SARS-CoV-2 variants

People are talking about it so much, I thought I'd post a little primer.

OK, how many variants do you suppose exist for the SARS-CoV-2? The initial one in China, then the dominant one now, then the other three, UK, South Africa, and Brazil, so five?

Brace for it:

There are 300,000 variants of the SARS-CoV-2. They are so many that we group them in lineages or clusters called clades; 8 in one classification (the GISAID one), 11 in another one (the Nexstrain one). There isn't a universally accepted classification system, yet.

Still another classification, proposed by a team called PANGOLIN (it's an acronym), proposes lineages, 5 major ones and some subtypes. They are called the Rambaut classification.

These three classifications overlap. For example, the variant B.1.5 by Rambaut, is included in the 20A cluster by Nextstrain, and the G clade by GISAID. Yep, complicated, huh? To make it worse, some variants have multiple names, and are named after the main mutations they have, or are called VoC with a date and a sequence (VoC stands for Variant of Concern). For example, the famous B.1.1.7 (in the Rambaut classification) is also called VoC202012/01, that is, the first variant of concern identified in December of 2020, a.k.a. the UK variant which is poised to become the most common one in Europe (and shortly, in the USA).

What's the most common one in Europe, as of now (before the B.1.1.7 finishes taking over)? It belongs to the clade 20A and is called 20A.EU1.

What about the South African strain? It is known as the 20H/501Y.V2 by Nextstrain, or B.1.351 by Rambaut. As you can see, the Nextstrain name incorporates its main mutation, the N501Y mutation that makes it more infectious.

Mutations are thousands and thousands, in specific regions of the viral genome. Typically we only talk about a distinct variant of concern when it has many different mutations, say, 17 mutations in the Spike protein. Most of the mutations mean nothing and don't influence how infectious or how lethal, or the antigenicity (how it responds to vaccines and monoclonal antibodies).

Another concerning mutation is the E484K: this mutation appeared in two new strains, called P.1 and P.2; these are the two new Brazilian strains; the P.1 from Manaus, also found in Japan, and the P.2 from Rio de Janeiro. It also appeared in the South African strain. It increases the escape from antibodies (thus decreases vaccine efficacy). The third concerning mutation is the D614G. It makes the virus slightly more infectious.

Currently dominant strains in the United States: 20G clade. Now, we got a new one in California. It's called CAL.20C. In the Rambaut nomenclature, it is called B.1.429 and it has spread to 50% of California.

What other concerning variants exist? One doesn't exist anymore: Cluster 5. It got into minks in Denmark and seemed dangerous, and was able to spread to humans. How was it extinguished? They killed all the minks. No kidding.

The newest one popped up in Germany, ten days ago. It hasn't been named yet. There's a relatively new one in Nigeria too, called B.1.1.207.

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OK, so, what strains are actually concerning?

None not listed below is concerning. They all basically have the same virulence, same infectiousness, and same lethality and they are susceptible to the existing vaccines. But these below are different, due to their more concerning mutations D614G, E484K and N501Y.

B.1.1.7 a.k.a. the UK strain: 56% more contagious. Contrary to what was initially though, may be up to 30% more lethal (more likely less than that). Entirely susceptible to the Pfizer, Novavax, and Moderna vaccines.

B.1.351 a.k.a. the South African strain: more contagious, more prone to escaping antibodies from infection by previous strains, monoclonal antibodies, and vaccines. The Novavax vaccine is only 49% effective against it. Pfizer and Moderna seem to be still protective but significantly less as well, although this hasn't been quantified (but antibody production drops six folds). Now here is the biggest concern: this strain seems to attack more young people with no underlying medical conditions and seems to be more lethal for this group than previous strains.

P.1 Strain, a.k.a. the Manaus (Brazil) one - still being studied but since it has both the E484K and the N501Y mutations, it is likely to be more contagious and to evade vaccines better. It is also suspected of causing more severe disease in young people.

P.2, a.k.a. the Rio de Janeiro (Brazil) one - only has the E484K mutation (among the concerning ones) so maybe not more infectious, but more able to evade vaccines.

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What do we have in the United States?

The B.1.1.7 is likely to become the most dominant strain by March. It is in most states, already.

The B.1.351 is in South Carolina.

The P.1 is in Colorado. We don't have the P.2 yet.

Why is this concerning?

The B.1.1.7 because it has the potential to trigger another wave of infections, despite our numbers dropping over the last two weeks, and despite our vaccination campaign. It is more infectious but our vaccines zap it just fine. The problem resides in more people sick therefore more overwhelmed hospitals and thus more deaths, and remember, it may be a bit more lethal.

The B.1.351 and the P.1 have just arrived but they are the most concerning. Not only they can cause more disease and more deaths in young and healthy people, but also they seem to be able to escape the vaccines with their efficacy dropping from the 90s to the 50s. They are more infectious too. These are the nightmarish strains.

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End of this prime.

 

The coronavirus itself is a nightmare that seems to never end in this life, just when we finally thought we had something to counter this thing it punches right back. Can science really beat this virus?

 

Yes, we can, but we won't because of politics, economics, and logistics.
We can tweak our mRNA vaccines to new strains in 6 to 9 weeks. The problem is, we're already having trouble vaccinating the population against the existing strains, getting today to 24.65 million people when we have 330 million people... Can you imagine redoing it all over again? Raw materials, vials, syringes, manufacturing, distribution, inoculation...
This virus will become endemic and will mutate periodically, and we'll have to keep tweaking the vaccines and keep revaccinating people. Meanwhile half of the country will continue to think that it's a hoax and no big deal and will continue to say insane idiocies like the death toll is inflated and fake because we doctors want to make more money (this is so not true in so many levels) and will continue to scream "My freeeeeeedoms!!!!" instead of wearing masks, so, basically, we're screwed.

 

As far as I know, it's not yet available to the general populace yet(due to logistic issues as you said, ignoring the politics part of that, because this is about life and death.) But I know that when it becomes available to the general public, I'll take one. I think the periodic mutation is like a certain virus, I don't remember the name of it but there are viruses that mutate and never go away completely.

 

Looks like Gaia has finally had her fill of humanity...

 

Yep, she is treating the "infection" quite efficiently. Hurricanes, forest fires, murder hornets... and Covid-19.

 

Corona is a nightmare that seems never to end IN THE MAINSTREAM MEDIA.

Men are not prisoners of fate, they are prisoners of their own minds, especially at the hands of the descendants of Bernays and Goebbels.

 

Correction: the P.1 strain was found in Minnesota, not Colorado.
New piece of info:
Johnson & Johnson (Janssen) vaccine phase 3 trial showed the shot being effective at 72% in the United states but only 57% in South Africa; this is the second vaccine that demonstrates that the current vaccines don't protect as well against the B.1.351 strain in South Africa (and now in South Carolina).

 

A couple of recent pieces of info regarding the South African and the Brazilian (P.1 Manaus) variant (The Brazilian P.2 variant in Rio de Janeiro doesn't appear to be as concerning).

Both the B.1.351 and the P.1 appear to be 50% more contagious (and had mentioned this characteristic in my OP but without quantifying it).

Given that the P.1 has three essential mutations in common with the B.1.351, N501Y, K417T, and E484K, it is likely that it will evade vaccines to the same proportion as the B.1.351.

Now, a very concerning issue with the P.1: Manaus, the city where it originated, was one of the hardest hit cities in the world in terms of number of infected people: 75% of the inhabitants were estimated to have already contracted Covid-19 from the previous prevailing strain. So, this was pretty close to herd immunity, right? Guess what, the new variant caused a spike and is now responsible for 42% of new infections.

This raises the spectrum of re-infections. Two cases of re-infection in Brazil have already been documented by genomic sequencing. Most likely there are thousands more in Manaus; they are not apparent just because Brazil has scarce capacity to do genomic sequencing in high numbers.

So, with P.1 showing up in Minnesota and 50% more infectious, we may see a rapid spread of a variant that is not only more infectious (like the B.1.1.7) but potentially also able to re-infect people who have had Covid-19 before, evading herd immunity, and to also partially evade vaccines.

Not good.

 

Health experts in South Africa have seen that the variant there has such a high rate of reinfection - up to 30% - that previous infection did not appear to protect people. Fauci has warned that if this strain becomes dominant we could see a large number of people who had the disease before, getting infected again.

Now, here is a VERY important point: even in South Africa, NOBODY who has received the Novavax or the Johnson and Johnson vaccines, has died of Covid-19 even when they got it.

While the vaccines seem to be less protective to avoid infection with the South African variant, they appear to be 100% effective in avoiding death from the variant.

So, the idea that these vaccines are failing given a drop in anti-infection effectiveness to 49% or 57% needs to be tampered by the fact that even though the protection is partial, it is still sufficient to avoid death.

This point is very important regarding all five Covid-19 vaccines - seven if we count the Chinese CoronaVac and the Russian Sputinik V - that have presented public data. Among some 85,000 people who got these vaccines in non-placebo arms of all the trials, nobody died of Covid-19. The rate of death in an equivalent US population for these 85,000 people, thousands of them being senior citizens, is about 170 people. Also, of all vaccinated people, only some 100 required hospitalization (but didn't die). The equivalent number without the vaccines would have been several thousand people, up to 17,000.

Now, let's look at the global vaccination numbers.

108 million people have been vaccinated by now. A huge chunk of them are the elderly above the age of 65 (some of the vaccinated people are younger healthcare workers, but once that group got vaccinated, countries moved to vaccinate their people aged 75 and up then 65 and up).

There was ONE death from Covid-19 of a vaccinated person. It's been established that the person already had Covid-19 and was battling a prolonged case, when he was vaccinated, in an attempt to enhance his defenses given that the vaccines foster focused, specific antibodies that seem more potent than the ones induced by natural infection especially in an elderly and fragile person like this gentleman. It didn't work and he died. Officials examining this case discarded that this death was related to the vaccine.

But nobody else who got vaccinated, has died of the disease.

So, let's look at what this number of 108 million people already vaccinated worldwide would represent in terms of possible death. Let's supposed what would have happened to them without the vaccine, if they caught the virus.

The CFR for people below the age of 65 has been about 0.5%. The CFR for people between the age of 65 and 75 goes up to at least 3.1% in developed countries (more in weaker countries but let's stick with the lower rate to be conservative) and for people above 75, to a whooping 11.6%.

Let's suppose that these 108 million people vaccinate so far worldwide, half are healthcare workers and other first responder below the age of 65, and for the other half of vaccinated people, half of them are 75 and older and the other half are between 65 and 75.

We would have: 0.5% of 54,000,000 = 270,000 people
3.1% of 27,000,000 people = 837,000 people
11.6% of 27,000,000 people = 3,132,000 people

Total: 4,239,000 people

So theoretically, 4,239,000 who could die without the vaccine, got reduced to... ZERO!!!

And some people still say that the vaccines are useless, like some people here have said in a thread? LOL

 

A related matter [which is really difficult to teach to the people] is that without following basic NBC rules it's impossible to contain a pandemic.
With this pace of vaccination, it will take around 8-9 months to reach a point near to the herd immunity and not on the entire planet.

But if in the meanwhile the population doesn't behave in a proper and suitable way, the circulation of the virus will remain high and there will be full hospitals and a lot of deaths.

This disease [Covid-19] is difficult to face also because it's "friendly" with the active sectors of the population. Persons under 50 risk almost nothing [if they haven't got other health problems like diabetes, obesity, hearth problems, kidneys problems ...]. This means that there isn't a "sense of danger" which is a pivotal psychological factor to persuade the population to adopt this or that behavior.

They substantially think that authorities should let them live their normal life [with open bars, restaurants, clubs ...].
This is a real and serious problem also in countries [like in Europe] where authorities have imposed strict rules. Without the active collaboration of the citizens it's almost impossible to obtain great results. Anyway authorites can impose enough rules to slow down a pandemic like this.

And here we come to the point about US: the new administration should impose those rules, finding a way to do this also at the level of the single states.
[To say all, the administrations of the single states should understand that it's necessary and urgent to impose basic NBC rules to the population].

What does this mean in numbers?
Let's compare US with Italy.

US has got a population of about 328,200,000 units and it records 26,321,163 cases with 443,355 deaths so far [data from Hopkins Uni https://coronavirus.jhu.edu/map.html].
Italy has got a population of about 60,360,000 units and it records 2,560,957 cases with 88,845 deaths so far.

Mortality rate in Italy is higher, but let's consider the diffusion rate: US = 8.02%; Italy = 4.24%
This means that Italian authorities have been able to slow down and contain the diffusion of SARS-Cov-2 well better than the American ones.
Ok, what if in US you did like us in Italy, recording a diffusion rate equal to 4.24%?
You would have recorded 13,915,680 cases with 234,396 death.

In other words it was possible to reduce the death toll in a considerable way [-208,959 deaths].

 

Going back to the matter of the variants, we've got also our own one: an Italian variant exists.
It's very similar to the British one with the difference that with a mutation in 501 our variant shows a mutation in 493.
Since the lineage appears to be almost the same and the Italian strain appeared in August, it's even possible that our variant is the "mother" of the British one.

 

Concerning development: the E484K mutation, the one that decreases response to vaccines, has been found in 11 cases of the British variant B.1.1.7. Before this development, while more contagious, the British variant wasn't evading the vaccine. Now it is equipped to do so. It's the same mutation seen in South Africa and Brazil. Converging evolution as this mutation has appeared spontaneously in the British variant.

One good point is that the UK is moving relatively fast, only behind Israel and a couple of Arab nations in the rate of vaccination per 100 inhabitants. So if they keep going fast, they may prevent the B.1.1.7 bugs with the new mutation (they will probably be called something else, soon, to account for the fact that they now have the mutation) from spreading too much.

Because, like I said, while efficacy of the vaccines decreases when SARS-CoV-2 strains acquire the E484K mutation, it doesn't drop to zero.

 

OK, now we have our own homegrown variant, in New York City, with the E484K mutation. Rising fast, already getting to 12.7% of the infections in one paper, 25% in another one. B.1.526

https://www.biorxiv.org/content/10.1101/2021.02.14.431043v2.full.pdf

@557 this doubles the number of US variants of concern.

 

I posted this message below in another thread. I'm copying it here because it belongs best to this thread and actually has more updated info than the original post here.

So, there are 300,000 variants and counting. Only a few of them are called "variants of concern" because to deserve this classification, a variant needs to display some sort of unique behavior that makes it more contagious, more lethal, cause more morbidity, more able to evade vaccines and natural antibodies (causing re-infections), more able to evade antivirals, increased risk of MIS or long-haul, more able to evade monoclonal antibodies or convalescent plasma, more dangerous to certain demographics (including youth), and/or a combination of two or more of these.

Of the above number of existing variants, most do not change the basic behavior of the initial Wuhan variant so they are not called variants of concern.

Currently we've been watching about nine variants of concern. Four of them are likely to be the most dangerous ones.

B.1.1.7 (in the PANGOLIN naming system), or 20I/501Y.V1 (in the Nextstrain naming system) is the Kent variant, and it contains the following main mutations: 69/70 deletion; 144Y deletion; N501Y; A570D; D614G; P681H. Observe that it doesn't have the antigen drifting mutation E484K, thankfully. But it appears to be 56% more contagious and may be up to 30% more lethal. Recent research out of the University of Edinburgh found that it may actually be 70% more lethal. Yikes.

P.1 or 20J/501Y.V3 is the Brazilian Manaus variant. It's a brunch of the B.1.1.28. Its main mutations are E484K, K417N/T, N501Y, and D614G. Observe that it has both the E484K that makes it more resistant to vaccines, and the N501Y that makes it more contagious. It's supposed to be between 50% and 200% more contagious. Apparently not more lethal but there is some hint that youngsters have more severe illness from the P.1 than from the original Wuhan variant.

B.1.351 or 20H/501.V2, the South African variant. Its main mutations are K417N, E484K, N501Y, and D614G. Apparently 50% more contagious, with pronounced antigen drift but not more lethal.

The Bristol variant (VOC 202102/02) which is basically a B.1.1.7 with the E484K mutation (double yikes!). Only seen in a few cases so far, but has been found in the USA as well (triple yikes!), so far only one case.

The other five, a bit less concerning, are the Liverpool variant (A.23.1) which is the Wuhan variant with the E484K mutation, the P.2 (Brazilian Rio de Janeiro; less is known about it; it has surfaced already in the Bay Area in California, and it seems to have the E484K but lack the N501Y so while it seems to be able to re-infect like the P.1, it doesn't spread as fast as the P.1 so it should have a hard time getting a foothold), the CAL.20C (California, with the L452R mutation), the B.1.525 in the UK with both E484K and a new mutation called F888L) and the Nigerian variant which has the P681H mutation and is called B.1.1.207.

In the past, the Cluster 5 variant of concern that got to minks in Denmark, got extinguished by... killing all the minks. Poor minks.

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After I posted the message above, we got one more, the B.1.526 out of New York City. Its main mutations are E484K, L5F, T95I, D253G, D614G, and A701V. Presumably more able to evade antibodies, more infectious, and maybe more lethal. That is, one of the bad ones.

 

I ran across this article today.

 

Well that’s unfortunate. Hope it wasn’t my jinx...

Perhaps the reason we are lagging is our lack of looking for and detecting variants of concern, not that they exist at lower rates here compared to elsewhere.

 

OK so maybe we'll see the emergence of yet another domestic variant of concern. This one doesn't even seem to have been named already, with only 9 cases.

This is the paper about it:

https://www.medrxiv.org/content/10.1101/2021.02.08.21251344v1

 

That is indeed one of the accepted possible explanations. We aren't sequencing as much as some other countries.

 

@557 Finally more research was done in Brazil about the P.1 variant.
Conclusions:
Between 1.4 and 2.2 times more infectious
Has the ability to re-infect between 25% and 61% of the people who had had Covid-19 before and get exposed to it.
Drop in antibodies from vaccines: 6 folds.

Yikes.

By now, the P.1 has been found in 5 US states: Alaska, Florida, Maryland, Minnesota and Oklahoma.

 

Given this, how long do you think it would take for it to reach the entire nation if we compare it to the spread of the original virus?

 

Hard to say because in Brazil it didn't have a competitor. It took over the less infectious ancestral strain. Over here it does have competitors, the B.1.1.7 and the California and New York variants. Maybe P.1 won't even spread here. We'll see. For now it is very limited, just a few cases in five states. Fingers crossed.

 

Interesting. Was there hard data on severity of re-infections? I wonder what neutralizing antibody levels are after recovery from re-infection? Just thinking ahead with the hypothetical that say a Brazilian child is infected with the wild type, then the variant. If they don’t get vaccinated for some reason down the line, what is their state of immunity and how will that affect infection rates going forward. Probably no answers yet, just thinking out loud.

Thanks for the update

 

There is this published case of confirmed reinfection with the P.1 in Manaus - not worse but not better, may have had higher viral load:

https://virological.org/t/sars-cov-...ant-of-concern-voc-p-1-in-amazonas-brazil/596

"Notably, the patient had equal moderate symptomatic infections during both episodes and higher viral load (SARS-CoV-2 RT-PCR Ct value) in nasopharyngeal and pharyngeal samples obtained at reinfection compared with those from primo-infection."

 

I don't know if I've posted this study of the P.1, I think I did, but in any case here it goes again:

https://github.com/CADDE-CENTRE/Nov...t/FINAL_P1_MANUSCRIPT_25-02-2021_combined.pdf