Thread by @DrMattMcCarthy

UPDATE: COVID medicine has changed substantially over the past few months. The questions we're grappling with today are very different than the ones we were dealing with just a few months ago.
Here are some of the #COVID19 questions recently posed to me by frontline doctors: 1/

1. Why isn't anyone using baricitinib? The drug just received emergency authorization but we never hear about it.
2. How does cenicriviroc work & why is the NIH studying it?3. Does dexamethasone cause secondary bacterial infections?
My thoughts:

1. Baricitinib is an arthritis drug. In November, it was authorized in combination with remdesivir for adults hospitalized with #COVID19 who need help breathing. The combo was better than remdesivir alone in reducing reducing recovery times. That's great!
nejm.org/doi/full/10.10…

But the trial was missing something: dexamethasone. RECOVERY showed a significant survival benefit with the steroid dexamethasone & the drug has largely become the standard of care for COVID patients with low oxygen levels.

Baricitinib and dexamethasone have important differences. Dex has a long half-life & reduces inflammation through a broad-pathway approach. Baricitinib has a short half-life & acts on targeted pathways to reduce inflammation. You can't compare the two or their trials.

If doctors are going to use baricitinib, we need to see a head-to-head study of the drug in a #COVID19 trial that reflects the current standard of care.
Takeaway: We're not using baricitinib if dexamethasone is available. And it's available just about everywhere.

2. The NIH recently launched a Phase 3 trial to evaluate 3 immune modulator drugs in hospitalized adults with #COVID19. The idea behind it: #coronavirus can unleash excessive amounts of inflammation (cytokine storm) that can be deadly. 
One of these 3 drugs might help fight that.

The study drugs are: abatacept, infliximab, and cenicriviroc. The first two are familiar; they're used to treat a conditions such as colitis and arthritis. The last drug, which we call CVC, is a bit of a surprise. It was recently developed as an HIV drug. journals.lww.com/aidsonline/ful…

CVC can also block #coronavirus from replicating in a test tube, but that's not why it was selected for the NIH study. It was chosen for its potent anti-inflammatory activity. The drug strongly antagonizes a chemokine receptor that decreases inflammation. pubmed.ncbi.nlm.nih.gov/19441905/

Takeaway: We're hoping cenicriviroc helps patients with #COVID19, but the precise mechanism by which it may do so remains unknown. This makes for sometimes-tricky conversations when I enroll patients in the trial.

3. Does dexamethasone cause secondary bacterial infections? Doctors often mention to me that they're seeing all sorts of infections in #COVID patients who receive dex, but they caution that their experience is anecdotal. A conversation today prompted me to look into this further.

We know corticosteroids (dexamethasone) can predispose patients to infections if given at a high dose for a long time. But what about the dosing for #COVID? Does the interaction of the drug and virus predispose to certain infections? Is antimicrobial prophylaxis ever warranted?

We're also trying to determine if #19COVID predisposes to bacterial infections the way influenza can lead to Staph pneumonia. This has important implications for antibiotic selection.
These are some of the many questions my research team hopes to address in 2021.