Thread by @kakape

Situation with new #sarscov2 variants is becoming harder to follow (and not just because of the names), so let me try and give a brief overview: Where are we at? What should we be worried about? And how worried?

Story is up here: sciencemag.org/news/2021/01/n…
And now a thread...

For now there are three variants with sufficient evidence for scientists to be really concerned and I‘ll start with the newest one: P.1.
This was described on Tuesday from December samples from Manaus and had already been picked up in Japan in travelers.
virological.org/t/genomic-char…

Why is it concerning? Three main reasons:
1. The place: P.1 is spreading in Manaus, which is experiencing a devastating surge after already experiencing a terrible wave of infections in March/April. @DrMikeRyan described the dire situation yesterday:

https://twitter.com/kakape/status/1350145043340931081

@DrMikeRyan In fact, a recent paper estimated that 75% of people in Manaus had already been infected before this wave. Any new variant spreading in that context is one to look at closely. And this is why scientists rushed to sequence genomes from there.
science.sciencemag.org/content/371/65…

@DrMikeRyan 2. The mutations: P.1 carries several mutations in the spike protein like E484K, K417T, and N501Y, that have been linked in the lab to escape from antibodies or better binding to cells. Remember though that we know little about how these mutations alone impact virus in real life.

@DrMikeRyan We know even less about what they mean together. As @K_G_Andersen told me about N501Y (Nelly): “Nelly might be innocent, except maybe when she’s hanging with her bad friends”. This is why the urgent task is to understand constellations of mutations not just individual mutations.

@DrMikeRyan @K_G_Andersen 3. The similarity: The pattern of mutations of P.1 is similar to that found in another varian of concern: N501Y.V2, the variant first identified in South Africa. Both have N501Y and E484K and both have a mutation at position 417 (though a different one).

@DrMikeRyan @K_G_Andersen And as @JesseBloom told me: “Anytime you see the same mutations arising and starting to spread multiple times, in different viral strains across the world, that’s really strong evidence that there’s some evolutionary advantage to those mutations.”

@DrMikeRyan @K_G_Andersen @JesseBloom IF 75% were already infected in Manaus, then 3 ways to explain surge, @EvolveDotZoo told me:
1. P.1 doesn’t matter. Immunity is waning and people are getting infected again.
2. P.1 is better at reinfecting people.
3. P.1 is more transmissible (threshold for herd immunity higher)

@DrMikeRyan @K_G_Andersen @JesseBloom @EvolveDotZoo It could, of course, also be a combination of these three factors. But it should be clear from this why the situation around P.1 is concerning and why figuring out what is going on in Manaus is one of the urgent puzzles of this pandemic.

@DrMikeRyan @K_G_Andersen @JesseBloom @EvolveDotZoo Even if P.1 and/or 501Y.V2 turn out to be better at reinfecting people that would likely be a gradual effect. It also doesn’t mean they are resistant to the vaccines. But that we are even talking about it is a warning sign. We need to adjust expectations and we need to prepare.

@DrMikeRyan @K_G_Andersen @JesseBloom @EvolveDotZoo As @BillHanage told me: "We spent months talking about how slow the mutation rate is. I think it is smart to get ready to make different vaccines, and smooth regulatory pathways, so that we can plug-and-play. Because this is going to keep happening.”

@DrMikeRyan @K_G_Andersen @JesseBloom @EvolveDotZoo @BillHanage Make no mistake: Most researchers I talk to agree on this. And it marks a shift. This shift is not simply due to mutations accruing which was to be expected. It’s because we are seeing the virus essentially make evolutionary “leaps” to certain combinations of worrying mutations.

@DrMikeRyan @K_G_Andersen @JesseBloom @EvolveDotZoo @BillHanage So what is needed? Basically what @WHO’s emergency committee called for:
More genomic surveillance and sharing of the data.
More research into what these variants really mean. (UK’s new consortium G2P-UK seems like a good start, but more needed.)

@DrMikeRyan @K_G_Andersen @JesseBloom @EvolveDotZoo @BillHanage @WHO Finally, a word about B.1.1.7, the variant first identified in England. The evidence has become stronger and stronger over time that this is more transmissible (but it likely has litte effect on immunity).

@DrMikeRyan @K_G_Andersen @JesseBloom @EvolveDotZoo @BillHanage @WHO I‘ve spent a lot of time in recent weeks explaining the evidence and why this presents a huge problem to the world.
Here, for example: sciencemag.org/news/2021/01/v…

@DrMikeRyan @K_G_Andersen @JesseBloom @EvolveDotZoo @BillHanage @WHO So let me end with what @angie_rasmussen told me about the US, where many hospitals are at capacity.
“Further increases in transmission can tip us over the edge where the system collapses. Then we’ll start seeing potentially huge increases in mortality.”

sciencemag.org/news/2021/01/n…

This should be Jesse Bloom (@jbloom_lab). Sorry!