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 (…) 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 (…).
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?
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!

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More from @ASPphysician

13 Jul
Really important study looking at daily sampling of early SARS-CoV-2 infection in 60 individuals, focusing on viral shedding for up to 14d.…
Lots of stuff to learn here:
1. Sore throat, runny nose, and muscle aches had strongest relationship with positive viral culture.
2. For most individuals, nasal VL > saliva VL and viral shedding peaks at least 1d earlier in saliva vs. nasal.
3. Viral load is not perfectly predictive of infectiousness.
*4. Massive (i.e. 40-fold) heterogeneity in individual level infectiousness, with imperfect correlation with age. This means that features of the "the spreader" can be a very important contributor to superspreading.
5. No clear explanation of increased transmissibility of VOCs.
Read 4 tweets
23 Jun
The 2021 AMR Preparedness Index is an excellent effort to look at what is 1 of our most pressing public health issues as some countries emerge from the COVID-19 pandemic: #AntimicrobialResistance

There are important findings for Canadians and their leaders:
1. We ain't so good!
2. We are behind the UK, US, France, Germany, India and Japan on a national strategy.
"Governments must make bolder financial investments ...
... should develop more ambitious National Action Plans and provide sufficient funding to achieve goals ... lean into AMR initiatives now"
3. We are kinda pathetic on governments' commitments to foster and support AMR innovation.
Govts "should implement pull incentive programs within the next 3 years ...
increase investments in AMR innovations for surveillance and diagnostics ...
ensure pricing reflects full value"
Read 7 tweets
17 May
To my colleagues & trainees who have contacted me in distress over the past few days, I see you and hear you.

I don't post my thoughts about the Middle East because—even though I have studied its history tremendously over the years—I recognize that there are more than one truth.
I understand how you fear—as Jews or people sympathetic to the tragedy that Israelis are experiencing—expressing your views or trying to counter views that see only one side of a dispute that is much older than the state of Israel.
I also understand how uncomfortable you have been made to feel when colleagues or supervisors use their (mostly) professional platform to acknowledge the unquestionable and tragic suffering of Palestinians yet fail to acknowledge the suffering many Israelis are also experiencing.
Read 9 tweets
9 May
Reluctantly, I feel I need to clarify some issues around why AZ doesn't make sense for most of Canada right now.

When NACI evaluated—using the hard endpoint of deaths—the risk-benefit of AZ vs. no AZ, it used a lower incidence 1 per 100 000.
With this modeling, it makes clear sense to give AZ vs. waiting for age 50-69 in a moderate incidence setting, and for all ages in high incidence setting.

But what happens if the VITT rate is 1:26 000 or 3.85/100 000? You get this ...
This means that it is only a slam dunk (vs. no vaccine) for age 50+ in high incidence (30 cases/100K/day) settings, and 40+ in very high incidence (60 cases/100K/day) settings. Even if VITT incidence is 1:40 000 (or 2.5/100K/day), your expected VITT deaths/100K are 0.63-1.0.
Read 9 tweets
8 May
Why am I now opposed to any further AstraZeneca vaccine being used in Canada? I want to walk you through the math we have available.

First, I am using some risk-benefit analyses used by @GovCanHealth in their NACI's most recent guidance…
It all hinges on the estimates of VITT. Yesterday @COVIDSciOntario posted a VITT brief… that gave updated estimates of risk: 1:26 000 to 1:127 000 (as opposed to govt doc using 1:100-250K), and I believe ours is the most accurate estimate of risk of VITT.
If we use the revised numbers, the incidence of an ICU admission from AZ vaccine becomes anywhere from 1.27-3.85/100 000. Using existing risk-benefit analysis, it means that it never makes "statistical sense" to use an AZ vaccine where the COVID incidence is moderate (7.5/100K/d)
Read 6 tweets
6 May
🔥 New Science Brief: Remdesivir for Hospitalized Patients with COVID-19 from @COVIDSciOntario…
Highlights for remdesivir
1. Not recommended for patients not on oxygen
2. Not recommended for patients mechanically ventilated.
3. Recommended for patients on low-flow supplemental O2
4. Consider for patients in between low-flow O2 and MV Image
Much of our advice comes from insights around this table of 28d mortality and the studies involved. We recognize that this isn't straightforward guidance. Image
Read 5 tweets

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