Substantial undocumented infection facilitates rapid dissemination of SARS-CoV2 | Hacker News Reader

Substantial undocumented infection facilitates rapid dissemination of SARS-CoV2

science.sciencemag.org

85 pointsdoener70 comments

Previous discussion: https://news.ycombinator.com/item?id=22598803

Any virologists here? Is it possible that we may have a grave future where a virus emerges with R0 value of 6-7 (such as measles virus), long incubation period (10 days, contagious on 2nd day) and a death rate of 50-100% (such as Ebola)?

A virus with the combination of all of the aforementioned properties would guarantee complete extinction of humans (or we get very close to it). Should we consider ourselves lucky?

Edit: my intent wasn't to incite panic, but to learn about the virology, molecular biology and the physics of transmission.

So could an asteroid impact, or Yellowstone volcano erruption, or thermonuclear war. The question is how likely is it.

it [pathogen] has happened already a number of times, the chance is not a marginal one, vs one little impact in russia that was witnessed,

Asteroid impacts and supervolcanoes have "happened already a number of times".

Certainly more than just "one little impact in Russia".

yes certainly but we havnt directly observed very many of them, and for most of them we were not even extant. the extension is that near earth objects are quite common but we dont notice a lot of them. just like disease epidemic or pandemic, a number of them have happened already we just are not good as a group at noticing those things probably due to preoccupation with little rectangles of paper with famous historical figures printed on them.

(Not a virologist)

As I recall, the virus in The Stand had a death rate of something like 99.4%.

However, if that actually happened, it seems like there would still be enough people to make a medium sized country, and wouldn't it rapidly evolve to be less virulent anyway?

But anyway, just on my vague sense of fate, this all might be an omen for what happens in ten or twenty years. I keep thinking of the 20th century kind of echoing, first there was WWI, the flu epidemic, the depression, WWII...early on you couldn't have imagined what was coming.

there is no directed selection like that.

its a luck of the draw and then selection for most apt to produce offspring.

the virus can become more lethal in effect over time, or take on troublesome characters such as asymptomatic contagion with extended incubation period.

the virus is so problematic right now due to a sponteneous mutation altering its previous character.

What do you mean "there is no directed selection"?

Any virus is reproducing as it spreads, so it seems to me impossible for there not to be evolution happening. Milder illness enhances the spread, so it's going to be selected for. What is the counterargument?

directed selection is not darwinist evolution and does not exist in accepted evolutionary theory. it is artificial selection.

directional selection is a very different thing it exists, it is part of evolutionary theory, it means there is a bias toward a particular allele [natural selection is a form of directional selection.

selection does not lead to a path of improvements, it leads to changes in frequencies of phenotypes.

there are other ways of enhancing spread, and retaining lethality, such as being communicable before symptoms become debilitating, this removes selective pressure that is based on communicability. If the host does not get sick enough to to be bedridden, they can contact other hosts. If the symptoms are mild or unseen there is no behavioral basis for other hosts to avoid the infected host. so by delaying expression of characteristics the virus may be highly communicable and highly lethal at the same time. high lethality is not subject to selective pressure in this case and will remain.

"directed selection is not darwinist evolution and does not exist in accepted evolutionary theory. it is artificial selection"

I don't know what that means or what your source is. It sounds like you're maybe saying that orthodox evolution theory doesn't apply when humans are involved. Why, what is the mechanism?

And how exactly do you get from the idea of a pathogen evolving to be less virulent to "artificial" selection? Stipulating that somehow artificial selection is different, what would make it artificial? It seems obvious that human behavior would factor in, but what is the definition that makes the evolution artificial?

directed selection:

https://en.wikipedia.org/wiki/Directed_evolution

...and this means directed selection is not an natural process by definition. natural evolution doesnt proceed toward a defined end, [bipedal primates with large cerebrum] [or from highly lethal-->moderately lethal-->nonlethal]

virus do not start from day one as very lethal and become progressively less lethal over successive replications.

communicability is an advantage to host to host transmission. breaking linkage between traits allows differing selective factors to act on these traits.

when a virus doesnt kill you or make you ill until after you have infected others then that virulence is not subject to the same selective factors as it previous partner [communicability]

"that virulence is not subject to the same selective factors"

It's a matter of degree, not a binary thing. You can't be 100% sure of anything, but as long as people are aware of something and act accordingly, there will be selection pressure. Reduced social contact has an effect regardless of whether specific carriers are identified.

Also, addressing your last paragraph, ultimately if something takes long enough to kill you, it doesn't matter in the limit because everybody dies of something. Conversely, anything people notice, like say HIV, is always going to have some pressure applied to it.

perhaps you could explain where lethal characteristics come from.

are virus always absolutely lethal and then lose lethality as they evolve?

or do virus of non lethal character spontaneously become more lethal?

My impression is that a new lethal virus is pretty much isomorphic to a macroscopic life form that becomes an invasive species. There's a period of time before it reaches a new equilibrium. But that adaptation always happens.

So, specifically in answer to your question, it seems obvious to me that "lethal characteristics" are context dependent, so they come from random chance when an organism (or virus) encounters a new environment that it can replicate in way easier.

All charcteristics derived from genetic structure are random chance, all of them.

when a virus has infected a host, replicated, passed to a secondary host, then symptoms appear, then X occurs,

You have a situation where X has no influence on reproduction, replication or transmission, it just is not even on the same blackboard as that equation.

here is some suggested reading for you, not everyone understands evolution or natural selection very well so it is a bit of a TLDR

https://en.wikipedia.org/wiki/Viral_evolution

"You have a situation where X has no influence on reproduction, replication or transmission"

It is true that a basic law of reality/nature is that causes must precede effects, so in a sense, I think I agree your statement is technically correct regarding the exact cycle you describe.

But when talking about evolution in a population, the cycle happens a huge number of times. So "X" will influence all of the instances of replication that in fact happen after it. It would be silly to talk about evolution in a context of one and only one reproduction event.

I don't think we are debating anything that has to do with specialist knowledge of viruses.

Surely such death rates would surely make people a lot more scared, thus a lot more likely to maintain quarantine and isolation. And the governments wouldn't suggest silly things like keeping schools etc running like normal.

Running schools isn't silly if children don't get infected. However, the jury still out on that one, it seems prudent to not take chances on unknowns.

Children do get infected and can spread infection. They are significantly less likely to die and have very very mild symptoms. (Not mild as in official "anyone not in hospital" but mild as in "super easy").

Complete extinction of humans is a high bar. Also I would expect that the reaction to such a disease would be extreme. It could certainly be much worse than the current crisis we are facing.

No need to speculate. Bird Flu (H5N1) has 50% mortality, and it's like a flu in other aspects.

It's only a few mutations away from human to human transmission.

I am truly alarmed and completely unqualified to say this but I'll throw it there anyways - I would vote for reducing military spending by 90% and increasing pandemic R&D, hygiene and medicine spending by 10000%. If a nation is nuclear armed, we don't need a massive military perhaps.

H5N1 doesn’t spread well it’s primarily only bodily fluids hence why we only had about 800 confirmed cases.

It also doesn’t survive long at 37c or higher temps (6 days at 37c and drops fast from there).

Birds have higher body temperatures which helps to regulate the virus so while they can be carriers they are usually asymptomatic since the virus can’t replicate fast enough to cause major issues.

Zombie movies are basically this, but with enough disruption everyone becomes desperate and would flee the cities looking anywhere for food.

And when the supply disrupts, the most readily available supply will be ... other humans.

The real danger would be if it stays in a host like bubonic plague, and even if you survive the direct human transmission, it still gets to you...

Also, those death rates were supposedly what native americans suffered when exposed to european diseases.

With a virus such as that, perhaps we would actually be allowed to use the treatments that get developed, instead of being told to let people die because "we want to do more studies" forever

I'm not sure what country you're located in, but at least in the US, there is the "Expanded Access" program - otherwise known as compassionate use. (https://www.fda.gov/news-events/public-health-focus/expanded...)

It was widely used during the HIV epidemic to provide pre-trial access to medications and my hypothesis is that the program will be used even more extensively for sars-cov-2.

If your country does not have a law like this, now is the time to push your representatives.

Note - this is different from allowing OTC access to chloroquine willy nilly. If that is the suggestion, I am in agreement with the government that physician mediated access is the wisest course. While we know the safety profile of the medication, the doesn't make is "safe".

That's why in the US after the president ordered the FDA to approve Choloroquine for use against COVID, the FDA immediately came out and demanded that it not be used, except for "compassionate use" in the most severe cases (people who will die anyway, even with treatment), and in the UK why after studies started to appear showing it to be highly effective, the UK banned the sale of the drug.

First rule of power: never waste a crisis. If we cure this thing now, before the destruction of all personal freedoms is complete, people won't be willing to go quietly into the totalitarian night. Therefore, it is critical that even news suggesting there might be a cure be suppressed.

Notice how for every one article you can find about the promise of Cholorquine + Azithromycin, you'll find 10,000 all talking about how it's a hoax/lie/fabrication, or else that more study is needed -- at least another 12/18/36 months? All long enough to ensure that the dismantling of our society can be completed before anybody can be treated.

Mortality and R0 will be inversely correlated viruses that excel at killing the host will be contained by the hosts dying rather than infecting many others.

Also the natural selection on viruses would result in them evolving into less deadly forms because those would be the ones that get more wide spread.

Other factors like long incubation and infectiousness are also often inversely correlated the incubation period is the time when the virus replicates while remaining mostly asymptomatic which often means for airborne viruses it’s also a period when the host isn’t particularly infectious.

What's the possibility of creating such a virus in a lab?

Fairly low while we can snip a few genes here and there the technology isn’t there.

When it will be it can also be used to easily create a cure if you can assemble viruses like legos it would be also incredibly easy to create inhibitors and anti bodies with the same technology.

This is also what we are doing atm basically playing a huge game of “Perfection” by trying to find anything that would fit one of the “holes” on the virus, our cells or those which open up during its assembly process like its viral protease.

I fear that now that we have witnessed the economic turmoil it can inflict on any community where this virus is released, there are entities out there who have taken notice and will explore this as a means to future warfare.

I believe it's the opposite now.

This virus has shown the widespread economic impact and unpredictability that the uncontrolled spread of a virus can unleash on the world.

After this, I'm sure no superpower will want to take a chance releasing a weaponized pathogen: it might just come bite them back in the ass.

It may just be my better understanding of bacteria, but I think it'd be significantly easier to engineer bacteria as a bioweapon where, largely, you are the one doing the spreading, via something like a crop duster.

I've heard a firsthand account from a guy who worked at Vector [0], that they had difficulty controlling viruses [1]. Accidental releases of weaponized bacteria also happened [2], but in that case they could prophylactically treat with antibiotics. That said, this was done using 1970's-1980's technology. I'm sure there's some more sophisticate bioweapons that are possible now. Maybe viruses are a more reasonable chassis.

[0] https://en.wikipedia.org/wiki/Soviet_biological_weapons_prog...

[1] https://en.wikipedia.org/wiki/Aral_smallpox_incident

[2] https://en.wikipedia.org/wiki/Sverdlovsk_anthrax_leak

bacteria are able to survive outside a host body, and exploit a wide range of resource compared to virus.

virus is good for control in the case of accidents such as a biowar implement crashes somehow and spills virus, the environment will destroy it quickly, the cleanup is simple compared to a bacterial agent, eg anthrax in spore form lasts many years-->

Someone always says this.

And yet here we are with a virus that has an r0 much higher than flu, and is ~10 times more lethal.

That the two things are correlated in certain modeling scenarios does not mean you can't end up something that both spreads and kills.

Influenza R0 has varied historically between 0.9 and 2.8 [0], where covid-19 is typically quoted as having an R0 around 2.3-2.5. It’s not substantially different in that regard.

Lethality estimates also suffer from being based on bad data. “Patients who have been tested for SARS-CoV-2 are disproportionately those with severe symptoms and bad outcomes.” [1]. For that reason, the CFR in the US at least has been around 1%, but the IFR could actually be significantly lower.

[0]: https://www.ncbi.nlm.nih.gov/pubmed/19545404/ [1]: https://www.statnews.com/2020/03/17/a-fiasco-in-the-making-a...

Otoh, the epidemic in the US is likely growing exponentially, and that encourages the current CFR to underestimate the actual CFR as new cases haven't had time to die.

In terms of estimating the IFR, it's hard; estimates are about 0.7, much higher than flu.

Your link says 'mean R0 1.3: range 0.9 to 2.1'.

Compared to the mean R0 of flu, this disease spreads substantially more and is more lethal, hence is a good counterpoint to the flawed argument of the post that I was replying to.

Stop comparing this to the seasonal flu, it's also quite likely that 3-4 years down the line when population wide antibody studies would be completed the CFR/IFR will drop by a factor of 10.

How many past events of rapid, steep population decline have we seen in the historical/archaeological record? Assuming that, historically speaking, travel isn't what it is today, I would expect such cases to be localized, but still I think it can go some distance to answering your question. We see instances of civilizations falling apart, but I'm certainly not aware of any where a top of your range disease was considered a reasonable possibility. Of those that come within your range, the only instances I can think of were in combination with other pressures... a large portion of the population gets very sick while at the same time the society comes under attack from outside peoples.

How many times do we see this sort of thing in nature? We do see infestations, like beetles destroying forests, but I'm not so sure we have many cases where we expect viral infections to be the likely candidate.

Of all the disease related scenarios I'm worried about, none match your scenario. I do think in some ways humans are "tuned" to apocalyptic thinking moreso than is perhaps is helpful. I think we're more prone to accept emotional arguments than we should be, causing us to possibly be more a danger to ourselves in the face of a terrible disease than the disease itself. I'm much more afraid of what we'll do to each other and ourselves, willingly, under pressure, than I am about even the most deadly viruses will do.

Having said all of this: it's all opinion and none of it comes from expertise. Others may point out evidence to the contrary.

Isn’t this is literally survivorship-bias? There are a lot of events that can happen in future which has no precedence. But I generally agree with you, it’s hard to speculate.

I don't think it is; assuming the questions of the original commentator asked can be read as a "how likely" sort of thing. I'm not saying look at the people here and you have your answer (aside from extinction level epidemics, which we can exclude because we are here), but complex life has existed for quite a while and even humans have on a relative basis. If the sort of thing the commentator is thinking is at all likely, it very well is likely to have happened before (assuming viruses more easily evolve than more complex lifeforms do). I'm saying that we should be able to learn from what isn't here, from what didn't survive... not from what did. When we look back at what didn't make it, I don't know of many (any) cases where we say that the sudden appearance of an extremely virulent pathogen likely did in this species or that civilization. This isn't to say its impossible, but unlikely... if you perform a historical study of random individuals that play the lottery, you'll find that it's just parting a sucker from their money... yet there is nonetheless usually a winner.

The Americas saw this rapid decline with arrival of Europeans. The diseases killed 90% of indigenous people ... Guns, Germs, and Steel, PBS adaptation ... "When the Europeans arrived, carrying germs which thrived in dense, semi-urban populations, the indigenous people of the Americas were effectively doomed. They had never experienced smallpox, measles or flu before, and the viruses tore through the continent, killing an estimated 90% of Native Americans." That far outstrips what we're likely to see in absolute numbers in this coming year worldwide from COVID-19.

The Black Death probably falls into that category, being thought to have killed 30-60% of the population of Europe, and followed up by multiple subsequent related plagues over the ensuing centuries. The Plague of Justinian might have wiped out a similar proportion of the population a few hundred years before that.

Modern medicine and hygiene would have significantly increased survival rates, especially since many of the most deadly plagues are thought to have been bacterial and transmitted by flea bites. The other big difference is transport of course; historically extremely virulent and deadly diseases in many parts of the world had limited ability to spread beyond that particular ill-fated town or city, and rats and fleas were more necessary as well as more effective in helping the disease spread.

I recently attended a virology lecture where this question was asked.

The answer was that this is very unlikely. In fact, the evolutionary direction of all known viruses is the opposite: from high towards low virulence. High virulence is observed in viruses which have recently jumped from one species to another and can be thought of as temporary maladaptation to the new species. As the virus adapts, the damage it does in the course of its reproduction process becomes less and less severe. Eventually, many viruses end up causing mild symptoms similar to the common cold, warts etc.

It’s untrue that natural selection always guides pathogens to be less lethal.

This is covered in ch. 64-66 of Quammen’s “Spillover”, which covers a seminal paper by Anderson and May[0] considering the case of myxomatosis.

Here’s some salient quotes:

Laboratory experiments showed that all field strains produced lesions that provided sufficient virus for transmission to occur,” he wrote. But the strains of very high virulence (grades I and II) killed rabbits “so quickly that infectious lesions were only available for a few days.” The milder strains (grades IV and V) produced lesions that tended to heal quickly, he added—and then the payoff, “whereas strains of grade III virulence were highly infectious for the lifetime of the rabbits that died and for a much longer period in those that survived.” Grade III, at that point, was still killing around 67 percent of the rabbits it touched. Myxoma virus, thirty years after its introduction, had found this level of virulence—being pretty damn lethal—to maximize its transmission. It was still capable of killing most of the rabbits it infected, but capable also of assuring its own survival with a continuous chain of infections. The first rule of a successful parasite? Myxoma’s success in Australia suggests something different from that nugget of conventional wisdom I mentioned above. It’s not Don’t kill your host. It’s Don’t burn your bridges until after you’ve crossed them...

...they[Anderson and May] plotted a relationship between virulence and success. Their result was a model-generated prediction: Given this rate of transmission, given that rate of recovery, given those unrelated mortalities, then . . . an intermediate grade of virulence should come to predominate. Son of a gun, it matched what had happened.

[0]: https://www.cambridge.org/core/journals/parasitology/article...

This is horrific. I am gonna use this term "Don't burn your bridges until after you've cross them" to communicate that contagious incubation period is extremely dangerous and the reason why the current Coronavirus epidemic turned into a global pandemic.

Thus, testing is by far the most important capability to have - it is a litmust test whether the pathogen is ready to build one of those bridges to cross.

basically the selection mechanism is about being able to make copies of yourself that can make copies this mean reproductive success. when you can make copies that make copies at a higher rate overall then all others competing along the same resource access, you have i higher frequency of copy than all others, that is differential reproductive success and is the foundation of neodarwinian models of evolution

A wonderful book that answers this and many other questions is 'Evolutionary Dynamics: Exploring the Equations of Life' by Martin Nowak.

Is there a reason why China hasn't done massive randomized blood testing in the city of Wuhan, to see what the real spread was? Surely that is data they would desperately want.

We know their infections were radically beyond the 80,000 they claim. For exmaple we know they changed their qualifications in late January / early February, to hide infection numbers by dropping non-severe results (which produced a fake taper off in their case expansion at that time). However, it would be an immense service to the world, if we could find out just how widespread the virus really is in populations. If anyone could do a million blood tests in a short amount of time, it would be China.

Did herd immunity help China bring the outbreak under control in Wuhan, because it had hyper spread there? It's crazy that we still don't know basic things like this.

Has Italy really had 500k-1m cases of it, not 47,000? Such that it took that many cases in the general population, most undocumented, to generate the ICU overload they're seeing.

It changes everything about how we handle the virus over the coming months, if it has already spread in large numbers across the population. Some large population country with a lot of infections needs to do this asap. China, US, France, Spain, Italy, Germany. Even Switzerland at this point might give us the data we need. Do they really have 60,000 cases, rather than 6,000?

We don’t have a clue what happened in Wuhan, and it seems pretty clear that China doesn’t want us to know what happened in Wuhan. The leaked videos, and other evidence of things that have happened there are not comforting though.

Can you share some leaked videos?

They were posted on Twitter in january

There are a number of different twitter Accounts that post 10-20 videos a day that come out of various WeChat groups.

This one that is allegedly cell phones outside of a crematorium is probably the most famous example: https://twitter.com/solomonyue/status/1241166393673801728?s=...

I’ll try to relocate the one primary account I was browsing a while back.

Here we go. This one has constant stream of new videos: https://twitter.com/PhdParody

The antibody tests needed are quite new and seems to be somewhat more time consuming. They are still trying to keep the virus in check so probably are dedicating all their resources to test for the virus and not immunity. However I’ve wondered if it does not make sense to find all people who have recovered and drafting them to help create a firewall in critical institutions to reduce the contagion rate.

> We know their infections were radically beyond the 80,000 they claim. [...] they changed their qualifications in late January / early February, to hide infection numbers [...]

I think you answered your first question right here. It may not be convenient for the CCP to get to the truth.

Wouldn’t it be in the CCP’s favour to report that the virus has a lower CFR?

Not if they're gleefully watching "the West" crush themselves in mass panic...

They have shared a lot of data and I've heard scientists in the west to be very thankful over that.

Does the tests for antibodies even exists yet? I heard it was some weeks away?

Well sure, you don't just lay all your cards out on the table when you've got a good hand going.

There are already rapid antibody tests available. It's extremely curious to me why they haven't been used or we at least aren't seeing any data that they have.

This isn't about a rapid test, but is still interesting: https://globalbiodefense.com/headlines/singapore-first-to-te...

That's not what they're doing. China is losing her biggest customer, possibly for an extended period of time. If America's economy collapses, China's likely will too.

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