CDC: Still Prescribe COVID Treatment Paxlovid Despite 'Rebound' Illness

Marcia Frellick

May 25, 2022

Editor's note: Find the latest COVID-19 news and guidance in Medscape's Coronavirus Resource Center.

The Centers for Disease Control and Prevention (CDC) is telling clinicians to continue  prescribing the oral anti-COVID-19 drug Paxlovid (nirmatrelvir/ritonavir) for early-stage treatment despite reports of "rebound" illness among some patients who took the medication.

In a health advisory issued Tuesday, the CDC alerted clinicians to the potential for recurrent illness, or "COVID-19 rebound," after taking Paxlovid,

Still, the agency reaffirmed its commitment to the treatment. "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 alert states.

In some recent case reports, patients with normal immune response who have completed the 5-day course for Paxlovid and recovered have reported recurring illness 2-8 days later, according to the CDC.

These patients — including those who had been vaccinated and/or boosted — had a negative SARS-CoV-2 test after Paxlovid treatment followed by a positive antigen and/or reverse transcriptase polymerase chain reaction (RT-PCR) test.

The CDC states that these rebounds did not represent reinfection or resistance to Paxlovid, and the illness resolved in 3 days on average without more anti-COVID treatment. There was no increased incidence of hospitalization or death.

While acknowledging limited data is available on the rebound effect, the CDC said "a brief return of symptoms may be part of the natural history of SARS-CoV-2."

Follow Isolation Guidelines

According to the latest CDC guidance, there is no evidence for adding treatment with Paxlovid or other anti-SARS-CoV-2 therapies in case of a rebound. Patient monitoring continues to be the recommended management.

Among the unanswered questions is whether transmission risk during rebound is the same as risk during the initial infection.

However, the updated information states, "Regardless of whether the patient has been treated with an antiviral agent, risk of transmission during COVID-19 rebound can be managed by following CDC's guidance on isolation, including taking other precautions such as masking."

Patients should re-isolate for at least 5 days, the CDC advises, and they can end their re-isolation period after 5 full days if fever has resolved for 24 hours (without the use of fever-reducing medication) and symptoms are improving. In addition, the patient should wear a mask for a total of 10 days after rebound symptoms start.

Paxlovid is available under an Emergency Use Authorization by the US Food and Drug Administration (FDA) for people at least 12 years old who weigh at least 40 kg (88 lb).

Advice for Prescribing

The CDC gives the following advice for providers.

Treatment should be started as soon as possible within 5 days of first symptoms among people who:

The advisory encourages providers to report cases of COVID-19 rebound to Pfizer after Paxlovid treatment using the following online tools: Pfizer Safety Reporting and FDA MedWatch

In a briefing to reporters last week, as reported by Medscape, experts from the Infectious Diseases Society of America explained potential drug interactions with Paxlovid and how to manage them.

Marcia Frellick is a freelance journalist based in Chicago. She has previously written for the Chicago Tribune, Science News, and, and was an editor at the Chicago Sun-Times, the Cincinnati Enquirer, and the St. Cloud (Minnesota) Times. Follow her on Twitter at @mfrellick.

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