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The CDC alert cited recent reports from researchers documenting some Paxlovid rebounds, including in patients who were vaccinated and boosted.
The CDC warning comes as two small but provocative new studies from separate teams of researchers in Boston and New York suggest such relapses may not be that uncommon. The scientists also found that in some rebound patients, the virus concentration was likely high enough to be contagious.
In addition, one study found that two patients accidentally infected family members relapsed. In one case, a symptom-free 67-year-old man infected a 6-month-old family member six days after completing Paxlovid treatment. The transfer has taken place after the CDC’s proposed window of isolation.
“It’s not uncommon, otherwise why do we see these clusters?” said dr Michael Charness, chief of staff for the VA Boston Healthcare System and co-author of the study that analyzed COVID infections in 10 patients aged 31 to 71 who were fully vaccinated and had received at least one booster shot. The study was posted online on Monday and has not been peer-reviewed.
Paxlovid is a home treatment prescribed at the first sign of infection to patients at high risk of serious COVID complications. The treatment consists of a total of 30 pills – three pills taken twice a day for five days.
When Paxlovid-maker Pfizer received emergency use authorization for the drug from federal regulators in December, its data showed that about 2 percent of patients in its study experienced recovery, as did about 1.5 percent of patients receiving a placebo.
The Charness study doesn’t directly refute Pfizer’s data, but it does suggest that rebounds are more common. Patients in this study experienced relapse symptoms that began between three and eight days after stopping treatment with Paxlovid, and symptoms lasted between three and 10 days.
Antigen tests performed on patients who relapsed showed that they remained positive for a median of six days and up to day 18 after their first positive test before Paxlovid.
For comparison, the Charness group looked at a separate cohort of COVID patients who hadn’t taken Paxlovid: nearly 1,000 employees at the National Basketball Association. None had a relapse of COVID. They have not published this data.
“We cite the NBA data to say that this is significantly different from what was 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 studies of Paxlovid, as well as physician and patient reports of rebounds. He said all of the data “consistent with our observations” from the company’s drug trial.
The new CDC alert notes that a COVID relapse with a brief recurrence of symptoms “may be part of the natural history of SARS-CoV-2 infection (the virus that causes COVID-19) in some individuals, regardless of treatment with Paxlovid and regardless of vaccination status”.
Federal data shows that as of May 14, more than 668,000 Paxlovid cycles have been prescribed. Doctors say that despite the rebounds, it’s an effective drug that has kept vulnerable people out of the hospital.
A second study by a team of Boston researchers analyzed seven patients who had recovered after taking Paxlovid and found live virus for up to nine days in three of them. One of the patient’s test samples showed live virus for 11 days after Paxlovid stopped.
“This has 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 non-peer-reviewed study.
“It’s not just that they’re recovering. It’s like they’re recovering and it seems like they’re starting over, their virus is going way up,” Siedner said. “It’s a really unique phenomenon.”
Siedner’s team found no evidence that the virus had developed resistance to Paxlovid.
Siedner and other researchers say the rebound phenomenon raises pressing questions about whether patients on longer-term treatment should be treated with Paxlovid, or perhaps another drug.
The CDC alert does not definitively answer that question.
“There is currently no evidence to suggest that additional treatment with Paxlovid or other anti-SARS-CoV-2 therapies is required in cases where COVID-19 rebound is suspected,” it said.
The rebounds with so many live viruses has Siedner wondering if There is something about Paxlovid that could be contributing to the phenomenon.
“We’re wondering, are we not using the drug properly or for long enough, or is that something about Paxlovid that doesn’t allow the immune system to intervene?” he said.
Siedner’s team, which includes researchers from Brigham and Women’s Hospital and the Broad Institute and Ragon Institute of MGH, MIT and Harvard, is launching a new study designed to answer some of these questions.
They will test the immune systems of people who have recovered to see if the immune response of those who received Paxlovid differs from those who didn’t.
dr Kathryn Stephenson, an assistant professor at Harvard Medical School and an infectious disease physician at Beth Israel Deaconess Medical Center, is also leading a Paxlovid studyMonitoring patients who have just started COVID antiviral testing for two to three weeks to detect rebound information on symptoms.
She said her and other small studies involving a few dozen people are helpful, but that much larger, rigorous studies are badly needed to understand and address rebounds.
“I think it’s Pfizer’s responsibility to produce and share this data quickly – it’s their drug.” [that received emergency use authorization,]’ Stephenson said.
“It’s not fair that individual clinicians and researchers are now trying to catch up and collect this data themselves.”
Kay Lazar can be reached at [email protected]. Follow her on Twitter @GlobeKayLazar.
