Pfizer’s antiviral COVID-19 drug Paxlovid has been hailed as a breakthrough in the fight against the disease, promising fast, convenient and dramatic protection from serious illness in older adults and others at higher risk from the virus.

But in recent weeks there have been growing concerns that some people who complete the five-day cycle of prescription pills will fall ill soon after and test positive again. Among them this week was Dr. Peter Hotez, dean of the National School of Tropical Medicine at Baylor College of Medicine in Houston, an expert often featured on national news programs.

“I thought COVID was over,” Hotez tweeted Tuesday, reporting that he had a runny nose, sore throat and “antigen test screaming +” for COVID-19 five days after completing his Paxlovid course. “We’ll find out eventually, but it’s still a mystery.”

The chairman of the medical department at UC San Francisco, Dr. Bob Wachter, who, with her permission, shared his wife’s journey through COVID-19 disease and the Paxlovid treatment on social media, added Wednesday that they were concerned enough about the likelihood of a “rebound infection” that may occur they watched TV together with masks – with open windows.

Can the virus, some of its mutant variants evade vaccine protection and prompt calls for multiple rounds of boosters, find ways to defeat the latest miracle drug, approved for emergency use only five months ago? Is Paxlovid still worth it?

Medical experts say they don’t know for sure why some people who fight back COVID-19 infection with Paxlovid test positive for the virus and start feeling nauseous again shortly after stopping the medication. But they say that it is still worth taking the antiviral therapy.

White House officials reported Wednesday that the drug has become an increasingly important weapon in the fight against the coronavirus, as 20,000 prescriptions a day are being written across the country. They, too, urged people not to overreact to reports of rebound infections.

“My concern with this whole conversation is that people are going to lose the wood for the trees and the benefits of Paxlovid,” said Dr. Peter Chin-Hong, professor of medicine and infectious disease specialist at UCSF. “It seems to be the exception rather than the rule and so far most people with Paxlovid are doing better and faster.”

Chin-Hong and others have described Paxlovid and another antiviral drug, Merck’s molnupiravir, approved around the same time, as leading the way in the fight against COVID-19, offering a safe, effective, and convenient way to reduce the risk of serious illness or Decrease disease of an infected person dying.

The antivirals are approved for people ages 12 and older who are considered to be at higher risk for COVID-19, either because of health conditions such as obesity or diabetes, or simply because of their age.

At a time when vaccine protection against new variants is fading and monoclonal antibodies, which require intravenous infusion, are becoming less effective, antivirals, prescribed when symptoms appear and taken at home, can help stave off infection. Pfizer’s drug blocks an enzyme the virus needs to reproduce and has been found to reduce the risk of hospitalization or death in high-risk adults by 89%. The effectiveness of the Merck drug is 30%.

Cases are resurfacing in the Bay Area and the rest of the country. Federal and state officials continue to urge Americans to get booster shots and wear face masks in crowded environments.

“There is nothing to worry about right now,” Gov. Gavin Newsom said of the rising case count as he received his second Moderna booster shot in Bakersfield on Wednesday.

“This waning immunity is a matter of — I don’t want to say it’s worrying — but something we need to monitor,” Newsom said. “The best protection against serious illness and hospitalization is vaccination and booster.”

Both Pfizer and the Food and Drug Administration have noted that during clinical trials, approximately 1-2% of patients who completed the five-day Paxlovid regimen tested positive again after initially testing negative, or had elevated levels of the virus . But they said the same thing happened at similar rates in those who received a placebo instead of the drug. And none of the reported rebounds resulted in a serious illness.

“It is therefore currently unclear whether this is related to the drug treatment,” said Dr. John Farley, director of the FDA’s Office of Infectious Diseases, in a guide for healthcare providers published online. “Most importantly, there was no increased incidence of hospitalization or death, or the development of drug resistance.”

Chin-Hong said the rebound phenomenon is not new and has been observed in other viral infections. But why it occurs in COVID-19 and Paxlovid is a mystery, he said.

“So many people have had such great experiences with it,” Chin-Hong said. “In my experience maybe one person had a rebound and they were fine and it was milder.”