Paxlovid is not a Panacea
COVID cases are surging here in DC. The new sub-variants of Omicron are doing the predictable dance of highly contagious, less severe versions of the “original” variant: causing a flurry of colds and flu-like symptoms—and a dizzying array of missed school and work days.
Naturally, one of the first questions my patients ask when they test positive is, “Should I get Paxlovid?”
The answer of course depends on the person—specifically their age, vaccination status, immunity from past infection, underlying health issues, and the duration of their symptoms at the time they call me. In other words, like most things in medicine, a prescription for Paxlovid is not a one-size-fits-all proposition.
What the heck is Paxlovid (which I’ll affectionately call “Pax”)? It’s an oral antiviral medication that has been rigorously studied but only in unvaccinated adults over 18 and showed a near 90% decrease in the risk for COVID hospitalization.
How does Pax work? It essentially puts a wrench into the replication cycle of the virus in order to tamp down the viral load and reduce the chance for serious outcomes—again, in unvaccinated adults. (Note: It makes sense that unvaccinated, non-immune adults would benefit the most from this type of medicine, as they are at the highest risk for serious outcomes—particularly non-immune people who are older and have underlying health problems.)
What about using Pax for vaccinated people? We don’t yet have data on Pax use in vaccinated people. In the meantime, it makes some intuitive sense that Pax might improve clinical outcomes for vaccinated people in the same way it does for unvaccinated people, right? Tamping down the viral load in a vaccinated person with COVID seems like it could only be a good thing, yes? Perhaps it would shorten the duration and/or severity of symptoms for vaccinated people and maybe limit their ability to infect other people? All of that seems reasonable. After all, this is what Tamiflu does for influenza.
So, I’ve been using Pax for some of my vaccinated patients—particularly those at higher risk for serious outcomes. (Note: We do this in medicine—use our clinical judgment and extrapolate from high-quality data to treat patients when the perceived and known benefits of an intervention outweigh the perceived and known risks.)
Does it work for vaccinated patients? It seems to have helped a handful of my vaccinated patients. Some have even reported feeling “much better” within 48 hours of taking Pax. This is anecdotal evidence, but I’m hearing the same from other doctors I trust and respect.
So why not prescribe it to anyone and everyone with COVID? The main reason is this: I’ve witnessed more than a handful of vaccinated patients with COVID develop what we’re calling “rebound COVID” after finishing the 5-day course of Pax. In other words, after the patient’s symptoms have improved and/or they start testing negative on a rapid antigen test, their symptoms return and/or they start testing positive again on a rapid test.
This phenomenon is being observed by many of my colleagues and is causing some head-scratching. It’s also actively being studied so that we can more confidently prescribe—or not prescribe—this medicine and know what the implications of “rebound” even are.
What does this rebound thing even mean? Are people contagious again when their symptoms return? Do they need to isolate a full 5 days again? What do rapid antigen tests (which I call “contagiousness tests”) really mean when they stay positive this long?
We don’t know the answers to these questions, but it makes intuitive sense that a newly positive antigen test alongside recurrent symptoms would indicate a “second coming” of the virus.
What is the mechanism of “rebound”? Many are hypothesizing that, in addition to temporarily halting the virus from reproducing, Pax might also tell our immune system to “back off” from the fight. Then when Pax is taken away on day 5, the virus comes back for a surprise party, outpacing the immune system that had been told to take a back seat. In other words, Pax might simply delay our own immune systems from appropriately crushing the virus.
But we don’t really know.
Regardless of the mechanism of rebound, I’m prescribing even less Paxlovid than I was even two weeks ago—not only because of this rebound phenomenon, but because vaccinated people already tend to do very well—and not land in the hospital—due to vaccine-induced immunity. In other words, the vaccine continues to work well against death and severe disease from the new variants.
For most, Pax simply isn’t necessary, especially for low-risk patients.
In addition, Pax interacts with a number of medications, like the statins (the common cholesterol-lowering drugs), that can make administering it a bit complicated. Pax can also have unpleasant side effects like a metallic taste in the mouth or diarrhea or other GI side effects.
That said, I am still prescribing Pax to some vaccinated patients, but mostly to high-risk patients and only after explaining the potential pros and cons.
What’s the upshot?
I think many of us were craving a silver bullet to further knock back this virus and the associated administrative, social, emotional, and logistical challenges. I, like a lot of doctors, had high hopes that it might limit the duration of symptoms (and therefore isolation) and even limit the risk of developing long COVID.
But like most things in life, it turns out it’s not that simple.
After all, science is not a fixed body of work; it’s a process. No one I trust in medicine is shocked that this Pax rebound thing is happening. After all, just because a medication or public health intervention might seem intuitively effective or appropriate does not mean it actually is.
The title of the book I’d love to write someday would be called Just Because We Can Doesn’t Mean We Should. Pax is a perfect example of something that is widely available and seemingly beneficial that isn’t a “one and done” proposition.
The same concept applies to any medical intervention: Everything we do has upsides and downsides. There are harms of “doing” and harms of “not doing.” The decision to mandate masks in May 2022 or to boost a healthy teen against COVID, for example, must be rooted in a careful assessment of the pros and cons—and not mere assumptions about benefits without context.
In the meantime, here’s my updated cheat sheet for what to do if and when you’re sick:
Testing. The rapid antigen home tests continue to do a great job detecting infectious levels of virus. Rapid antigen tests are essentially “contagiousness” tests. If you test positive, you have enough virus in your body to infect other people. Rapid antigen tests can remain positive (meaning: people can be at risk to other people) for up to 14 days, though most vaccinated people are no longer contagious after 5 days.
Isolation. The CDC recommends a 5-day isolation period after a positive test (whether it’s a PCR or rapid antigen test), starting from the day of the positive test or symptom onset, whichever came first. I go a step further with my patients and suggest only leaving isolation after a negative rapid antigen test at day 5. If positive at day 5, isolate another day and test at day 6, and so on.
What about people who’ve already had Omicron? People who’ve had Omicron already, say between December 2021 and March 2022 (i.e., with BA.1) are able to get reinfected, though the chances of serious disease after reinfection looks to be extremely low. In other words, if you have Omicron now and your household had Omicron earlier this year, it’s ideal to isolate from them but also not critical.
Treatment. Most of my vaccinated and immune patients are managing their symptoms at home pretty well with Ibuprofen, Tylenol, other over-the-counter medications, hydration, and rest. Of course treatment decisions are nuanced and should be made in consultation with your own primary care provider. While it’s tempting to “just do something,” the evidence is clear that there’s no benefit to zinc or vitamin D supplementation, Azithromycin, or Pepcid or other antacids in treating COVID.
Down the road, we may learn that Paxlovid is safe and effective for average-risk patients, perhaps to reduce the duration and severity of COVID symptoms, if given for, say 10 days instead of 5. We may learn that it helps reduce the risk of developing long COVID.
While that research is being done, let’s get vaccinated and boosted if eligible; work on our underlying health conditions; care for other people by staying home when we’re sick; ask our doctors for Evusheld if we’re immunosuppressed; and know that one-way masking can offer another layer of protection for people who want or need it.
— new on the podcast! —
I'm THRILLED to share the newest episode of Beyond the Prescription with you tomorrow! I sat down with my dear friend and Hollywood actor, director, and producer Will McCormack to talk about everything from his battle with alcoholism to winning an Academy Award—and the bumpy road along the way.
There’s not much Will hasn’t done in Tinseltown, but behind the scenes of his successful career, he was abusing alcohol and drugs to cope with the pressure of performance.
In this episode of Beyond the Prescription, Will opens up to me about the struggles of addiction, the joys of fatherhood, and finding gratitude and self-awareness on the path to sobriety.
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I will see you next week. Until then, be well.