Paxlovid: You'd have expected more | Hacker News Reader

Paxlovid: You'd have expected more

science.org

84 pointshelloworld84 comments

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.

> That indicates that paxlovid actually works

It had no measurable effect in the measured group. You can't say that it works based on that. If it had a measurable effect in that group, you would expect to see improvement in the treatment group between the two scenarios.

If (65-69 no treatment) == (70-74 no treatment) and also (65-69 no treatment) == (70-74 treatment), then (70-74 treatment) == (70-74 no treatment) by the transitive property of equality.

Now the reason for (65-69 no treatment) == (70-74 no treatment) may be its own mystery, but we expect to see at least _something_ happen anyway between (70-74 no treatment) and (70-74 treatment) if the treatment had some benefit for that group, and apparently they didn't see that.

They were comparing two time points as well as two age groups: before vs after Paxlovid became available, and late 60s (disallowed Paxlovid) vs early 70s (allowed Paxlovid).

There was no significant different before or after Paxlovid became available to the early 70s patients. This updates us against Paxlovid being effective in this patient population, for the specific outcome metrics.

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.

But only in high-risk patients, it should be noted.

There's some evidence in lower risk groups too. It's alas not an on-off switch, and you can't file a complaint Covid sorted you in the wrong group.

Does that mean we should all absolutely take Paxlovid? No, quite likely not. But the question is more "how close to the high risk group are you" than "are you high risk".

For e.g. 20-yo white men, the answer in both cases is roughly the same. But say they're 55 (or 65 and healthy as a horse) it probably deserves a bit more thought

No, any type of patient can get long covid. I suspect a heathy adult gets it from a combination of bad luck and/or not resting enough, doing too much, etc. post infection.

I think the comment you’re replying to was just noting that, according to Derek’s read on it, paxlovid may not reduce the risk of long covid in low-risk patients.

Nothing supports your 'only' comment.

It's a lot easier and less risk to just pop the pills and put up with the disgusting taste and maybe being sicker a bit longer, than it is for you and your doctor to sit down and try to do a whole bunch of fuzzy calculations to figure out just exactly how high-risk you might be and whether that meets the threshold for using paxlovid.

Particularly given we almost certainly don't know all the high risk factors, not every doctor is able to keep up with all the latest research, and the patient and/or treating physician might not even be aware the patient has a particular risk factor.

Depending on how far down the rabbit hole you go - there's an opportunity cost to a physician's time, too, and them spending more time trying to figure out if someone REALLY needs paxlovid means they have less time to spend with other patients.

Note: only in situations where it likely matters a lot.

Thanks.

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.

The extremely well-documented strength of the placebo effect is exactly why medical trials need to be so robust.

I had Covid once. No drugs, no vaccine (don’t jump me it wasn’t available yet). No long covid or brain fog. Sleepiness, loss of taste, flu symptoms for 5 days. Completely better in 10 days.

Anecdotes aren’t usually helpful for effectiveness testing. My experience can vary greatly between my neighbor even with identical demographics and characteristics.

How doy ou know it kept your symptoms at bay?

Plenty of people don't get long Covid, why were you sure you'd get it if you didn't take paxlovid? Same with brain fog?

Took paxlovid also. The symptoms go away really really suddenly and fast.

Sure, you need to run a study to be absolutely certain, but it just takes one experience to notice the effect.

It's interesting how religiously "correlation is not causation" is repeated here - except when it's about personal anecdotes.

Yeah you can read very similar anecdotes from people who took ivermectin. This is why controlled experiments are so important.

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.

Likewise. I was 2-3 days into testing positive and had a fever that could not be controlled by maximum strength OTC antipyretics, awful cough producing glue-like greyish globs, headache, blood oxygen consistently 2-3% below typical for me, extreme fatigue.

~48 hours after beginning Paxlovid I felt almost back to normal. spO2 returned to typical wake / sleep levels, lungs clearing, little fatigue, etc.

Based on how sick I was when I started treatment, if historical patterns of recovery from respiratory illness are any indication I would have expected an additional ~9-14 days of tapering symptoms at minimum.

Instead I was basically totally normal again after ~5-6 days.

If I get COVID again I will absolutely ask for Paxlovid.

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

I’ve had Covid 5 times— I’m pretty familiar with how it progresses. The most recent time was the most severe— I went to the ER with a temp of 103 with ibuprofen. Got Paxlovid— the major symptoms nearly switched off like flipping a light switch. Of course there’s a possibility it would have done that anyway, but I’m sure as hell going to take it again if necessary.

I definitely will take it again, no question. It worked really well for me. Side effects weren't too bad either.

Dealing with the drug interactions when prescribing paxlovid j find to be a bloody nightmare. Must have handed it out like 10 times in my last run of shifts

Yes, but these drugs (and the vaccines) don't make nearly as much money if only taken by those with high risk profiles.

The copays were pretty expensive! On the order of $400.00.

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.

This was more or less what happened to me with covid and I didn't take anything at all. It started as a cold, rapidly progressed to being so bad that I spent an entire day in bed, then rapidly subsided to "recovering from a bad cold but feeling mostly normal".

So I wouldn't put much confidence in your experience being down to the drug, personally.

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).

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.

It worked extremely fast for me, I took it within 16 hours of symptoms that were increasing rapidly. Within 6-8 hours I started feeling much better, instead just dealing with the Paxlovid side effects. I don’t think my body fought off Covid that fast. Anecdotal of course, but I’d take it again in a heartbeat. I did get a rebound infection the next week but I couldn’t feel it, just tested positive for a couple days.

> I took it within 16 hours of symptoms that were increasing rapidly. Within 6-8 hours I started feeling much better

So about 24 hours? I took nothing when I got COVID, and the major fever and body/head aches only lasted about that long. One day I started feeling absolutely awful, and I woke up the next day feeling substantially better but unable to smell anything but smoke for the next week.

It is possible that the paxlovid helped you, but given the few details you've shared so far it's also possible that it didn't do much that wasn't already going to happen.

It was dramatic and started just a few hours after the first dose. I was worsening all morning and by mid afternoon a reversal, coinciding with the Paxlovid side effects. It wasn’t an overnight thing where rest was a factor, I was awake and bedridden. So I’m pretty convinced, enough to drop $1,500 retail if need be in the future for it.

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.

What did having low body temperature feel like?

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.

I did not take anything special either, vaccinated, and have had more or less the same experience. I got from not being able to even sleep the night due to the pain, to feeling great the very following afternoon. Completely bizarre. None of the people I know experienced it like this, though.

This is why properly controlled trials are needed for stuff like that. It is easy to attribute the change to whatever random thing I tried at that point out of desperation.

Yeah, that's what happened to me too. I felt substantially better the next morning.

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

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

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

Thanks to a helpful pharmacist who let me know about it, I used the manufacturer's copay coupon (I think this is it: https://www.paxlovid.com/paxcess-terms-and-conditions ) and the cost of the drug for me (with insurance!) went from $400 to zero.

I don't know about "potentially no effect." It sure seemed to work well for me, and I've had covid with and without it. The difference was pretty big. I'm fairly certain the more profound difference is for those who are older or otherwise at risk, of course.

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!

Same. I had one night of fever and incredible chills. Thought for sure I was going to get very sick. Got Paxlovid next day. Felt better the following day. It was like having a cold, and I don't think that would have happened without the Paxlovid.

I also had one night of fever and incredible chills, followed by two days of no symptoms. No Paxlovid. (But then I did get bad cold-like symptoms for a week, and what seems to be long Covid...)

Sorry you got long covid. I hope you recover quickly!

That metallic taste still gives me shudders when I think about it, but I’m very grateful for Paxlovid.

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.

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

The Paxlovid dosing guidelines probably need to be changed, but given the current climate and cost it's unlikely to ever happen.

Similarly, the initial two-shot vaccine guidelines probably needed more time in between the doses for more effectiveness, but that's what was tested so that's the official recommendation.

agreed on changing guidelines, disagree its unlikely to happen.

the study is done and just needs to be formally published. then recommendations can "officially" change although the science has been clear about this for quite some time now with this specific drug.

other antivirals dont have this problem because they are actually effective for 10+ days even if you take it for 5 days (Ensitrelvir).

there's countless candidates in the pipeline as well for vaccines, antivirals, and monoclonal antibodies. as they keep getting better, the guidelines will shift slowly but surely.

i personally wish we did this with more urgency.

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.

Another example is Joe Biden, who had this exact thing happen (covid twice in a row with paxlovid).

Notable because while the chance of him just catching it again from someone are not 0, but about as low as it can go (an elderly POTUS under intense medical supervision and quarantine procedures).

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?

Just like it's possible to get COVID again and again. Neither your immune system nor COVID variant are stay the same over time.

Several ways.

To start with, I'm pretty sure it was established early on that the various vaccines don't prevent infection necessarily, but rather reduce the severity of the symptoms.

Vaccines are always one step behind, like they are for Influenza. You can get vaccinated against last years, and still catch this years.

Maybe the vaccine that was given was not given or stored correctly. There were also stories of anti-vaxxer medical staff giving fake vaccinations to people.

And biology is weird and complicated. Given the large human population and diversity, at some point there'll be an exception.

Vaccines aren't total protection. Notably, you can get chicken pox as a child despite having been vaccinated for it, it simply reduces the severity.

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.

What do you propose? Continue social distancing and masking? About the only middle ground is masking in medical settings and crowded, non-social spaces. I guess vaccination rates are low, but that should be a good thing for people who are vaccinated.

Indoor air filtering might help?

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.

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

I am criticizing two things.

1. Science magazine's association with his recurring "editorially independent blog". I've been a subscriber for many years and have never enjoyed it personally.

2. His opinion on this topic in general. The drug lived up to the hype even beating some international antivirals on efficacy terms.

Today's science is a bit further ahead still. For example, Pfizer will publish acute 10d data soon? which already has preliminary data showing faster symptom resolution and less rebound.

NIH/Yale/Karolinska will publish their 25d/15d/15d Long COVID Paxlovid studies to see what phenotypes may benefit from extended durations.

And next gen Paxlovid is already on an accelerated approval path and showed great results at IDWeek. https://clinicaltrials.gov/study/NCT06679140#study-plan

It is odd to me because he even wrote a piece about the next gen Paxlovid? Why didn't he reference it! It's in phase 3... https://www.science.org/content/blog-post/next-paxlovid

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.

here's my page with countless findings on the topic (you be the judge and feel free to search for other studies too): https://x.com/search?lang=en&q=(paxlovid%20OR%20Nirmatrelvir...

my general thoughts on this article and science "journalism" lately: https://x.com/atranscendedman/status/1856467031157289327

background: 4 years of long covid, work on nih efforts to cure it, and i don’t want anyone to suffer like millions of us do. so i share reliable info with the world.

note: paxlovid is a first-generation drug. in 2025, derek should follow more science rather than zeroing in on one study or griping about the taste when it can prevent your life from flipping upside down with long covid. he has literally written on the next version of it as well.

many elderly patients who are only vaccinated still develop long covid and are often dismissed due to their age. nobody deserves that when an antiviral is available until next-gen vaccine 2b trials finish soon and more treatment options hit the usa market later this year.

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 upvoted because you were gray, apparently wrongthink was being thunk by you. That's pretty sick.

MY father, 83 and stable on his meds for years, died 10 days after his first Moderna. COVID tested negative, pulmonary thrombosis. I didn't think that was a coincidence at all, hell no. I'm glad your dad is all right. Let's all try to avoid these coincidences in the future. Maybe my post will be flagged as wrongthink too, it's become a badge of honor at this point.

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.

Ensitrelvir is looking to apply for global approval. It may be a much more affordable option.

for poor people like me, the cost made me hesitate, then the best timing of taking it was gone.

so if banning this med is the only way to make the world more equal, I'm all for it.

You would rather have everyone be worse off than a few be better off?

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.

Reply on news.ycombinator.com