The CDC warning cited recent reports from researchers documenting some Paxlovid rebounds, including among patients who have been vaccinated and boosted.
The CDC warning comes as two small but provocative new studies from different teams of researchers in Boston and New York suggest that such relapses may not be so unusual. The researchers also found that in some rebound patients, viral levels were likely high enough to be contagious.
other than that a study found that two patients who relapsed unintentionally infected family members. In one case, an asymptomatic 67-year-old man infected a 6-month-old family member six days after finishing Paxlovid. The transfer took place after the time window proposed by the CDC for isolation.
“This is not uncommon, otherwise why do we see these clusters?” said Dr. Michael Charness, chief of staff at the VA Boston Healthcare System and co-author of the study, who analyzed COVID infections in 10 patients ages 31 to 71 who were fully vaccinated and had received at least one booster shot. The study was posted online Monday and has not been peer-reviewed.
Paxlovid is a home treatment that is prescribed at the first sign of infection for patients at high risk for severe COVID complications. The treatment consists of a total of 30 pills – three pills taken twice daily for five days.
When Paxlovid manufacturer Pfizer received emergency use permit for the drug in December from federal regulators, its data showed that about 2 percent of patients in the trial experienced a recovery, as did about 1.5 percent of those receiving placebo.
The Charness survey does not directly reject the Pfizer data, but suggests that rebounds are more common. The patients in this study experienced relapse symptoms that began between three and eight days after stopping Paxlovid, and the symptoms lasted between three and ten days.
Antigen tests performed while patients had recurrence indicated that they remained positive for a median of six days, and until as long as day 18 after their first, pre-Paxlovid positive test.
By comparison, the Charness group looked at a separate group of COVID patients who had not taken Paxlovid: nearly 1,000 employees of the National Basketball Association. No one had a relapse of COVID. They have not published that data.
“We cite the NBA data to say that this is clearly different from what had been observed” by Pfizer, said Dr. David Ho, director of the Aaron Diamond AIDS Research Center at Columbia University and co-author of the Charness and NBA studies.
A Pfizer spokesman said the company continues to monitor data from its ongoing investigations into Paxlovid, as well as reports from doctors and patients with rebounds. He said all data are “consistent with our observations” from the company’s drug trials.
The new CDC warning notes that a COVID relapse with a brief recurrence of symptoms “may be part of the natural history of SARS-CoV-2 (the virus that causes COVID-19) infection in some individuals,” regardless of Paxlovid treatment and regardless of vaccination status. “
Federal data show that more than 668,000 courses of Paxlovid had been prescribed on 14 May. Doctors say that despite the relapses, it is an effective medication that has kept vulnerable people out of the hospital.
Another study from a team of Boston researchers analyzed seven patients who had returned after taking Paxlovid and found levels of live virus in three of them for up to nine days. One of the patient’s test samples showed live virus for 11 days after finishing Paxlovid.
“This greatly increased the suspicion that they are contagious,” said Dr. Mark Siedner, an infectious disease clinician and researcher at Massachusetts General Hospital and co-author of the study, has not been peer-reviewed.
“It’s not just that they get up. It’s that they rebound, and it seems like they’re starting from the beginning, their virus is going up a lot,” Siedner said. “It’s a really unique phenomenon.”
Siedner’s team found no evidence that the virus developed resistance to Paxlovid.
Siedner and other researchers say the rebound phenomenon raises urgent questions about whether patients should be treated with a longer course of Paxlovid or perhaps another medication.
The CDC warning does not definitively answer that question.
“There is currently no evidence that further treatment with Paxlovid or other anti-SARS-CoV-2 therapies is needed in cases where COVID-19 rebound is suspected,” it said.
Rebounds with such high levels of live viruses have led Siedner to question whether there is something about Paxlovid that may be contributing to the phenomenon.
“It makes us wonder if we are not using the drug properly or long enough, or is this something inherent in Paxlovid that does not allow the immune system to strike?” he said.
Siedner’s team, which includes researchers from Brigham and Women’s Hospital as well as the Broad Institute and the Ragon Institute of MGH, MIT and Harvard, is launching a new study that hopes to answer some of these questions.
They will test the immune system in people who have returned to see if the immune response from those who received Paxlovid is different from those who did not.
Dr. Kathryn Stephenson, an assistant professor at Harvard Medical School and an infectious disease physician at Beth Israel Deaconess Medical Center, also heads a Paxlovid studymonitoring patients who have just started antiviral with COVID testing for two to three weeks to detect rebound information on symptoms.
She said her and other small studies of a few dozen people are helpful, but that much larger, rigorous studies are imperative to understand and address relapse.
“I think it’s Pfizer’s responsibility to produce and share this data quickly – it’s their medicine [that received emergency use authorization,]said Stephenson.
“It is not fair that individual clinicians and researchers are now trying to obtain and collect this data themselves.”