Yesterday, @COVIDSciOntario released updated treatment guidelines, focusing on patients with mild illness. It is a substantial change from prior guidance, so we thought we would walk people through the noteworthy changes.

You can find the document here: covid19-sciencetable.ca/sciencebrief/c… First, as always, this is the work of +++people incl. the, er, volunteers of the Drugs & Biologics Clinical Practice Guidelines Working Group of @COVIDSciOntario. Co-chair is @MPaiMD.

Second, the update is a response to:
1. New data & evidence
2. Changes in drug supply & demand.

🔥JUST RELEASED: New clinical guidelines for COVID now including #Paxlovid (nirmatrelvir/ritonavir).

A 🧵 on why Paxlovid is NOT first-line.

covid19-sciencetable.ca/sciencebrief/c… "W-w-wait! Paxlovid is NOT first line? I thought everyone was saying this is the best thing since the mute function!"
You have it right. If you look carefully at our guidelines on the 2nd page (where we cover outpt therapy for "Mildly Ill Patients") you can see where it lies.

Clinical Practice Guideline Summary: Recommended Drugs and Biologics in Adult Patients with COVID-19 - Ontario COVID-19 Science Advisory Table covid19-sciencetable.ca/sciencebrief/c… The guidelines are based on a blend of pathogenesis, clinical trials, and local realities of drug supply and burn rate.

If we got it right, phew!
If we got it wrong, recognize that this is a rapidly evolving situation, with new evidence, new variants, and new drug availability.

I have received messages, texts, and reply-tweets regarding my stance on COVID management in ON (and elsewhere). As a strong early proponent of a #COVIDzero approach for a variety of reasons which, I believe, will show merit historically, I have never minimized COVID. However ... 1. I continue to have uncertainty regarding the severity of Omicron. I believe we will establish considerably more certainty in days ahead. Certainly, some evidence is emerging of a lesser severity—both mechanistically & epidemiologically—but I remain uncertain and thus cautious.

The latest COVID Therapeutics Guidelines from @COVIDSciOntario are now available here (covid19-sciencetable.ca/sciencebrief/c…)

Lots of new stuff, so let's take a drive ... 1. The dominance of Omicron in cases means that the monoclonal antibody cocktail of casirivimab + imdevimab is no longer useful. It is sotrovimab or bust!
2. Because we don't have tons of sotrovimab, we are recommending it for the groups most likely to gain overall benefit.

A few thoughts on the anticipated Omicron wave:

1/ People are increasingly fed up with COVID, so measures to control Omicron cannot/should not rely on measures used for prior waves. (Which means that governments would be wise not to allow COVID to reach a crisis situation.) When I highlighted several days ago that case growth was worrying me, several Twitterati assumed that I was alluding to lockdowns. (I was doing nothing of the sort)

But failure to pay attention to cases in EUR shows that countries can be forced into lockdowns if they don't act.

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.

Really important study looking at daily sampling of early SARS-CoV-2 infection in 60 individuals, focusing on viral shedding for up to 14d. medrxiv.org/content/10.110…
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.

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!

https://twitter.com/MWHodin/status/1407687365590716421

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"

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.

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 ...

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 document.canada.ca/content/dam/ph… It all hinges on the estimates of VITT. Yesterday @COVIDSciOntario posted a VITT brief covid19-sciencetable.ca/sciencebrief/v… 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.

🔥 New Science Brief: Remdesivir for Hospitalized Patients with COVID-19 from @COVIDSciOntario
covid19-sciencetable.ca/sciencebrief/r… 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

Inhaled budesonide. A thread.

There has been a lot of energy being given to budesonide in COVID-19, with some tweeterati referring to it as having "strong evidence".

Also, FPs/ED MDs would love a Rx that works!

It merits discussion.
Let me explain (long thread alert) ... There are 2 RCTs available on inhaled corticosteroids:
STOIC (thelancet.com/journals/lanre… and clinicaltrials.gov/ct2/show/NCT04…) and PRINCIPLE (medrxiv.org/content/10.110… and isrctn.com/ISRCTN86534580)

I will start off by saying what we know about systemic corticosteroids in patients with COVID:

It's possible that the best decision for the population and the best decision for individuals are different.

In a young otherwise healthy person where other vaccines are available soon and they can mitigate their risk, the risk of illness/death from AZ > risk of death from COVID Would a parent give their 12yo kid AZ if it were shown to be safe and efficacious in studies but still carried the VIPIT risk? I seriously doubt it. Then how about a 15yo? 20 yo? 21?

At some age benefit > risk. NACI decided that that inflection point is 55y. I agree with them.

Why is this #ThirdWave in Ontario more worrisome?

1. Let us first be very clear—we are in a 3rd wave—and epidemiologically, we are somewhere comparable to early-mid December 2020. From @COVIDSciOntario @Billius27 2. A huge difference is ICU capacity. In mid-December, we had around 276 patients with COVID in ICUs, and around 181 on ventilators.

https://twitter.com/DrKaliBarrett/status/1339565667037696000?s=20

Right now, that number is 355 and 205, the ICU workers are tired, and those numbers are just starting to rise.

As all of Ontario waits with baited breath to learn how @fordnation has decided to act on what the mostly leaked Science Table shows, I thought it important to explore what "all options on the able" look like.

A 🧵:

First, there are no MUST DOs. There are places around the world who have kept schools open and seen cases drop, and there are places who have managed to drop without closing borders, restricting travel, or curfews.

But COVID is transmitted by people interacting, usually indoors in prolonged close contact.

What is #COVIDzero? What is elimination? What is strategy? A primer

1. #COVIDzero is a slogan. It is aspirational. It sets a high bar for a country that has failed to set a bar. @JustinTrudeau yesterday said that it doesn't make sense to have a unifying mssg. I beg to differ. 2. Elimination, in the proper sense of the term, means reducing incidence of infection or disease to zero in a geographical region for a period of time, with continued efforts.

Nobody seriously believes you can keep the cases of COVID at zero for any sustained period of time.

I am friends/like/respect @BogochIsaac and have listened/read his views. Unsurprisingly, we agree on ~ everything.

Main areas of disagreement:
1. Feasibility: if there is PUBLIC/POLITICAL WILL to protect small businesses, older adults, vulnerable and down-the-road freedom ✅

https://twitter.com/BogochIsaac/status/1328561463947096064

2. Time/severity of hardship: these are, again, public and political DECISIONS. People need to know what they are choosing. If I told everyone facing today that we could have avoided the certainty of today's hardship with a bit more hardship, would we have endured it? ✅

I have drafted multiple rage-tweets following today's 2 pressers, but realize that I am just emotionally exhausted from the inevitability of it all:
- people getting sick
- families and businesses ruined
- healthcare overwhelmed

Let's start with what won't work: 2- TO 4-WEEK CIRCUIT-BREAKER:
These WILL reduce the case load. But, if we take the examples of Melbourne and Belgium, the halving time will be somewhere between 7-14 days, depending on completeness and adherence of any "circuit-breaker".

What is wrong with Ontario's latest approach to COVID?

It is #So1stWave. Emerging from the first wave, we were happy we survived it, and thought that if we could just keep case counts reasonably low or prevent hospitals or ICUs from being overwhelmed, we would win the battle. This is the ExCUSE (Examples of Canada, US, and Europe) approach. The govt. released their new plan predicated on this thinking. If I were to bet, it was conceived over 6 weeks ago (i.e. around Sept. 23). To remind you, this was ExCUSE total deaths and cases 6 weeks ago.