Opinion | COVID-19 Mid-Pandemic Assessment

It's a blue moon pre-election Saturday night Halloween, and the second wave of COVID-19 is upon us. We're staving it off here in New York, but it's doubtful that can last. Other U.S. states have it worse at the moment.

While progress in vaccine research has been excellent, and there may be an announcement before the end of the year, it will be spring before COVID-19 vaccination will be widespread, leaving us to face a difficult winter.

The vaccine timeline is about what I figured it would be when I set out in late February 2020 to read and write about COVID-19 therapeutics development. I figured, as was the case with AIDS, antivirals would be ready first. That hasn't happened, but there is hope.

When it comes to treating the symptoms of severe COVID-19 in hospital, three medicines have clearly proven themselves. Two of those are glucocorticoids (steroids) that arrest runaway inflammation: dexamethasone and methylprednisolone. Experts disagree which is better, both clearly work, so it’s either / or with other steroids being runners-up.

The other winner is the anticoagulant low molecular weight heparin. Other anticoagulants are being experimented with, and may work as well, but right now low molecular weight heparin is the proven go-to.

What about remdesivir, which recently became the first FDA approved drug specifically for COVID-19 despite a WHO study concluding it’s ineffective? Most doctors think its efficacy is marginal at best, which points to a problem with our system of clinical trials and drug approval in the U.S.; it serves the interest of investors more than the public. As it stands, remdesivir is administered late in the course of the disease, by I.V. Would it be effective if administered earlier? (President Trump got it earlier than most.) The answer is, we don’t know. What hope there is for remdesivir making a difference lies with the inhaled form, which is in clinical trials. If we give a drug with real, proven antiviral activity early enough it could save lives and reduce pressure on hospital ICUs.

There are the “biologics”, of course, the monoclonal antibodies being trialed by Regeneron (that’s the one President Trump received), Eli Lilly, and others. Here in the United States, they’re the hot topic, but they, too need to be given early to work. The arm of the NIAID / Eli Lilly trial giving that antibody to severely ill hospitalized patients has been halted after patients receiving the antibody got worse, so all eyes are now on the outpatient trials that administer antibodies immediately upon diagnosis or to quarantined people with known exposure.

Another category that's getting attention is interferons. As I've written about at Cuba Might Have the Best Covid Antiviral Yet, researchers there are all over it. An interferon called peginterferon lambda from Eiger BioPharmaceuticals is in clinical trials in the U.S. and Canada. Mt. Sinai Hospital is listed as a trial site, but it's not clear whether that study is yet active. There's an active British study of inhaled interferon, and U.S. authorities are looking at making interferon part of a government funded study. My suspicion is that interferon could be VERY effective if given VERY early in the disease course, but that getting it to people early enough will take a MAJOR pre-symptomatic testing / screening effort.

Meanwhile in the antiviral category, there are two strong candidates that were not included in the WHO SOLDIARTIY study: favipiravir and camostat mesilate, both with origins in Japan, both available as pills. Even if they had been included, WHO SOLIDARITY, like so many other clinical trials to date, suffered from being a study of hospitalized patients, not early-stage outpatients. So in the antiviral category (which means we exclude for the moment the anti-inflammatories and anticoagulants) the landscape looks something like this:

If I, or anyone in my household, were to test COVID-19 (SARS-COV-2 virus) positive today, my first phone call would be to Regeneron:

844-734-6643

clinicaltrials@regeneron.com

I'd sign up for their trial and try to get that first dose as immediately as possible, and by the way, if someone I live with tests positive but I haven't, Regeneron might even pay me to be part of their clinical trial. While anecdotes are not evidence, it does seem like getting REGN10933+REGN10987 monoclonal antibodies early might have worked for President Trump.