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T. Ryan Gregory

@TRyanGregory

Sep 6 • 16 tweets • 4 min read Twitter logo

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https://twitter.com/shay_fleishon/status/1699377508632641789

BA.2.86 is clearly spreading, even based on the very limited testing these days. On paper it looked bad but lab tests suggest it shouldn't really compete well with existing XBBs. The fact that it is nonetheless showing up around the world is a bit puzzling and concerning. 🧵

1/

https://twitter.com/shay_fleishon/status/1699377508632641789

Maybe there's something going on with BA.2.86 outside of what we've come to expect based mostly on immune escape and ACE2 binding. Of course there's more to the virus than spike protein. It could be concerning if it's doing something pretty different.

2/public.tableau.com/app/profile/ra…

But again, my main concern isn't really with BA.2.86 itself. The issue for me is that it represents the founding of a new *lineage* that recently made a major switch in evolutionary environment.

3/

https://twitter.com/TRyanGregory/status/1697387659537133766?t=boorw-CLzryyy0Ij_a6d3g&s=19

BA.2.86 (Pirola) was evolving within a single host for a year. Now there's clearly enough of it out there that it's evolving at the among-host level. Very different traits/mutations will be under selection now. Its descendants are what worry me more than stock BA.2.86.

4/

I keep referring to the example of XBB. The first XBB was concerning (we hadn't seen a recombinant with that much potential before). It did well enough in Singapore but didn't take off globally. Then came the descendants lineages like XBB.1.5*, XBB.1.9*, XBB.1.16*, XBB.2.3*.

5/

XBB had potential and our alert level increased, but when it didn't take off globally it was dismissed by some. Now, almost everything circulating is an XBB descendant, including the clans Kraken (XBB.1.5), Hyperion (XBB.1.9*), Arcturus (XBB.1.16*), and Acrux (XBB.2.3*).

6/

We also have new lineages emerging from the above clans, including Eris (EG.5.1*) and Fornax (FL.1.5.1*), which are XBB.1.9 descendants. We already have Kraken + FLip (XBB.1.5.70), Eris + FLip (HK.3), etc. as well.

7/

https://twitter.com/TRyanGregory/status/1687632569385328640?t=paz4eIszffa1RUDZ5zgGFA&s=19

There's already a Pirola descendant designated (BA.2.86.1) which has another mutation in a region outside the spike gene. It may not do much either, but it shows this is a *lineage* with mutations occurring beyond spike (most of what set BA.2.86 apart were spike mutations).

8/

So what does this mean? I think several things:

1. BA.2.86 is surprising in several ways. It's *not* surprising that it exists at all (we've been talking about the possibility very different variants showing up from within-host evolution for a long time), but...

/9

... it *is* surprising that a) lab data indicate that BA.2.86 is less competitive than we might have expected just based on projections from spike sequence information, but b) it is doing much better globally than we'd expect based on that low competitiveness.

10/

2. We really need to restore global surveillance. Unfortunately, the amount of effort devoted to this has dropped off precipitously.

11/

https://twitter.com/RajlabN/status/1691190408506687488?t=boorw-CLzryyy0Ij_a6d3g&s=19

3. We're indebted to the independent (and often volunteer) variant trackers, lab scientists, and science communicators who have been *by far* the main source of timely information. We only know about BA.2.86 because it was found, announced, analyzed, and tracked by them.

12/

4. We need to stop thinking about variants like we did in 2021-early 2022. It hasn't been about whether each individual variant will cause a tsunami for more than a year. It's not about specific variants, it's about evolving *lineages*.

13/

5. The "don't tell people about/don't nickname variants because they might panic and/or might not panic enough when we tell them it's time to" narrative is getting really old.

14/

https://twitter.com/TRyanGregory/status/1696125694676197724?t=PP-tx20wyWIYNd3HOl2TEA&s=19

6. The formal nickname system is broken. We're back to using technical names, which is *vastly* more complex now than it was when Greek letters were being assigned in 2021. There won't be a BA.2.86.1.X. It will be JM.1 or whatever is next.

15/

https://twitter.com/TRyanGregory/status/1695506954909626796?t=PP-tx20wyWIYNd3HOl2TEA&s=19

https://twitter.com/TRyanGregory/status/1693422681612275948?t=boorw-CLzryyy0Ij_a6d3g&s=19

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More from @TRyanGregory

T. Ryan Gregory

@TRyanGregory

Sep 7

If you want to know what is top of mind for me with variants these days, it's the following:

🧵

1/

1) Combinations of mutations that confer both strong immune escape and ACE2 binding, most notably "FLiP" mutations (S:L455F + S:F456L). We already have these in multiple lineages, including Kraken + FLip (XBB.1.5.70, GK*), Eris + FLip (HK.3*), and Centaurus + FLip (DV.7.1*).

2/

https://twitter.com/TRyanGregory/status/1689977348383223809?s=20

More info about mutation notation and FLip mutations in this 🧵of🔗:

3/

https://twitter.com/TRyanGregory/status/1689977348383223809?s=20

Read 21 tweets

T. Ryan Gregory

@TRyanGregory

Aug 31

A bit about the two levels of viral evolution and BA.2.86. 🧵

BA.2.86 (Pirola) recently switched from evolving within a single host (someone with a long-term infection) to being transmitted among hosts. What evolves within a host is different from what evolves among hosts.

1/

Within a host, there will be a "swarm" or "quasispecies" of slightly different versions of the virus (because the host was infected by more than one version and/or due to mutations happening in viral lineages within that host).

2/

Whether a random genetic error (mutation) is fit or unfit depends on the environment. The mutations that confer an advantage within hosts are often different from those that are advantageous among hosts in a population with significant existing immunity.

3/

Read 12 tweets

T. Ryan Gregory

@TRyanGregory

Aug 29

I know I keep repeating these things, but they are important.

It's not all about individual variants because...

🧵

1. A notable individual variant may not take off, but its descendants might.

Two notable examples:

i) BA.2.75 (Centaurus). People thought it was overhyped. It didn't do a whole lot. However, almost everything circulating today is its descendant, including XBB recombinants.

ii) XBB (Gryphon). People thought it was overhyped at the time too. It didn't do a whole lot. However, almost everything circulating today is its descendant, including XBB.1.5 (Kraken), XBB.1.16 (Arcturus), EG.5 (Eris), FL.1.5.1 (Fornax), etc.

Read 11 tweets

T. Ryan Gregory

@TRyanGregory

Aug 22

I can't advise on vaccine choice or timing, but I can tell you that a) I've had 'em all (AZ, Pfizer, Moderna, Novavax), b) I'll be getting the updated booster as soon as I'm eligible, c) I would be fine with whichever one is available.

Pfizer, Moderna, and Novavax will all be monovalents targeting XBB.1.5 (Kraken). All 3 should work vs other XBB variants incl. Eris (EG.5.1), Fornax (FL.1.5.1), Arcturus (XBB.1.16), and Acrux (XBB.2.3) to prevent severe acute illness (but much less so transmission or long COVID).

Moderna:

investors.modernatx.com/news/news-deta…

Read 6 tweets

T. Ryan Gregory

@TRyanGregory

Aug 21

I remain hopeful that Pirola (BA.2.86) will not become a significant problem.

However, in the context of the usual statements that we see whenever a concerning new variant arises, it's important to note the following:

🧵

1/

1. A new variant does not need to be more severe / virulent / pathogenic than previous variants in order to cause a lot of illness and death. A lot more infections can override a lower average severity per infection. We should have learned this lesson with Omicron vs. Delta.

2/

2. The issue is not just large waves with sharp increases and high peaks (tsunamis). A moderately high baseline sustained for a long time (high sea level) can cause as much or more total illness (area under the curve).

Read 13 tweets