Thread by @ASPphysician

So much talk about introducing 3rd doses in Canada. This hits close to home because ... I live in Canada!

But I have lived in LMIC, have a parent from a LMIC, and believe that vaccine equity is incredibly important.

Nevertheless, widespread 3rd doses are getting pushback. 🧵

1. Do vaccines work and vaccine efficacy wane?
Hell ya! We have tons of data demonstrating this. Here is just one figure from @FT that shows waning immunity (and then booster effect).

Yes, mRNA is better than AZ, but both wane from their peak efficacy d/t decr neutralizing Abs.

This paper from @ScienceMagazine yesterday (science.org/doi/10.1126/sc…) shows that nAbs are the 💣 when it comes to protection from COVID-19.

And this RCT—coupled with epidemiologic data from Israel, UK, and others—submitted to FDA clearly shows that a 3rd dose massively improves vaccine efficacy (with a relative efficacy of 95%). The results are not subtle.

On top of this, most jurisdictions in the 🌍 who had early access to 💉 are now moving to boost their populations. US now giving 3rd dose to as many ppl as possible, whereas some other jurisdictions are being more strategic. (e.g. UK says >6m post-2nd dose AND 40yo+, HCW, etc.)

This has helped the UK and Belgium. We likely don't want to be like Netherlands (who just started boosting widely days ago). @FT @jburnmurdoch

So why isn't Canada doing the same?
Could it be that we think the laws of immunology are different in the Great White North?
H/T @chaim_bell to this 🔥 scene from "My Cousin Vinny" where the lawyer asks if the "Laws of Physics cease to exist on your stove"?

Well, 🇨🇦 did choose to give a 2nd dose ~12 weeks after the first dose. How protective will that prove? Who knows? We do know that it gave a higher post-2nd dose nAb titre, but waning still started shortly thereafter (sciencedirect.com/science/articl…).

We also know that real world experience in Canada (e.g. Ontario and BC) is that the vaccines have been holding up for now. Smart colleague @DrJeffKwong a few weeks ago showed that VE for symptomatic disease was at 81% and it was 90% for severe disease. BUT ...

6m ago, we only had vaccinated <5% of our popn. Over the ensuing 2 months, we administered 19M people. Those 19M will be starting to reach 6m very soon.

Maybe they won't need boosters at 6m, but at 7m or 8m. Almost doesn't matter.

I won't go into the math of it all, but if you look at data from @COVIDSciOntario dashboard, there are hints of the vaccine efficacy waning—I mean, hospitalizations for unvaxed are roughly where they were in Aug or Oct; not so much for fully vaxed. But this is very early days.

I hope you have stayed with me:
1. Vaccines work.
2. Vaccines wane.
3. 3rd doses protect us +++ better than a waned 2nd dose.
4. Spread out dosing was good, but we don't know how good and for how long.

Now, the final questions (drum roll please) ...

What probability would you give that VE will wane in a clinically meaningful way for most people after 6-8m of getting 2nd dose? (25%? 50%? 75%?)

What probability would Canada be able to give 3rd dose to 19M (along with giving 2 doses to 5-11) from, say, Xmas day to February 24?

So:
Do we need to give 3rd to everyone now? No

But it is a strategic mistake
- to convey that a 3rd dose is a "luxury" rather than appropriate evidence-based prevention
- to take a chance and start giving 3rd doses once we see a problem—because it will come at us hard & fast.

Will we need more doses? Maybe. Probably.

In fact, there is already a hint from Israel that further doses are likely.

I call this a 3rd dose, but we don't know how much more (if any) we will need.

Finally: the world is producing lots of vaccine now, and it is increasing. Thankfully. Because, WE NEED LMICs VACCINATED.

But TODAY COVID is proximally a northern hemispheric crisis (largely of our own making, of course); tomorrow may be a different story.

Administering 3rd doses is evidence-based, and we should be giving evidence-based life-saving therapy if we have it. Period.

If we give it a month or 2 early, no big deal. Give it late? Just ask the Dutch.

Let's go, Canada!