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CDC issues advisory on management of ‘COVID-19 rebound’ after Paxlovid treatment

May 24, 2022

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There is no evidence that additional treatment for COVID-19 is needed for patients experiencing “COVID-19 rebound” after taking the antiviral Paxlovid, according to a health advisory from the Centers for Disease Control and Prevention (CDC).

COVID rebound has been reported to occur two to eight days after initial recovery and is characterized by a recurrence of COVID-19 symptoms or a positive viral test after having tested negative. The CDC recommends that health care providers continue monitoring patients with recurring symptoms and advise them to take precautions to prevent further transmission.

The CDC issued the health advisory Tuesday amid reports that some patients who tested positive for COVID-19 and were treated with Paxlovid had a recurrence of COVID-19 symptoms.

Paxlovid is a combination of nirmatrelvir and ritonavir from Pfizer. The Food and Drug Administration (FDA) granted emergency use authorization (EUA) of the antiviral to treat non-hospitalized people ages 12 and older weighing at least 40 kilograms (88 pounds) with mild to moderate COVID-19 who are at risk of progressing to severe disease. Treatment should be initiated as soon as possible and within five days of symptom onset.

Paxlovid continues to be recommended for such patients, and CDC officials say the antiviral helps prevent hospitalization and death due to COVID-19.

In the advisory, the CDC recommends health care providers advise patients with COVID-19 rebound to follow its guidance on isolation. Patients should re-isolate for at least five days. They can end their re-isolation period after five full days if fever has resolved for 24 hours (without the use of fever-reducing medicine) and symptoms are improving. The patient should wear a mask for 10 days after rebound symptoms started.

Health care providers also should consider clinical evaluations of patients who have COVID-19 rebound and symptoms that persist or worsen. Providers are encouraged to report cases of COVID-19 rebound after Paxlovid treatment using the Pfizer Safety Reporting tool and to the FDA MedWatch program.

Recent case reports show some patients with normal immune response who have completed a five-day course of Paxlovid for laboratory-confirmed infection have experienced recurrent illness two to eight days after initial recovery. 

A brief return of symptoms may be part of the natural history of SARS-CoV-2 infection in some people, independent of treatment with Paxlovid and regardless of vaccination status, according to the CDC.

Limited information available from case reports suggests that patients treated with Paxlovid who experience COVID-19 rebound have had mild illness; there are no reports of severe disease. There also is no evidence that additional treatment is needed with Paxlovid or other therapies for SARS-CoV-2 when COVID-19 rebound is suspected.


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