‘Paxlovid rebound’: How long should COVID antiviral treatment last?

[Shiloh]

Source: https://www.wwlp.com/news/health/co...w-long-should-covid-antiviral-treatment-last/

‘Paxlovid rebound’: How long should COVID antiviral treatment last?
by: Joseph Choi, The Hill via Nexstar Media Wire
Posted: Aug 4, 2022 / 09:42 AM EDT
Updated: Aug 4, 2022 / 09:42 AM EDT

(The Hill) — President Joe Biden testing positive for COVID-19 again days after completing a course of Paxlovid has raised the question of whether the length of the antiviral treatment should be reconsidered.

Just days after he completed a five-day round of Pfizer’s COVID-19 antiviral treatment, Biden’s physician Kevin O’Connor said in a letter on Saturday that the president had tested positive once again. As of Wednesday, Biden is still testing positive for COVID-19.

This phenomenon has come to be known as “Paxlovid rebound,” when a person tests positive for coronavirus again even after initially testing negative following a round of treatment with the antiviral. A recent preprint study found that Paxlovid rebound occurred among 3.5 percent and 5.4 percent of coronavirus infections at the 7-day and the 30-day mark after treatment respectively. Biden’s chief medical advisor Anthony Fauci also experienced Paxlovid rebound after contracting the virus and started a second round of treatment.

Some experts have called for studies into extending Paxlovid treatments to be prioritized, as early research has suggested that Paxlovid rebound could occur due to insufficient exposure to the drug. Researchers from the University of California San Diego School of Medicine said last month that the drug may not be reaching enough infected cells in the allotted time...

 

[Emily]

Chair of UCSF Dept. of Medicine. All his assumptions were wrong - the wife got long Covid symptoms. They were double boosted and she used Paxlovid. He was fine. Wife was very scrupulous and anxious about spreading Covid. She wore a mask for a nine hour drive to protect him when she was ill and should have been breathing in as much oxygen as possible. He wore a mask to protect himself. He did not get long Covid.


https://twitter.com/Bob_Wachter/status/1523539613012299781

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Bob Wachter

@Bob_Wachter

She feels crummy, and she’s likely to have a few bad days, but the key fact is that her vaccines, boosters, and Paxlovid bring her odds of a truly bad outcome (hospitalization, ICU, and death) down to near zero. As for Long Covid, there is good evidence that being fully… (22/23)

12:45 AM · May 9, 2022·Twitter Web App

… vaccinated halves the odds, and at least theoretical reasons to believe that early use of Paxlovid might also help. If I turn positive in the next few days, my odds will be similarly favorable. So – though getting Covid still sucks – there’s a lot to be grateful for. (23/end)


12:45 AM · May 9, 2022·Twitter Web App

https://twitter.com/Theyllfixyou/status/1523653815819706368

Alex J Murphy, BSN, RN

@Theyllfixyou

Replying to@Bob_Wachter

What do you think her odds would be if she had no vaccines, boosters or Paxlovid?

8:19 AM · May 9, 2022·Twitter Web App


Just an FYI, 64% of patients currently hospitalized in MA are fully vaccinated...has been the majority since booster implementation.


8:21 AM · May 9, 2022·Twitter Web App

He starts to question Paxlovid in this interview below. We should be questioning a lot more.

https://twitter.com/inthebubblepod/status/1557486951011213313

In the Bubble
@inthebubblepod

The Paxlovid rebound. What is it and should it discourage you from taking Paxlovid in the first place. @Bob_Wachter
talks to @ASlavitt about his wife’s experience with the drug. Listen: https://link.chtbl.com/InTheBubble

5:00 PM · Aug 10, 2022·Twitter Web App

 

[JJackson]

There seems to be some confusion about what Paxlovid is doing. It is an inhibitor of the protease which cleaves the polyprotein translated from ORF1 into its biologically active subunits. Viral replication principally occurs before and during the week of symptom onset, which is when this antiviral is taken. The second week is when symptoms worsen due to the host's immune reaction, despite viral levels becoming very low. This might seem like the virus rebounding, but happens with or without antivirals. Extending the duration of treatment with this drug is not going to have any benefit for most immune competent people. All the available trial data shows Paxlovid to be highly effective (80% plus) in preventing escalation to severe disease and death for those at high risk due to age. Its only real downside is there are other medications and conditions which it should not be used with.

 

[Emily]

JJackson, feeling ill when the immune system kicks in makes sense, but people are testing positive again at that point and some are taking another course because of that. Maybe the virus levels does go up, but the immune activity would knock it back down and clear it even without a second course?
In the video embedded in the Twitter link from Aug 10, Wachter is interviewed by someone in the Biden admin. He said at the time that he would still take Paxlovid for the benefit you mention. (He's in his 60's) But he does wonder about a connection to long Covid. Also he thinks the rebound phenomenon is more common with Paxlovid than without and you are infectious again if that happens.

 

[JJackson]

Emily
See https://www.nejm.org/doi/full/10.1056/NEJMc2205944?query=infectious-disease
and https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciac481/6607746?login=false

I would also note that q RT PCR use as a proxy for viable virus is likely to be fairly reliable early in the infection but less so after the first week due to the detection and amplification of residual RNA fragments from inactivated virions and lysed infected cells.

 

[Emily]

Thanks, JJackson, I'll look at those. Makes sense that the PCR could be a red herring in these cases. I suppose even if they aren't actually infectious or even harboring live virus, the rest at home will do them good. In 1918, it was returning to work too early that seemed to kill a lot of people.

The only question I still have, (and you may have covered it in your links), is how would they go negative for awhile and then later test positive if contamination is the issue? Maybe it is just random chance and we are just hearing about the high profile cases?

 

[JJackson]

When I have seen plots of ct values from multiple patients over short time periods, they jump up one day and down the next. This may be real or an artefact of the swab collecting wildly different amounts of material. It is common in many illnesses to seem to be recovering and then have a bit of a relapse before full recovery COVID is no different, it may feel a bit more noticeable if an antiviral was working well, and then it is just the immune system coping. If it has done its job, then it suppressed viral replication long enough for the immune system to clean up without having to go into overdrive. The risk in extending from a 5 to 10 day course is it increases the chance of developing resistance to the antiviral. There are trials to test a longer course to see if it is worth that risk, and the data so far shows it does not readily develop resistance. It has not been used in volume for long enough to say what impact it will have on long COVID, but I would expect it to reduce the risk because it reduces the severity of symptoms, which have been shown to correlate to long COVID.

 

[Emily]

I'd be surprised, too, if Paxlovid increased odds of long Covid of any nature. There is a new clinical trial starting to see if it can actually treat long Covid. People are excited.

https://clinicaltrials.gov/ct2/show/NCT05595369

Had a chance to look at the papers - interesting!

 

[JJackson]

I doubt Paxlovid will be of any use as a treatment. PCR is hypersensitive, if run to >30 cycles, and if it is not picking up replicating virus then it is difficult to see how such a low level of viral replication would be causing symptomatic disease or how Paxlovid would completely remove it if the immune system can not. I like that the trial clearly states what it is using as a placebo but am surprised that it includes one of the components of the active arm - very odd.

 

[Emily]

That is peculiar about the placebo - hadn't seen that! As I understand it, the ritonavir has no activity against sars2. It's used to block a liver enzyme that degrades nirmatrelvir, which is active against sars2. That way, an effective amount stays in circulation.
I can understand curiosity about ritonavir alone: if the treatment group gets sicker, then you can see if the ritonavir is the issue if that group gets sicker, too. Also, if the treatment group does better, and then if the placebo does as well, it might be that their symptoms are due to another virus that ritonavir is treating. (I don't know if ritonavir is active against any other virus but HIV, though.)
It would be nice to have a true placebo arm, but money might be tight. They did one of the acute disease treatment trials like this, too.