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Can you take Paxlovid twice if COVID rebounds?

Medically reviewed by Leigh Ann Anderson, PharmD. Last updated on Nov 6, 2023.

Official answer


No, a second round of Paxlovid treatment is not needed after the initial 5-day treatment if COVID rebound occurs. Case reports suggest that most people who develop COVID rebound after completing 5 days of treatment have either no symptoms or mild illness. To date, there is no association between Paxlovid treatment and COVID rebound.

An FDA analysis has stated that COVID rebound associated with symptoms and / or a positive viral test may occur as part of the natural course of the disease, whether or not you take Paxlovid.

COVID rebound has also been reported to occur with Lagevrio (molnupiravir), another COVID antiviral medicine, in people who have not taken any treatment, and those who are vaccinated or not vaccinated.

At this time, the original 5-day treatment period for Paxlovid is recommended in the product labeling and by the Centers for Disease Control and Prevention (CDC). In studies, Paxlovid has been shown to reduced hospitalizations and deaths due to COVID-19 by about 89%.

Most clinicians agree that the use of Paxlovid in patients at high risk for severe disease far outweighs the potential risk of minor rebound symptoms. Severe complications due to rebound have been rarely reported.

Data from studies (EPIC-HR, EPIC-SR; both randomized placebo-controlled trials) showed that rebound in SARS-CoV-2 (RNA or virus) shedding or self-reported COVID-19 symptoms occurred in a subset of patients but happened at similar rates in patients receiving either Paxlovid or placebo. According to the FDA, no association between Paxlovid treatment and COVID-19 rebound has been proven.

What symptoms occur with COVID rebound?

Case reports suggest that people who develop COVID rebound after completing 5 days of treatment show either no symptoms or mild illness. Symptoms can vary but the most commonly include cough (44%), fatigue or tiredness (35%) and headache (35%).

Symptoms typically return 2 to 8 days after finishing treatment but are transient and usually clear up in 1 to 3 days. There have been no reports of deaths related to COVID rebound.

What does Paxlovid treat?

  • Paxlovid (nirmatrelvir and ritonavir) is an oral antiviral treatment and is approved by the FDA to be used for early-stage treatment (within 5 days of symptoms onset) of mild to moderate COVID-19 in adults at high risk for progression to severe disease, hospitalization or death.
  • Paxlovid treatment should begin as soon as possible and within 5 days of COVID symptom onset among persons eligible to receive the treatment.

Paxlovid is also available under an Emergency Use Authorization (EUA) to treat patients 12 to 18 years old (weighing at least 40 kg) for mild-to-moderate COVID-19 who are at high risk for progression to severe COVID-19, including hospitalization or death.

Some medicines may interact with Paxlovid and can cause serious side effects. There are certain medicines you cannot take with this medicine.

  • Tell your healthcare provider about all the medicines you take, including over-the-counter medicines, vitamins and herbal products.
  • Have your healthcare provider complete a drug interaction review prior to starting treatment with Paxlovid.

Related Questions

Do I have to isolate if I have Paxlovid rebound?

  • If you test positive again after finishing Paxlovid you should restart isolation for at least 5 full days and contact your healthcare provider for further instructions. You may still be shedding virus and be contagious.
  • You can end your rebound isolation period after 5 days if your fever is gone for 24 hours (without the use of fever-reducing medication) and your symptoms (such as cough, body aches, shortness of breath) are improving.
  • Wear a mask for 10 days after your rebound symptoms start, even if you've ended the 5 day isolation period.
  • Some people continue to test positive 10 days after COVID-19 rebound begins, but are much less likely to be contagious by this time.

How quickly does Paxlovid (COVID-19) rebound start?

COVID-19 rebound has been reported to begin between 2 and 8 days after initial recovery. You may develop a recurrence of COVID-19 symptoms and / or a new positive viral test 2 to 8 days after having tested negative.

Case reports suggest that symptoms and positive test results improve or resolve most commonly within a 3 day period, but can be shorter or longer.

This rebound effect is not a new COVID infection or due to Paxlovid resistance. The CDC reported no other respiratory pathogens were identified among known cases.

How often does rebound occur with Paxlovid?

The exact incidence is not known. Rebound has been reported to occur in about 8% of people, but numbers could be greater because some people may never retest if they remain asymptomatic (without symptoms). In the EPIC-HR study, rebound was observed in 8.3% of people who took Paxlovid compared to 5.7% of people who took a placebo (inactive) treatment (p=0.04%)

COVID rebound was also reported in a retrospective study that looked back at the history of patients who took no COVID treatment.

  • Rebound associated with symptoms was reported in 26% of people in this study, most commonly 11 days after initial symptom onset.
  • However, both symptoms rebound and high-level viral testing rebound was observed in only 3% of participants.

This is not all the information you need to know about Paxlovid (nirmatrelvir and ritonavir) for safe and effective use and does not take the place of your doctor’s directions. Review the full Paxlovid product information and discuss this information and any questions you have with your doctor or other health care provider.


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