger cities probably do. Where that puts immunity no one knows. It seems to be enough (for now, with mitigations in place).
The "common cold" is a blanket term for several viruses that cause similar symptoms. My understanding is that most are rhinoviruses. A mild influenza virus will also give "cold" symptoms. And, as talked about here, there are a handful of coronaviruses as well.
It currently appears that Covid-19 is more dangerous than other circulating coronaviruses, but it is important to keep in mind that the "common cold" can already kill people in vulnerable groups. It is possible that the biggest issue with Covid-19 is that it is novel. No one has much immunity to it, so it spreads rapidly and causes worse symptoms than it might if we had more latent resistance.
So, once enough people have been exposed to the virus, it might result in it being no worse for the general population than any other bad flu. That doesn't mean that it won't kill people, but it won't spread as easily, and people who do get it might have better immune responses. So, in the long run, without a vaccine, it will probably just fizzle out, eventually. However, that will either take many years (if ever) or a lot of deaths.