After taking the Covid-19 antiviral treatment Paxlovid, many patients experience a rebound of symptoms in the days following their recovery—but a new study published in JAMA Network Open found that a recurrence of Covid-19 symptoms can occur even in individuals who did not take the antiviral, Knvul Sheikh writes for the New York Times.

Study details and key findings

For the study, researchers evaluated Covid-19 symptoms in 158 individuals who tested positive for the coronavirus between August 2020 and November 2020. The median age of the participants was 47 and 50% were women.

On average, participants had a six-day window from the onset of symptoms to their enrollment in the trial.

The participants, who received a placebo instead of an antiviral treatment, were evaluated for 29 days. Each participant was asked to keep a daily log of their symptoms from the time of their enrollment to day 28. Participants assigned a score of absent, mild, moderate, or severe to 13 Covid-19 symptoms. After their symptoms were resolved, the researchers assessed the frequency of symptom rebound.

Overall, 108 participants reported an improvement in their symptoms without antiviral treatment, with completely absent symptoms for at least two consecutive days. Among those participants, 44% experienced a recurrence of symptoms during the four-week follow-up period.

"Symptom return is common," said Davey Smith, lead study author and the chief of infectious diseases and global public health at the University of California-San Diego School of Medicine. "It doesn't mean that things are going south. It's just the natural way the disease goes." However, he noted that the number of participants that experienced a rebound was surprising.

"The good news is that nobody who had their symptoms return needed to go to the hospital or died or even got severe symptoms," Smith added. Of the participants who experienced rebound, 85% said their symptoms were mild and 15% reported at least one moderate symptom.

According to Smith, the most common complaints patients reported during a symptom rebound were coughing, fatigue, and headache—similar to the symptoms reported during the active phase of participants' Covid-19 infection.

Why do symptoms rebound?

Symptoms recur in several respiratory diseases, including the common cold, flu, and respiratory syncytial virus.

"People have never really paid a lot of attention to it in the past, to be honest, as long as the patient is clinically doing better," said Bruce Farber, the chief of public health and epidemiology at Northwell Health.

Sometimes, symptoms go away before manifesting again because of the body's own immune response to infection, Farber noted.

"While initial symptoms like a fever, cough or runny nose may be triggered by the virus itself, the body produces its own alarm signals when it senses a foreign invader," Sheikh writes. "These signals come in the form of proteins that help inactivate viral RNA and tell white blood cells where to find more of the pathogen, speeding its removal from the body. At the same time, these reactions create inflammation in the body, which can give you a headache, make you feel exhausted or prolong the duration of a cough."

"I call this friendly fire," Farber said. "The immune system is very well intentioned and 100 percent needed, but it is clearly overreactive at times, and that often causes problems."

What you need to know about Paxlovid rebound

As reports of Paxlovid rebound increased, concerns over symptom recurrence when taking Paxlovid and molnupiravir—another antiviral Covid-19 treatment—seem to have discouraged some people from taking these treatments. 

However, Smith noted that the new study demonstrates that rebound is possible with or without an antiviral treatment. "I hope this can help people to be less afraid of a potential rebound," Smith said.

"If you're young and healthy, and you've been vaccinated and boosted, then I don't push Paxlovid on people, for the most part," Farber said.

Still, experts agree that individuals who become ill and are at high risk of developing severe Covid should receive the treatment.

For individuals who experience a rebound after antiviral treatment, experts have said there is no evidence that supports starting another course of Paxlovid.

Instead, Smith suggested staying in isolation in case you are contagious and managing your symptoms with pain and fever-reducing medicines, home remedies, and time. "I recommend staying hydrated, watching 'The Golden Girls' and eating chicken soup," he added. (Sheikh, New York Times, 10/27; Smith et al., JAMA Network Open, 10/27)