COVID-19 Catchup: New Pills, Steroid Dosing

Volume 9, Issue 2

In the early iterations of this column, COVID-19 drug therapies appeared frequently. When all of the early fads (see hydroxychloroquine and ivermectin) eventually settled down, it became less necessary to dedicate space to this topic. However, in the last few weeks, several news stories have broken that warrant some attention.

Point 1: New COVID-19 Pills Are a Game Changer

Molnupiravir is a potent ribonucleoside analog that inhibits the replication of SARS-CoV-2. A clinical trial of at risk patients with mild to moderate COVID-19 found that this drug cuts the risk of hospitalization and death by half. The drug is already available in some European countries, and the US government plans to purchase $1B worth of the compound.

Unfortunately, emerging data from India suggests the drug is minimally effective against more severe forms of COVID-19 disease, so it does seem to have a sweet spot as part of early treatment for patients with milder disease.

Paxlovid, an oral SARS-CoV-2-3CL protease inhibitor manufactured by Pfizer, recently showed an impressive 89% reduction in death and hospitalization for ambulatory patients within 3 days of COVID-19 symptom onset. There were no adverse safety concerns found when compared to placebo in this trial.

One notable feature of this drug is that it seems to be coformulated with low-dose ritonavir, which is very noteworthy from a drug-interaction standpoint. For instance, the interaction with ritonavir and tacrolimus is so strong that it may be unsafe to use this medication routinely in solid organ transplant patients, which is catastrophic, given the excessive risk that these patients have for adverse outcomes with COVID-19 infection.

Point 2: Keep Steroid Doses Low

Corticosteroids, specifically dexamethasone, have become the standard of care for patients with severe hypoxemia secondary to COVID-19 infection. The only dose studied has been 6 mg/day of dexamethasone, until this week when a new trial was published in the Journal of the American Medical Association.

In this randomized trial that included 1000 patients with COVID-19 and severe hypoxemia, treatment with 12 mg/day of dexamethasone resulted in 22.0 days alive without life support at 28 days, compared with 20.5 days in those receiving 6 mg/day of dexamethasone. While this trial may have been underpowered to detect a difference, at this time we can conclude the 6 mg/day should remain the standard corticosteroid dose for patients with severe COVID-19 infection.