"COVID rebound," in which evidence of the illness disappears and then returns days or weeks later, is surprisingly common, even among patients who did not take the antiviral Paxlovid, finds a study.

Pfizer's antiviral drug Paxlovid consists of nirmatrelvir and ritonavir tablets, co-packaged for oral use.

In clinical trials, Paxlovid has been shown to reduce the odds that a person at risk of severe COVID-19 would need to be hospitalised by almost 90 per cent compared with a placebo. It received emergency use approval in late 2021 from the US Food and Drug Administration (FDA). But reports of COVID-19 rebound started appearing in the medical literature in 2022.

According to a new study led by researchers at the Scripps Research Translational Institute in the US, "rebound after clearance of SARS-CoV-2 test positivity or COVID-19 symptom resolution is more common than previously reported in both treated and untreated patients."

To understand, the team offered a COVID test kit for the study participants to check if they had a verified positive test. Each participant was asked to take a test and fill out a symptom questionnaire every other day for 16 days.

The team then compared the rates of rebound for those who did and didn't opt to take Paxlovid. Rebound was measured in two ways: a positive test result after a negative test, or a reported recurrence of symptoms after symptom resolution.

For this preliminary analysis, there were 127 people in the Paxlovid-treated group, and 43 in the non-Paxlovid group.

Either way, rebounds were measured, and the Paxlovid group experienced them at a higher rate: 14.2 per cent vs. 9.3 per cent for antigen test rebounds and 18.9 per cent vs. 7.0 per cent for symptom rebounds.

While the findings must be validated with a larger number of participants, the preliminary results, published in the journal Clinical Infectious Diseases, already make clear that the rebound rates for both treated and untreated groups are higher than the rates reported in prior studies.

For example, an analysis of their clinical trial results by Pfizer found rebound rates of only about 2 per cent in both Paxlovid and placebo groups over a two-week period.

"We're hoping to answer key questions about the rebound phenomenon, such as whether it's enhanced by Paxlovid, how much it depends on the viral variant and what is the role of the patient's immune system," said lead author Jay Pandit, Assistant Professor at the Scripps.

"We're going to need a larger set of participants and more extended follow-up to better understand this rebound phenomenon," he added.