Resurgence of COVID-19 symptoms in patients treated with Pfizer Inc.’s Paxlovid appeared far more common than has been reported, and rebounding patients still risked spreading the disease, doctors said in a report on a series of cases in a top medical journal.
The article published Wednesday in the New England Journal of Medicine documented 13 fully vaccinated patients whose rapid COVID tests turned strongly positive and symptoms reappeared several days after finishing five-day courses of Paxlovid. One patient apparently transmitted the virus to a 6-month-old baby during rebound, while another who spent time with his wife, brother-in-law and sister-in-law just as his rebound was beginning saw all three become infected.
This summer, researchers reported high viral loads and the isolation of infectious virus in patients who rebounded after Paxlovid treatment, and the article adds to suspicions that they can spread the disease. Although small, it also adds weight to indications that Paxlovid rebound is by no means uncommon: lead study author Michael Charness, chief of staff of the VA Boston Healthcare System, said that all three members of his family who took Pfizer’s drug, including himself, experienced rebound and both members of his co-author’s family who got Paxlovid had the same experience.
The U.S. government has ordered 20 million doses of Paxlovid and nearly 1.8 million courses are currently available. Powerful evidence of its life-saving benefits continues to mount; a recent study found that it cut deaths and hospitalizations among vaccinated high-risk patients by 45%.
The possible inconvenience of a rebound “should not dissuade people,” from taking it, Charness said in a interview. “Given the large numbers out there who will be taking Paxlovid, we just wanted people to be aware.”
The frequency of rebound in the case series — as well as in a preprint study last month that found the phenomenon in 3 out of 11, or 27%, of Paxlovid-treated patients — is far out of sync with Pfizer’s numbers. The company has said that rebound generally occurs in untreated patients, along with those that get Paxlovid, at rate of about 2%, although data from Pfizer indicated that Paxlovid-treated patients had a rebound rate of almost 5%.
A Pfizer spokesperson described rebound as “uncommon and not uniquely associated with any specific treatment.”
Yet cases have been reported frequently. Both President Joe Biden and first lady Jill Biden are among those reported to have experienced relapses after taking the Pfizer pills; presidential medical adviser Anthony Fauci also said he was hit with rebound after taking Paxlovid.
The risk that rebounding patients remain contagious prompted the Centers for Disease Control and Prevention to recommend they resume isolation and masking.
Because word about Paxlovid rebound has spread, “there’s unfortunately some hesitancy among some of our patients” to take the drug, said Jonathan Li, an infectious disease specialist at Harvard Medical School and Brigham and Women’s Hospital in Boston. “But in the end you have to keep your eyes on the prize, which is that we want to prevent severe disease, hospitalizations and death, and Paxlovid does that, despite these cases of rebound.”
The rebounds are clearly real, Li said, but with or without the pills, “recovering from COVID is not a linear process. It waxes and wanes.” A study he co-authored found roughly one-quarter of COVID patients overall experience some symptom recurrence.
Part of the coronavirus’s replication involves using a chemical scissors called a protease to cut big chunks of protein into small pieces that make more virus. Some of those chunks can persist in infected cells for days after Paxlovid treatment, said David Ho, a Columbia University virologist who co-authored the journal study. That may allow the virus to start replicating again after the effects of the drug fade, he said.
Whether longer treatment could prevent Paxlovid rebound remains unknown. Pfizer said it plans to study patients who may need retreatment with Paxlovid. Both Fauci and Biden reportedly tried a second round of the pills, which are normally taken twice daily for just five days.
Concern about rebound may change the risk calculation for some patients considering Paxlovid: The potential for longer disruption to their lives may make the pills look less appealing.
Ultimately, risk from COVID lies on a spectrum, said Li from Harvard. For those with more mild risk factors, doctors and patients face some Paxlovid “shared decision making,” which could include some initial wait-and-see. “And for those who are at the higher end of that spectrum, there’s no doubt in my mind that Paxlovid is the right course,” he said.
