Dr. Loh: Oral antivirals can help treat COVID, but needs long-term monitoring

·4 min read

The best way to stay healthy is to not get sick. Duh. That brilliant insight actually underpins the entirety of preventive medicine but works at cross purposes with our profit-oriented healthcare system. And, actually, even that term “health” care is a functional misnomer. Our for-profit system is actually a “sick” care system since few patients go to their doctors because they are too healthy.

Many illnesses that befall humans have preventable components, although the underlying substrate and susceptibility for disease often has a genetic basis. Indeed, diet and lifestyle seem to play outsized precipitating roles in leading causes of death such as heart disease and cancer, yet it is commonly appreciated that picking your parents carefully is at least as important.

Then there is COVID-19. There is, at least for now, no known genetic predisposition to get COVID, although there may be a link to one’s inability to process information. But that’s another topic altogether. Lifestyle does play a significant role in the prevention of COVID as public health and epidemiological data have unequivocally demonstrated. And, once again, prevention is far better than getting an illness and then having to receive treatment. So judicious behavior, and getting fully vaccinated, are the best strategies. And even with breakthrough infections in vaccinated individuals, the odds of being hospitalized or having a seriously bad outcome are hugely reduced.

But for someone who does get COVID and is yet not ill enough to be hospitalized, are there other options? Most have heard about the two approved antiviral antibody cocktails that are indeed effective, especially for outpatients, but require intravenous infusion of the therapeutic agents. What about oral treatments? We heard about hydroxychloroquine from various “influencers” which had no validating evidence when actually tested in clinical trials. An old, inexpensive medication, colchicine, actually shows some statistical benefit, but it is not large and is fraught with side effects.

But starting in October, some intriguing and potentially impactful data have emerged about some oral antivirals that have significantly reduced the need for hospitalizations in COVID patients. They were both evaluated in unvaccinated subjects with at least one risk factor for severe complications. Please note that these are preliminary data and more details will be needed and scrutinized.

The first agent is molnupiravir, which appears to reduce risk of hospitalization by 50% and prevent deaths in a large randomized clinical trial. It needs to be given within five days of onset of symptoms. It works by interfering with the RNA virus’ ability to reliably replicate.

In November, the second agent, Paxlovid, reduced hospitalizations by an even more impressive 89% and also cut mortality. This agent is a protease inhibitor that prevents the viral proteins from being functional. It also works best when given within a few days of symptoms onset. This drug needs an oral booster, ritonavir, to achieve its efficacy since it interferes with an enzyme that would otherwise inactivate Paxlovid.

One cannot view these results as comparing apples to apples since the clinical trials were designed differently and trial design and execution is everything. But these data are very encouraging, especially when one realizes that no one on active treatment with the investigational product died, and that all the mortality in both trials occurred in the control group, despite everyone getting the same standard therapies.

Remember that these positive results were in unvaccinated patients. There are no data on whether vaccinated patients who get infected should get these pills since these drugs were not studied in that population. Indeed, there was a third antiviral agent that failed to show efficacy, possibly because they opted to study vaccinated patients and too few infections occurred to provide enough data points to draw conclusions.

The real obvious advantage of these oral therapies is that they are pills, not infusions or injections. The disadvantage, such as it is, is that they require early diagnosis and our testing infrastructure is still playing catch up from early missteps. At-home kits are becoming more readily available, as long as they are certified to be accurate. Caveat emptor.

Cost and availability are still to be determined, but are moot until these agents are actually approved by the FDA. And, as a trialist, long-term monitoring of treated patients should be mandatory to monitor for long-term adverse events. We are all, or mostly all, in this pandemic together, so we should do our part to help humanity out of this mess.

Irving Kent Loh, M.D., is a preventive cardiologist and the director of the Ventura Heart Institute in Thousand Oaks. Email him at drloh@venturaheart.com.

This article originally appeared on Ventura County Star: Dr. Loh: Oral antivirals could have impact in treating COVID