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Harvard Medical School-affiliated researchers published research on Nov. 14 showing that one in five patients who used the antiviral drug Paxlovid experienced a rebound case of Covid-19, compared to 2 percent of patients who did not use the drug.

Paxlovid is a drug used to treat high-risk Covid-19 patients. Previous studies on the efficacy of Paxlovid demonstrate that the drug is effective in reducing hospitalization and death rates in high-risk patients by 80 percent, according to Mark J. Siedner, an associate professor of medicine at HMS and a senior author on the paper.

High-risk patients are typically immunocompromised or have other chronic conditions, including lung disease, high blood pressure, and cardiovascular disease, according to Siedner.

Siedner said the researchers were interested in understanding the prevalence of Covid-19 rebound cases among patients using Paxlovid.

“I think our study was really designed to say, ‘Is this anecdotal or is this rebound phenomenon truly happening? Is it common or is it rare?’” Siedner said. “We tried to help answer that question by doing a study that the clinical trial actually just wasn’t designed to do.”

Though Pfizer — which developed Paxlovid — mentioned Covid-19 rebound rates as a potential effect in original clinical trials, researchers chose to focus on viral decay, or the rate at which the viral load decreases.

In contrast to the clinical trials, Siedner and the other researchers aimed specifically to measure rebound rates through more frequent data collection.

“I think the real difference in our study and their study is that because we sampled people multiple times a week, for the first two weeks of infection, we were able to see changes in the virus — including return of the virus after initial suppression — in ways that they just weren’t able to do in their initial study,” Siedner said.

Though Paxlovid was correlated with rebounds, Siedner said the drug should not be explicitly encouraged or discouraged. Instead, the researchers concluded that health care professionals should advise patients with acute Covid-19 about the potential risk of transmission during the rebound period.

“I think it’s really important to make sure that message is highlighted and that our study isn’t used to say, ‘Well, maybe people shouldn’t be taking this potentially life saving therapy,’” Siedner said.

Further research directions could expand the number of study participants or look at whether those who experienced rebound cases saw more severe health outcomes, according to Siedner.

“I do think it’s important for us, if possible, to continue to study this phenomenon and understand whether or not rebound itself is associated with changes in clinical outcomes," Siedner said.

Siedner said drug development processes demonstrate the ways that “science is humbling.”

“We’re constantly wrong, in fact, we’re wrong most of the time,” he said. “We need to continue, always, whenever we develop a new drug, or test a new hypothesis, to keep in mind that we can be wrong and that we may discover things we didn’t expect to initially.”