>Paxlovid and symptoms. Paxlovid has never been shown to reduce symptoms of Covid-19 in a randomized controlled trial.
I realize I have just an anecdote, but the statement feels bizarre to me. I finally experienced Covid this summer and had the five-day course of Paxlovid. It sure seemed effective.
Symptoms began at 22:00 of Day 1. I had mainly light symptoms before my Paxlovid doses took effect. Then, I had a big relief from the symptoms from Days 5 through 10. But I would rate my symptoms on Days 11 through 13 as like a BAD cold. But none of them brought me to ER and they passed. I first tested negative on Day 20, with coughing and an inability to smell being the remaining complaints.
After 2 days of decreasing test signals, I tested negative the morning of Day 10; only complaint was a stuffy nose. But the Paxlovid course had run out and on Day 12, I tested intensely positive again.
I speculate that I, if I had taken Paxlovid for at least 8 days instead of 5, I might have been spared the more-intense symptoms.
Hi Richard, Thank you for sharing. I can't say to what degree Paxlovid impacted all of that, and that's why we have clinical trials. I agree that we should be studying 10 day courses to see if rebounds like that can be avoided. I suspect they can be.
That all said, have you read my counter-anecdote on Paxlovid? I think it's a useful story and I hope you take a look! Thx!
Thank you for your reply, Jeremy. I didn't read your counter-anecdote when you published it; it was paywalled and I hadn't yet paid you.
Aside: the bitter taste was only a mild nuisance for me. I understand that it is idiosyncratic. I also noticed mention of a newer anti-viral for Covid that can omit the nuisance ingredient.
I agree, an anecdote, no matter how well documented, tells only what was observed, but not how or why.
Clinical trials tell what was observed in a large, and we hope well-characterized, population, but still not why... and does not tell what happens in an individual case, past or future. We trust that statistically similar results will come in the aggregate from that therapy in the future, but only in the aggregate. I'm an individual, and we don't know what's different in an individual case.
Why does rebound occur?
Other kinds of research (other than huge clinical trials) try to learn how and why effects happen. I've read that Paxlovid is intended to work by reducing viral replication... as long as I take it. I have not read (of) research about why rebound happens. The only hypothesis that I've read is that the virus remains in the body during Paxlovid therapy and resumes replicating when Paxlovid is discontinued. Why wouldn't it?
Has this been studied and published?
In this view, Paxlovid has no role in clearing the disease; that's the immune system's job, and when a patient has a disease of the immune system (e.g., CLL), that takes longer. Paxlovid supports the patient and reduces viral shedding.
The only discussions that I've read about Paxlovid rebound seem to be empirical, on a large scale, but individual immune system competence varies with many factors.
I suppose it is unavoidable that antiviral therapy will be administered for a fixed period of time. If the viral activity is slowed so much that it doesn't show up on antigen tests, how else do you determine whether the infection has been cleared other than discontinuing therapy and watching for rebound? Do PCR tests still show that the virus is present? Does PCR show it reliably?
DM, my reason for mentioning CLL was that CLL is a disorder of the immune system (specifically of certain white blood cells), which is what should be fighting my Covid! I thought that it might be relevant because I needed longer than the average bear to recover, taking 20 days before I finally tested negative and stayed negative.
Was there any discussion at this ER conference about how ERs are failed services? Any idea generation about how to improve ERs so patients can arrive there with anticipation of good care?
Yes indeed (I don't agree with the phrase "failed services," but I get what you are saying). The conference has a wide variety of programming, including a great deal if discussion on how we can improve conditions and care.
If the study shows that Paxlovid has never been shown to reduce symptoms of Covid-19, why is it still being prescribed? Even Fauci still recommends it for high risk people. But why?
Paxlovid was shown to reduce progression to severe disease requiring hospitalization and death in a population of high risk people who had not been vaccinated or previously infected. On that basis it became the standard of care. However, since then, that high risk population has actually become much lower risk (though still higher than "average") and it is unclear if it still does this. In the study I mentioned, the reduction in hospitalization in high risk vaccinated adults was too small to be significant. But it was not the intended "main outcome" of the study (i.e., the study was not chiefly designed to measure that) and so that is not definitive enough to change the standard of care. I think a new study from the UK coming out later this year may change things, but we will see. It's likely that study will either be negative or weakly positive for Paxlovid, whereas the initial study from 2022 was a slam dunk hugely positive result.
As to why Fauci recommends it, I can't say. I have read the studies carefully and we may differ on the interpretation. He tends to be a little overexubernt on the positives. For example, remdesivir is a drug that barely did much, but Fauci was very excited about it. I think that's because the fact that it did anything at all (reduced length of hospital stay by a bit during the early pandemic) was a huge boost to morale and an indicator that we were on the right track with our new therapeutics. So I think he just tends to be a little more optimistic/rosy in his reads of the data and I simply don't share that in all cases , based on the merits of the studies themselves.
That said, I still recommend Paxlovid to some patients--mainly very high risk people, such as people who get hospitalized for various other reasons in a given year. If they are that high risk from their other medical issues, I think Paxlovid might be warranted. But again, we'll see what the UK data show us.
I just read your link to Covid effectiveness and it seems like somebody over 65 - I’m 76 actually- should take Paxlovid. At least based on the study your link led to on high risk (older) people.
The study to which you provided a link was on encephalitis, not meningitis — patients whose presentation was consistent with meningitis were excluded from the study. That has very different clinical implications than saying that 1/4 of patients with meningitis may have initially negative csf studies.
That is an excellent point. I got it right in my presentation but was typing hastily last night when I wrote this. I'll fix it. In any case, I still think that normal white count in the csf in 25% of cases is still quite high, so I think my approach holds up. Do you agree?
Agree, it is quite high. Not sure about the number in “pure” meningitis, but it can happen. (My personal anecdote: As an EM R2 in 1979, I did a csf Gram stain on a child and saw Gram negative diplococci. All csf studies negative — no cells. No one believed it until csf grew out meningococci!).
the gram stain is the first place we need to look!!!!!!!! We are obsessed with the white count because we want that champagne tap. But the money is in the gram stain. You saved that kid's life, I bet.
Glad your colleagues appreciate you, like your readers do - enuf to ask you to speak. Re: Paxlovid though, I thought it was you (maybe somebody else) who wrote that despited the study it did reduce the degree of virus in the nasal area and therefor might have some value anyway. I also think the counting of the infections is probably more due to underreporting than to immunity. I think increased "immunity" may be reflected in the lowered severity of many cases to a degree where many people don't even know they have it. But they can transmit it to the more vulnerable who may be hospitalized and/or die.
What's interesting is that in people with antibodies (i.e., some degree of immunity), the decrease in viral load was actually almost negligible. That's a point that is not commonly appreciated.
Interesting. I guess it wasn’t you who I remembered as having said that despite the “trashing” of Paxlovid it might be of value since it reduced viral load. Does this mean that I should toss out my Paxlovid?
>Paxlovid and symptoms. Paxlovid has never been shown to reduce symptoms of Covid-19 in a randomized controlled trial.
I realize I have just an anecdote, but the statement feels bizarre to me. I finally experienced Covid this summer and had the five-day course of Paxlovid. It sure seemed effective.
Symptoms began at 22:00 of Day 1. I had mainly light symptoms before my Paxlovid doses took effect. Then, I had a big relief from the symptoms from Days 5 through 10. But I would rate my symptoms on Days 11 through 13 as like a BAD cold. But none of them brought me to ER and they passed. I first tested negative on Day 20, with coughing and an inability to smell being the remaining complaints.
After 2 days of decreasing test signals, I tested negative the morning of Day 10; only complaint was a stuffy nose. But the Paxlovid course had run out and on Day 12, I tested intensely positive again.
I speculate that I, if I had taken Paxlovid for at least 8 days instead of 5, I might have been spared the more-intense symptoms.
I have early-stage CLL.
Hi Richard, Thank you for sharing. I can't say to what degree Paxlovid impacted all of that, and that's why we have clinical trials. I agree that we should be studying 10 day courses to see if rebounds like that can be avoided. I suspect they can be.
That all said, have you read my counter-anecdote on Paxlovid? I think it's a useful story and I hope you take a look! Thx!
https://insidemedicine.substack.com/p/paxlovid-works-but-dont-ask-anyone?utm_source=publication-search
Thank you for your reply, Jeremy. I didn't read your counter-anecdote when you published it; it was paywalled and I hadn't yet paid you.
Aside: the bitter taste was only a mild nuisance for me. I understand that it is idiosyncratic. I also noticed mention of a newer anti-viral for Covid that can omit the nuisance ingredient.
I agree, an anecdote, no matter how well documented, tells only what was observed, but not how or why.
Clinical trials tell what was observed in a large, and we hope well-characterized, population, but still not why... and does not tell what happens in an individual case, past or future. We trust that statistically similar results will come in the aggregate from that therapy in the future, but only in the aggregate. I'm an individual, and we don't know what's different in an individual case.
Why does rebound occur?
Other kinds of research (other than huge clinical trials) try to learn how and why effects happen. I've read that Paxlovid is intended to work by reducing viral replication... as long as I take it. I have not read (of) research about why rebound happens. The only hypothesis that I've read is that the virus remains in the body during Paxlovid therapy and resumes replicating when Paxlovid is discontinued. Why wouldn't it?
Has this been studied and published?
In this view, Paxlovid has no role in clearing the disease; that's the immune system's job, and when a patient has a disease of the immune system (e.g., CLL), that takes longer. Paxlovid supports the patient and reduces viral shedding.
The only discussions that I've read about Paxlovid rebound seem to be empirical, on a large scale, but individual immune system competence varies with many factors.
I suppose it is unavoidable that antiviral therapy will be administered for a fixed period of time. If the viral activity is slowed so much that it doesn't show up on antigen tests, how else do you determine whether the infection has been cleared other than discontinuing therapy and watching for rebound? Do PCR tests still show that the virus is present? Does PCR show it reliably?
Dick
What's CLL?
CLL is a slow growing cancer that can become problematic but often does not. It really depends. https://www.cancer.gov/types/leukemia/patient/cll-treatment-pdq#:~:text=and%20treatment%20options.-,Chronic%20lymphocytic%20leukemia%20(CLL)%20is%20a%20type%20of%20cancer%20in,that%20usually%20gets%20worse%20slowly.
Thx
DM, my reason for mentioning CLL was that CLL is a disorder of the immune system (specifically of certain white blood cells), which is what should be fighting my Covid! I thought that it might be relevant because I needed longer than the average bear to recover, taking 20 days before I finally tested negative and stayed negative.
Very sorry to hear about your CLL and glad it apparently didn’t prevent your system from clearing the virus.
Was there any discussion at this ER conference about how ERs are failed services? Any idea generation about how to improve ERs so patients can arrive there with anticipation of good care?
Yes indeed (I don't agree with the phrase "failed services," but I get what you are saying). The conference has a wide variety of programming, including a great deal if discussion on how we can improve conditions and care.
Love it!
If the study shows that Paxlovid has never been shown to reduce symptoms of Covid-19, why is it still being prescribed? Even Fauci still recommends it for high risk people. But why?
Paxlovid was shown to reduce progression to severe disease requiring hospitalization and death in a population of high risk people who had not been vaccinated or previously infected. On that basis it became the standard of care. However, since then, that high risk population has actually become much lower risk (though still higher than "average") and it is unclear if it still does this. In the study I mentioned, the reduction in hospitalization in high risk vaccinated adults was too small to be significant. But it was not the intended "main outcome" of the study (i.e., the study was not chiefly designed to measure that) and so that is not definitive enough to change the standard of care. I think a new study from the UK coming out later this year may change things, but we will see. It's likely that study will either be negative or weakly positive for Paxlovid, whereas the initial study from 2022 was a slam dunk hugely positive result.
As to why Fauci recommends it, I can't say. I have read the studies carefully and we may differ on the interpretation. He tends to be a little overexubernt on the positives. For example, remdesivir is a drug that barely did much, but Fauci was very excited about it. I think that's because the fact that it did anything at all (reduced length of hospital stay by a bit during the early pandemic) was a huge boost to morale and an indicator that we were on the right track with our new therapeutics. So I think he just tends to be a little more optimistic/rosy in his reads of the data and I simply don't share that in all cases , based on the merits of the studies themselves.
That said, I still recommend Paxlovid to some patients--mainly very high risk people, such as people who get hospitalized for various other reasons in a given year. If they are that high risk from their other medical issues, I think Paxlovid might be warranted. But again, we'll see what the UK data show us.
I just read your link to Covid effectiveness and it seems like somebody over 65 - I’m 76 actually- should take Paxlovid. At least based on the study your link led to on high risk (older) people.
The study to which you provided a link was on encephalitis, not meningitis — patients whose presentation was consistent with meningitis were excluded from the study. That has very different clinical implications than saying that 1/4 of patients with meningitis may have initially negative csf studies.
That is an excellent point. I got it right in my presentation but was typing hastily last night when I wrote this. I'll fix it. In any case, I still think that normal white count in the csf in 25% of cases is still quite high, so I think my approach holds up. Do you agree?
Agree, it is quite high. Not sure about the number in “pure” meningitis, but it can happen. (My personal anecdote: As an EM R2 in 1979, I did a csf Gram stain on a child and saw Gram negative diplococci. All csf studies negative — no cells. No one believed it until csf grew out meningococci!).
Addendum: Repeat LP by inpatient team next day showed > 1000 wbc.
the gram stain is the first place we need to look!!!!!!!! We are obsessed with the white count because we want that champagne tap. But the money is in the gram stain. You saved that kid's life, I bet.
Glad your colleagues appreciate you, like your readers do - enuf to ask you to speak. Re: Paxlovid though, I thought it was you (maybe somebody else) who wrote that despited the study it did reduce the degree of virus in the nasal area and therefor might have some value anyway. I also think the counting of the infections is probably more due to underreporting than to immunity. I think increased "immunity" may be reflected in the lowered severity of many cases to a degree where many people don't even know they have it. But they can transmit it to the more vulnerable who may be hospitalized and/or die.
What's interesting is that in people with antibodies (i.e., some degree of immunity), the decrease in viral load was actually almost negligible. That's a point that is not commonly appreciated.
Interesting. I guess it wasn’t you who I remembered as having said that despite the “trashing” of Paxlovid it might be of value since it reduced viral load. Does this mean that I should toss out my Paxlovid?