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I think one thing that is highly undervalued, both from a human and an economic perspective, is "feel better." I have a number of friends who took Paxlovid in their 30s-40s. They had mild reasons to qualify (asthma, weight, etc). All felt the full blunt of Covid, and within 4-6 hours they felt human again. By the 3rd day of Paxlovid, they were able to meaningfully be up and engage with the world. Even though it didn't impact their risk of hospitalization, it made them feel way better and from a capitalism perspective, all were able to at least check their work messages and see the state of things. There's a lot of value in that and I feel like it's understated.

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Please note that multiple asthma control medications contain salmeterol, for example Advair. Would you consider editing the text of this article to reflect that Serevent is not the only medication containing salmeterol? And thank you for this information. I use Advair and didn't know of this potential interaction. If I do need paxlovid in the future I am glad to be armed with this information.

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Very interesting to read after my own experience with Pax in May. I'm 26 but have comorbidities, and my rebound was fairly intense compared to my initial symptoms while taking Pax. I also take buspirone and the interaction was very, very interesting. My partner and I both got Covid and took Pax along with buspirone...we ended up getting very emotional because of that, and it actually saved our relationship. I'm not going to say I'm glad we got Covid, but we're getting married next year now so I guess that's the only 'side effect' I didn't hate, lol.

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Very interesting. Several people at my workplace currently have COVID. Only one has been prescribed an anti-viral - a healthy, vaccinated person who is in his early 20s. Sounds like there is still a lot that is being figured out.

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Thank you Dr. Jetelina for the updated information. I had Covid the beginning of September. Despite being double vaxxed and double boosted, I was very ill. I have no preexisting conditions , am in good health, but am "almost 65". My PCP left the Paxlovid decision up to me, and it was hard to know what to do as both the Bidens and Dr. Fauci had just been in the news with rebound.

As far as drug interactions, there are quite a few that need to be withheld for 5 days ( not just statins). This is a great tool to use to check for drug interactions:

https://www.covid19-druginteractions.org/checker

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Sorry if I wasn't clear. I had Covid the beginning of September. Had a +PCR ( after a negative home antigen) at that time, called my internist the day I received the + PCR and she could not really give me clear guidance as to whether to take it or not, so I decided to take it. Took the first dose that evening ( the day I got my + PCR).

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Also, at that time I used the drug interactions tool myself to check for interactions with both my Prescribed and OTC meds, it was extremely helpful.

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A good post, and call to action for prescribers and patients - especially for older individuals to take Paxlovid early and not wait to see "if things get worse." Too late by that time.

I continue to hold on to the intuitive hope that antivirals will reduce the risk of long Covid and other subclinical damage we are seeing, even with mild Covid. Reducing viral load by up to 90% with Paxlovid just has to have benefits beyond hospitalization and death. Some evidence of this is emerging from studies showing that sick patients' viral load/nucleocapsid antigen levels correlate directly with prognosis in severe disease.

Possible neurological damage like cognitive decline, increased cardiovascular risk for month/years after infection, and even a consistent finding of lung parenchymal damage in children (even with mild disease) all keep me up at night!

Intuitively, a 90% reduction in viral load has to reduce the systemic collateral damage, wouldn't we think?

Imagine what a fruit cake looks like with 90% less troublesome dried fruit, for goodness sake. I've been hanging on to this notion since Paxlovid first rolled out (https://mccormickmd.substack.com/p/what-is-your-paxlovid-plan), but I know it's not evidence-based yet. Thanks for at least including a final sentence about the possibility.

Fingers crossed, and prescribing Paxlovid freely here.

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Re: the study that found that only 10% of people who rebounded without Paxlovid had symptoms, what does it mean to rebound without symptoms? To be infectious but feel fine? If so, it seems this could lead to a lot of covid spread.

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My husband-61, with epilepsy was denied paxlovid because of a contraindication with a seizure medication. (They said it magnified the effect of the seizure Med, and it wasn’t worth trying to decrease the dose and risking the seizure since he was otherwise low risk. My FIL was also not given Paxlovid due to poor kidney function. (Was given monoclonal antibodies instead since he is an octogenarian with multiple risk factors.)

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A little off topic but does anyone know the schedule for approving elementarybaged kids (5/6+) for the new bivalent? I saw that both Pfizer and Moderna submitted for approval about two weeks ago (9/26), but I don’t see anything yet on a schedule for an FDA/CDC review.

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Oct 7, 2022·edited Oct 7, 2022

Thank you for clearing up many of the mysteries surrounding Paxlovid.

A doctor pointed me to this article yesterday, which tries to define how often Paxlovid rebound happens, yet since I don't understand why there's a difference in the 3 different bar charts, I'll leave it to somebody who understands this stuff to summarize (or perhaps explain why its a flawed study):

https://www.nature.com/articles/d41586-022-02121-z

I would venture to guess that because of the likelihood of rebound, Paxlovid actually *increases* overall transmission in society. People with Covid take Pax for 5 days, test negative, and then go back to restaurants, airports and work places - unmasked - only to unknowingly spread the virus to others before they later rebound. (Side note, didn't the Bidens return to normal unmasked life after testing negative for two consecutive days, only to rebound? How many people did they unwittingly infect in that interlude period? Where did this "you only need to test negative for 2 days" guidance come from, anyway?)

As far as the definition of rebound (takes Paxlovid, tests negative, then tests positive): my husband never tested negative on the days following his last dose of Paxlovid, and four days later, his fever and other symptoms returned. In all, he tested positive for 12 consecutive days, and isolated for 17. Luckily, we had a lot of tests on hand, and he was able to work from home.

Also, now that society is primarily relying on the at-home tests, which (best case) only detect covid about 80% of the time, that means about 20% of the time, people test negative even though they actually have covid. Convinced they are fine, they go out unmasked and spread the virus.

So, we need better at-home tests that detect the newer variants. If you don't test positive, you can't get Paxlovid.

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There's no evidence that home tests can't detect the new variants.

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Oct 13, 2022·edited Oct 13, 2022

"The risk of inaccurate results seems to be higher among symptomatic people infected with the latest dominant Omicron subvariant, BA.5, compared with earlier versions.”

Source: https://www.latimes.com/california/story/2022-08-17/california-officials-warn-of-misleading-covid-test-results

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You’re talking about “Ref 1” with the three bars? Those all seems to be people who didn’t take paxlovid and their changes of having rebounded 1) symptoms, 2) viral test, 3) both. It doesn’t seem to say anything about paxlovid.

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@Fred - thanks for your clarification. Yes, I'm talking about Ref 1. I'm having trouble squaring it with the text of the article describing a different study, specifically:

"The study, led by infectious-disease physician and vaccine scientist Kathryn Stephenson at Beth Israel Deaconess Medical Center in Boston, closely followed 11 people who took Paxlovid for COVID-19 and 25 who did not. More than one-quarter of the Paxlovid recipients rebounded, based on levels of SARS-CoV-2, compared with just one of the 25 untreated people. Moreover, people with Paxlovid rebound had high levels of virus for several days, as if they had new acute infections."

This is a smaller study, yet would suggest rebound occurs 25+% of the time for those who take Paxlovid, and 4% of the time for those who are untreated. In addition to problems with sample size and statistical significance, it's impossible to know whether the treated and untreated groups are otherwise "apples to apples" (vaccine/booster status, natural immunity, age, gender, health, etc).

I have seen comments on this substack from other readers that Paxlovid in no way creates a greater likelihood of Covid rebound, and at least according to this smaller study, as well as anecdotal evidence (Fauci, POTUS, Dr Biden, etc), that simply cannot be true. Taking Paxlovid increases the risk of Covid rebound. How much? At least 6 times based on this small study.

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The article talks about (at least) 2 studies. The figure is the first one which only looked at untreated. The second study compared treated and untreated.

You are right that the two studies numbers don’t like I’m great. The first found Cora rebound in 11% of untreated. The second found it in only 4% of untreated, but 27% of treated.

The sample sizes in the second study are especially small, 1 of 25 and 3 of 11. And as you point out the treated group has a greater instance of comorbidity. I’m not sure I’d put great weight in such a small study like that.

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Oct 7, 2022·edited Nov 26, 2022

PS unless there are better studies out there, I think that’s why Dr Katelyn limited it to saying “rebound *MAY* happen more frequently” with Paxlovid. The data isnt sufficient to be convincing yet. And even if it is more frequent though, rebound doesn’t seem like a big enough deal to avoid taking it over given the benefits.

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For someone who started out admitting that you don't understand this stuff, you seem remarkably confident in your conclusions.

And FYI, "Anecdotal evidence" is an oxymoron. And comments on this or any other substack are not representative of anything other than comments on substack, unless the person doing the commenting knows what they're talking about and can back it up with something other than "anecdotal evidence" and comments on substack.

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There are some anecdotes that are “one offs” and prove nothing.

There are other anecdotes, such as “I know 20 people who took Paxlovid, and nearly a third had rebounds.” This doesn’t meet the rigor of a scientific study, but it does nonetheless convey some element of truth.

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It conveys exactly as much truth as any other unvalidated statement.

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Shouldn't there be enough for *everybody* now? According to HHS there are over 613,000 going out a week, compared to an average daily case rate of about 40,000.

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Enough of what?

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Weekly allocation of Paxlovid: 615,000 courses

Daily case rate: 40,000

That's enough for everyone who tests positive to get Paxlovid

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Thanks! Weird, maybe they’re stocking up for winter?

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No idea, but a lot of the justification used for only giving it to certain individuals reminds me of the early days of the pandemic when they were telling people to spare high quality masks for people who were deemed more worthy. For Paxlovid, the cutoff at age 65 seems arbitrary, and I'm certain you'd see every age group benefiting if it was broken down more finely (Simpson's paradox)

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My understanding is the cutoff isn’t age 65 for Paxlovid.

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I've seen different age cutoffs, but I wouldn't be at all surprised to learn in a few months that *everybody* benefits from it.

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The current guidance for rebound, whether related to Paxlovid or not, is restarting isolation: Another 5 days home isolation and then another 5 days masking. I’m a public health nurse who speaks to positive cases all the time, and you’d be hard-pressed to convince me rebound doesn’t happen much more often with Paxlovid. However, if older or at high risk, it certainly seems worth it to take the med. If young/low risk, you can be looking at a lot more missed work for little to no benefit, and a fair number of people with no underlying conditions/not meeting any age threshold are being prescribed a course. My other concern is the COVID spread. I’ve fielded many a rebound call after someone has been out to a restaurant, the dentist, etc, most likely while infectious again. For that reason, I do hope dosage/length of course will be studied to maybe reduce the frequency of rebound.

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My husband is 76, and I turned 70 in May. In mid September, we both got Covid for the first time. Both double vaxxed and double boosted. My husband has a lot of issues related to neuropathy but is otherwise healthy and I’m in good shape. Neither of our health provides pushed us to take Paxlovid. And, we both got over Covid seemingly without long term issues. Is that unusual? Surely it’s not a binary choice between taking Paxlovid or winding up in the hospital, for people in our age group. Today’s edition of the NYT Morning almost makes it sound like it’s irresponsible *not* to take Paxlovid, but doesn’t address those of us who do fine without it. Very confusing.

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I think the trick is that one doesn't know if you'll "do fine without it" until you either do, or do NOT do fine. And then it may be too late. As with all antivirals, Paxlovid is most effective taken early in the exposure/infection, so it can help your body minimize viral invasion. It is a much steeper task if you wait until the virus has begun to wreak havoc on your organ systems, to then try to reverse the virus AND heal any organ damage done.

So, if someone over 60 waits to see, they may not know until they require hospitalization that they aren't doing well, and then Paxlovid might not even be an option, or might not be as effective in reducing the severity or improving their outcomes.

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I guess? I filled the scrip on Day 1 of symptoms, decided I’d start taking it if I felt worse, but never felt bad enough to do it. It’s on hand if either of us get it again.

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I mean mostly I’d say, why not? I mean if let’s say have 10% chance of being hospitalized without it (far from certain but not nothing), then you have about a 1% chance with it. Unless you have some contraindication, seems totally worthwhile.

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Outstanding summary. Thanks!

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I recently sent this letter to the regulators at the FDA concerning rules about the prescription of Paxlovid. I would value your opinion.

Hello,

I have read and understand the regulation regarding distribution of Paxlovid only to patients with a positive COVID test, who qualify because of age or immune status, etc.

I do not understand why this rule could not be changed, given the current situation in which (as I understand it) there is no shortage of Paxlovid for those who need it.

From my point of view it would be best for elderly travelers (>65, without contraindications) to consult with their OWN providers before they travel, in order that they might be evaluated as candidates for paxlovid should they acquire COVID while traveling. They could at that time be instructed as to its potential use (within 5 days of onset of COVID symptoms and a positive test), and thus be prepared if they fall ill far from home in a location where such counsel, and the drug itself, might be unobtainable.

Travelers to locations with endemic diseases are routinely given medications to carry with themselves for potential illnesses while abroad.

In the face of a worldwide pandemic with this dangerous virus, in a world where other precautions which might protect older travelers have been relaxed (such as masking on planes), older people often feel they are being tossed to the wolves and told it is up to them to take care of themselves.

I think that a slight change of the rules, one that would allow them to travel with paxlovid in case of becoming ill with COVID while away from home (a very distinct possibility) is only fair and logical from a personal and public health standpoint.

Sincerely,

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Wondering what the guidance is for taking Paxlovid repeatedly for subsequent infections (>3 months apart, not rebound)? I'm particularly interested to know if there's data for low-risk populations (asking for a friend ;-), but I suspect there's not much available..

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