Thread by @DrEricDing

BREAKING—A new #SARSCoV2 variant (aka B.1.1.248) identified by Japan 🇯🇵 in ✈️pax from Brazil 🇧🇷. This new one has both the more infectious N501Y mutation (not affect vaccine), as well as the disruptive E484K mutation that escapes neutralizing antibodies.🧵
bloomberg.com/news/articles/…

2) Why are we so worried about this one? Because like the SA B1351 variant, this new one also has the E484K mutation. In a recent study by @jbloom_lab, E484 mutation (inside the #SARSCoV2’s spike’s critical receptor binding domain) seemed to escape neutralizing antibodies—bad.

3) More on the E484K mutation. Escaping neutralizing antibodies could mean some convalescent plasma, some antibody drugs, and maybe even vaccines could be disrupted a little. But need more studies to prove it

https://twitter.com/alinouriphd/status/1347016588579508224

4) To be clear, B11248 (Brazil origin) and B1351 (SA origin) are not the same as the infamous B117 infectious variant from 🇬🇧. The B117 does *not* have the E484K (see top post’s figure that doesn’t show it in B117’s row). But the B117 is the one worrying Denmark 🇩🇰 CDC right now.

https://twitter.com/drericding/status/1346899021621813249

5) again, the N501Y mutation (shared by all three) seems to bind the human ACE2 receptor more strongly, and more infectious, but doesn’t seem to affect the vaccine says new study. But beware many headlines don’t make it clear it’s only this mutation that doesn’t vaccine affect.

https://twitter.com/drericding/status/1348421268505296896

6) that said, within the same person, this fraction that escape antibodies also changes over time. On day 18, there was a lot of escape w/ E484, but on day 94, much less. Hence lots of uncertainty about vaccine or MAB drugs long term.

7) That said, BioNTech founder says it only takes them 6 weeks to synthesize a new mRNA vaccine for any new variant. Tricky question is how much clinical testing needs repeated / how long before it can be deployed: 10 mo w/ Phase 3 again? Or shorter P1&2? google.com/amp/s/www.axio…

8) How much affect? the E484K shows a 10x reduction of neutralization (“neutralization” = stopping the virus)
by various antibodies compared to wildtype (common #SARSCoV2) in some patients —a rather bad thing. It means the virus with E484K is worrying for “immune escape”.

9) Is it common in Brazil 🇧🇷 yet? We have no idea because Brazil doesn’t really sequence. We only know of the new #B11248 strain because Japan sequenced it, upon request for help by Brazil from Japan.

https://twitter.com/tak53381102/status/1348448274806497282

10) That said, some rare people are not affected by E484K mutation as much (instead by G446V, which thankfully not in the 3 above variants). But this person was only 1 out of many—most people did experience a degree of escape from neutralizing antibodies.

11) E484K is not just a 1 time fluke. Italian virologists decided to see what mutations can help the virus escape from patients w/ convalescent plasma immunity. So they soaked the virus w/ CP over 12x times to force evolution—80 days later what appeared? ➡️Mutation *E484K arose*!

https://twitter.com/ncholia/status/1347555563400519682

12) Side note—Air travel ✈️ is a great modern thing, but they also helps bridge continents for viruses during a pandemic. We know US’s NYC spring 2020 record outbreak was due to virus coming from Italy and Spain (not China). I worry now about these new worrisome variants.

13) Many experts think maybe it’s the use of synthetic monoclonal antibody drugs and maybe CP in a few chronically sick immunocompromised person long term that drove the evolution of the virus in such ways to adapt. This is why we must end the pandemic w/ #ZeroCovid to win this.

14) Dr Tedros is now warning about the new variants. This is unusually large move.

https://twitter.com/drericding/status/1348710699036516355