The twice-vaxxed, twice-boosted First Lady, Dr. Jill Biden, tested negative for COVID after taking Paxlovid. And then she rebounded, just like her husband did weeks ago or like Director of the National Institute of Allergy and Infectious Diseases (NIAID) and Chief Medical Advisor to the president Anthony Fauci did in June or like the 1 to 10 percent of patients who take the drug have done since it was approved last December.

No one should give up on Paxlovid, but we do need to temper our expectations of the drug and perhaps curtail our use of it in vaccinated people.

The Food and Drug Administration granted an Emergency Use Authorization (EUA) for Paxlovid after a study showed an 88 percent effectiveness in preventing severe disease, which the study defined as COVID-19-related hospitalization or death in patients at a higher risk of severe disease (over 60 years of age or presence of another risk factor such smoking history, being overweight, or chronic disease). Such a high rate of success made Paxlovid look like a dream come true.

But that study was conducted on unvaccinated subjects; it makes sense that it would be effective as compared to a control group of unvaccinated, untreated people. It made Paxlovid look more like a wonder drug than it deserved.

That may explain why providers are writing 40,000 Paxlovid prescriptions per day.

Not all of these prescriptions may be necessary. During the Omicron surge, two doses of a vaccine — even being more than six months out from the last shot — demonstrated 57 percent effectiveness in preventing hospitalization without any other treatments.

But with a recent booster shot, vaccination’s ability to prevent hospitalization increased to 90 percent. We don’t have data on booster shots’ effectiveness at preventing hospitalization with the currently dominant variants, BA.4 and 5, and we had some evidence that immunity wanes, even after patients’ third and fourth vaccines. Adding Paxlovid on top of that doesn’t provide that much more protection.

There are currently no peer-reviewed studies examining the real effectiveness of Paxlovid in vaccinated and/or boosted patients; early indications are that Paxlovid doesn’t lower the risk of hospitalization in 40-64-year olds. In 65 year and older patients, it lowers the risk of hospitalization by less than one percent.

Combining the Paxlovid interim data with the Omicron vaccine data, only one in 588 boosted patients without additional risk factors treated with Paxlovid will avoid severe disease.

It seems like a marginal benefit, especially when the pill poses the risk of this “rebound” among other side effects like a metallic taste or diarrhea. Many patients, like President Biden, have to temporarily stop some of their other medications. This seems like a minor inconvenience but skipping doses of medications like immunosuppressants and migraine treatments can cause a cascade of other health problems in certain patients.

The rebounds have non-medical consequences, too, even with the Centers for Disease Control and Prevention relaxing rules; people who test positive are still asked to quarantine. With these rebounds, patients miss more work and may lose income. As a physician, I experienced this myself. I rebounded and had to quarantine for 14 days, double the time I would have been isolated without the rebound.

The real problem with rebounds is that Paxlovid’s five-day course of treatment may not be enough to prevent them. Rebound patients are probably individuals who metabolize Paxlovid faster so that the drug never reaches an adequate level.

The EUA allows for a five-day course of treatment. A recent study found that more time spent taking Paxlovid may prevent the rebound so the drug would either require approval or the EUA would need to be modified. Studies that test a longer than five-day treatment course are currently underway.

The federal government paid for 20 million doses late last year. At our current rate of prescription, we will likely exhaust this supply next year. Paxlovid isn’t cheap; a five-day treatment course costs around $530. When our initial stockpile runs out, the issues of affordability and insurance coverage emerge and reignite the debate over access to health care.

Paxlovid is no ivermectin; its use isn’t entirely misplaced during the pandemic. For one, the use of Paxlovid in the unvaccinated is warranted, as it is in vaccinated people with a higher risk for severe disease. There’s also anecdotal evidence it helps with long COVID. Prescribing it to the president was completely reasonable.

But for the average vaccinated and recently boosted patient, it may not be. Physicians — and patients — need to keep that in mind.

Benjamin P. Geisler is a hospitalist.

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