COVID symptoms recur more often in those who took Paxlovid, study finds

You’ve been free of COVID-19 symptoms for two days. Then the coughing, fatigue and headaches return. Join the growing number of people experiencing what’s being called COVID rebound.

And a new study by a team of University of California, San Diego researchers found that those who took the antiviral drug Paxlovid to alleviate their initial symptoms are more likely to see a recurrence.

A research letter that just appeared in the journal Infectious Diseases studied 158 San Diego County residents who received the drug early in their courses of illness. Of those, 108 saw their symptoms resolve for at least two consecutive days within a 28-day period after they became infected. But that illness-free period was short-lived for 48 people, meaning that 44% reported those telltale signs of coronavirus infection resurfacing.

It’s a kind of boomerang effect that hints at the overall coronavirus experience, with a fresh set of variants now starting to appear. Returning symptoms are not restricted to those who have taken Paxlovid. Researchers found that about one in three with COVID-19 who were untreated also saw symptoms return. Other studies have recently made similar estimates.

The good news? This returning threat wasn’t so bad. Among those in the UCSD study who had an unwelcome return, the most common relapse was cough, followed by fatigue and headache.

But the COVID-19 comeback is not gently received by patients. Dr. Davey Smith, the study’s lead author and infectious disease director at the university, said many demand more medication.

“I see panic all the time with my patients and colleagues like, ‘Oh my God, now I have a runny nose again and my cough came back, I need another course of Paxlovid,’” Smith said. “No, you just need to hold on for a second.”

While it’s no fun to have this one come back after it appears to have gone, Smith said that there should be comfort in the fact that returning symptoms are overwhelmingly mild to moderate on the severity scale.

“The big thing is that this disease course has a natural waxing and waning of symptoms, whether somebody has been treated with a medication like Paxlovid or not,” Smith said. “There is no need to panic. If you’re just having mild symptoms return, it’s probably going to go away in a couple of days.”

Rebounding symptoms are somewhat counterintuitive among those who have received medication that generally reduces the severity of new infections by blocking key enzymes that coronavirus needs in order to replicate itself in the body.

Shouldn’t those who have less virus in their bodies have a smaller chance of their symptoms returning than those who just toughed out their infections with bed rest and over-the-counter medications?

Davey said the exact explanation for recurring symptoms has not been proven empirically. The working notion is that when antiviral drugs such as Paxlovid block the virus from replicating, the body ends up generating a comparatively smaller immune-system response than it does when viruses are able to keep invading cells and copying themselves unchecked.

“Probably, the virus is still hanging around and there weren’t enough immune responses to keep it from having a rebound,” Smith said. “That’s our working hypothesis anyway.”

At the moment, the pandemic itself is not yet resurgent across the nation. Though viral detections in wastewater have recently been heavier in Midwest states, San Diego’s numbers have continued to trend downward.

That may be because the new variants that have recently caused new surges in Europe are not here yet.

It’s hard to say for sure at the moment, because SEARCH, the San Diego region’s wastewater detection coalition, is experiencing some technical difficulties.

SEARCH recently estimated that 58% of the coronavirus found in wastewater samples was the BQ.1.1 subvariant, one of those causing surges in Europe. A number that high would seem to strongly suggest a surge should be occurring.

But SEARCH recently posted an undated notice to the public on its website indicating that there is “considerable uncertainty” in the most recent dates due to the low amount of virus currently being found in wastewater samples. Labs are investigating the issue. (By John Sisson, Seattle Times)