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What is Paxlovid Rebound?

According to the Centers for Disease Control and Prevention, Paxlovid is recommended to treat mild-to-moderate COVID-19 in its initial stages of the disease when people are at elevated risk that their disease may progress in severity. Paxlovid treatment helps reduce the risk of disease progression, hospitalization, and death.

Whether or not you have been vaccinated, for some people who take Paxlovid, COVID-19 symptoms seem to diminish and then return. Symptom rebound typically occurs between 2 and 8 days after symptoms appear to improve. Sometimes, people do not report a return of symptoms but test positive for COVID-19. This rebound in symptoms also occurs in people who do not take Paxlovid, and it is not considered to be a side effect linked to Paxlovid.

If you have a recurrence of your symptoms and test positive again, whether or not you took Paxlovid, follow the CDC guidelines for isolation. You should restart isolation for a full five days after the positive test result (the next day). End isolation after five days if you are fever-free (without taking fever-reducing medications) and your symptoms are improving. Following this, you should wear a mask for a total of 10 days, starting from the time your symptoms started.

What Is Paxlovid?

Paxlovid (nirmatrelvir tablets; ritonavir tablets) is a prescription oral antiviral drug used to treat mild-to-moderate COVID-19 infections in people at increased risk for more severe disease. The U.S. Food and Drug Administration issued an Emergency Use Authorization (EUA) to Pfizer to manufacture Paxlovid to treat adults and children over the age of 12 who meet the prescribing guidelines.

Paxlovid is not authorized to be used:

  • To treat patients requiring hospitalization for severe or critical cases of COVID-19
  • For pre- or post-exposure prophylaxis to prevent a COVID-19 infection
  • To be used for longer than five days

Paxlovid clinical trials were conducted, and 2,113 participants were randomized to receive either Paxlovid or placebo, one dose (300 mg nirmatrelvir and 100 mg of ritonavir) by mouth every 12 hours for five days. Anyone with a history of COVID-19 infections or who was vaccinated against COVID-19 was excluded from the trial, as were people taking medications that may adversely interact with Paxlovid.

Clinical trial data supported Paxlovid’s efficacy. It reduced the proportion of adults who were hospitalized or died by 86% when compared to placebo. Patients in the study were treated within five days of symptom onset, and they did not receive monoclonal antibody treatment.

On May 25, 2023, the U.S. Food and Drug Administration approved Paxlovid for treating mild-to-moderate COVID-19 in adults who are at high risk for progressing to severe disease.

COVID-19 coronovirus

Signs of Paxlovid Rebound

Symptoms associated with a Paxlovid rebound would be the same as with an initial COVID-19 infection. The symptoms are typically described as mild to moderate in severity:

  • Cough
  • Fatigue
  • Headache

Whether you believe you have a new-onset COVID-19 infection or a rebound infection, take a COVID-19 test. If your at-home COVID-19 test is positive following a negative one, follow the CDC isolation guidelines. Contact a doctor on the TelegraMD platform to receive access to a doctor 24 hours a day. They can discuss your COVID-19 test results and symptoms and determine whether a prescription antiviral medication is an appropriate treatment.

How Common Is Paxlovid Rebound?

According to data from the two Phase 2/3 Paxlovid clinical trials, Paxlovid rebound occurs in 1% to 3% of patients.

According to a preprint article published in medRxiv that examined the rates and relative risks of COVID-19 rebound in 92 million patients treated with Paxlovid or Molnupiravir between January and June 2022, researchers found rebound rates were as follows:


  • 7-day COVID-19 rebound rate: 3.53%
    • with symptoms: 2.31%
    • hospitalized: 0.44%
  • 30-day COVID-19 rebound rates: 5.4%
    • with symptoms: 5.87%
    • hospitalized: 0.77%


  • 7-day COVID-19 rebound rate: 5.86%
    • with symptoms: 3.75%
    • hospitalized: 0.84%
  • 30-day COVID-19 rebound rates: 8.59%
    • with symptoms: 8.21%
    • hospitalized: 1.39%

Results from the EPIC-HR, EPIC-SR 2021 (pre-Omicron), and EPIC-SR 2022 (Omicron) study data that Pfizer shared with the FDA showed that rebound rates after taking Paxlovid ranged from 10.4% to 15.8%. Rebound rates in the placebo group ranged from 13.6% to 14.1%, leading researchers to theorize that the viruses that cause COVID-19 cause a waxing-waning symptom course.

How Long Does Paxlovid Rebound Last?

In one study, after 28 days, 68% of participants reported their symptoms had resolved. Of these, 44% reported at least one symptom came back. For the most part, these symptoms were described as mild. None of the participants who had symptom relapse reported severe symptoms, had a hospitalization, or were treated with Paxlovid.

Is Paxlovid Rebound Worse Than the Original Symptoms?

No, most sources report that the symptoms related to Paxlovid rebound are mild to moderate. Symptoms may feel more severe because they are unexpected.

Side Effects of Paxlovid

Based on the results of two Paxlovid clinical trials, the most common side effects were:

  • Dysgeusia: a change in taste
  • Diarrhea: runny, frequent bowel movements

Other side effects that were reported after Paxlovid was granted EUA include:

  • High blood pressure
  • Stomach (abdominal) pain
  • Nausea
  • Vomiting
  • Fatigue
  • Headache
  • Severe skin rashes
  • Hypersensitivity reactions
  • Anaphylaxis

Other Antiviral Treatments for COVID-19

Other antiviral treatment options are available to treat COVID-19, including:

  • Remdesivir: This antiviral medication is an FDA-approved alternative to Paxlovid. It requires intravenous (IV) infusion for three days.
  • Tocilizumab: This medication is approved to treat hospitalized adults with COVID-19 who receive systemic steroids and require supplemental oxygen.
  • Baricitinib: This medication is approved to treat hospitalized adults with COVID-19 who receive systemic steroids and require supplemental oxygen.

If you have mild-to-moderate COVID-19 symptoms and are unsure whether you qualify for antiviral therapies, contact a doctor on the TelegraMD platform to receive an online diagnosis. They can help you with COVID-19 screening and testing and, if appropriate, transmit an online prescription to your local pharmacy to treat your COVID-19 symptoms. You will probably find it more cost-effective to consult a doctor online than other on-demand options, especially if you do not have insurance.  

Viral particles and a person graphic with his hand up

Why Prevention Is Still Important

Vaccination is the most effective way to prevent COVID-19. Ask your doctor or healthcare provider whether you are a suitable candidate for the booster vaccine.

COVID-19, influenza, and respiratory syncytial virus are all respiratory viruses that spread through close contact with the respiratory secretions from a person infected with the virus. All three classes of viruses have vaccines that reduce the risk of severe disease. Everyone’s immune system is different. We will all respond to vaccination slightly differently, and we will all respond to COVID-19 infection slightly differently as well. Talk to your doctor to better understand your risk versus benefits ratio for vaccination and if you have COVID-19, for treatment.

Considerations for Healthcare Businesses

COVID-19 and other pathogens are constantly evolving. New medications and treatment options come on the market all the time, challenging businesses such as online pharmacies and labs to continually review the most recent clinical trial and prescribing information so they can advise patients on such topics as COVID-19 rebound.


While we strive to always provide accurate, current, and safe advice in all of our articles and guides, it’s important to stress that they are no substitute for medical advice from a doctor or healthcare provider. You should always consult a practicing professional who can diagnose your specific case. The content we’ve included in this guide is merely meant to be informational and does not constitute medical advice.