Study: COVID Rebound Can Happen Even Without Paxlovid

COVID test

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Key Takeaways

  • A preprint study found that 27% of the participants saw rebound COVID-19 symptoms even without taking antivirals like Paxlovid.
  • Viral rebound may occur if the viral levels briefly fell below the detection limit or if the virus re-emerged after remaining in a reservoir. 
  • If you have viral or symptom rebound, assume that you are still infectious and practice the necessary health precautions.

Some COVID-19 patients have experienced a recurrence of symptoms after their initial recovery. Reports have attributed these rebound cases to Paxlovid, one of the most common antiviral treatments for COVID-19.

However, more than a quarter of patients reported having "COVID rebound," regardless of whether they’ve taken Paxlovid, according to a small preprint study.

The study found that 27% of participants experienced COVID-19 symptoms again after seeing improvements, and 12% tested positive again several days after testing negative.

It’s normal for COVID-19 symptoms to return after they’ve initially gone away, according to Stanley H. Weiss, MD, a professor of medicine at the Rutgers New Jersey Medical School.

“In the early COVID-19 pandemic, it was very common for people to get better and then develop severe illness in a second phase,” Weiss told Verywell. “With vaccinations, the severity is lessened.” 

What Is a COVID Rebound?

According to the CDC, COVID-19 rebound has been reported to occur between two and eight days after initial recovery and is characterized by a recurrence of COVID-19 symptoms or a new positive viral test after having tested negative.

Why Does Viral Rebound Occur?  

The researchers evaluated the participants on the fifth day after their enrollment as a baseline date, for the purpose of simulating the end of a five-day Paxlovid course. They found that most of the viral rebound cases—meaning people who tested positive again—occurred within five days after the baseline date and lasted for one day.

Weiss said that viral rebound for COVID-19 is not uncommon and the estimates in the study seem accurate. Viral rebound can happen if the viral loads briefly fell below the detection limit despite an ongoing infection, or the virus may have remained in an organ system and re-emerged, he explained.

Notably, Pfizer’s clinical trial for Paxlovid reported that the frequency of viral rebound was generally similar among Paxlovid and placebo recipients.

Are You Still Infectious? 

According to the study, it's rare to have symptom relapse and viral rebound at the same time.

If you have a viral or symptom rebound, it’s important to watch out for the progression of symptoms and seek medical attention when necessary, said Irfan Hafiz, MD, chief medical officer and infectious diseases specialist at Northwestern Medicine McHenry Hospital.

Hafiz added that the persistence of symptoms would likely correlate with ongoing infectivity. 

A small JAMA study found that 50% of infected patients who test positive five days after symptom onset or the initial positive test are likely not contagious anymore.

Although it’s possible for the rapid antigen or PCR test to detect viral particles that aren’t infectious, it’s best to presume that you’re still contagious and continue to isolate, Weiss suggested.

“Some, perhaps many, people will remain positive for more than five days,” Weiss said. “Continue isolation precautions until you feel better and your viral test turns negative.”

What This Means For You

COVID rebound could happen several days after your symptoms improve. Experts recommend continuing to isolate yourself until you feel better and get a negative test result.

The information in this article is current as of the date listed, which means newer information may be available when you read this. For the most recent updates on COVID-19, visit our coronavirus news page.

3 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. Deo R, Choudhary MC, Moser C, et al. Viral and symptom rebound in untreated COVID-19 infection. MedRxiv. Published online August 2, 2022. doi:10.1101/2022.08.01.22278278

  2. Pfizer. Fact sheet for healthcare providers: Emergency use authorization for Paxlovid.

  3. Cosimi LA, Kelly C, Esposito S, et al. Duration of symptoms and association with positive home rapid antigen test results after infection with SARS-CoV-2. JAMA Netw Open. 2022;5(8). doi:10.1001/jamanetworkopen.2022.25331

By Carla Delgado
Carla M. Delgado is a health and culture writer based in the Philippines.