President Joe Biden came down with COVID-19 this past summer, then felt better and tested negative a week later — only to rebound within a few days with renewed symptoms and another positive test.

I understood exactly what he was going through. Just a week prior to Biden’s COVID rebound, I had experienced one myself.

He and I are hardly alone: Although the exact numbers are impossible to come by, doctors and patients say COVID rebound is increasingly common.

What Is COVID Rebound?

COVID rebound occurs when a person who has COVID-19 tests negative, then within two to eight days has a recurrence of symptoms or a new positive test. This definition comes from the Centers for Disease Control and Prevention (CDC), which issued an advisory on the phenomenon in spring of 2022.

Many people put the blame on Paxlovid, the antiviral drug regimen both Biden and I took early in the course of our disease.

But in its advisory, the CDC stated: “A brief return of symptoms may be part of the natural history of SARS-CoV-2 (the virus that causes COVID-19) infection in some persons, independent of treatment with Paxlovid and regardless of vaccination status.”

A recent study bears this out. The research, published in October 2022 in JAMA Network Open, concluded that COVID-19 recovery is “variable and undulating” and that symptoms often return even after a person appears to have beaten the virus.

The investigators followed 158 people diagnosed with COVID-19, none of whom were treated with Paxlovid. Over the course of the 29-day study, the researchers found that around one-third of those who seemed to have completely recovered (meaning they were symptom-free for two consecutive days) reported the return of one or more COVID-19 issues — most commonly cough, fatigue, or headache.

Even from the earliest days of the pandemic, long before the advent of Paxlovid, patients were experiencing COVID rebound, says Jill Weatherhead, MD, PhD, assistant professor of infectious diseases at Baylor College of Medicine in Houston. “However, this pattern has become more apparent with the use of Paxlovid treatment for the current circulating omicron variants,” she says.

My COVID-19 Luck Finally Ran Out

Thanks to measures like wearing a mask in crowded indoor locations and working from home — plus a lot of good fortune — I managed to avoid getting COVID-19 for more than two years. But my status as a COVID virgin ended when I traveled to my cousin’s wedding in another state.

The wedding ceremony was held outdoors, but the reception occurred inside a small, intimate venue. No one, including me, was wearing a mask.

I tried to keep some distance from others by staying off the very crowded dance floor, but I knew that if even one of the more than 150 guests plus staff members was harboring the virus, by the end of the evening we would likely all be sharing their germs.

As it turned out, somebody (or multiple somebodies) was indeed infected.

Testing Confirmed I Had COVID-19

I flew home on a Sunday night and woke up Monday morning with one of omicron’s telltale symptoms, a sore throat. (The incubation period for COVID-19 — the time it takes between becoming infected and having symptoms — can range from 2 to 14 days after coronavirus exposure. The CDC says that the median incubation time for omicron is three to four days.)

Before I could even perform a home test, one of my cousins who also attended the wedding texted that she and her husband now had COVID-19. In the end, more than 40 guests at the wedding got sick.

I dug out one of the home antigen tests in my stockpile, which included the government’s free tests and those paid for by my insurance. I opted for one of the generic government tests distributed by Roche, even though my husband jokingly suggested I tip the scales by choosing one of our Abbott’s BinaxNow kits, which we’d been using throughout the pandemic. (“It was always negative,” he said.)

Not five minutes into the 15-minute test, my sample line turned bright red. I had COVID.

By the end of that first day, I was feeling awful. I had a cough, a runny nose, and a worsening sore throat. The most debilitating symptom was fatigue. I got into bed on Monday afternoon and barely got out for the entire week.

I was surprised to be hit so hard, because I was vaccinated and double boosted. And because, starting on the second day, I’d begun a five-day course of Paxlovid.

What Is Paxlovid?

Paxlovid is an oral treatment from Pfizer that is recommended for people who are older, immunocompromised, unvaccinated, or have an underlying medical condition like diabetes or heart disease that puts them at risk of hospitalization or death from COVID-19. Paxlovid is exceptionally effective at preventing these individuals from developing severe COVID-19.

Paxlovid is composed of two separate medications. One is nirmatrelvir, a type of drug called a protease inhibitor that blocks the coronavirus from replicating in the body. The second component of Paxlovid, ritonavir, gives nirmatrelvir a boost by slowing the rate at which it is metabolized by the liver.

A typical treatment regimen is to take two nirmatrelvir pills and one ritonavir pill together in the morning and then again in the evening, starting within a few days of developing COVID-19 symptoms or testing positive. The full course of treatment is five days.

It’s important to note that ritonavir can also slow the rate at which the body metabolizes a variety of other medications a person may be taking, which could increase the concentration of those drugs in the blood. Those drugs include statins, oral contraceptives, and HIV medications, according to the U.S. Food and Drug Administration.

A physician can help you manage those interactions, which is why it’s crucial to tell your doctor about all the medicines you take when considering whether you are a candidate for Paxlovid.

Studies Suggest Paxlovid Might Help Prevent Long COVID

Some scientists also suspect that antiviral medications like Paxlovid might reduce a person’s odds of developing long COVID, the constellation of often debilitating symptoms that can linger for months or even years after an acute bout of the disease.

Recent research supports this view: A new study by researchers at the U.S. Department of Veterans Affairs found that subjects who took Paxlovid had a 26 percent reduced risk of developing a number of long COVID conditions, including heart disease, blood-clotting issues, fatigue, muscle pain, brain fog, and shortness of breath. (The study was published online as a preprint, meaning it has not yet been reviewed by other scientists.)

Nine Days After Testing Positive for COVID, I Felt Better — Until I Didn’t

I took Paxlovid for five days. While the treatment did not seem to make my bout with COVID-19 any easier, it did give me the opportunity to experience “Paxlovid mouth” — a common and annoying side effect that involves a periodic weird taste that is part metallic, part morning breath.

Finally, nine days after testing positive (which in COVID-19 lingo is defined as the eighth day, because test day is day zero), I finally started feeling better. The next morning, I decided to take a rapid test: no line.

I was COVID-free, or so I thought. That glorious state would not last long.

COVID Rebound Strikes

Later the following day, I was sitting in my home office working when I started to feel tired again. Knowing it can take weeks or longer to fully recover from any virus, I thought I would lie down for a short nap.

I woke up four hours later. Worse, the sore throat and stuffy nose had returned.

Knowing that a rebound was possible, I took another rapid COVID test — a BinaxNow one — and the line appeared as quickly and as clearly as it had when I’d first gotten the virus. (So much for my husband’s theory about a guaranteed BinaxNow negative test!)

What to Do When You Rebound from COVID-19

In a health advisory issued in May, the CDC recommended that people with rebound COVID isolate again for at least five days: “Per CDC guidance, they can end their re-isolation period after 5 full days if fever has resolved for 24 hours (without the use of fever-reducing medication) and symptoms are improving. The patient should wear a mask for a total of 10 days after rebound symptoms started,” the advisory stated.

Staying home for five more days was easy for me, because for the first four I was exhausted and spent a lot of time in bed.

5 Days of Paxlovid May Not Be Enough

Scientists aren’t yet sure why people who take Paxlovid are vulnerable to COVID rebound. “The cause is currently under investigation,” Dr. Weatherhead notes.

One possibility might be that five days of Paxlovid is not enough. “It is possible that five days of treatment, particularly in patients with high viral loads, leads to insufficient drug exposure,” Weatherhead says. The virus may be beaten down by the Paxlovid in your system, but it’s not completely defeated, so it comes back when the medication is gone.

Rebound didn’t occur in significant numbers during Pfizer’s clinical trial for Paxlovid. But that trial happened when delta was the predominant coronavirus variant. Back then, fewer than 2 percent of people taking Paxlovid rebounded.

But omicron typically leads to higher viral loads than delta did, Weatherhead points out.

Scientists Continue to Speculate About Why COVID Rebound Occurs After Treatment

A preprint study posted online in June tracked rebound cases following courses of both Paxlovid and another oral COVID-19 treatment, Lagevrio (molnupiravir).

The people in the study who rebounded “were significantly more likely to have risk factors for COVID infection such as heart diseases, immunologic disorders, or cancer,” says Pamela Davis, MD, PhD, dean emerita of the school of medicine at Case Western Reserve University in Cleveland and a study coauthor. These people might have weaker immune systems or possible organ damage that may make them more susceptible, Davis says, “but that is pure speculation.”

Fortunately, most rebound cases are more annoying than they are dangerous. In the Case Western research, hospitalization rates after rebound were very low — less than 0.8 percent.

Do I Regret Taking Paxlovid?

I finally tested negative for the second time four days after the rebound and two full weeks after I had first gotten sick. My symptoms disappeared for good a day later.

Am I sorry I took Paxlovid? No.

Even with the potential link to rebound, the CDC and other infectious disease experts continue to recommend Paxlovid for high-risk individuals, noting that the treatment “helps prevent hospitalization and death due to COVID-19.”

“There is still a lot to learn about rebound cases, particularly as new variants arise. However, at this time, the positive benefits of Paxlovid in people in the early course of disease with a high risk of progression to severe disease outweigh the risk of rebound illness,” Weatherhead says.