My excellent colleague @akelvinlab has this right: we will have more variants as long as SARS-CoV-2 continues to replicate.

Also worth pointing out that we don't know much yet about C.1.2, but we do know that it's not "mutating faster." That wouldn't even necessarily be bad.
C.1.2 is an emergent lineage of variants, meaning it's actually a cluster of several different variants. Here's the preprint describing it, by @CathrineSch07 and colleagues:
medrxiv.org/content/10.110…
Misinterpretation of panel C in the above figure led to 🚨MUTATES TWICE AS FAST 🚨 insanity a few days ago. That's wrong.

The amino acid substitution rate (new mutations that result in a change in a protein) is on par with other emerging variants.
What does that mean?
1. ScDs in nutritional epidemiology and siren emojis don't qualify someone to provide expert opinions on molecular virology or viral evolution.
2. This isn't mutating faster than any other variant. Faster/more mutation isn't always advantageous for viruses.
Mutation is a random process that occurs when the enzyme (called a polymerase) that copies the genome makes mistakes. In nature, it's not directed to certain parts of the genome. It occurs randomly. Sometimes it provides a benefit, sometimes it is harmful.
Organisms with DNA genomes (like us) have proofreading capability in our polymerases. It can basically correct genetic typos. In RNA viruses, the RNA-dependent RNA polymerase (RdRp) doesn't have that capability. RdRps are thus more error-prone, thus there's a higher mutation rate
CoVs are a little unusual, though in that they have another protein, ExoN, that can carry out *some* proofreading, so their mutation rate is actually lower than most RNA viruses, but still higher than organisms with DNA based genomes.
Proofreading is important, because a mutation rate that is too high can drive an organism to what is called error catastrophe. This is when a genome acquires so many mutations that it drives that organism to extinction. Wikipedia explains:
en.wikipedia.org/wiki/Error_cat…
RNA viruses have relatively faster mutation rates than other organisms and smaller genomes, so a mutation is more likely to be functionally important. This is good and bad: they are more readily adaptable to a host, but also more susceptible to error catastrophe.
Thus RNA viruses need to exist in a sweet spot where they can rapidly adapt to a host (as they are obligate parasites, this is essential to evolutionary survival), but also stable enough that they won't acquire enough harmful mutations to be negatively selected.
A great deal of work has been done to study how RNA viruses exist in this sweet spot. Studies increasing the fidelity of the RdRp (decreasing error rate) have shown that these viruses are less fit because they can't adapt quickly enough.
However, an important class of antiviral drugs, nucleoside analogs (these include ribavirin & remdesivir), work by increasing the mutation rate & driving viruses to error catastrophe. Here's a classic polio paper from @profshanecrotty's graduate career!
pnas.org/content/98/12/…
So back to C.1.2: this cluster does have many mutations, but they didn't get there because it mutates "twice as fast." We'd expect to see more mutation any time a virus like SARS-CoV-2 gets lots of opportunities to replicate, which unfortunately it has via uncontrolled spread.
C.1.2 has a lot of mutations in spike, some of which we've seen before & are associated with immune evasion. But it's not a foregone conclusion that these mutations in combination are a recipe for disaster. Some mutations are better for the virus in the real world than others.
Delta has fewer mutations in spike compared to beta or gamma and it has resoundly kicked their ass over and over again in head to head competition.

More is not necessarily better. For example, here a PhD in virology trumps two in unrelated fields like nutrition or non-ID epi.
Whether C.1.2 is going to be a problem remains to be seen. It's something to watch and characterize, but not something to scream about. We don't know how it will impact vaccines or whether it will become dominant. We should remain vigilant.
The solution here is not to freak out about it. Sensationalist interpretations are both wrong and harmful, because they don't empower people to understand why this lineage is of interest or what to do about it. The latter hasn't changed.
What to do:
-Don't freak out
-GET VACCINATED ASAP
-Mask
-Distance
-Ventilate
-Avoid crowds/enclosed spaces
-Test if you can/if symptomatic
-Stay home if sick
-Wash hands
-Disinfect high touch surfaces

Remember, risk reduction is additive, for C.1.2 & every other variant.
*resoundingly

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More from @angie_rasmussen

31 Aug
Just came back to Canada after being a groomsman in the wedding of one of my dearest friends. This trip was a joyous occasion but also a stark reminder of how badly the US has failed in its COVID responses, and continues to fail.
1. US requires an antigen test to reenter. In Canada, you can get a company to come to your home to administer a proctored test at your convenience for about $75 US. We were asked to show our test results multiple times at YXE & YVR. US CBP did not ask for our test results.
2. At the wedding, I learned to my chagrin that there were going to be some eligible attendees who refused vaccination. The wedding was fully outdoors, but I was still concerned. I thought maybe I could provide rapid tests for all guests as a gift to the couple.
Read 13 tweets
19 Aug
So here's the final chapter in my thread just answering the lab leak community's "just-asking-questions" questions.

These threads all concern our paper exploring the evidence, fresh out of peer review today in @CellCellPress. Give it a look!
cell.com/cell/pdf/S0092…
But first, catch up with thread 1 here, where I present the evidence for SARS-CoV-2 zoonotic origin:
And thread 2 here, where I present evidence against lab origin, which I'll continue here:
Read 29 tweets
19 Aug
Okay, as promised here's the second part of this thread. Earlier today, I covered the evidence that points toward zoonotic origins. Now let's go over the evidence that points AWAY from laboratory origins.

Here's the paper, out today in @CellCellPress!
cell.com/cell/pdf/S0092…
Here's a link to the first thread in case you missed it. Like that thread, what this lacks in GIF-underscored innuendo will be hopefully balanced by a critical appraisal of the actual evidence.
And let's just get this out of the way: YES, Shi Zhengli's lab at WIV had isolated 3 bat CoVs from field samples. Dr. Shi also stated on the record these experiments were done in BSL-2 containment.

Could an accident have happened? Sure. Accidents have happened before.
Read 24 tweets
19 Aug
Today our review of the evidence for the origins of SARS-CoV-2 graduated from a pre-print to peer-reviewed pre-proof in @CellCellPress.

Can we rule out a "lab leak"? No, but if we objectively follow the evidence, it leads us away from that hypothesis.
cell.com/cell/fulltext/…
In anticipation of the inevitable bad faith threads and Medium posts that will ensue from the more conspiracy-minded in the origins world, I'll preemptively address some common questions. But please do read the entire thing:
cell.com/cell/pdf/S0092…
Let's start with the sole affirmative evidence that suggests a lab leak.

SARS-CoV-2 emerged in Wuhan. The Wuhan Institute of Virology is also in Wuhan. They study bat CoVs at WIV. SARS-CoV-2 could have been one of those viruses.

That's it. Everything else is speculative.
Read 26 tweets
17 Aug
@jwgale has written a fantastic piece on the live animal trade in Wuhan.

While the lab leak contingent has blithely dismissed this origin hypothesis, there’s increasingly some really compelling signals that this deserves closer consideration.
bloomberg.com/news/features/…
The common refrain from lab leak proponents is “why haven’t we found the intermediate species like we did with SARS?”

Unlike with SARS, by the time WHO investigators showed up, the animals were long gone. But it’s clear they were there. Including many SARS2-susceptible species. Image
If you are into cover-ups, then consider this: the wildlife trade is illegal but highly lucrative. I’d argue that failing to mitigate the known* risk posed by a multi-billion dollar industry is more scandalous than a lab accident.

*this is exactly how SARS emerged 20 yrs ago Image
Read 4 tweets
17 Aug
I’m very glad the vaccines have been deployed and so far it doesn’t appear that there’s been any onward transmission. We’ve come a long way with Ebola.

BUT maybe it’s time to think of immunizing more broadly than just the ring approach?
The idea behind the “ring strategy” is that you swiftly vaccinate a few degrees of contacts of a known case, forming an immunized “ring” that protects those contacts and prevents transmission outward from that vaccinated circle.
The rVSV-GP Ebola vaccine provides very potent sterilizing immunity in the short term, so this works very well with an important caveat: it depends on quickly identifying cases and performing contact tracing. It also requires those contacts’ willingness to be vaccinated.
Read 13 tweets

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