Paxlovid – CDC issues advisory on possible rebound of COVID-19

The U.S. Centers for Disease Control and Prevention (CDC) has issued an advisory about Paxlovid to healthcare providers in that country. The CDC notes that since the treatment was approved there have been reports of a rebound of COVID-19 in some Paxlovid users.

In its advisory, the CDC first provided the following reassurance:

“Paxlovid continues to be recommended for early-stage treatment of mild-to-moderate COVID-19 among persons at high risk for progression to severe disease. Paxlovid treatment helps prevent hospitalization and death due to COVID-19.”

Second, the CDC made the following statement about possible rebound in some uses of Paxlovid:

“COVID-19 rebound has been reported to occur between 2 and 8 days after initial recovery and is characterized by a recurrence of COVID-19 symptoms or a new positive viral test after having tested negative. A brief return of symptoms may be part of the natural history of SARS-CoV-2 (the virus that causes COVID-19) infection in some persons, independent of treatment with Paxlovid and regardless of vaccination status. Limited information currently available from case reports suggests that persons treated with Paxlovid who experience COVID-19 rebound have had mild illness; there are no reports of severe disease. There is currently no evidence that additional treatment is needed with Paxlovid or other anti-SARS-CoV-2 therapies in cases where COVID-19 rebound is suspected.”

The CDC provides the following advice for healthcare providers whose patients experience COVID-19 rebound after completion of Paxlovid treatment:

  • There is currently no evidence that additional treatment for COVID-19 is needed for COVID-19 rebound. Based on data available at this time, patient monitoring continues to be the most appropriate management for patients with recurrence of symptoms after completion of a treatment course of Paxlovid.
  • Advise people with COVID-19 rebound to follow the CDC’s guidance on isolation and take precautions to prevent further transmission. Patients should re-isolate for at least five days. Per CDC guidance, they can end their re-isolation period after five full days if fever has resolved for 24 hours (without the use of fever-reducing medication) and symptoms are improving. The patient should wear a mask for a total of 10 days after rebound symptoms started.
  • Consider clinical evaluation of patients who have COVID-19 rebound and symptoms that persist or worsen.

—Sean R. Hosein


  1. CDC. COVID-19 Rebound after Paxlovid Treatment. CDC Health Advisory. 24 May 2022. Available at:
  2. Rubin R. From positive to negative to positive again – The mystery of why COVID-19 rebounds in some patients who take Paxlovid. JAMA. 2022; in press.