Thread by @ASPphysician

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.

Omicron has shortened the presymptomatic period, but we have little certainty of the rest of the time course.

In general, antivirals and monoclonal antibodies help early on, and anti-inflammatories (steroids and otherwise) help later on, but there is clear overlap.

There is no reason to believe that the inflammatory phase of OMICRON is NOT associated with a coagulopathy, although it is something worth trying to understand.

For OUR @COVIDSciOntario guidelines, we define severity this way—it has proved incredibly useful and durable, recognizing that every classification system has its own challenges.

We have avoided therapeutics that are no longer work (e.g. casirivimab + imdevimab), are not yet approved in Canada (molnupiravir, nirmatrelvir/ritonavir (Paxlovid), and tixagevimab/cilgavimab (Evusheld)), or we have previously deemed of no benefit.

In some populations receiving immunosuppressive therapy, the concern for chronic strongyloides infection and precipitation of hyperinfection remains. Serology can help.
Our guidance: doi.org/10.47326/ocsat…

Whether we want to say it outright or not, we are now in a situation of rationing therapeutics:
scarce resources going to those most likely to benefit
considering the pressure on the healthcare system, with a prevented ICU admission worth more than a prevented hospital ward admit

As you can see here, vaccination status is the most potent predictor of a) hospitalization and b) ICU admission.
covid19-sciencetable.ca/ontario-dashbo…

Also, we know that age has been an extremely important predictor of hospitalization, especially over age 50 (gulp), and then rising exponentially.

But the interaction of vax & age is really potent.

Our guidelines are discounting the role of breakthrough infection a bit, as our on-the-ground intel suggests that 2 doses remain fairly protective against moderate and critical illness—although we are watching this closely.

This is ideal.
However, most of Ontario has run out of tocilizumab and sarilumab, and several hospitals have been unable to get baricitinib.

As I mentioned in a tweet yesterday, @WesElyMD has been a leader in baricitinib for COVID.

Today, we released our brief on baricitinib (apologies, but we are an under-resourced and busy volunteer group!) Trust me, it is worth the read!

TL;DR It works
doi.org/10.47326/ocsat…

Our Working Group has not had time to deal with the reality of no IL-6 or JAK 1/2 inhibitor, but it is reasonable to consider dexamethasone 12mg daily based on this underpowered COVID-19 study below (doi:10.1001/jama.2021.18295) and doi.org/10.1016/S2213-….

I remain uncertain.

Here is our take on remdesivir, and you can see our full brief at doi.org/10.47326/ocsat….

@DrToddLee has looked at this in a more sophisticated manner and agrees with its clear (in our minds) benefit.

#SOLIDARITY should be publicly chastised for not sharing their data.

In patients who are moderately ill, not only are we suggesting dex + remdesivir, but we suggest holding off on a second immunomodulator because of drug shortages—yes, we are kinda rationing.

Finally, we generally think therapeutic anticoagulation is helpful.

Our brief explores this more fully, and can be found here: doi.org/10.47326/ocsat…

Why does it have a yellow triangle? Because the potential trade-offs are not minor. So assess for bleeding risk and if not increased, it likely makes sense for those pts. who are not critical.

Mildly ill patients appear in and out of hospital, but have been STUDIED only as ambulatory patients. Thus, our recommendations most strongly apply to those patients, but we have not differentiated for nosocomial cases or those in LTC or retirement homes.

This table—adapted from a paper led by @DrToddLee and accepted in Open Forum Infectious Diseases—shows why we have prioritized the agents as we have for mild disease.
Importantly, in Ontario, we do not have enough sotrovimab to meet demand AND the ability to infuse RDV is limited

It is very clear that sotrovimab (1-time infusion, easier) or remdesivir (infusion daily x 3) prevent progression to hypoxia/hospitalization.

But we just cannot give it to all. So it is going to those with the biggest bang for the buck.

Who are they? These people.

Unfortunately, these folks are at increased risk, but we cannot offer them these agents at this time. So we are recommending at least 1 of budesonide or fluvoxamine.

We are not fully convinced of either of these, but believe benefits > risks/costs.

This gives us a flow chart for mild disease looking like this.
Fluvoxamine is especially tricky because of drug interactions and it was not perfectly tolerated in trials. (Brief to be posted soon!)
Budesonide, especially, seems to make people breathe easier.

Also, take a look at covid19-sciencetable.ca/about/#:~:text…
These are the amazing volunteers who develop all this stuff—don't give them grief—who @MPaiMD and I get to learn from.

@tiffany_kan is the incredible GraphicDesignerWhenNotPharmacisting.

Finally: this is not how students are taught to do clinical practice guidelines. There is no GRADE or AGREE, etc. But we are in a freaking pandemic, and sometimes you need to make calls.

We are comfortable with our decisions/calls, and they will continue to evolve over time.