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COVID-19 Treatment – Paxlovid FAQ

Published May 26th, 2022

At PHM, our team of PhD-led research experts continuously monitors the latest news, research, and developments for new insights on the COVID-19 pandemic to improve the health and safety of our clients. Here’s the latest:

1. What is Paxlovid and how does it work?

Paxlovid is an oral antiviral drug approved for the treatment of mild-to-moderate COVID-19 in individuals at high risk of severe disease. It was developed by Pfizer and received emergency use authorization by the FDA on December 22, 2021.

According to the Centers for Disease Control and Prevention’s May 24th health alert, 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. The standard treatment using Paxlovid is three pills twice daily for five days. Paxlovid inhibits the replication of the virus and while it doesn’t prevent COVID-19 infection, it has been found to reduce the risk of hospitalization or death by 89% in unvaccinated, high-risk adults with symptomatic COVID-19.1

2. What is rebounding in the context of Paxlovid treatment?

Some patients have experienced “rebounding” after being treated with Paxlovid. After taking the medication, they start to feel better and may even test negative for COVID-19 during or shortly after treatment. However, they then experience a relapse of symptoms and/or a positive COVID-19 test approximately 2 to 8 days after initial recovery.2 The recurrent symptoms appear to be mild during the rebound phase of the infection.

3. Does Paxlovid cause rebound of symptoms? How frequently does this occur?

In Pfizer’s clinical trial, rebound occurred in 1-2% of patients, but at almost the same rate in the treatment and placebo groups. In fact, rebound of symptoms in COVID-19 patients has been observed throughout the pandemic, but this data is not being tracked in the real world. Thus at this time, we don’t have enough information to determine whether treatment with Paxlovid can lead to a rebound of symptoms.

4. Should I still be treated with Paxlovid despite the potential risk of rebounding?

Yes. You should still seek Paxlovid treatment if you are at high risk for severe illness due to COVID-19. Paxlovid is very effective at preventing severe COVID-19 outcomes (hospitalization and death), including from Omicron.  Moreover, rebounding doesn’t mean Paxlovid isn’t working. People who rebound have relatively mild symptoms and typically recover quickly.

5. What should I do if I experience rebound after I receive a Paxlovid treatment?

If you experience a recurrence of COVID-19 symptoms and/or test positivity, assume you are contagious and re-start your isolation period, isolating for a minimum of 5 more days. You can end your isolation on day 6 if your symptoms are resolving. We also strongly recommend taking 1-2 antigen tests, taken at least 24 hours apart, at the end of your isolation, to ensure you are COVID-19 negative. You should also wear a mask for 10 days after rebound. Contact your doctor if you experience difficulties and/or severe symptoms. Additional information can be found on the CDC website.

6. Can I do anything to prevent rebound after taking Paxlovid? 

At this time, there are no known preventative measures that can be taken to reduce the risk of rebounding.  Over time, we hope to have more information on possible preventative measures, such as extending the treatment course or re-treating.

7. Should I be treated with Paxlovid again if I rebound?

According to the FDA, there is no current evidence of benefit for a repeat Paxlovid course when experiencing a rebound infection. Further research is needed to determine the potential benefit of Paxlovid re-treatment or prolonged treatment. PHM recommends speaking with your healthcare provider to determine the best course of action for you.

8. If Paxlovid is causing rebounding, why might this be happening?

The CDC has been consulting with the National Institutes of Health to discuss methods for investigating the rebounding phenomenon in relation to Paxlovid. While waiting for the data, some explanations for why Paxlovid may lead to rebound include the following:

  • A brief return of symptoms may be part of the natural course of COVID-19, independent of treatment with Paxlovid or vaccination status.
  • Paxlovid was initially evaluated during the Delta wave, and Omicron changed the game. Omicron replicates faster than Delta, and once the five-day Paxlovid course is completed, it only takes a small amount of residual Omicron virus in the body to cause  a rebound.
  • Some people have a longer disease course than others, so a longer course of Paxlovid could be helpful for these individuals. Unfortunately, there is no way to know in advance who they are.
  • Vaccinated individuals show symptoms earlier compared to unvaccinated individuals, so it’s possible that they are starting Paxlovid treatment earlier in their disease course. This earlier treatment may be occasionally leading to a rebound since the immune system needs time to ramp up to fight the remaining virus once the Paxlovid course is completed.


  1. Hammond, J., Leister-Tebbe, H., Gardner, A., Abreu, P., Bao, W., Wisemandle, W., Baniecki, M., Hendrick, V. M., Damle, B., Simón-Campos, A., Pypstra, R., & Rusnak, J. M.. (2022). Oral Nirmatrelvir for High-Risk, Nonhospitalized Adults with Covid-19. New England Journal of Medicine386(15), 1397–1408.
  2. Gupta, K., Strymish, J., Stack, G., & Charness, M.. (2022). Rapid Relapse of Symptomatic SARS-CoV-2 Infection Following Early Suppression with Nirmatrelvir/Ritonavir.