This appears to be a hasty conclusion. Older people with paxlovid did equally well as younger people without paxlovid. That indicates that paxlovid actually works, given that older age leads to covid mortality! The author's only refutation of this is that the same pattern was observed before Paxlovid was around. But that pattern itself is an aberration that is not true of the general population, it's only true in that one geographical area due to, I would assume, a statistical anomaly.

For most people now, the whole reason to take Paxlovid is the avoid long covid. The hospitalization risk is less of a concern. The article points out at the end that this drug has shown evidence of avoiding long covid.

I took Paxlovid twice. Horrible bitter taste, but kept the symptoms at bay. No long covid or persisting brain fog unlike some of my friends. Tested negative by the end of the treatment. My fiancé didn't catch it from my while I isolated.

Derek doesn't have to take Paxlovid next time, but I will.

Here is the new 2024 result (all ages) that says mean time to symptom alleviation didn't significantly change on Pax:

https://www.nejm.org/doi/full/10.1056/NEJMoa2309003

I was surprised to read it.

I am in my 70s and within a few hours of taking PAXLOVID my symptoms went away. I took it the first time I had Covid. When I had Covid a second last year I decided to suffer the symptoms without PAXLOVID so I felt crappy for three or four days.

I really think treating Covid for older people is a very different than treating young people.

That said, when I took PAXLOVID my daughter, son in law and grandson had the same Covid strain I did at the same time and their symptoms were very bad and lasted ten days to over two weeks.

My impression has been that taking Paxlovid resulted in faster recovery and less severe symptoms. This is an anecdotal observation with a tiny small sample size so I wouldn't discount placebo or a weaker variant. Still, I'd like to see a broader study that looks into long COVID and severity.

I have quite a bit of anecdata that Paxlovid works very well in helping very sick elderly people stay out of the hospital.

I will say for me when I took it, I could barely get out of bed. I slept 17 hours that day. It was maximum effort just to go downstairs to the kitchen and get food out of the refrigerator.

Anyhow I got the first dose at about 6pm and went to sleep, and when I woke up I felt pretty good and went down to my office to start catching up on my email. It was an amazing turnaround.

I took paxlovid and still got hospitalized with pneumonia and I’m 35. it was probably the worst week in my entire life. Paxlovid is so bitter, it actually lingers on your mouth for a few days after you take your last dose. It’s absolutely horrible. But maybe it helped me, the pneumonia was a light one so after the hospital it took me like 2-3 weeks and everything was kinda normal. If it helped me, it’s kinda sad that it costs like ~1000€ in Germany, of course my medi care paid everything.

Always enjoy Derek Lowe's writing.

n=1 here, though I've heard others say the same -- but I (fairly healthy 30s male, vaccinated) found Paxlovid massively reduced symptom intensity for me. Within a day my symptoms went from "top 5 fevers I've ever experienced, normal function significantly impaired" to "feels like a cold; can reasonably handle myself around the house and even take a software engineering interview".

I most likely would not have got a severe infection and probably would not have got Long Covid, given my age / health / vaccine status, even if I hadn't taken it; but nonetheless I'm glad I was able to get it. Definitely worth it for the weird taste (hard candy helps).

Checking GoodRX, Paxlovid ranges from $1,497 at CVS to $1,696 at Costco. Expensive for something that potentially has little effect.

I don't have any insight into hospitalizations, but as someone who was not vaccinated at the time I came down with COVID-19, Paxlovid was the difference between feeling utterly horrible and barely being able to get out of bed to being able to work remotely at full productivity. I took the first dose on the first morning and by the next morning the difference was night and day. I too experienced the bizarre changes in flavors, but that was a very small price to pay for immediately ending my symptoms. I still did the full quarantine duration, but the quality of life was so much better!

People always complain about replication crisis and a lack of publishing of negative results. From my surface level reading then, it seems nice to have a paper getting attention for just confirming what the original Paxlovid study already found.

My experience was odd. And this is just a description with no science.

I was vaccinated, got COVID. At no point were my symptoms serious. Because of age and past heart issues I was given paxlovid. Two weeks after the paxlovid (or something like that) I became sick again, more seriously. With COVID. The symptoms I experienced were much worse but not life threatening and I recovered fully. However, it was odd that the COVID came roaring back. My conjecture is that the paxlovid suppressed COVID, but that caused my body to falter in terms of building immunity. So when the paxlovid wore off, I was actually worse off. In the same situation I would NOT take the paxlovid again unless it was clear I had serious symptoms - like I was going to end up hospitialized. I acknowledge there is no science here, but on the other hand none of the doctors were able to suggest why I had a second episode so quickly and why it was more severe.

My conclusion is that there was a lot of guessing, placebo, reassuring, best guessing going on. I think that is the take away if we face such a thing again.

Paxlovid? You'd have expected more people to be doing more to not get infected & reinfected by COVID, and trying to stop the spread. But here we are. 5 years in.

I believe Science would benefit from a different approach to reporting, as Derek’s analysis over the past four years has been consistently lacking.

A responsible science reporter should present the full body of evidence rather than drawing conclusions from a single study.

Currently, a 900-person study is exploring Paxlovid’s potential for three clusters of Long COVID patients using a novel ultra-sensitive single-molecule assay. While many question its effectiveness in short treatment durations, there is reason to believe it could have extended benefits, similar to treatments for hepatitis C or feline coronavirus infections.

Having read and shared thousands of studies on SARS-CoV-2 and Long COVID, I find it irresponsible to dismiss a drug based on a single study, especially when broader research suggests that access to antivirals may reduce the risk of developing Long COVID, even among vaccinated individuals.

New antivirals are awaiting FDA approval, and an updated version of Paxlovid is in development. Derek’s analysis is not only misleading but also incorrect, and it would be best if he reconsidered the reach of his words.

My father almost died on Paxlovid. Almost immediately after taking it, he ended up in the ER, complaining of cardiac issues (severe arrhythmias and pain) and saying he felt like death. It wasn’t exactly a cardiac arrest, rather an “event”. While one could say it was Covid, the timing of the symptoms were too coincidental to ignore. It took him 2 months to start feeling normal. He had had covid twice before and was sufficiently vaccinated.

I love Derek Lowe as much as anyone else, but this piece is a bit weak.

The (currently) first comment on his site is right on point:

  > I don’t really see what point this article is trying to make. I’m 65. Vaxxed for covid to the max. Finally got covid. Before I had much in the way of symptoms I took Paxlovid for 5 days. Covid symptoms stopped. Tested clear of Covid after 5 days. Then I had rebound Covid for about a week but it was mild. If I ever get Covid again I’ll take paxlovid again. I don’t care what anyone else thinks.

Here are some reasons the article is weak.

1. I'll start with my own anecdote. I got the initial 2 shots of Moderna and later the booster when it became available. Still, I contracted Covid in early 2022 and it was not very fun. Then I contracted Covid in early 2024 and I got Paxlovid this time, and it was a breeze.

2. The mechanism of action of Paxlovid is different from the mechanism of action of the Pfizer/Moderna vaccines (I guess other vaccines as well). The vaccines train the body to recognize the spike protein of the virus, while Paxlovid attacks a protease (called M-pro) that plays some role in the virus's replication cycle. As the Covid virus mutates and the vaccines bases on the older strains become less effective, the added benefit of a drug with a different mechanism of action increases. Note that I said the added benefit, not the absolute benefit, which could very well decrease too. So, a study based on observations between April and October 2022 is likely to understate the benefit of Paxlovid today (for the vaccinated people).

3. Derek does not mention if the study was powerful enough. Absence of evidence is not evidence of absence. Since this was an observational study based on an existing cohort, the observers did not have a chance to do design the experiment to ensure enough statistical power. The conclusion that Derek draws is based on multiple indirect comparisons, and in all of them Derek treats statistical insignificance as equality.

4. Derek talks about long term effects. In my own anecdote, I did suffer from hearing loss for many months after my Covid episode with no Paxlovid. Nothing close to getting me to a hospital. But very annoying. Absolutely no Covid short or long term effects when I took Paxlovid.

5. This statement "if a drug's not doing you any good then you really shouldn't take it at all" is a big error. Derek jumped from "we have no evidence that the drug is good" to "the drug is doing you no good". Boom. Blink and you don't see it.

GoodRX, Paxlovid ranges from $1,497 at CVS to $1,696 at Costco.

Fuck me! Only for rich muppets then?

In my local Boots chemist Aspirin is about £2.00 for 28 tablets.

Paxlovid is a combination of 2 medicines called nirmatrelvir and ritonavir. Nirmatrelvir stops the virus from growing and spreading, and ritonavir helps nirmatrelvir from being broken down in your body long enough to do its job.

Fuck me! again.

i wonder how the calculus changes when the variant is poorly matched to the last vaccine you got

HN hosting more right-wing COVID-denier dribble. It has nothing to do with tech and HN, but it stays up anyway.

"I think it's very likely that if there had been a Paxlovid trial early on with a median age of 70 among unvaccinated adults (instead of the real median age of 42) that it would have shown much more than that 5.5% improvement in hospitalization risk! "

I find it wholly consistent with the entire "Have Faith in Science" trend of the COVID years for someone to say something like this.

I think it very likely that we don't know and shouldn't assume.

How do you know that it was Paxlovid that made you better, rather than coincidentally convalescing? There's a tendency for fevers to break as the body gets the upper hand on an infection, so if you started taking Paxlovid during a high fever your body might have been nearly done mopping up.

I'm not saying Paxlovid didn't help you, just that it's tricky to distinguish from placebo without a study.

Interestingly I had the weird side effect of going from COVID fever to low body temperature by my 2nd-3rd day of Paxlovid. If I remember correctly, it was in 95F-96F range.

My doc advised to stop taking it, but after reading on Reddit that a few others had had similar experience, decided to finish the entire treatment.

Same here. I got really sick the second time I had Covid (despite it being a more “mild” strain - Omicron I believe). Was bedridden for almost two weeks and had a rebound fever. With Paxlovid however, most of my symptoms subsided after a few days of taking it and I didn’t have a fever. This was the third time I got Covid.

Obviously I don’t know for sure how much I can attribute to the medication, but I will be taking it again if I catch Covid.

Both times I had COVID I went from "worst fever ever / my body feels like I've been hit my a bus" to "I have a pretty average cold" in less than 36 hours. Utterly bizarre. (Vaccinated, good health, 40s male)

Edit to clarify: I didn't take anything other than paracetamol and ibuprofen.

n=2, same, generally healthy 28yo male, basically identical anecdote.

maybe technically n=3 since I've taken it twice!

If you take Paxlovid for 5 days, there is a risk of rebound. It's not guaranteed that the rebound will be "mild". Basically, if you take it early, the virus is suppressed before your immune system ramps, so if it recovers, you get potentially a regular course of COVID....

There's some talk that maybe the course should really be for 10 days, but the pharma companies are charging insane prices for it far beyond their costs.

there are a number of computational/modeling studies suggesting paxlovid needs to be given for at least 7+ days to slow the viral load and prevent rebound.

Pfizer did a preliminary study(the FDA asked them) and quietly published their results on the topic. their data implies a second treatment might shorten the overall duration of the infection consistent with the studies i allude to above. but you probably haven't heard about this news!

https://clinicaltrials.gov/study/NCT05567952?tab=results

Research "Paxlovid rebound". It sounds like that is what hit you.

To add to the anecdata here, I had covid for a week (bedridden but otherwise not that bad), then had a single day in which I tested negative, and then it rebounded for a week, due to Paxlovid. Sounded like it was pretty common. So that was a waste of 15 days. On the plus side, my second week was much the same as the first week as far as symptoms go.

There was a study out about a year ago that showed that you were pretty likely to rebound if you took it on the first day of symptoms, and very unlikely (it was something like 0/30 people) to rebound if you waited until the third day.

> I was vaccinated, got COVID

How is this possible?

In the Pipeline is an “editorially independent blog,” [1] so I’m not sure that it’s fair to criticize Science or Derek Lowe for the “reporting.”

I’m a big fan of Derek’s blog. And I think his comments about long COVID at the end of the post are enough to convince me to ask for Paxlovid if/when I get COVID again (I’ve taken Paxlovid before).

[1] https://www.science.org/blogs/pipeline

Your comment does not cite any scientific evidence that contradicts the assertions in the article. The study you mention is ongoing and small. For comparison, one of the articles cited involves 280k patients with 35k treated.

If you're going to call an analysis incorrect, you should should say what's wrong with it.

With a comment this strong, I think you should disclose a little more of your own background / stance on the subject. Have you written a self-published book on Long Covid? (It looks like yes, but tl;dr.) My sympathies if you have suffered it.