What is Paxlovid rebound?

‘Antivirals change the dynamics of symptoms, change the dynamics of the immune response and change the dynamics of how you shed’ the virus

President Joe Biden tested positive for Covid-19 for a second time on Saturday, nine days after his original diagnosis and several days after testing negative.

The president’s physician, Dr Kevin O’Connor, said the most recent infection was due to “rebound COVID positivity” as a result of treatment from the drug Paxlovid.

So what is Pavloxid rebound?

A series of studies have shown that people with Covid-19 can stay infectious long into their second week with the virus after they initially experience symptoms.

Harvard TH Chan School of Public Health infectious disease specialist Yonatan Grad told Nature that ten days is a good rule for when people should no longer be infectious.

But he added that a small number could be infectious beyond ten days, with some of those cases being connected to the use of the antiviral drug Paxlovid.

“There’s a rebound phenomenon where people will see that their symptoms seem to resolve and they may even test negative on a rapid test, but then a few days later symptoms and the virus come back”, he told Nature.

In a 30 July memo, the physician to the president, Dr O’Connor wrote that “as described last week, acknowledging the potential for so-called ‘rebound’ COVID positivity observed in a small percentage of patients treated with PAXLOVID, the President increased his testing cadence, both to protect people around him and to assure early detection of any return of viral replication”.

“After testing negative on Tuesday evening, Wednesday morning, Thursday morning and Friday morning, the President tested positive late Saturday morning, by antigen testing. This in fact represents ‘rebound’ positivity”, Dr O’Connor added.

“Folks, today I tested positive for COVID again”, Mr Biden tweeted at 2.45pm on Saturday. “This happens with a small minority of folks. I’ve got no symptoms but I am going to isolate for the safety of everyone around me. I’m still at work, and will be back on the road soon.”

“The President has experienced no reemergence of symptoms, and continues to feel quite well”, Dr O’Connor added. “This being the case, there is no reason to reinitiate treatment at this time, but we will obviously continue close observation.”

Infectious-disease specialist at Massachusetts General Hospital, Amy Barczak, told Nature that “it’s very unusual for people to stay infectious after ten days”.

Mr Biden first tested positive on 21 July – nine days ago.

Dr Barczak told Nature that “antivirals change the dynamics of symptoms, change the dynamics of the immune response and change the dynamics of how you shed” the virus.

“I think this is really important, because people are out in the world thinking they’re not infectious after ten days. But if they have Paxlovid rebound they might be”, she added.

In a health advisory from the Centers for Disease Control and Prevention on 24 May, the agency said that “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“ and that the “treatment helps prevent hospitalization and death”.

“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”, the agency added. “A brief return of symptoms may be part of the natural history of ... the virus that causes COVID-19 ... in some persons, independent of treatment with Paxlovid and regardless of vaccination status.”

The agency also said that “limited information currently available from case reports suggests that persons treated with Paxlovid who experience Covid-19 rebound have had mild illness; there are no reports of severe disease”, adding that “there is currently no evidence that additional treatment is needed with Paxlovid or other ... therapies in cases where Covid-19 rebound is suspected”.