Antibodies responding to covid-19 coronavirus, illustration

Data from a new study by researchers at Mass General Brigham found that 20% of patients who were treated for severe symptoms had COVID-19 return after being treated with Paxlovid after an initial recovery and negative test result. Only 2% of patients who recovered from COVID-19 and didn’t take Paxlovid experienced this virologic rebound.

Reporting their findings in the Annals of Internal Medicine, the team also found that patients experiencing virologic rebound of the disease may remain contagious.

“We conducted this study to address lingering questions about Paxlovid and virologic rebound in COVID-19 treatment,” said corresponding author Mark Siedner, MD, an infectious disease clinician and researcher at Massachusetts General Hospital. “We found that the virologic rebound phenomenon was much more common than expected—in over 20% of people taking Paxlovid—and that individuals shed live virus when experiencing a rebound, implying the potential for transmission after initially recovering from the virus.”

Paxlovid, which is a nimratrelvit-ritonavir combination, has shown it is effective at reducing hospitalizations and death among patients with severe symptoms of COVID-19, but as more people have been prescribed the drug, a significant number of patients have reported COVID-19 returns. While the earlier EPIC-HR Phase III clinical trial suggested that only up to 2% of all patients taking Paxlovid experienced a return of the virus, this new study suggests it occurs at a much higher rate.

“Paxlovid remains a life-saving drug I prescribe to high-risk patients,” said co-senior author Jonathon Li, MD, an infectious disease physician and researcher at Brigham and Women’s Hospital. “This study, while informative, does not change the fact that this drug is very effective at preventing hospitalizations and death. Instead, it offers valuable insights to Paxlovid patients, helping them understand what to expect and how long they might be contagious.”

Siedner, Li, and team used data from the ongoing Post-vaccination Viral Characteristics Study (POSITIVES), that is following people diagnosed with acute COVID-19 infections. The investigators selected 142 people from the period March 2022 to May 2023 based on positive COVID-19 tests, medications, or physician referrals. They then identified those who had taken Paxlovid and those who did not and tracked their viral loads and symptoms. The investigators defined virologic rebound as two consecutive increases in viral load after experience an initial reduction.

Using this definition, the researchers found 20.8% of patients who were prescribed Paxlovid saw COVID-19 return versus only 1.8% of patients who had not received the treatment. Viral shedding also persisted longer in the that patients that rebounded compared with those who hadn’t been treated, an average of 14 days compared with less than five days. Siedner noted that an important finding was that patients did not exhibit any signs of drug resistance.

The authors noted that their study is not intended to dissuade clinicians from using what can be a life-saving medication, rather to use this information to be able to openly share the risks of viral rebound and that if they do experience a rebound being able to take measures to prevent the spread of the virus to others.

While the earlier EPIC-HR study showed virologic rebound at a significantly lower rate, that study only assessed patient outcomes at two time points. The investigators of the new study aligned the data they had collected with the EPIC-HR timeline and found virologic rebound in only 2.4% of participants, suggesting the prior study did not capture the full extent of recurrence.

“In our study, we were able to closely monitor patients from the onset of COVID-19 infection through treatment and rebound,” explained Li. “Unlike in the EPIC-HR study, which only assessed outcomes at two time points, we followed up with patients three times a week, sometimes for months, and performed in-home sample collection. Having both viral RNA levels and viral culture data also allowed us to paint a more comprehensive and nuanced picture of a patient’s experience with Paxlovid.”

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