People not taking Paxlovid experienced the viral rebound phenomenon only about two per cent of the time, the researchers at the Mass General Brigham hospital, Boston, US, found.
Paxlovid, which is a Nirmatrelvir-ritonavir therapy taken orally, has been previously studied to be effective in reducing hospitalisation and death in severe COVID-19 infections.
“We conducted this study to address lingering questions about Paxlovid and virologic rebound in COVID-19 treatment,” said corresponding author Mark Siedner, M.D., MPH, an infectious disease clinician and researcher in the Division of Infectious Diseases 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.”
This study, being an observational one and not a randomised clinical trial, could not ascertain if solely the use of Paxlovid caused the increased rebound rate in patients, the researchers said in their study published in the journal Annals of Internal Medicine.
However, they said that their findings should not discourage clinicians from prescribing the medication, but should prompt them to counsel patients about the risk for viral rebound and potential transmission while taking the medication and to advise them to re-test and isolate, should this happen. “Paxlovid remains a life-saving drug I prescribe to high-risk patients,” said co-senior author Jonathon Li, an infectious disease physician and researcher at the 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,” said Li.
For the study, the researchers at the hospital-based research institute selected 142 individuals between March, 2022 and May, 2023 based on positive COVID-19 tests, medication prescriptions or physician referrals.
The team classified the participants as those taking a five-day Paxlovid regimen versus those not and tracked their viral loads and symptoms, cultured viral samples and also performed whole genome sequencing.
The researchers then separated the patients testing positive for Covid after previously testing negative and those exhibiting two consecutive increases in viral loads following an initial reduction as the ones experiencing ‘viral rebound’.
The ‘viral rebound’ group also experienced prolonged viral shedding – for an average of 14 days compared to less than 5 days in those not experiencing rebound – indicating potential contagion for much longer, the researchers said.
They now plan to investigate the possible biological mechanisms triggering or causing the rebound phenomenon associated with Paxlovid and determine if changing the regimen length could help combat this rebound effect, they said in their study.
The World Health Organization, in its recent update on treatment guidance for Covid patients, has recommended the use of nirmatrelvir-ritonavir in patients with “non-severe COVID-19 at high and moderate risk of hospital admission”.