Covid-19 cases returning after Paxlovid antiviral treatment confuse doctors

Blakeney, a 43-year-old researcher at the University of Washington School of Nursing, has survived breast cancer. The Seattle resident says she doesn’t meet a strict definition of immunodeficiency, which can increase a person’s risk of Covid-19. Both Blakeney and her husband are fully vaccinated and boosted. But she didn’t want to take any chances because she takes medication to prevent cancer from coming back and lost a family member to Covid-19 in November 2020.

Testing positive on April 3, she contacted a doctor via a telemedicine visit and received a prescription for a Covid-19 antiviral drug, Paxlovid.

Blakeney knew that to be effective, Paxlovid had to be taken early, within a few days of symptoms appearing. She and her husband did that. They didn’t get very sick and continued to improve until their five-day treatment was over.

She finished treatment on a Thursday and tested negative the next day. She thought she was done with Covid-19, at least for a few months.

But on Monday she started getting constipated again. When she woke up on Tuesday April 12th, she found that she was really sick. So was her husband.

“We both did rapid tests, and we both came back very positive, and we were like, ‘Oh my God, what just happened? We’ve never heard of that,'” Blakeney says.

“It’s just a little bit mysterious”

dr Michael Charness, a neurologist who practices at Boston’s Brigham and Women’s Hospital and VA Boston Healthcare System, also hadn’t heard of it until he saw it with his own eyes.

His patient was a 71-year-old man with asthma who started taking Paxlovid on day one because of his age and underlying condition.

The drug worked quickly. By the second day, his patient’s symptoms had almost completely disappeared. His patient stopped taking the pills after five days and tested negative on home tests on the seventh day. On the ninth day after his first positive test, the man’s symptoms – including a runny nose, sore throat and wheezing – returned. He tested positive again.

“Right now, I’d say it’s just a little bit mysterious,” Charness said. “There are many possible explanations for what is going on. They are all speculation and need much more investigation.”

Paxlovid, manufactured by Pfizer, is a combination of two antiviral drugs. The US Food and Drug Administration approved it for emergency use in December after a clinical study found that a five-day course reduced the risk of hospitalization or death in unvaccinated people at high risk of serious complications from Covid -19 reduced infection by 88%.

Many in the healthcare community hailed Paxlovid as a game changer because it was so effective, convenient, and had the potential to keep people out of the hospital.

Last week, in his very first tweet, Charness described his patient’s recurrence of Covid-19 infection after Paxlovid. His colleagues urged him to join social media after seeing other reports of Covid relapses in patients taking the drug.

His patient, who was fully vaccinated and refreshed and in good general health, was tested for Covid-19 several times during his treatment and shortly after his symptoms returned.

Charness and his colleagues sequenced the man’s coronavirus genome. It was the same throughout the course of the infection, so it wasn’t reinfection. And they couldn’t find any mutations that had suddenly evolved, so the virus hadn’t suddenly changed to develop resistance to the drug. They also looked for 21 other respiratory pathogens that could make the man sick and found nothing.

Charness says he doesn’t want his case to deter anyone from taking Paxlovid, which has proven extremely effective in preventing mild cases of Covid from becoming more severe or even fatal.

Covid-19 test-to-treat program hampered by lack of services and technical issues
The FDA noted these rebound cases in his own analysis the data from the clinical studies. The phenomenon was noticed in a small percentage of cases around 10 to 14 days after starting treatment with Paxlovid. It is not clear how common these can be. A clinical trial of the drug is ongoing.

In a statement to CNN about the potential for a rebound after taking the drug, Pfizer said that in the clinical trial, a small number of patients in both the group taking placebo pills and the group taking Paxlovid had a higher viral load 10 to 14 days after starting treatment compared to their viral load on day 5. Because the researchers noticed this phenomenon in both groups, the company doesn’t think it’s related to the drug. They also saw no connection between the viral load of the patients and the subsequent serious illness.

“We remain confident in its clinical efficacy in preventing severe outcomes from Covid-19 in high-risk patients,” the company said in a statement.

Charness said the possibility that patients could recover regardless of treatment is interesting, and he hoped Pfizer would release the data from its clinical trial so doctors could better understand what’s happening in these cases.

Unanswered questions

Charness and his colleague Dr. Paul Sax, an infectious disease physician at Brigham and Women’s Hospital, says it’s important to understand why and how often the infection returns.

“Now that we know what’s happening, we need to include in our messages to people that it could happen, and my own opinion is that people should stay away from others while they test positive,” Sax said.

The White House is working to make Pfizer's Covid-19 antiviral pill
That US Centers for Disease Control and Prevention says People who have had Covid-19 can return to their normal activities after five days, provided they have been fever-free for 24 hours and their symptoms improve. The agency does not recommend that a person wait until they are negative on a rapid test to return to activity, although some experts say rapid home tests are helpful for knowing when you can still pass the virus on to others.

Sax says if people test positive after Paxlovid, doctors and patients need to know if they’re actually contagious, and that’s not clear at this time.

He thinks it would also be helpful to know if people who recover can get a second treatment since they are outside the original window of symptoms.

Researchers and doctors are still learning how Paxlovid works. For months, most people’s main concern has been finding some. Patients and doctors scoured the internet for pharmacies that stocked the pills.

These issues prompted the US government to launch a test-to-treat program and set up one-stop shops such as pharmacies where people could be tested for Covid-19, get an antiviral prescription at an in-store emergency clinic, and have that prescription to be filled out in the same store, which makes the process much more convenient.

This week, the Biden administration announced that supplies are no longer restricted and is taking new steps to increase use of the drug.

A new perspective on the pandemic

Many people who have a rebound infection say their symptoms tend to be mild the second time around.

FDA approves remdesivir to treat young children with Covid-19

But Blakeney was much sicker when her symptoms returned. She had a high fever, a fast heartbeat and a “really terrible” cough. She says her breathing was very wheezy.

“I ended up going to the ER,” she said. Her case baffled ER doctors, who wondered how this could have happened after Paxlovid.

“They said, ‘We’ve never heard of that,'” Blakeney said.

After she ran tests to make sure she didn’t have a blood clot or pneumonia, they prescribed her an inhaled medication called albuterol to help her lungs and an antibiotic to treat what they thought was a secondary bacterial infection.

Blakeney got better after taking these drugs. She has mostly recovered now, although her cough has persisted.

She says the experience got her thinking about how we are dealing with the pandemic.

“If we live in a world where we don’t have a mask requirement, should we have people tested to come out of isolation? I would think so,” she said. “Or should we do something like the food safety guides they have in restaurants that say, ‘This place has good air circulation and follows best practices to create as safe an environment as possible’? So I think it raises a lot of questions.

“It was a surprising experience. It wasn’t what we expected.”

Comments are closed.