For some people, including President Joe Biden and National Institute of Allergy and Infectious Diseases Director Anthony Fauci, relief from the disappearance of COVID-19 symptoms and a negative test is fleeting. Biden, Fauci and many others have seen their tests come back positive or return to unpleasant symptoms after taking a five-day course of the antiviral Paxlovid. Other people, including my husband, have had a rebound of infections even without taking the medication.
Multiple studies have described cases of “Paxlovid rebound” after treatment. In one, seven patients treated with Paxlovid had the rebound virus to high levels after treatment ended, with symptoms returning for six of them, virologist Jonathan Li and colleagues reported in June in Clinical Infectious Diseases. Samples from three patients even contained infectious virus, a hint that some recovering people could infect others. Another study that has not yet been peer-reviewed by other researchers found that fewer than 6 percent of people in the study who had been prescribed Paxlovid They had rebound infections in the month after finishing treatment.
It’s not clear why Paxlovid rebound occurs, says Li, of Brigham and Women’s Hospital and Harvard Medical School. Studies show that people receiving the drug still develop a strong immune response to the virus after five days of treatment. “I think what happens in that situation is that the replication of the virus has been inhibited. Suddenly the drug is gone and the virus has a momentary chance to replicate. And it replicates at high levels,” says Li. But by then, the immune system has learned to defend itself against the coronavirus. If newly trained immune cells encounter newly created viruses and set off alarms, symptoms may briefly reappear.
Some people may not want to take the drug because they’re worried about rebound, Li says. But Paxlovid itself is probably not the cause. The drug is not failing. It is still very effective in preventing serious diseases. “I wouldn’t hesitate to give my patients Paxlovid,” says Li. “I tell them to watch for rebound symptoms. But it doesn’t deter me from prescribing it.”
Fauci took another Paxlovid course in the wake of his rebound. The US Food and Drug Administration says there are there is no evidence that 10 days of treatment is more effective than five days, or that patients need a repeat. But the researchers are try whether to take the medicine for a longer period of time could prevent rebound.
COVID-19 rebound is not limited to patients taking Paxlovid. Li remembers that even in the early days of the pandemic, some patients would come to him in the hospital to tell him that they had started to feel better but then got worse again. It’s hard to know how to interpret such anecdotal reports, he says. Researchers are still learning what an untreated viral infection can look like in the body. While the brief invasion of the virus (hopefully) may seem straightforward on average, with virus levels in the body rising to a peak before slowly declining as a person recovers, not everyone follows that pattern.
My husband contracted COVID-19 two months ago. His symptoms lasted about a week, and he was delighted to see the line on his antigen test weaken. Still, despite feeling perfectly healthy, the line suddenly returned to full strength almost immediately after he added his sample to a new test days later. He was frustrated and, as a social person, he regretted having to remain isolated.
Studies show that you are not alone. When Li and her colleagues studied the course of disease in COVID-19 clinical trial participants who received placebo treatment, 1 in 8 people experienced a rebound, with recurrent symptoms in 1 in 4 people. However, that rebound typically lasted about a day, and few had high viral loads and recurring symptoms, the team reports in a preliminary study published Aug. 2 on medRxiv.org that has not yet been peer-reviewed.
In this case, there is no drug that disappears. Any recurring symptoms without a positive test could be due to something else, such as allergies or a different respiratory virus, Li says. It is also possible that the virus replicates in different parts of the body at different times. Some tests can come back negative when the body clears the virus from the throat, for example, but it still replicates at low levels in the nose.
That last scenario may have happened with my husband. In a confusing twist, she tested negative on two saliva PCR tests while continuing to test positive for nasal antigen tests. A PCR test is much more sensitive, so we expected the opposite to be the case. Since the experts say that consider a positive antigen test as a sign that you are still contagioushe remained in isolation until he finally tested negative for an antigen test two weeks after his first symptoms appeared.
Fortunately, he is now fully recovered and has no desire to repeat the experience. That means we both continue to wear masks in public spaces and take other precautions. We know we are not done with this pandemic.