Thread by @PeterKolchinsky

This new variant is making a lot of people REALLY nervous. Here’s why it should & shouldn’t. I’ll hit on infectivity, lethality, vaccine effectiveness, & some “what ifs”. Yes, it’s more infectious. That means that w/ comparable carelessness... 1/17

...new variant will infect more people. Once a person is infected... new variant is not more lethal (though like original strain, it’s bad enough). While not more lethal at level of individual person once they are infected, it’s more lethal at societal level b/c more infectious.

Lethality aside for a moment, not enough attention has been given to what this virus does short of killing. For example, it can rob you of sense of smell, which means taste, for weeks or months. Sound mild until you experience it- it’s a pretty miserable condition. 3/17

Worse, when neurons rewire, they can rewire incorrectly, making delicious food smell putrid (brain telling you it thinks it’s toxic so you won’t poison yourself). Imagine spending months eating food your brain is making you think is rotten. It’s torture. medicalxpress.com/news/2020-07-c…

Back to the variant. Most common question I hear is whether it has rendered current vaccines obsolete. Answer to that is NO. The vaccines we have now will protect people against all known variants. If you consider a vaccine to be akin to a mug shot that shows police...

...what a bad guy (virus) looks like, then new variant has a few new freckles & a different nose ring, but police (immune system) has no problem recognizing bad guy. It’s not like virus has swapped its face (a trick flu can pull off, while taking hours to eat a peach). 6/17

Current vaccines and those coming down the pike show immune system all or most of viral spike protein, which means that we develop antibodies that can target many nooks and crannies of the protein to shut down the virus. Virus has to change a lot of itself to evade them all.

There is a type of drug therapy that the variant could potentially be resistant to, which is a monoclonal antibody. What monoclonal means is really “a single antibody”. And if a company develops a monoclonal antibody that recognizes the bad guy’s nose rings, then...

...changing that one feature could cause a viral variant to evade that one therapy. It’s the virus equivalent of bacteria becoming resistant to one antibiotic. That’s why we sometimes use antibiotics in combination and why companies have been developing monoclonal cocktails. 9/17

Well, more than one “monoclonal” isn’t really “monoclonal”. It’s “polyclonal”, which is actually how our immune system works. It generates many individual antibodies. So when companies makes specific antibodies & combine them, they are approximating natural immunity.

But while companies combine couple of monoclonal antibodies, vaccines train the immune system to generate dozens, even hundreds, of effective ones, truly a polyclonal cocktail. So virus would need to mutate a lot of its features to get around such polyclonal defenses.

But let’s say SARS2 did mutate enough to circumvent immunity generated by current vaccines... a common question is how quickly we could modify existing vaccines. In case of mRNA vaccines, companies could probably start churning out new vaccine versions within 6-8 weeks. 12/17

Trouble is you would need to double up the dose. You would have to vaccinate people against both original & mutant strain (since original isn’t being replaced by variant), just like current flu vaccines consist of 4 versions to protect against 4 most common strains each season.

But doubling dose of mRNA would be painful. mRNA vaccines are already more uncomfortable than any other vaccines out there (Shingrix) b/c of how strongly they stimulate immune system. Giving 2x the dose might be too much for some people. Other vaccines more easily combined.

For example, flu vaccines are made of proteins, not mRNA. You can easily vaccinate against two or more SARS2 variants using protein vaccine. Trouble is they take a bit longer to modify in response to emergence of a new variant. I would estimate 3-4 months. 15/17

So if new variant emerged that could get around existing vaccines, I think mRNA would be a literally painful but fast solution & comfortable protein vaccines would come to rescue, albeit painfully slowly. But this “what if” is just excuse to get gratuitously nerdy w/ you about...

...vaccine tech b/c I don’t really think SARS2 will mutate to point of needing a new vaccine. More likely, next time we see a coronavirus that requires a new vaccine, it’s going to be SARS3. 17/17

For more plain English SARS2/virology/Covid explainers, see pinned tweet. Lots of FAQ addressed there. Stay safe and I hope you’ll get vaccinated when you can. They are well-studied, safe, & effective.