When Berkeley resident Myriam Misrach tested positive for the coronavirus last month she started taking the Paxlovid COVID antiviral pill the same day. During the five days of treatment, her cough and shortness of breath mostly subsided, but a few days after taking the last pill, her symptoms returned.
For 48 hours afterward, she also had a fever, headache, nausea, a runny nose and lost her sense of taste, she said. And she tested positive for the virus again – despite having tested negative and feeling much better a few days before.
“I had everything in the book,” said Misrach, 66, who is vaccinated and boosted. “It was not a mild case at all.”
Misrach continued to test positive for two weeks after that and today he is still coughing, although the other symptoms have subsided. What was even more confusing, she said, was that her husband had also just taken Paxlovid and for him it “worked like a charm” – he started feeling better almost immediately and stayed that way. , although he also tested positive after initially testing negative.
“I don’t blame Paxlovid but I think they need to study it more,” she said.
As the number of Americans taking the Pfizer drug skyrockets, many people are reporting a similar “rebound” after taking the drug – including some vaccine scientists and doctors who have documented their experiences on Twitter. As well as a recurrence of symptoms, the rebound also means that someone who thought they had recovered could still be contagious and should self-isolate for additional days.
All known cases of viral rebound from Paxlovid appear to have been resolved without requiring patients to be hospitalized, say doctors who prescribe the drug and researchers studying the matter. They overwhelmingly agree that this does not stop them from prescribing the antiviral drug, which in clinical trials reduced the risk of hospitalization and death from COVID by almost 90%. They say that if someone is eligible for Paxlovid, the patient should still get it, despite the potential for rebound symptoms, because it delivers on its promise by effectively keeping people out of hospital.
Rebound, also known as relapse, is not uncommon in infectious diseases. Doctors often see it in patients who have taken antibiotics or antivirals, where the infection returns after treatment is finished because the virus or pathogen has not been completely eliminated, Dr Prasanna Jagannathan said. , a Stanford immunologist and infectious disease physician.
The Paxlovid rebound phenomenon is an example of what happens when a new drug – probably the most watched drug in recent memory, second only to COVID vaccines – starts being widely used in the real world and causes results that may not have been observed in clinical trials at such high levels. That doesn’t mean the drug is flawed, the scientists and doctors noted, but rather that it needs to be studied further and its dosage or duration of use may need to be changed.
It is not known why the bounce occurs, or how often it occurs in the real world. In Pfizer clinical trials, this happened in 2% of people who took Paxlovid. Many doctors who prescribe the antiviral say they hear about rebound anecdotally from patients, and it appears to be more common than it was in trials. But that could be partly due to reporting bias, where people who experience a rebound are more likely to report it than those who didn’t.
“We’ve all heard anecdotes from patients we’ve cared for who are going through this experience, so it’s clearly a phenomenon,” said Jagannathan, who prescribed Paxlovid to 25 to 30 patients and saw a rebound in two of them. between them. “What that real number is, no one knows yet.”
Pfizer and the U.S. Food and Drug Administration are tracking rebound cases for further study. Providers and patients can report cases to Pfizer’s and the FDA respective adverse event reporting systems.
Researchers are considering a few potential explanations for viral rebound.
A small study, which has not yet been peer-reviewed, suggests that the problem is likely not drug resistance due to a viral mutation or a problem with a patient’s immune response. On the contrary, patients may not have been sufficiently exposed to Paxlovid. This could mean that instead of the five-day course currently allowed by the FDA, people might need to take the drug longer or at a different dosage. The study, which was published on a preprint site this week, looked at three vaccinated and boosted adults who took Paxlovid, including one who rebounded. This person was infected with the BA.2 omicron subvariant.
Patients and healthcare providers can report cases of suspected Paxlovid rebound to Pfizer and the US Food and Drug Administration, which are monitoring the phenomenon for further investigation.
To report to Pfizer, go to Pfizer’s COVID-19 Treatment Adverse Event Reporting Website and submit an online form.
To report it to the FDA, go to FDA medical oversight and submit a form online or by fax to 1-800-332-0178. Call 1-800-332-1088 with any questions.
“Our guess or our best guess at this point is that we think there is insufficient drug exposure to get rid of the virus,” said study lead author Dr. Aaron Carlin of UC. San Diego, which studies emerging and re-emerging viral infections and how they interact with the immune system. “There will probably be studies to see if people need 10 days instead of five days to try and stop this rebound from happening.”
Another small study, originally published in late April and updated last week by the VA Boston Health System, also suggests that the reason for the relapse is not because the virus mutated after patients took Paxlovid. The authors said more research is needed to determine the cause of the relapse.
Pfizer’s Paxlovid trials were performed in vaccinated and unvaccinated people when delta and earlier variants were circulating. Now it is people infected with omicron and omicron subvariants who take the drug, many of whom are vaccinated. So it’s possible their immune systems are responding to the drug a little differently, which could help explain the rebound. It could also be that omicron and its subvariants lead to a longer viral shedding period than delta, so people may now need treatment longer than five days.
The UC San Diego study analyzed several coronavirus variants and their susceptibility to Paxlovid, and found no significant differences in how they responded to the drug. But there is evidence to suggest that the neutralizing antibody response in vaccinated people is weaker against omicron than delta, “so there may be something about omicron and the immune system that contributes to that (rebound), but we don’t understand it yet,” Carlin said.
If the virus is found to become resistant to Paxlovid in the future, combining it with other antivirals may help. Treating HIV with a single drug leads to drug resistance almost immediately, but treating with three drugs does not, Carlin said.
“It’s a warning, but I don’t think it’s a reason people shouldn’t take the drug,” Carlin said. “It’s always very effective. We just need to figure out if it can be used in a way to make it even better to avoid bouncing.
Catherine Ho (she) is a staff writer for the San Francisco Chronicle. Email: cho@sfchronicle.comTwitter: @Cat_Ho
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