When Paxlovid (nirmatrelvir + ritonavir) was given emergency use authorization (EUA) on December 22, 2021, by the FDA, there was a lot of excitement. At long last, there was an oral anti-viral medicine that was supposed to be highly effective against COVID-19. Now, though, there are numerous reports ofPaxlovid COVID rebound following the initial 5-day treatment program. What’s up with that?
Initial Enthusiasm for Paxlovid:
On November 5, 2021, the maker of Paxlovid (Pfizer) offered the following statement about the drug’s effectiveness:
“The scheduled interim analysis showed an 89% reduction in risk of COVID-19-related hospitalization or death from any cause compared to placebo in patients treated within three days of symptom onset (primary endpoint); 0.8% of patients who received PAXLOVID™ were hospitalized through Day 28 following randomization (3/389 hospitalized with no deaths), compared to 7.0% of patients who received placebo and were hospitalized or died (27/385 hospitalized with 7 subsequent deaths)…In the overall study population through Day 28, no deaths were reported in patients who received PAXLOVID™ as compared to 10 (1.6%) deaths in patients who received placebo.”
We were impressed and wrote about the promise of Paxlovid in this article.
Is the Oral Pill Paxlovid an Answer to COVID-19?
What should you know about PAXLOVID, an oral medicine against COVID-19? How hard is it to get an Rx? What about dangerous interactions?
Puzzling Paxlovid COVID Rebound:
Several weeks ago we began hearing through the COVID grapevine that some patients were experiencing Paxlovid COVID rebound. People who were vaccinated against SARS-CoV-2 were coming down with the infection and were promptly started on the antiviral drug Paxlovid. Within a day or two they were getting better. After finishing the five-day course of treatment, they assumed they were “cured.” They tested negative for the virus and were feeling pretty good.
Then something strange happened. Instead of continuing to feel fine and resume normal activities, some of these patients began experiencing Paxlovid COVID rebound within a couple of days. That is to say, they were developing symptoms of the coronavirus all over again. They were also testing positive for COVID-19. They isolated themselves from family and friends and assumed they were infectious once more.
One renowned physician, Bob Wachter, reported an informal poll.
This is not scientific, but he noted in his Twitter feed that:
“about 46% in my poll who had COVID, took Pax, turned neg, then rebound w/ reversion to + test…”
Please keep in mind that this “poll” is not science. There is no way to know at this time the actual rate of Paxlovid COVID rebound.
What Does the FDA Say about Paxlovid COVID Rebound?
We asked some key executives at the FDA what the agency’s position is on the Paxlovid rebound phenomenon. First, we were told that
“We are on the case.”
A follow-up message from a different FDA exec added this:
“…based on the data the benefit still outweighs the risk of rebound. ‘The benefit of a 5-day treatment course of Paxlovid was demonstrated in the clinical trial that supported the EUA. This study showed that among non-hospitalized patients at high risk of progression to severe disease, treatment with Paxlovid reduced the risk of hospitalization or death by 88.’”
“In light of these reports, additional analyses of the Paxlovid clinical trial data have been performed. In the Paxlovid clinical trial, some patients (range 1-2%) had one or more positive SARS-CoV-2 PCR tests after testing negative, or an increase in the amount of SARS-CoV-2 detected by PCR, after completing their treatment course. This finding was observed in patients treated with the drug as well as patients who received placebo, so it is unclear at this point that this is related to drug treatment. Additional analyses show that most of the patients did not have symptoms at the time of a positive PCR test after testing negative, and, most importantly, there was no increased occurrence of hospitalization or death or development of drug resistance.”
How Good Are the Data?
This sounds reassuring, but we fear that this rebound phenomenon has not been extensively studied. Physicians do not know how to treat it. The manufacturer has suggested that people experiencing rebound take another course of medication.
However, both the FDA and the CDC disagree. Instead, the agencies recommend that patients isolate themselves from others for five days from the start of new symptoms and wear effective masks for at least ten days, just as if they had developed a new infection.
Here is the official CDC response (May 24, 2022) on Paxlovid COVID rebound:
“Paxlovid treatment helps prevent hospitalization and death due to COVID-19. COVID-19 rebound has been reported to occur between 2 and 8 days after initial recovery and is characterized by a recurrence of COVID-19 symptoms or a new positive viral test after having tested negative. A brief return of symptoms may be part of the natural history of SARS-CoV-2 (the virus that causes COVID-19) infection in some persons, independent of treatment with Paxlovid and regardless of vaccination status. Limited information currently available from case reports suggests that persons treated with Paxlovid who experience COVID-19 rebound have had mild illness; there are no reports of severe disease. There is currently no evidence that additional treatment is needed with Paxlovid or other anti-SARS-CoV-2 therapies in cases where COVID-19 rebound is suspected.”
Here are some questions we have for the FDA, the CDC and Pfizer:
- How common is Paxlovid COVID rebound?
- Do some people experience COVID rebound without symptoms but remain infectious for another week or two?
- How long does Paxlovid COVID rebound usually last?
- Do patients who experience rebound go on to develop long COVID or does Paxlovid protect them from these lingering complications?
- Is there any data to support a 7-10 day course of Paxlovid? Would it reduce the likelihood of rebound?
It seems to us that there is much more research necessary about the benefits and risks of Paxlovid.
Dr. Bob Wachter recently Tweeted a couple of days ago:
“I was asked by a reporter today if I’d take Paxlovid if I had Covid. Last month, this would have been easy: as a 64-year-old person w/ asthma, the answer was an unequivocal YES.
“Today, it’s a closer call–
“I would still take it, mainly based on my teetering but still fairly high confidence that it would lower my chance of an awful outcome (hospitalization/death), and my confidence that rebound would be inconvenient, but not ultimately super-risky.”
Faced with a similar choice, I would probably take Paxlovid as well.
Dr. Wachter is a brilliant physician. He happens to be chair of the Department of Medicine at the University of California, San Francisco. “In 2021-22, the Department was ranked the best internal medicine department in the nation by U.S. News & World Report. Wachter is author of 300 articles and 6 books. He coined the term “hospitalist” in 1996 and is often considered the “father” of the hospitalist field, the fastest growing medical specialty in the U.S. history. He is past president of the Society of Hospital Medicine and past chair of the American Board of Internal Medicine.”
So, when Dr. Wachter speaks, physicians listen! I certainly do.
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