Looks like both U.S. President Joe Biden and Anthony Fauci MD, the Chief Medical Advisor to the President, have been caught on the rebound, so to speak. Back on June 30, I covered for Forbes how Fauci had suffered a so-called Paxlovid rebound. That’s not a basketball term but instead represents when a person tests positive again for Covid-19 after initially testing negative following a five-day course of the antiviral Paxlovid. Now essentially the same thing has happened to the President. Biden had originally tested positive for Covid-19 on July 21 and then began a course of Paxlovid. Things seemed all peachy-keen when he subsequently tested negative for three straight days on July 26, 27, 28, and 29 before, whoops, testing positive again today on July 30. This led Biden to go back into isolation, which Biden tweeted out on Saturday:
That same day, Biden provided a follow-up tweet with a video of him taking off his shades and saying, “I’m feeling fine, everything’s good,” which suggested that he may be experiencing only mild symptoms:
As you can see in Saturday’s earlier tweet, Biden had said, “This happens with a small minority of folks,” with “this” presumably being a Paxlovid rebound. But, umm, is that really the case?
Similar type of language came from a White House memo issued on Saturday by Kevin O’Connor, DO, the Physician to the President. O’Connor wrote that such a rebound in Covid positivity is “observed in a small percentage of patients treated with Paxlovid.” However, Eric Topol, MD, founder and director of the Scripps Research Translational Institute, took issue with this “small” statement in the following tweet thread:
Instead, Topol called such Paxlovid rebound “extremely common,” which would be kind of a different message. If someone were to tell you that an anvil falling on your head would either happen in a small percentage of cases or be extremely common, you’d probably want a little more clarification.
Biden and Fauci have not been the only ones to report such a rebound. Simply searching social media for terms such as “Paxlovid rebound”, “Covid rebound”, “not again”, and “arrghh” will reveal a number of identifiable human beings (as opposed to anonymous social media accounts) posting about their rebound experiences. One example is the following from Avital Y. O’Glasser, MD, an Associate Professor at the Oregon Health Sciences University (OHSU):
Yeah, very few people would say, “I love Covid.” A Covid-19 rebound can be kind of like watching the movie Deuce Bigalow: Male Gigolo in the theater and then thinking that you’ve left the theater before it’s done but then realizing that you can’t leave the theater. As you can see, Alex Levin, MPH, a student at OHSU, responded to O’Glasser’s tweet with a “damn” and remarked that the observed rate of rebound seemed a lot higher than a “small percentage.”
So what is it? A small percentage or extremely common? Or something in between? This is a case where size does mater because it can help set expectations for those contemplating whether to take Paxlovid. It also affects how long folks may end up isolating after getting infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is kind of, sort of really important for everyone around them.
It’s true that Pfizer’s clinical trials which got the U.S. Food and Drug Administration (FDA) to grant emergency use authorization (EUA) for Paxlovid showed only a relatively “small percentage” of such rebound cases. But there are like big butts, one cannot lie, in assuming that such clinical trials results will continue to hold. In a tweet thread, Peter Hotez, MD, PhD, Dean of the National School of Tropical Medicine, pointed out that while in these trials “rebound was rare maybe 1-2% of the time,” such trials were done in pre-Omicron times:
In other words, the clinical trials came before the more transmissible Omicron variant and subvariants established a foothold or rather a spikehold in our population. A lot has changed since 2021 when the trials were initially run.
Secondly, when clinical trial results come via pharmaceutical company press releases. take them with a fanny pack or Ugg boot of salt. For example, a June 14 press release from Pfizer reported that those taking Paxlovid had a 51% lower risk of hospitalization or death from Covid-19 than those taking placebo with this number climbing to 57% among adults who were already vaccinated against Covid-19. While such number may sound good, such press releases don’t provide nearly enough details to properly assess the clinical trial and its results. Relying on pharmaceutical company press for scientific information can be like making life decisions based on the advertisements and as a result wishing that you were an Oscar Mayer Weiner. Instead, it’s better to rely on peer-reviewed studies published in reputable scientific journals, especially those conducted by scientists who are not directly connected to Pfizer in any way.
The rise of the Omicron family hasn’t been the only thing that’s been different since 2021. Back in 2021, a lot more people were maintaining various Covid-19 precautions such as social distancing and face mask wearing. Now that many people have dropped face masks as if they were soiled underwear and may be spewing out virus in greater quantities, could the virus levels that you are exposed to on average be higher? Could getting exposed to higher doses of the SARS-CoV-2 potentially result in higher viral loads on average, which, in turn, might affect how well your infection responds to Paxlovid? Again, it’s important to remember that the clinical trials conducted by Pfizer probably didn’t capture all the complex factors that may affect how effective an antiviral can or can’t be.
As I have covered previously for Forbes, Covid-19 rebound may result because the Paxlovid hasn’t suppressed virus replication enough for your immune system to have successfully cleared the SARS-CoV-2 from your body. One possibility is that the five-day duration of Paxlovid treatment is not long enough, that a seven or a 10 day course may be needed. Another possibility is that the antiviral is not as effective against the newer variants and subvariants. Changing the dosing of Paxlovid or combining Paxlovid with other treatments may be the answer, but more studies are needed first to determine whether any of this makes sense. The tweet threat from Hotez did allude to some of the ongoing research and the fact that the real rate of Paxlovid is still not known:
All of this brings up a key point. Since the start of the pandemic, there has been a tendency to prematurely hail something as the single magical single solution, the single magical Mjölnir, or the single magical velour track suit to deal with the pandemic. This happened when the Covid-19 vaccines first came out, with some touting the 90% plus effectiveness initially reported from the clinical trials without appropriately tempering expectations. Such a premature declaration of success inevitably led to confusion and disappointment as Covid-19 vaccinations weren’t and aren’t like concrete full-body condoms. You can’t rely solely on them to protect you. Similarly, while Paxlovid can be very helpful, it ain’t a magical pill or solution either. Getting vaccinated and boosted and having Paxlovid available does not mean that you can simply abandon other precautions such as face mask wearing and run into an area with high Covid-19 coronavirus activity yelling “freedom” as if you were Mel Gibson in the movie Braveheart.
Don’t forget what you learned previously about Swiss cheese. It is yummy and formed the basis of that “Swiss cheese” diagram that was being circulated earlier in the pandemic. This diagram emphasized that each available intervention has its holes and that the key to combatting the pandemic was to layering interventions on top of each other so that no holes are left exposed. Well, this hasn’t changed. Layers of Swiss cheese are still delicious, and maintaining multiple layers of interventions is still the better way to go as long as virus activity remains very high.
Throughout this pandemic, it seems like every time a new idea or finding emerges, there can be a tendency to forget older ones. For example, why did public health authorities originally recommend that you stay isolated for 10 days after getting infected with the SARS-CoV-2? If you recall, this was because studies had showed that a significant percentage of people can continue to shed the virus beyond five or even seven days. And guess what, it’s not as if someone went back in time via the Quantum Realm or a DeLorean to eliminate those studies. Yet, in December 2021, the Centers for Disease Control and Prevention (CDC) shortened the recommended isolation period for many to five days.
With growing reports of Paxlovid rebound occuring well beyond the five day mark, it’s time to reconsider this five-day-why-was-this-changed-in-the-first-place isolation guidance. Sure businesses may want employees to return as soon as possible. And there’s only so much Squid Game you can binge watch while in isolation. But you don’t want anyone to catch what you have on the rebound.