SARS-CoV-2 spike D614G variant confers enhanced replication and transmissibility

https://www.biorxiv.org/content/10.1101/2020.10.27.357558v1

by MKais • 6 years ago

146 90 6 years ago

biorxiv.org

jlgaddis• 6 years ago

Off-topic:

... made available under a CC-BY-ND 4.0 International license.

I'm quite pleased to see more and more academic and scientific papers being licensed as such in recent times!

anticensor4• 6 years ago

Why ND and not BY-SA?

ashleyn• 6 years ago

Derivative works from a biology paper can result in disinformation.

murphyslab3• 6 years ago

Use of the CC BY ND license is meant to reflect the common practice of sharing academic papers, which was often done informally, as opposed to a paywall. I can send you a copy of my paper; you can pass on copies to colleagues. But in doing so, you wouldn't edit it. That's not a freedom which is necessary for sharing a paper. The paper is a complete product. Moreover it would be a breech of the integrity of the work to edit it. If a correction is required, there is a proper route for that: erratum or corrigendum, published in the original venue.

The first catch of "ND" is that this excludes translation, but that really is not considered to be an issue for two reasons: (1) Scientists are generally expected to be proficient in English and able to read a paper in English - as once was the case for chemists being proficient in German. (2) For popularization and dissemination, media outlets are able to write summaries in other languages.

The second catch is that we really should have some kind of formal secondary license for images and figures within a paper (ideally CC-BY), to allow them to be used separately, since reuse of these should be as frictionless as possible. As a former grad student, it was a pain when writing the review section in a thesis! Though many journals & academic publishers achieve this through having blanket forms that an academic can download for permission to re-use images; for others one needs to consult with the authors of a paper which can be tricky.

And to counter your other comment:

Ancillary and auxiliary sources are key to scientific criticism.

The licensing does nothing whatsoever to prevent scientific criticism. The Berne Convention [1] explicitly allows for quoting from other works, even if not licensed whatsoever:

10.1 It shall be permissible to make quotations from a work which has already been lawfully made available to the public, provided that their making is compatible with fair practice, and their extent does not exceed that justified by the purpose, including quotations from newspaper articles and periodicals in the form of press summaries.

Criticism is never a matter of editing someone else's work; it's commenting about the work. You don't need a license to do that. If one has free access to the full text, which CC BY ND provides, then one has everything necessary to understand the criticism.

[1] https://wipolex.wipo.int/en/text/283698

omginternets• 6 years ago

One thing isn't clear to me, for lack of background knowledge: have there been several strains since the beginning of the pandemic, or is this study based on evidence of mutation in the wild?

It sounds like the former, but since it wasn't explicitly addressed in the abstract, I thought I'd ask.

melville• 6 years ago

Doesn't the first phrase of the abstract state that the latter is the case: "During the evolution in humans ...."?

remote_phone• 6 years ago

There have been variants but none so dissimilar that they are considered a new strain. The terminology is very precise here but the media have been mixing it up, causing confusion.

https://medium.com/swlh/variants-lineages-and-strains-of-cor...

ismail• 6 years ago

Thanks for this link. From the article she states:

“Mutations that alter any of the following can lead to a new strain:

pathogenicity virulence immunogenicity.”

And

“ Another way that the term strain is used is when a particular variant of the virus (the virus with a specific set of mutations) ”

This sounds like the mutation referenced in the paper could be considered a “new strain” given the above?

“ Until there is clear evidence supporting functional or immunogenic differences among the variants, it is appropriate to consider all of these lineages of the same virus.”

Raidion• 6 years ago

This is not my area of expertise, but I think I can help answer the question. Everything mutates a lot, so there is a lot of genetic variability. These are usually pretty minor, but really help with tracing, as you can correlate "family trees" of mutations. The big one early in the pandemic was you could see the difference in the genome between the China/West Coast USA and Europe/East Coast USA infections.

I'm not sure of the strict scholastic definition of a strain, but I think they're derived from branches of that family tree. Most of those branches behave pretty similarly as they have mutations that aren't really impactful, but some of those behave differently, and those are the "strains/variants" we're talking about.

On an interesting note on how genetics are used to target therapies, what researchers can do is look at all the different mutations and they can find parts of the genome that change a lot, and parts that change very little. The parts that change very little are often critical for the function of the virus. Mutations to those still happen, but because of the critical nature of the part that mutated, the virus isn't able to reproduce as effectively and so doesn't show up as often. Researchers can use those as targets for treatments, as disrupting those can impact the effectiveness of the virus.

If I got any of that wrong (or I'm using the wrong vocabulary), I'd love to hear from someone with an actual background in this stuff.

murphyslab3• 6 years ago

There are thousands of mutations which have been observed. Some are consequential - changing the virus' behaviour - others are not. What constitutes a "strain" is fuzzy, since viruses are constantly evolving and it's an artificial category or human construct. To get away from that, it's often helpful to think in terms of phylogeny or genetic relationships.

You can see a phylogenetic tree of the clades (essentially a "family tree" determined through mutations of the virus) & a map showing the distribution of the different clades of the virus worldwide on GSAID platform:

https://www.gisaid.org/epiflu-applications/phylodynamics/

otherme1232• 6 years ago

With our current knowledge we can only say that there's only one strain, but they are accumulating changes randomly. Usually those changes are deletereous (bad for the virus), some are neutral and a very minor amount increase the fitness of the virus (good for the virus).

It has been proposed that one of those mutations (D614G) increases the fitness of the virus. If that was the case, viruses with D614G would slowly take over the population. The problem here is that if some "founder effect" [1] happens, it will appear exactly like some mutation gives an increased fitness but what happened in reality was that some guy travelled to a meeting and infected 100 people.

This mutation was first reported in january-2020 in Germany (AFAIK), so it's a very posible that it was just one of the very first viruses to arrive in Europe and "founded" a new population when the virus was spreading almost freely. Then some scientist noted that a lot of european sequences included the mutation and hipotesized that the change was behind the quick spreading of march and april.

Right now, about 80% of the sequences reported to Gisaid include that mutation, but that is about the same percentage than in april/may. I'm personally inclined to believe that D614G is close to have neutral effects, as other variants of the virus without the mutation are also being quite successful in spreading and keeping themselves in the population.

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

cephaslr• 6 years ago

Something I have been wondering about, wouldn't a virus naturally evolve to be less deadly and more contagious over time? I.e. virus's tend to achieve a steady state like the cold and flu in the long run. If you are too deadly it hinders spread so I would expect Covid to get less deadly and more contagious over time, which kind of fits the data?

kingbirdy• 6 years ago

Influenza isn't in a steady state, there are hundreds of strains[0] that compete with each other and recombine to form novel versions. Each year's flu vaccine targets four of them based on modeling as to which will be most prevalent in the upcoming flu season[1/2].

0: https://www.cdc.gov/flu/about/viruses/types.htm

1: https://www.cdc.gov/flu/prevent/quadrivalent.htm

2: https://www.fda.gov/vaccines-blood-biologics/lot-release/inf...

vharuck• 6 years ago

Evolution is a random and long-term process. What you're thinking of is natural selection. Even that does not guarantee things will get better. For example, there was a worse second wave of Spanish Flu. Natural selection only implies there's less chance these terrible things will last. And, to adapt an economic adage, "The disease can remain deadly longer than you can remain alive."

jacquesm2• 6 years ago

Natural selection is the basic mechanism that enables evolution, the one is part of the other.

hamaluik• 6 years ago

Generally, yes. But also we’re a bit unlucky that it isn’t very deadly: SARS was way deadlier To start with but as a result spread several orders of magnitude less (both naturally and because humans had a stronger reaction to “shut it down at all costs“).

The H1N1 virus from the 1918 pandemic grew less deadly over time, and essentially evolved into a seasonal flu that is still affecting people around the world today. Personally, I expect COVID19 to go the same way.

packetlost• 6 years ago

The h1n1 is a bit of a strange case though because it jumps species boundary very often and mutates very quickly. COVID-19 appears to evolve much, much slower. Based on my limited understanding of virology, I think this means it's unlikely to become a seasonal problem unless the general populations immune system does not retain immunity to the same strain for a significant period of time.

jaypeg25• 6 years ago

It's already clear that the vaccine, when it gets released, won't be a one time thing and we'll need more in the future to counter the mutations. Unfortunately, just in anecdotally talking to friends about it, it doesn't seem that this is widely known. It will be interesting to see how things play out as more people start to realize this. I suspect a lot of anti-vaxxers will be even more emboldened by it.

onlyrealcuzzo• 6 years ago

Look for counter examples. Have we seen this in HIV? Smallpox? It's a plausibility. It's far from a guarantee.

And the opposite, /could/ happen, too. The virus could mutate to have a longer incubation period, or be more deadly, or both.

rimliu• 6 years ago

I have seen a statemen somewhere tha for viruses it goes "transimissability, mortality, stealthiness: pick two". Not sure how true it is, but looks plausible.

throwaway22453• 6 years ago

Conventional wisdom often claims that virus evolve to become less fatal - but I don't think that matches the historical record.

There's evidence for influenza virus existing thousands of years before 1918. As such, it seems to have evolved into a much more deadly strain at that point.

Reproducing more efficiently is a win for natural selection and will normally result in a dominant strain: whether that strain is more deadly or not is going to be random.

We might optimistically anticipate some regression to the mean fatality rate (where the mean is close to 0).

feanaro• 6 years ago

Reproducing more efficiently is a win for natural selection and will normally result in a dominant strain: whether that strain is more deadly or not is going to be random.

The conventional wisdom is such because a virus that is swiftly fatal and/or has more dramatic health consequences would have less chance to propagate to other hosts. For instance, because the original host will be unable to move or will look threatening to others so they will know not to reside close to them. This should make it less than random.

Unless of course some unforeseen factor makes this reasoning untrue.

aaron_m04• 6 years ago

I think what happened with the 1918 pandemic (and the 2019 one for that matter) is a virus hopping between species can "reset the clock" on that trend and start as very fatal for humans.

Izkata2• 6 years ago

There's evidence for influenza virus existing thousands of years before 1918. As such, it seems to have evolved into a much more deadly strain at that point.

Influenza refers to a class of viruses, not a single virus.

backtoyoujim2• 6 years ago

I can imagine that a single nucleotide polymorphism doesn't care about what seems natural.

neuronic• 6 years ago

No, but its effect on the virus population kind of does.

sp332• 6 years ago

But the way viruses evolve to be less deadly is that the deadlier strains kill a bunch of people quickly, before they can spread too much. So that's not exactly reassuring for any given mutation.

scotty79• 6 years ago

Only if they are so deadly that it's harming their transmissibility.

davidf560• 6 years ago

I keep wondering what unintended consequences our nearly-unprecedented efforts on non-pharmaceutical interventions ("lockdown", social distancing, masks, etc.) might end up having on the virus - for example, could all our isolation and distancing be accidentally selecting for strains of the virus that transmit more readily over further distances?

Zenst2• 6 years ago

That will be a tough one to measure.

However measurement of the impact of lock-downs/social distancing upon existing known virus's like colds and flu's would give an insight into that whole area.

estebank• 6 years ago

The mitigations are effective in slowing the spread (to varying degrees, due to a multitude of factors), which in turn slow down the rate of mutation. In any case, I would expect the dispersion of the virus to follow a pattern similar to https://www.youtube.com/watch?v=plVk4NVIUh8

Zenst2• 6 years ago

That is mostly due to the way they are spread as a less impacted infected person would be more outgoing and spread that virus more. When somebody more impacted by a virus would be more isolated due to the impact. So the less impacting one gets more exposure and spread.

So that in itself would be a factor, however virus can mutate in various ways and it is the mutations that effect the incubation period and that window of being infectious but not showing any symptoms - that is always going to impact things and certainly a large factor in why COVID managed to spread better than expected.

But much hindsight and data analysis will play out for years and years, after all - we are still looking at the Spanish flu data and seeing different aspects to this day.

zerobits• 6 years ago

You would think – but viruses don't necessarily become less deadly.

The virus wants to maximize transmissibility, and that might require trading off further against the host's health and increasing its death rate.

An example is Myxoma virus. It was intentionally introduced to pest Australian rabbit populations (to cull them) and studied.

After ~30 years of evolution, they found the dominant strain had a 70-95% death rate and left long-lasting lesions. Other strains with higher (~99%) and lower (~50%) death rates weren't as stable & prevalent.

Once a virus is transmitted (enough), what happens to the health of its host is irrelevant.

[1] https://www.sciencedirect.com/topics/immunology-and-microbio...

libertine6• 6 years ago

It basically needs to be extremely contagious without symptoms that stop the spread - like killing the host.

Which in part this virus has, asymptomatic and pre-symptomatic are as contagious as symptomatic. If it's enough to spread, doesn't matter much if the host dies after a few days or not.

nikolay• 6 years ago

It's not like the virus has a brain. Statistically most could become less deadly, but it doesn't mean all will follow the same pattern. In this case, the virus becomes less deadly as we know how to treat it better and most infected and tested now are younger people.

noodlenotes• 6 years ago

We're unlucky in that Covid takes such a long time to kill. It's a little under a week until symptoms onset, another week until serious illness [1]. Hospital patients aren't dying of Covid until almost 2 weeks after admission [2]. So we're talking about victims dying maybe a month after exposure.

With other illnesses there's evolutionary pressure to be less deadly so that the host doesn't die before infecting others, but that's not a problem for Covid where people are most contagious before symptom onset.

[1] https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-guida...

[2] https://www.bmj.com/content/369/bmj.m1923.full

CyanLite2• 6 years ago

If you look at the death rate compared to March, it is dramatically lower, even though we're having 2x the cases. This could be because of better treatment, or because the virus itself is getting milder.

Fnoord2• 6 years ago

Or because more people (with mild symptoms) get traced and tested. We had a shortage of tests and masks on start of pandemic.

titzer• 6 years ago

There are a lot of factors contributing, in particular the age distribution of those people getting infected.

One thing is "viral load", which has to do with how much of the virus is present at initial infection. Because immune system response takes time to ramp up, e.g. 10x more virus in the beginning means that it can do much more damage before the immune response. It's likely that social distancing and masks have reduced the average viral load at infection time.

TheGallopedHigh2• 6 years ago

In purely theoretical models virulence naturally evolved to a smaller value.

major505• 6 years ago

Is a shit thing when a virus got a firmware update in 2020, but not my android phone.

herodotus• 6 years ago

Thanks for the laugh. So needed for this crappy year of hell.

m101010• 6 years ago

for me it helps to know that this pandemic (including all the lockdowns) would be way worse without all of the digital innovations from the last 10-20 years.

SilasX• 6 years ago

And the virus updates make it more effective but every update makes my iPhone worse. Random freezes if you touch the screen at the wrong time, double-tap to zoom barely working...

baxtr• 6 years ago

AFAIK this is the variant that formed in northern Italy back in February and is since ruling the world

libertine6• 6 years ago

That's why it's not good to have a new virus going around in among us. That's why the whole response should have been - isolate and eliminate the virus.

Not, "hey, lets live with this guy until we can make a vaccine that works"...

ulfw• 6 years ago

The Asian vs. the Euro-American model.

yomly• 6 years ago

Could someone with some background ELI5 this for those of us who lack expertise?

dehrmann2• 6 years ago

This is what worries me a little about widespread mask use. It will start selecting strains that spread more through aerosols, touch, or are easier to contract.

otherme1232• 6 years ago

Masks imposes such a hurdle on spreading that, even in the (incredible improbable) event that some virus strain gained a 20% more effectivity of transmission through masks, the mask itself would be restricting 99.99% of the spreading. Overall it means that in place of 1 transmission each 10,000 contacts with mask you'll have maybe 2-3 transmissions of this super-virus even with masks, but 5,000 transmissions without masks.

topbanana• 6 years ago

https://www.biorxiv.org/content/biorxiv/early/2020/10/27/202...

SARS-CoV-2 spike D614G variant confers enhanced replication and transmissibility

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