
- Clinical trials showed that some re-emergence, or rebound, of COVID-19 symptoms, was possible in people who take Paxlovid, but reported levels seem higher.
- The cases of rebound may have less to do with Paxlovid and more to do with a disease-versus-immune-system tug of war.
- Some research suggests that rebounds are more likely in people with the same underlying conditions that place them at higher risk for COVID-19.
On December 22, 2021, the FDA granted emergency authorization for the use of , Pfizerâs drug for treating mild to moderate COVID-19.
A United States White House press release described it as âan oral antiviral pill which reduces the risk of hospitalization or death by about 90%.â
Yaleâs infection diseases specialist Dr. Scott Roberts tells Yale Medicine: âI think it is the beginning of a game-changer. Itâs really our first efficacious oral antiviral pill for this virus. It shows clear benefit, and it really can prevent hospitalization and death in people who are at high risk.â
Since that time, however, some people taking Paxlovid have seen a return of their COVID-19 symptoms after treatment ends. This includes the two most prominent White House occupants, President Joe Biden and his wife, Dr. Jill Biden, whose Paxlovid rebounds have been widely reported.
While Paxlovid has been, in general, very successful in treating COVID-19, the press coverage has left some with questions about Paxlovid and the chances of their experiencing a rebound.
Medical News Today asked the experts six key questions about COVID-19 rebounds.
Dr. Robert Wachter, professor of medicine and chair of the Department of Medicine in the School of Medicine at the University of California, San Francisco, explained rebound to MNT.
âRebound,â he said, âis the phenomenon of getting better from your COVID infection, both in terms of symptoms and your rapid test going from positive to negative, and then relapsing later â usually with both the return of symptoms and the return of a positive rapid test, which means that the amount of virus youâre carrying has increased.â
âItâs not entirely clear why it happens, but we think itâs mostly that the virus and your immune system are in a tug of war,â added dr. Wachter.
âYour immune system wins for a while â which is why you improve â and then the virus turns things around to take the lead. Eventually, your immune system kicks back in and, in virtually all cases, you improve again,â he noted.
Dr. Amesh Adajla, assistant professor at Johns Hopkins School of Public Health told us that â[i]t appears to be more frequently reported in the past several months [versus] earlier in the pandemic.â
âWe know that COVID symptoms fluctuate a lot, so rebound is not really new,â said Dr. Davey Smith, professor of medicine at the University of California, San Diego.
âPeople have been more in-tune with this after treatment with Paxlovid. Rebound of symptoms is even common for people who were not treated with anything,â he pointed out.
Dr. Rong Xu is a professor of biomedical informatics and the director of the Center for AI in Drug Discovery in the School of Medicine at Case Western University.
In answer to this question, she told MNT:
âThere are many anecdotal reports [about COVID-19 rebounds] â e.g., on social media â and CDC-issued health advisories. Therefore, it is not a new phenomenon, and it is also not unique for Paxlovid. But there is a dearth of data in systematically characterizing COVID-19 rebound[s]. In addition, our
recent study shows that COVID-19 rebound is more likely to happen for BA.5 than the BA.2.12.1 subvariant.â
âThey did,â said Dr. Wachter, âbut in a very small percentage of people.â Dr. Smith agreed, noting that â[c]linical trials have shown this phenomenon since the beginning.â
âIn the early tests of Paxlovid,â continued Dr. Wachter, ârebound was seen in about 2% of people who were on the drug, but in a similar fraction of people who werenât. So, it didnât seem like a big deal.â
âOf course, real-life experience has been different; while the published evidence still cites a relatively low probability of rebound with Paxlovid, most of us believe it is far more common â like in the 10-20% range,â he added.
âJust think about it: both Bidens, Fauci, virologist Peter Hotez⌠And my wife got it, and many friends â it simply canât be 2â5%. But we really donât have a good number for it.â
â Dr. Robert Wachter
âThere may be differences between trial population and real-world patients,â said Dr. Xu. âOmicron subvariants may also play some role, as our recent study indicates.â
Dr. Adajla also suggested âthat [the lack of clear information about the prevalence of rebound symptoms] may be a result of trials occurring during times when non-Omicron variants were prevalent.â
Dr. Adajla pointed out that while â[r]ebound is anecdotally being reported in users of Paxlovid, [âŚ] it can occur in individuals who are not prescribed any antiviral as well.â
âWe do not know who is at greater risk for rebound of symptoms. Looks like it can happen to anyone,â said Dr. Smith.
According to Dr. Wachter:
âThere are no great demographic or disease predictors â young/ old, vaccinated or not, severe initial case or milder. Seems to be pretty random. Some people think there may be some connection to starting on Paxlovid quickly, which has led some to recommend waiting a few days. (Paxlovid works as long as you start it by day 5.) But thereâs no strong evidence backing this up.â
Dr. Xu pointed out, however, that the research in which she is involved suggests otherwise:
âOur data show that patients with underlying medical conditions â e.g., heart diseases, cancer, obesity, diabetes, hypertension, immune-related diseases â are more likely to have COVID-19 rebound.â
âRebound can happen 2 and 8 days, or even 30 days, after the last course of the drug,â she added.
âGreat question! We donât know yet, and we are actively investigating it,â answered Dr. Xu.
According to Dr. Wachter, â[an] average case lasts about 5 days [and] â[i]t is virtually always mild.â
âOnly a handful of rebound cases that required hospitalization have been reported, and Iâve never heard of a rebound case leading to death,â he told us. âThe downsides are: youâre infectious again, so [you] should go back into isolation, you may feel crummy again, [and that] it is unclear whether rebound is a risk factor for long COVID, but it might be.â
There may be some occasional cases of long-lasting rebound, but according to Dr. Wachter, these are likely very rare:
âIâve heard of one person who continued to test positive for 20 days, but thatâs distinctly unusual. Typical is that someone turns negative on about day 8, turns positive again (rebound) on day 12-13, and then turns negative (and stays negative) on day 18 or so.â
Dr. Smith largely agreed that rebound COVID-19 tends to be mild and short-lived. âIt differs for everyone, but usually only lasts a few days and is generally mild,â he noted, while also admitting that â
âMaybe,â said Dr. Smith, âbut this needs to be studied before it is widely recommended.â
âLikely,â said Dr. Xu, âbut we donât know yet,â pointing again to the lack of good data.
âLonger courses of Paxlovid are being studied,â noted Dr. Adajla, âto see if [the] duration of antiviral treatment has any bearing on the incidence of this phenomenon, but much more work is necessary to understand what governs rebound.â
Dr. Wachter expressed concern that the answer to this question remains unknown at the time of writing.
He did not mince words about this issue: âI think itâs scandalous that this hasnât yet been tested in a clinical trial. This is really the big question.â
Still, he surmised that âa 7- or 10-day course [of Paxlovid] would prevent most cases of rebound, but there has not yet been a reported clinical trial.â