[HN Gopher] Antiviral compound blocks SARS-CoV-2 from entering c...
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Antiviral compound blocks SARS-CoV-2 from entering cells
Author : WaitWaitWha
Score : 166 points
Date : 2021-10-15 13:30 UTC (9 hours ago)
(HTM) web link (medicine.wustl.edu)
(TXT) w3m dump (medicine.wustl.edu)
| dukeofdoom wrote:
| I was reading that the flue shot also works against covid
| according to a study. The world will learn to live with covid.
| I'm more worried about the authoritarians taking advantage of the
| current crisis.
| whatanorigtht wrote:
| We already have a treatment that works fine. Get some ivermectin
| and chill.
| throwoutway wrote:
| > We already have a treatment that works fine. Get some
| ivermectin and chill.
|
| This isn't a helpful comment. Please read the hacker news
| guidelines
| whatanorigtht wrote:
| It is helpful. Ivermectin works so well Pfizer is copying it.
| robflynn wrote:
| https://apnews.com/article/fact-checking-067310377629
| bananabiscuit wrote:
| Just like every other [fact-check] I've seen recently,
| this just attacks the most weak and absurd version of the
| fact. The reason people are saying it's repackaged
| ivermectin is not because it's literally the same
| chemical in new packaging, but because the mechanism of
| action for Pfizer's new antiviral (3CL protease
| inhibitor) is something that Ivermectin also does.
| pacerwpg wrote:
| This is from the fact check and it sounds to me like
| they're treating the claims fairly and not using a
| ridiculous version.
|
| 'Several posts circulating online wrongly suggest that
| the pills are the same because ivermectin also acts like
| a protease inhibitor and keeps the virus from
| replicating. Ivermectin continues to be studied in
| relation to COVID-19, however, it has yet to be proven
| that it can treat COVID-19.
|
| Images of the structure of Pfizer's new pill and
| ivermectin can be found online and do not show
| similarities like the posts describe.
|
| Ivermectin binds to glutamate-gated chloride channels and
| is used to treat parasite infections, said Joseph Glajch,
| a consultant in pharmaceutical and analytical chemistry.
|
| "These two are so far apart," he said. "If you look at
| how they interact with the body..., they don't even go to
| the same pathways or receptors."'
| whatanorigtht wrote:
| Sorry, I don't care to read your government propaganda.
| ccn0p wrote:
| I find fact checkers quite interesting in the way they've
| been deployed over the last few years. As if one source
| is the "truth" and that settles things. Usually when you
| get to the end of "false" claims, you find some tidbits
| that make you wonder... such as:
|
| "Several posts circulating online wrongly suggest that
| the pills are the same because ivermectin also acts like
| a protease inhibitor and keeps the virus from
| replicating. Ivermectin continues to be studied in
| relation to COVID-19, however, it has yet to be proven
| that it can treat COVID-19."
| nuerow wrote:
| > _Usually when you get to the end of "false" claims, you
| find some tidbits that make you wonder... such as:_
|
| Could you please explain what exactly did you interpreted
| from a statement that boils down to "no one showed that
| this actually works"? The fact check looks pretty cut and
| dry to me.
| artificialLimbs wrote:
| Not op, but "We don't know" != "False"
|
| Also, op does not claim "no one showed this actually
| works." Your comment is not in good faith.
| nuerow wrote:
| > _Not op, but "We don't know" != "False"_
|
| That's not what the fat checker states. At all.
|
| The fact checker states, and I quote:
|
| > _however, it has yet to be proven that it can treat
| COVID-19. "_
|
| "It is yet to be proven" means, quite literally, anyone
| who looked into it never saw it work, ever. At all.
| naasking wrote:
| > "It is yet to be proven" means, quite literally, anyone
| who looked into it never saw it work, ever. At all.
|
| This claim is quite literally false. If no one saw an
| effect, then we wouldn't still be talking about it. Most
| of the studies listed here [1] all claim to have seen it
| work. You can of course claim these are poor or
| unconvincing studies for various reasons, but they still
| falsify your claim that no one who looked into it ever
| saw it work.
|
| [1] https://ivmmeta.com/
| raphlinus wrote:
| Your link is an oft-debunked misinformation campaign[1].
|
| In my opinion, the best current review is the Cochrane
| review[2]. And indeed, I think "anyone who looked into it
| never saw it work, ever. At all" is overstating the case.
| There is _weak_ evidence that it works. That could easily
| go one of two ways: a highly powered RCT (like ACTIV-6)
| could show that it doesn 't work at all, or we could find
| that it shows some improvement but is definitely not a
| silver bullet.
|
| [1]: https://ebm.bmj.com/content/early/2021/05/26/bmjebm-
| 2021-111...
|
| [2]: https://www.cochranelibrary.com/cdsr/doi/10.1002/146
| 51858.CD...
| naasking wrote:
| Sure, don't take ivmmeta.com analysis at face value, but
| I was pointing out that they link to numerous legitimate
| studies which did find positive results, thus refuting
| the OP's claim that nobody who looked into this ever
| found anything.
| raphlinus wrote:
| That's fair. The Cochrane review links to many of the
| same studies, for what it's worth.
| vmception wrote:
| > "It is yet to be proven" means, quite literally, anyone
| who looked into it never saw it work, ever. At all.
|
| [yet].
|
| There are studies ongoing. Not in the anti-vaxxer "I'm
| still doing research" sense, but in the sense that there
| are actual non-Facebook studies ongoing. Even that AP
| fact checker article mentions that.
|
| When the context says there are studies ongoing and yet
| to be proven is mentioned, it means that the conclusion
| has not been drawn.
|
| In isolation, when yet to be proven is written with no
| other context, it means what you interpreted: that nobody
| has ever seen it work, and we need a nice way to say
| that.
|
| The fact checker and this conversation both accurately
| conveyed how different ivermectin is from what Pfizer is
| developing: the compounds are different, the molecules
| are different, everything is different. They don't say
| the result is different. Ivermectin - a completely
| different compound and molecule - has a hypothesis and
| limited result showing it functions as a protease
| inhibitor. It does omit where there are similarities
| being studied and what those hypothesis are.
|
| This is actually new information to me and I found that
| looking for a response to you. This isn't about
| Ivermectin or laughing at Republicans turn their whole
| states blue from a lack of oxygen as well as the
| remaining population, its just about what is omitted from
| the fact checking article.
| gizmo686 wrote:
| The top-line claim in the linked fact-check is "Pfizer's
| new pill to treat COVID-19 is just ivermectin
| repackaged".
|
| The claim is explicitly countered by claims in the fact
| check: "They are dramatically different molecules. The
| drugs are different in their structure and their
| molecular size".
|
| I have not fact-checked the fact check, but to suggest
| that the headline claim of "false" is misleading or
| inconsistent with the body of the article is simply
| wrong.
|
| The comment about Ivermectin still being studied and not
| yet known to be effective is not relevant to the claim
| under review, but merely added to provide the reader with
| context.
| ccn0p wrote:
| Thanks for the response. You're right, but, I'm not
| _trying_ to say that the headline claim of "false" is
| misleading _with the body of the article_.
|
| I'm trying to say something more nuanced... that the
| headline claim of "false" is misleading from the actual
| conversations happening out there right now. Which in a
| way is not a problem with just fact checkers, but the
| Internet as a whole.
|
| BUT... In my opinion, "fact checkers" by nature of their
| name have a greater responsibility to Internet discourse
| than the random comment thread or opinion article because
| they claim to be an authoritative source.
|
| I can't help but think of the Ministry of Truth.
| sdenton4 wrote:
| Why keep reading an article that's placed wrong
| information front and center? The false info should lower
| your prior on anything else the article says...
|
| Unless of course you're just looking to confirm your
| biases, in which case you'll find whatever you want to
| find.
| ashtonkem wrote:
| So basically someone proved their position thoroughly
| with regards to this singular claim, but you're still
| skeptical towards the fact checkers because ...? Kinda
| seems like the fact checkers were right here, and yet you
| still persist for whatever reason.
| ccn0p wrote:
| The problem with "fact checkers" is you can design them
| any way you want to get the answer you want. Here's how
| this is done with this one:
|
| Yes, the claim that Pfizer's new pill is "just repackaged
| Ivermectin" is certainly verifiably false, so the second
| line of the article can claim false followed by a
| supporting expert quote to drive it home. Statistically
| something like 95% of readers will stop there. Case
| closed. They're convinced.
|
| But it's not hard to find lots of front-line doctors who
| are seeing success with Ivermectin. Even the 4th-to-last
| paragraph in the factcheck article (that I cited) admits
| that Ivermectin "acts like a protease inhibitor" which is
| how the new patented "covid pills" will also act.
|
| If you follow many of these voices like I do, you see
| patterns that they aren't really even claiming that the
| new drug is exactly like Ivermectin. So even framing the
| question like this is a failure and doesn't capture the
| actually-useful voices out there. Probably just the
| Twitter mobs which always _seem_ like the majority these
| days, but are far from it.
|
| This doesn't prove anything, nor am I claiming that
| Ivermectin works, but advancing the conversation is so
| much more nuanced than framing something and then calling
| it false. We, dear Hacker News readers, should know this
| better than most.
| nuerow wrote:
| > But it's not hard to find lots of front-line doctors
| who are seeing success with Ivermectin.
|
| If that was true then how do you explain the fact that so
| far no study was able observe or reproduce that effect
| under a controlled environment?
| naasking wrote:
| Technically not correct. Most blinded, randomized
| controlled trials showed improvements in symptoms and
| timeline [1,2,3, among others], but they are generally
| underpowered and so many consider the results to be not
| compelling. All the headlines you may have read that
| ivermectin studies found no results are way overblow;
| science journalism has never been great to begin with,
| and now politics has thoroughly infected this so signal
| to noise on this question is terrible. Some better trials
| are underway now, so we'll see.
|
| Not surprising, the patentable drug got a decent trial
| since pharma actually has a much bigger financial
| incentive there.
|
| [1] https://ejmo.org/pdf/A%20Comparative%20Study%20on%20I
| vermect...
|
| [2] https://journals.sagepub.com/doi/pdf/10.1177/03000605
| 2110135...
|
| [3] https://www.sciencedirect.com/science/article/pii/S25
| 8953702...
| AshamedCaptain wrote:
| It is not hard to find lots of front-line doctors who
| have success with sugar pills (see: homeopathy). This
| means absolutely nothing.
|
| People always seem to have trouble with statistics when
| stuff is not digital-like clear cut. In many areas (e.g.
| anything involving social studies), your noise levels are
| huge. The fact that you hear "some success stories"
| usually means that there is absolutely nothing, rather
| than indicative of something. When there is interest (and
| thus publication bias), the noise level actually
| increases.
|
| For something in medicine to be actually plausibly
| effective, what you need to hear is more like "few
| failure stories". "Some success stories" doesn't even
| start to cut it. Our current research/publish system just
| cannot be used to identify treatments that have low
| effectiveness (which may actually be a good thing). We
| went over this topic not long ago in HN.
| [deleted]
| [deleted]
| swader999 wrote:
| It deserves consideration. Saved my but.
| twofornone wrote:
| Interesting. So this drug, in addition to the novel compound
| being developed as a covid treatment by Pfizer, is a protease
| inhibitor, targeting TMPRSS specifically...just like a certain
| "horse dewormer" from recent memory[0]. Yeah, I know, "in vitro".
| Did you also know that the emergency vaccine authorization is
| explicitly contingent on there being "no adequate, approved, and
| available alternative to the product" for covid19[1]? Very
| interesting indeed.
|
| 0.
| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8203399/#!po=12...
|
| 1. https://www.google.com/amp/s/theconversation.com/amp/what-
| ar... NOTE: it's getting hard to search for sources that mention
| this fact, and now that what little faith I've had in our
| institutions has effectively been destroyed, I suspect this is an
| emergent, collective, deliberate exclusion. Wouldn't want to give
| the proles any strange ideas about "conspiracy theories" and
| such.
| elevenoh wrote:
| Inconvenient to vaccine mandates & pharma lobbyists, so will we
| see it prescribed?
| penagwin wrote:
| > PNAS October 26, 2021 118 (43) e2108728118;
| https://doi.org/10.1073/pnas.2108728118
|
| I'm curious how was this published October 26, 2021? (Currently
| Oct 15)
| beakerbreaker wrote:
| That's the real advance! :)
|
| PNAS recently moved to a continuous publication process so the
| paper comes out in the planned issue whenever ready rather than
| effectively coming out twice: once ahead-of-print and once in
| the issue.
|
| https://www.pnas.org/page/updates#pnas-continuous-publicatio...
| vidanay wrote:
| Probably the date of the print publication.
| ashtonkem wrote:
| I wonder if they actually used human lung cells for this test;
| the article doesn't seem to specify. Past tests have used Vero
| cells, which are apparently the norm for virology research, but
| aren't a good analogue for human cells for Covid infection. This
| seems to be why some compounds worked well in a Petri dish, but
| didn't work in actual humans.
| raphlinus wrote:
| Here's the actual paper:
| https://www.pnas.org/content/118/43/e2108728118
|
| There's a lot of detailed discussion about different types of
| cells. Vero cells don't have TMPRSS2, but Calu-3 (human lung
| epithelial) cells do. To dramatically oversimplify, this
| compound works on the latter type but not the former.
|
| They also did a little safety testing in a mouse model. This is
| _early_ stage, as you point out there are a lot of things that
| work well in the lab and not so much in real humans, but still
| I find it promising.
| ashtonkem wrote:
| I'm not the best reader of scientific papers, but it looks
| like they used human lung cells and Vero cells. I'm not
| qualified to speak to the rest of the experimental design,
| but it looks like they've at least avoided that old mistake.
|
| > We analyzed pseudotype entry driven by the spike protein of
| SARS-CoV-2 (SARS-2-S) or the glycoprotein of vesicular
| stomatitis virus (VSV-G) into the TMPRSS2-positive human lung
| cell line Calu-3 (7, 29). VSV-G was used as a control, as it
| does not depend on TMPRSS2 for host cell entry. Besides
| Calu-3 cells, we further used Vero cells (African green
| monkey, kidney) as a control, as these cells do not express
| TMPRSS2, and therefore any reduction in SARS-2-Sdriven entry
| would be related to either unspecific side effects or
| cytotoxicity.
| raphlinus wrote:
| I'm starting to get pretty optimistic. There seem to be a bunch
| of antivirals with very different mechanisms of action - this one
| blocks entry of the virus to cells, Molnupiravir fucks up
| accurate replication of the virus (nucleoside analog), others are
| protease inhibitors, which are very effective against HIV.
|
| There's a caveat, _most_ treatments that look promising don 't
| pan out, but there are a lot in the pipeline and it seems likely
| that some will. What I think will happen is a cocktail of
| antivirals, and together these will significantly reduce the
| mortality. We need that, because it looks like the virus will
| probably be circulating endemically. The other great thing about
| a cocktail (as opposed to a single antiviral) is that the virus
| developing resistance is both less likely and less of a problem
| if it does happen.
| lamontcg wrote:
| Mortality is going to be dramatically reduced once nearly
| everyone has T-cells+B-cells that recognize the virus. If
| everyone got vaccinated we'd be out of the pandemic phase and
| into the endemic phase with a virus that looked more like just
| a flu/cold.
|
| Vaccines are a 10x or 20x improvement in death and
| hospitalization rates. That's just a fact. All these antivirals
| won't have that kind of impact and are closing the barn doors
| after the horse has escaped. Which is not to say we don't
| research both, but vaccination is the simple easy and effective
| answer. There's a considerable technological fetish with
| antivirals while boring vaccines are now treated with
| skepticism, which is backwards. Antivirals should be used after
| vaccines have failed in vulnerable populations, the major
| weapon against viruses is vaccines, and they work.
| gizmo686 wrote:
| A limiting factor for the effectiveness of anti-virals for
| Covid is time. Maximum viral load happens often happens before
| any symptoms are present, and the most severe diseases occurs
| weeks after infection as a result of the bodies inflammatory
| response instead of the virus itself. This means that by the
| time you know that a patient will have severe Covid-19, it is
| likely too late for any treatment that is based on interfering
| with the virus itself.
|
| Having said that, we have a good demographic understanding of
| who tends to get severe Covid-19, and a large testing capacity,
| so a cheap anti-viral treatment with few side effects could
| still be effectively deployed.
| UncleOxidant wrote:
| Given that time is of the essence with antivirals, we need to
| give people lateral flow antigen tests they can take at home
| (very accurate if they come up positive) as well as some kind
| of pre-presciption (show the pharmacist your positive test
| result and get the antivirals or some such). Waiting for a
| doctors appointment will take too much time.
| russdill wrote:
| And I'm going to hazard a guess that the likelihood of not
| getting early testing correlates strongly with the likelihood
| of not getting vaccinated.
| swader999 wrote:
| There are some interesting nasal sprays that wipe out early
| viral load in the nose and throat that are available right
| now. ImmuneMist and XClear for example.
| dangerlibrary wrote:
| ImmuneMist is already facing warnings of regulatory action
| for their false claims re: covid
|
| https://www.ftc.gov/enforcement/warning-letters/warning-
| lett...
| gizmo686 wrote:
| As is XLear https://www.ftc.gov/enforcement/warning-
| letters/warning-lett...
| swader999 wrote:
| There's enough studies since this was sent in April to
| make an educated decision on how to use these.
| sterlind wrote:
| Some nasal sprays do seem to be effective as prophylaxis
| for COVID infection. I'm not sure about Xlear, but
| povidone-iodine nasal sprays seem effective and are
| already used as prophylaxis by dentists.
|
| See:
|
| https://scholar.google.com/scholar?hl=en&as_sdt=0%2C48&q=
| pov... https://jamanetwork.com/journals/jamaotolaryngolog
| y/fullarti...
|
| They're not FDA-approved for this but as long as you're
| taking other precautions, they can't hurt right?
| wongarsu wrote:
| I imagine the willingness to get tested would also be a lot
| higher if the result of a positive test was a reasonably
| quick antiviral treatment instead of weeks of quarantine.
|
| Sure, there will always be sceptics, but for large parts of
| people, organisations and governments having less perverse
| incentives might improve things a lot.
| dukeofdoom wrote:
| Rapid antigen tests take take about 20 minutes.
| SketchySeaBeast wrote:
| But you'd need to get tested for every minor sniffle, or if
| the claim about no symptoms being a time of maximum viral
| load, you'd have to constantly get tested even without
| symptoms.
| mywittyname wrote:
| I feel like I'm pointing out the obvious, but another,
| extremely effect and quick "treatment" is vaccination. And
| it works great without the constant need for testing. I
| have to imagine that anyone willing to undergo treatment at
| the very start of getting covid, would have also been
| willing to be vaccinated.
|
| The vaccine-hesitant aren't going to go for treatment until
| the outlook is dire.
|
| Additionally, in my experience, physicians aren't terribly
| concerned about infections in vaccinated individuals. When
| I was last tested, the physician essentially just assured
| me that vaccinations have been shown to drastically reduce
| the likelihood of complications, and not to really worry
| about it. Granted, I could have had a less rigorous
| physician, or it could that I'm totally healthy.
| TurkishPoptart wrote:
| Not anymore. Because it turns out mRNA vaccination
| efficacy drops off after 6-9 months, which is why they're
| rolling out booster shots in my country. I fear that soon
| "fully vaccinated" will mean one has had a series of 4
| shots by that point. (And if you don't like that, we're
| taking away your job).
| UncleOxidant wrote:
| > The vaccine-hesitant aren't going to go for treatment
| until the outlook is dire.
|
| Many of them seem quite willing to get ivermectin
| (whether it works or not is another issue). This is a
| tribal thing: one tribe has determined that the vaccine
| isn't something their tribe gets, but many of them seem
| willing to try other treatments that are acceptable to
| the tribe. (and yes, that's not rational, but humans are
| often irrational)
| wongarsu wrote:
| There's also the perceived seriousness of a treatment. A
| nasal spray is harmless, a capsule is more substantial,
| an injection is serious business. You see the same thing
| with placebos, with saline injections being more
| "effective" than sugar tablets. And a vaccine is not just
| an injection, it's some kind of miracle thing that cures
| an infection you don't even have yet.
|
| It's not surprising people are far more willing to try
| out sprays and tablets than injections, even if there
| wasn't any misinformation and tribal politics
| UncleOxidant wrote:
| There are nasal covid vaccines in development. I suspect
| some of the hesitant would take them, but I've talked to
| anti-vaxxers who still would not even take a nasal
| vaccine.
| Symmetry wrote:
| It's too bad we couldn't arrange it so that one vaccine
| could be the "Trump vaccine" that Republicans could get
| and another could be the "Fauci vaccine" for Democrats.
| Then people could express their political affiliations in
| their medical choices but still get vaccinated. There
| were a lot of Democratic politicians talking about not
| trusting rushed vaccines a year ago and if that could
| have focused on specific vaccines and kept going maybe
| we'd be in a better place today with regards to
| vaccinations.
| sterlind wrote:
| My partner is ex-Christian Scientist (a faith-healing
| cult that doesn't believe in disease or medicine.) Zir
| whole family finally relented and got vaccinated, but
| they all got J+J. I don't know why that vaccine in
| particular (maybe because it's single-shot, so they only
| have to deal with hypocrisy once?) but that vaccine is
| popular with that cohort.
| __blockcipher__ wrote:
| Just out of curiosity- they used to be a christian
| scientist and now they're not and go by xe/zir style
| pronouns? That's quite a journey if so.
|
| As for J&J, yes it's generally the fact that it's one and
| done so it feels less risky to people that didn't want to
| get vaccinated. Then there's the whole mRNA thing as
| well.
| sterlind wrote:
| Zie grew up in CS, but was queer, and CS (at least back
| then) was very anti-LGBT. Principia, the CS university,
| would expel openly gay students and fire openly gay
| professors, and zir parents were homophobic too. The mom
| would listen to testimonials of people's "healings" of
| their same-sex attraction.
|
| That made zir not fit in, and accelerated zir dropping
| out of CS and discovering the LGBT community, and non-
| binary identity.
| __blockcipher__ wrote:
| Thanks for that context. I learned a bit about something
| new :)
| InitialLastName wrote:
| It could just be GP's preferred way of anonymizing their
| SO without having to resort to the dreaded singular
| specific "they". Call it light-weight anonymization to
| make it more difficult to be casually doxxed.
| speeder wrote:
| I wanted JJ because not mRNA and is accepted in several
| countries.
|
| The JJ mechanism of action is better understood and less
| risky, in my view at least it is more acceptable for
| emergency approval.
| subsubzero wrote:
| I agree, but vaccines in this case have their definite
| drawbacks as seen in vaccine-heavy Israel in that their
| effectiveness wears off after a few months.
|
| I have personally heard of a number of pretty bad
| breakthrough cases where a person has had a fever for
| almost a month, another was extremely sick and there are
| still people who are afraid of covid for this very
| reason(and they are vaccinated). Having an effective
| anti-viral solution will bring down the fear about these
| scenarios and get people back to work and bring normalcy
| to society again.
| bluGill wrote:
| Lets be careful there. While vaccines do wear off, they
| are not wearing off nearly as fast as most people using
| that line are saying.
|
| Also, Isreal is no longer vaccine heavy. They were an
| early leader, but many other countries exceed their
| vaccine rates these days.
| LurkingPenguin wrote:
| > I feel like I'm pointing out the obvious, but another,
| extremely effect and quick "treatment" is vaccination.
|
| Does every discussion of about post-exposure prophylaxis
| have to have comments about vaccination?
|
| > And it works great without the constant need for
| testing.
|
| A primary reason for testing has been to help stop the
| spread of the virus (test positive = isolate), not
| necessarily to let people with mild symptoms or no
| symptoms know that they're infected.
|
| Vaccinated individuals can still spread the virus and
| some people are at higher risk even when vaccinated, so
| testing is still of value.
|
| > I have to imagine that anyone willing to undergo
| treatment at the very start of getting covid, would have
| also been willing to be vaccinated.
|
| That's quite an assumption. Without passing judgment
| about his decision not to get vaccinated and to throw the
| kitchen sink at COVID once he was infected, Joe Rogan is
| an example of a person who is willing to treat an
| infection but not get vaccinated. I doubt he's the only
| one.
|
| > Additionally, in my experience, physicians aren't
| terribly concerned about infections in vaccinated
| individuals.
|
| Vaccination certainly reduces the incidence of
| hospitalization and death, and the data to date suggests
| that vaccinated individuals are less likely to develop
| "long COVID" symptoms. But there's still a lot we don't
| know. Research indicates that individuals with
| breakthrough infections can have viral loads that are as
| high as unvaccinated individuals, and some percentage
| report courses of illness that are virtually identical to
| a typical course of illness in unvaccinated individuals
| (respiratory symptoms, extreme fatigue, etc.) so I think
| it's premature to make too many assumptions. Especially
| since in immunologically naive people, some with "mild"
| or even largely asymptomatic infections also report
| lasting issues too.
| bawolff wrote:
| > Research indicates that individuals with breakthrough
| infections can have viral loads that are as high as
| unvaccinated individuals, and some percentage report
| courses of illness that are virtually identical to a
| typical course of illness in unvaccinated individuals
|
| But that's totally expected (depending of course on how
| you define "some"). If the vaccine had 100% efficacy, it
| would be shocking. The fact that it doesn't is not a
| surprise.
|
| I'm assuming the point you're trying to make is vaccines
| aren't as good as expected. If the point is just that
| there is still value in developing treatments even with
| vaccines, than yes i agree with you.
| space_fountain wrote:
| Edit: My understanding of the science here was at least
| slightly wrong. Please see the reply from LurkingPenguin
| and eventually my reply to them
|
| I think results like vaccinated individuals "can" have
| viral loads as high as unvaccinated individuals are next
| to useless. I need to know how likely I am to have high
| viral loads and my understanding of the science there is
| that vaccines still do a decent job of lowering the odds.
| I know you aren't really arguing against vaccination
| here, but it seems like it needed to be said and I think
| the "vaccinated individuals can have high viral loads"
| line is particularly bad
| LurkingPenguin wrote:
| > I think the "vaccinated individuals can have high viral
| loads" line is particularly bad
|
| https://www.medrxiv.org/content/10.1101/2021.09.28.212642
| 62v...
|
| https://www.ucdavis.edu/health/covid-19/news/viral-loads-
| sim...
|
| How is a statement about what some researchers are
| finding "particularly bad"? If vaccinated individuals
| routinely have viral loads as high as those seen in
| unvaccinated individuals, it warrants more research into
| how the virus affects their bodies and what, if any,
| risks they might face both short term and long term.
|
| According to one study[1], vaccination reduces the risk
| of long COVID by 49%. Given that some studies have found
| the incidence of long COVID is in the double digit
| percentages[2], exploring this issue is not purely
| academic. It is pertinent to the hundreds of millions of
| vaccinated individuals who are still at risk of
| infection, even if their risk of hospitalization and
| death has been significantly reduced.
|
| Science works when we ask and investigate important
| questions. It doesn't work when we ignore these questions
| because we're afraid of the optics and how they might be
| misconstrued by some people.
|
| In fact, when it comes to COVID generally, it seems
| evident to me that shying away from difficult questions
| has had the opposite of the intended effect. It has
| probably caused more people to adopt anti-science views
| and reject beneficial measures like vaccination.
|
| [1] https://www.usnews.com/news/health-
| news/articles/2021-09-02/...
|
| [2] https://www.medicalnewstoday.com/articles/more-than-
| one-thir...
| space_fountain wrote:
| Welp, this is making me realize I was just wrong. My
| understanding of the science was something like you can
| find asymptomatic vaccinated individuals with similar
| viral loads to asymptomatic unvaccinated people, which is
| a bit meaningless when you're choosing a threshold for
| "infected" and when random chance will just see some
| people at any level. So to be clear it's not that I think
| the questions shouldn't be investigated, but a statement
| like "some vaccinated cases have high viral loads" is
| meaningless to explaining what my risk of spreading covid
| is.
|
| Trying to avoid the sort of bias that comes from trying
| to reinforce rather than question existing views, but I
| do still think the statement "No Significant Difference
| in Viral Load Between Vaccinated and Unvaccinated,
| Asymptomatic and Symptomatic Groups Infected with SARS-
| CoV-2 Delta Variant" despite being much more precise is
| still a bit unintuitive in it's implication. Because
| essentially what this means right is that they sampled
| people's viral loads, and then cut out everyone below a
| value they choose to mean "infected". It's still true
| that even if I had symptoms because I'm vaccinated my
| odds of having a high viral load are much lower.
| Presumably if you didn't remove all the samples with less
| than some concentration you'd see significant
| differences.
|
| I think that something the scientists got wrong
| consistently with covid was not unflinchingly
| communicating what was likely to be true mostly out of a
| fear that the public would take interventions that only
| moderately improved their safety like wearing a mask, and
| start doing riskier things or because of a bias towards
| doing nothing when clear evidence didn't exist. It can
| feel like similar things are happening with vaccination
| where it does seem pretty clear that getting vaccinated
| reduces your risk of passing on covid both because you're
| less likely to ever get a colony of the virus sufficient
| to count as "infected" and because you're likely to have
| a shorter infection.
| LurkingPenguin wrote:
| > Because essentially what this means right is that they
| sampled people's viral loads, and then cut out everyone
| below a value they choose to mean "infected".
|
| Huh? Please cite the part of the study you're referring
| to to argue that the title of the study means the exact
| opposite of what it says.
|
| _Every_ manufacturer of a PCR test specifies a Ct cutoff
| above which the result is considered false.
|
| > It's still true that even if I had symptoms because I'm
| vaccinated my odds of having a high viral load are much
| lower. Presumably if you didn't remove all the samples
| with less than some concentration you'd see significant
| differences.
|
| The study says the exact opposite:
|
| > _There were no statistically significant differences in
| mean Ct-values of vaccinated (UeS: 23.1; HYT: 25.5) vs.
| unvaccinated (UeS: 23.4; HYT: 25.4) samples._ In both
| vaccinated and unvaccinated, there was great variation
| among individuals, with Ct-values of <15 to >30 in both
| UeS and HYT data (Fig. 1A, 1B). Similarly, no
| statistically significant differences were found in the
| mean Ct-values of asymptomatic (UeS: 24.3; HYT: 25.4) vs.
| symptomatic (UeS: 22.7) samples, overall or stratified by
| vaccine status (Fig. 1B). Similar Ct-values were also
| found among different age groups, between genders, and
| vaccine types (Supplemental Figure 1).
| space_fountain wrote:
| > The study says the exact opposite:
|
| Maybe I'm misinterpreting the study. I interpreted that
| as being among the fraction of people who are infected
| both because that's what the title says, and because they
| say later that "75% of the positive samples were from
| unvaccinated individuals" which would seem to be
| inconsistent with the groups having similar viral loads.
|
| I thought we were dealing with a random variable composed
| something like this
|
| VIRAL_LOAD = INFECTED ? LOAD_FOR_INFECTED :
| LOAD_FOR_UNINFECTED
|
| And the study is saying that the random variable
| `LOAD_FOR_INFECTED` isn't correlated with vaccination
| status. That's indeed an interesting fact, but since
| `INFECTED` still was correlated (I think) overall for
| some random person `VIRAL_LOAD` would be too. Honestly a
| table would make all of this more clear.
| spfzero wrote:
| I think partly what's going on is that some people have
| immune systems that have a hard time generating an
| effective response, whether or not they area vaccinated.
| Vaccination gives the immune system a chance to respond
| and memorize, as best it can. If it can't do that
| effectively, there is higher likelihood of a serious
| outcome.
| __blockcipher__ wrote:
| I think this is very unlikely to significantly explain
| what we've seen. It's much more likely just the natural
| result of artificial immunity waning much more rapidly
| than naturally acquired. As well as the fact that natural
| immunity involves exposure to the whole virus and
| therefore much broader types of epitopes for the immune
| system to "learn".
| walterbell wrote:
| In addition, intramuscular vaccines only provide
| blood/serum antibodies, while nasal infection also
| provides nasal/mucosal antibodies. Those who recover from
| Covid infection gain sterilizing immunity (less than 1%
| will be reinfected) that stops future infections in the
| upper respiratory tract.
|
| That's why the CDC website says Covid (leaky, non-
| sterilizing) vaccines only provide protection (in blood)
| against serious illness, not infection (in nose). A
| future nasal vaccine may provide sterilizing immunity
| (what most people assume they are getting from a
| "vaccine", like their personal experience with the MMR
| vaccine).
| 8note wrote:
| "sterilizing" seems to get a different definition every
| time I hear it.
| walterbell wrote:
| There's a stable definition in textbooks.
|
| If 2021 consumer media is offering variable definitions,
| _Cui Bono?_
| space_fountain wrote:
| I think these things are hard to be sure about, but there
| still is good evidence that covid vaccines are
| sterilizing in a lot of cases. The rate of infection is
| still lower for vaccinated people right when controlling
| for other demographics?
| jaywalk wrote:
| >there still is good evidence that covid vaccines are
| sterilizing in a lot of cases.
|
| What? No, there isn't. The Covid vaccines we have today
| are not sterilizing. Period. This isn't a conspiracy
| theory or anything like that, it's just a simple fact.
| space_fountain wrote:
| Maybe I'm just not understanding the terms correctly. My
| understanding is that covid vaccines do still reduce the
| odds of becoming infected with covid when exposed. We
| don't have conclusive evidence of this because the sort
| of people who get vaccinated aren't identical to those
| who don't but it's decently convincing just based on case
| counts. I also see a number of studies suggesting
| vaccination reduces the probability of spreading covid
| even with delta.
| jaywalk wrote:
| A sterilizing vaccine means that you cannot get infected
| when the vaccine works successfully. Not "less likely to
| get infected" or "less likely to experience severe
| symptoms if you get infected" like the Covid vaccines.
| walterbell wrote:
| Covid vaccines reduce symptoms. They increase the risk of
| asymptomatic transmission, since the person would
| otherwise self-isolate.
|
| BBC article on immunity,
| https://www.bbc.com/news/health-58270098
|
| _> There is a whole different suite of antibodies (known
| as immunoglobulin As) in the nose and lungs, compared
| with those (immunoglobulin Gs) that we measure in the
| blood. The former is more important as a barrier to
| infection. Natural infection, because it is in the nose
| rather than a jab in the arm, may be a better route to
| those antibodies, and nasal vaccines are being
| investigated too._
|
| Intramuscular (arm injection) vs intranasal (inhaled)
| vaccines: https://news.ycombinator.com/item?id=28165287
|
| Nasal vaccine trials:
| https://news.ycombinator.com/item?id=28284504
| dukeofdoom wrote:
| I think also something that should be considered how the
| vaccine works if the immune system is already battling
| something. Anecdotally I know a person who's tumor had
| doubled in size after she took the vaccine. It could be
| coincidence. But at the same time, do we know how much an
| immune system directs it resources, and does it
| prioritize and immediate infection vs one that is latent.
| [deleted]
| pfdietz wrote:
| If the antivirals are highly effective one could really slam
| the immune system to stop any damaging response without the
| virus again going out of control.
| beakerbreaker wrote:
| That's a good point on the limitation, and to expand on your
| last point, an immediate demographic this could help is
| frontline healthcare workers and similar jobs who do get
| routine testing and are at higher risk in general.
| mlyle wrote:
| Yup.
|
| I'm a teacher and vaccinated. If I found out that I was
| exposed, and then tested positive... post-exposure
| prophylaxis sounds _great_.
|
| Also there's my dad, who has an immune condition due to old
| age. He's vaccinated, but who knows how effective the
| vaccine was for him. The existence of PEP could make it
| possible for him to do more at a similar level of safety...
| vs. the current option of staying in a small bubble for the
| rest of his life despite being otherwise able-bodied and
| capable.
| grey413 wrote:
| FYI, your dad would most likely already qualify to
| receive the antiviral antibody treatments that have been
| given emergency authorization by the FDA.
|
| https://www.covid19treatmentguidelines.nih.gov/therapies/
| ant...
| angelzen wrote:
| > Molnupiravir [interferes with] accurate replication of the
| virus
|
| At first glance this sound like a really bad idea, given that
| the #1 concern is future covid mutations.
| ralusek wrote:
| It specifically causes non-viable mutations. Therefore, the
| concern isn't currently that it'll cause mutations in the
| virus and create new strains, but rather that we have to be
| very confident that it isn't resulting in mutagenicity in
| mammalian cells.
|
| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8136050/
| angelzen wrote:
| Thanks, I wasn't aware of that.
| thehappypm wrote:
| It's almost like we're emerging into a world just like the
| world when antibiotics were invented, but for antivirals. We
| basically had just a small handful of treatments for viruses,
| now there's a huge pipeline all of a sudden. Maybe in the
| future, having effective antivirals for just about any virus
| will be the norm, not the exception.
| tim333 wrote:
| Molnupiravir seems pretty good. I think in the trials eight
| people died in the placebo group, zero with the drug.
| ashtonkem wrote:
| mRNA vaccines look extremely promising too. It's entirely
| possible that some classes of cancer will be effectively
| eliminated in our lifetime because of it, along with HIV and/or
| Malaria. The latter would probably be the biggest reduction in
| human death and misery since the invention of the Polio vaccine
| mschuster91 wrote:
| I wonder if the final stage will rather be direct production
| and injection of tailored antibodies instead of going around
| the corner by having ordinary cells express proteins that
| then trigger the immune system.
| JumpCrisscross wrote:
| > _direct production and injection of tailored antibodies
| instead of going around the corner by having ordinary cells
| express proteins that then trigger the immune system_
|
| Triggering the immune system does a lot more than produce a
| single wave of antibodies.
| meepmorp wrote:
| Does "going around the corner," mean vaccines?
| tombert wrote:
| I've been saying for roughly a year now that if nothing else
| good can come from Covid, we at the very least are dumping a
| ton of time and resources and research into mRNA vaccines.
|
| I know basically nothing about virology, but I remember
| hearing a podcast a million years ago talking about mRNA
| vaccines, and I remember after it was over thinking "if this
| is even half as cool as it sounds to a lay person, the
| implications of this are _huge_ ". It appears that it's
| substantially more than half as cool as it sounded, and the
| fact that we are even having discussions about being able to
| wipe out malaria is mind-boggling to me (in a good way).
| orra wrote:
| We developed several working vaccines, and in record time.
| A triumph of scientific engineering.
|
| I too am very hopeful for mRNA vaccines, although I don't
| know how much I should temper my expectations. The idea of
| _curing_ certain cancers, not just preventing them, is
| wild.
| vibrato2 wrote:
| Except we had to change the definition of "working
| vaccine" to fit these new therapies.
|
| Traditionally a vaccine has to keep efficacy for a year.
| We haven't got a year of data but the efficacy has
| dropped significantly
| raphlinus wrote:
| I call bullshit. Antibodies wane but the memory cell
| response is robust and holds up over what looks to be a
| pretty long period (studied intensively for 6 months but
| with no sign of decline). Here's a new paper that shows
| that in detail (paper itself is dense but Twitter thread
| is fairly accessible):
|
| https://twitter.com/rishirajgoel/status/14487119460107100
| 23
|
| By basically all measures, these vaccines work better
| than the flu vaccine, which for some reason doesn't
| attract the same sort of criticism.
| [deleted]
| angelzen wrote:
| Great link, summarizing recent research showing strong
| post-vaccination long-term B cell response.
|
| Then Twitter surfaces a recent breakthrough infection
| study among 620k US veterans in the "More Tweets"
| section:
| https://twitter.com/EricTopol/status/1448815262522773520
| After six months from initial vaccination (Mar-Aug) the
| J&J vaccine appears to have zero (!) VE against
| infection. Pfizer is holding at a modest 53% against
| infection. Worse, the curve has the same shape as J&J,
| merely 2 months delayed.
|
| In spite of very promising cellular and molecular
| studies, I am left scratching my head: are the vaccines
| any good at preventing infection in the long term, where
| we define long term as a few years down the road? The
| question is somewhat rhetorical, as we don't have epi
| studies from 2025 yet.
|
| PS. I am more than happy to make a distinction between
| infection and severe infection. The main reason I pay
| attention to VE against infection are vaccine mandates
| and the whole stigma buildup against unvaccinated people.
|
| PS2. > the flu vaccine, which for some reason doesn't
| attract the same sort of criticism.
|
| People are free to get or not get a flu vaccine. Not
| getting a covid vaccine means loss of livelihood, loss of
| basic liberties and social ostracism.
| orra wrote:
| It's weird to be so focused on infection, when efficacy
| against severe disease is more practically relevant. And
| the latter remains high, around 92% or higher, even
| against Delta.
|
| Vaccine protection isn't binary. Even if you end up
| infected your disease will be less severe AND you will be
| less contagious.
| [deleted]
| tombert wrote:
| I don't know enough about vaccines to dispute what you're
| saying (though I feel like I have heard contrary data on
| this), but even if it's only fully effective for 8-9
| months, isn't the fact that we had a vaccine that
| accomplished at least _some_ of its goals safely designed
| and tested in record time a really cool thing?
|
| Even if it's only effective for 6 months, that's still 6
| months of slowing the spread, and conceivably we can
| extend the efficacy by administering booster shots.
| SketchySeaBeast wrote:
| It's not as though the concept of a vaccine booster is
| new, after all we get annual flu shots. It's also a
| question of efficacy of the vaccine versus the new
| predominate variant. Delta didn't exist when the vaccines
| were finalized.
| mywittyname wrote:
| My understanding is that all vaccines have similar
| "effectiveness curves", in that they are highly effective
| in the first weeks, and effectiveness degrades over time
| down to some low base level of immunity, where your body
| is no longer actively producing antibodies, but it has
| the ability to restart production quickly if necessary.
| JamesBarney wrote:
| It's efficacy as measured as "chances of getting sick"
| declines significantly, but it's still pretty effective.
|
| But the protection against hospitalization and death is
| still very robust even after almost a year.
| tombert wrote:
| I haven't even heard about the curing cancer part, that's
| awesome if it's true.
|
| I think I'm going to temper my expectations to "faster
| and more vaccines increasingly exotic diseases" for now.
| I would absolutely love to be proven wrong though.
| adolph wrote:
| _Chimeric antigen receptor (CAR) T-cell therapy is a way
| to get immune cells called T cells (a type of white blood
| cell) to fight cancer by changing them in the lab so they
| can find and destroy cancer cells. CAR T-cell therapy is
| also sometimes talked about as a type of cell-based gene
| therapy, because it involves altering the genes inside T
| cells to help them attack the cancer._
|
| ...
|
| _In CAR T-cell therapies, T cells are taken from the
| patient 's blood and are changed in the lab by adding a
| gene for a man-made receptor (called a chimeric antigen
| receptor or CAR). This helps them better identify
| specific cancer cell antigens. The CAR T cells are then
| given back to the patient._
|
| https://www.cancer.org/treatment/treatments-and-side-
| effects...
|
| Right now this is done in a very personalized and labor
| intensive way. I think the thought is mRNA is potentially
| a gigafactory compared to artisanal methods.
| anonfornoreason wrote:
| They also can only target cancers that have specific
| markers that are unique to the cancer and not normal
| cells, lest the treatment kill non cancer cells. Early
| experiments here did lead to patient deaths (in advanced
| already going to die cancer patients). Not all cancers
| have these unique markers so this therapy only works on a
| few types,m.
|
| Fantastic podcast covering topic by interviewing the
| father of these therapies:
|
| https://youtu.be/pVMl0LgdnOU
|
| Podcast available on Apple podcasts etc. The Drive
| episode 177.
|
| can't recommend enough.
| notsureaboutpg wrote:
| >I know basically nothing about virology, but I remember
| hearing a podcast a million years ago talking about mRNA
| vaccines, and I remember after it was over thinking "if
| this is even half as cool as it sounds to a lay person, the
| implications of this are huge".
|
| Sounds like scientism. A guy on a podcast said these are
| promising and you said for a whole year, without
| understanding anything about virology, that it was really
| important and good to pour time and resources into these
| things?
|
| I mean, maybe you are not wrong, but this is a terrible way
| to determine priorities for spending and work...
| [deleted]
| raphlinus wrote:
| A really excellent survey on the prospects for mRNA
| technology from Derek Lowe:
| https://www.science.org/content/blog-post/what-mrna-good-
| and...
| vibrato2 wrote:
| Biggest pharma shill in media
| nekt wrote:
| This blocks TMPRSS2 which is the exact protein ivermectin blocks.
| randomopining wrote:
| Ivermectin doesn't have any legit studies with large samples to
| show that it's even that useful against covid.
|
| Also, what happened to hydroxychloroquine? That was the big
| thing in 2020. guess 2021 is ivermectin.
| LMYahooTFY wrote:
| Based on what metric?
|
| The vaccines were authorized under emergency use with trial
| participants comparable to samples conducted with Ivermectin.
|
| How is it not worth considering for a drug that's already
| known to be safe to administer and cheap?
|
| Beyond that, there are practicing doctors advocating that
| they've had good results. This should be more than enough to
| consider it's use, and not dismiss it as some 'thing of the
| year to dismiss'.
| randomopining wrote:
| "The Phase 3 clinical trial of BNT162b2 began on July 27
| and has enrolled 43,661 participants to date, 41,135 of
| whom have received a second dose of the vaccine candidate
| as of November 13, 2020."
|
| Wow so there was an ivermectin study with 44k people? Where
| is it?
|
| I agree that it should be able to be studied and probably
| used. But what's going on is that people are looking for an
| ALTERNATIVE to the vaccine... which is detrimental when the
| vaccine is proven to be our best tactic against
| death/serious illness.
| bluGill wrote:
| > Wow so there was an ivermectin study with 44k people?
| Where is it?
|
| There wasn't. Once you eliminate the studies that made up
| their data it is clear ivermectin doesn't work in the few
| studies that are left so nobody would bother doing a big
| study.
| __blockcipher__ wrote:
| Fun fact: the trial you referenced failed to show any
| benefit of COVID vaccination in reducing all-cause
| mortality in the population they studied:
|
| https://www.medrxiv.org/content/10.1101/2021.07.28.212611
| 59v...
|
| > During the blinded, controlled period, 15 BNT162b2 and
| 14 placebo recipients died; during the open-label period,
| 3 BNT162b2 and 2 original placebo recipients who received
| BNT162b2 after unblinding died. None of these deaths were
| considered related to BNT162b2 by investigators.
|
| There was actually one more death in the experimental
| group, albeit that's not significantly significant.
|
| So some combination of the following must be true:
|
| (1) The vaccination is effective at reducing COVID
| mortality, but COVID mortality for people in the trial
| was such a joke that eliminating 95% of COVID mortality
| doesn't actually change one's risk of dying in a non-
| negligible manner
|
| (2) The vaccination is effective at reducing COVID
| mortality, which does spare lives, but it ends up killing
| just as many from adverse events / side effects
|
| (3) The vaccine isn't effective and they doctored the
| numbers.
|
| My money is mostly on (1) with a sprinkling of (2),
| personally.
|
| ---
|
| And since people like to be binary thinkers, this is
| where I mention that I'm not an Ivermectin shill and as a
| medical nihilist I'm strongly skeptical of treatments in
| general. And while I haven't looked at the IVM data very
| much at all, what I have seen is incredibly weak evidence
| at best, as well as a bunch of really crappy associative
| arguments from the IVM crowd ("Africa uses IVM and Africa
| has less COVID mortality than the US!" as if that proves
| anything)
|
| To quote (slightly paraphrased) the great Jacob Stegenga:
|
| > If we consider the ubiquity of small effect sizes in
| medicine, the extent of misleading evidence in medical
| research, the thin theoretical basis of many
| interventions, and the malleability of empirical methods,
| then our confidence in medical interventions ought to be
| low.
| phonypc wrote:
| > _Fun fact: the trial you referenced failed to show any
| benefit of COVID vaccination in reducing all-cause
| mortality in the population they studied:_
|
| Is the implication that we should have expected it to?
| The study endpoints are clearly "vaccine efficacy (VE)
| against laboratory-confirmed COVID-19 and safety data".
| __blockcipher__ wrote:
| I think most people would have expected it to. Whether
| that's a reasonable expectation or not is up for debate.
| But yeah, many if not most people in the US were
| convinced that COVID was a threat so severe that it
| warranted completely uprooting life as we knew it. A
| sizeable minority of people are convinced that COVID
| vaccination is so important that people should be coerced
| into it by almost any means necessary. So I think
| understanding that we don't have a single randomized
| controlled trial that actually shows a reduction in all-
| cause mortality when given this intervention is pretty
| important.
|
| It's a general principle of medicine (or at least, it
| used to be) that the important outcomes are the actually
| clinically relevant outcomes. Did people die less? Did
| they achieve a better quality of life? When you get into
| proxy metrics you get to this weird place where you can
| show that something is insanely effective for proxy
| metric X, and yet it makes no difference (or is even
| deleterious) in thing-you-actually-care-about Y.
| j-wags wrote:
| I initially skipped over this post because it appeared to
| be written in bad faith [1]. But I gave it another shot
| and read the linked paper, and I agree with the summary.
| Thanks for pointing this out -- your post has changed my
| understanding of the vaccine's effectiveness.
|
| For skeptical readers - The linked paper is a medrxiv
| preprint, with authors from several locations. Many of
| the authors list affiliations with Pfizer, and the last
| author is an MD at Pfizer. This seems to be a required
| report from the ~6-month point of a clinical trial. There
| really are 14 and 15 all-cause deaths reported in the
| placebo and treatment groups, respectively. The causes of
| death for each group are in table S4 [2]. The incidence
| of COVID in the treatment group is much lower than in the
| placebo group.
|
| I'm surprised by these results because I would have
| expected to see significantly lower mortality in the
| vaccine group.
|
| One possible reason for this surprising result is that
| only a small fraction of people - even in the placebo
| group - caught COVID at all. I'm not sure how to account
| for possible missed infections but Figure 2 of the main
| text indicates that 0.08% of the placebo group became
| CASES (which I think means something like "person felt
| bad enough to see a medical professional, who then
| diagnosed them with COVID"), and the table in Figure 2
| indicates that there were 1034 "occurrences" out of
| ~22,000 people in the placebo group (which I read as "~5%
| confirmed infections").
|
| So, it's possible that the beneficial effect of the
| vaccine is still hidden in the statistical noise since
| there have been so few infections in the placebo group.
| It's also possible that some people _were_ harmed by
| receiving the vaccine (see table S4 [2]), so there's a
| fixed harm upfront to the vaccine group, which may
| eventually be surpassed once more of the placebo group
| gets infected.
|
| Thanks for posting this!
|
| [1] I really do appreciate you making this post, and it
| helped me learn something. I would have been more willing
| to read it initially if it had excluded the phrases "such
| a joke", "since people like to be binary thinkers",
| "crappy associative arguments", "to quote the great...".
| It seems like there's a silent majority of HN lurkers
| that are interested in all perspectives, and really are
| open to quality arguments like this, but might dismiss
| this post before reading it because of the choice of
| phrases.
|
| [2] Link to supp material PDF is on this page: https://ww
| w.medrxiv.org/content/10.1101/2021.07.28.21261159v...
| __blockcipher__ wrote:
| [meta: this was supposed to be a quick response and then
| I ended up getting real longwinded]
|
| Glad you got some value out of my comment!
|
| Thanks for the feedback on my tone. In particular the
| references to specific examples was very helpful to me.
| I'll [try to] be mindful of its effect in the future.
|
| Not that it's necessary but just because it's kind of
| interesting to psychoanalyze, I think some of the tone
| comes as a [maladaptive] response to past times on HN
| where I'd go really deep into analyzing certain studies,
| etc and then would get downvoted or even flagged because
| the conclusion was that lockdowns were deleterious or
| that mandates are a bad idea, etc.
|
| The binary thinkers comment specifically (you're right
| that it will tend to put people off btw) was because in
| general (not just on HN) it happens all the time that if
| I point out, say, how we don't even have an RCT that
| shows a reduction in all-cause mortality from getting
| COVID-vaccinated, very often I'll get a response to the
| tune of "Ivermectin doesn't even work you dummy" because
| most people seem to only have two boxes to put people in
| (you're either team trump or team biden, team vaccine or
| team ivermectin, etc). But obviously even if I had done
| it in a more diplomatic way, making reference to people
| being binary thinkers is only going to distract from the
| actual points being made.
|
| I am curious of your mentioning of being offput by "to
| quote the great...". Did it sound like I was being
| sarcastic, or was it something else about it? Because I
| intended it in the literal sense, i.e. indicating my
| respect for Stegenga and his work.
|
| ---
|
| Back to the actual study:
|
| > One possible reason for this surprising result is that
| only a small fraction of people - even in the placebo
| group - caught COVID at all. I'm not sure how to account
| for possible missed infections but Figure 2 of the main
| text indicates that 0.08% of the placebo group became
| CASES (which I think means something like "person felt
| bad enough to see a medical professional, who then
| diagnosed them with COVID"), and the table in Figure 2
| indicates that there were 1034 "occurrences" out of
| ~22,000 people in the placebo group (which I read as "~5%
| confirmed infections").
|
| Yes. I suspect that this is partially due to the fact
| that they actually take some steps to confirm that it
| really is COVID, whereas in the real world (at least in
| 2020, but probably still now) they'd run a PCR test with
| an absurdly high cycle threshold cutoff and then call
| that COVID even if you were completely asymptomatic
| (which as an aside is an oxymoron because COVID is
| supposed to stand for "Coronavirus Infectious Disease",
| and yet an asymptomatic individual is not diseased (nor
| are they very infectious btw)). So one interpretation is
| that when care is taken to actually be somewhat careful
| about calling something a COVID case, that the prevalence
| of COVID infection ends up being quite low. Whereas when
| that care is not taken (whether due to negligence or
| institutional incentives to drum up case counts / fear in
| general) you end up with much higher apparent case
| counts.
|
| This is quite speculative, I know. I'd really like to
| look at a chart of reported COVID cases in the US versus
| the rate of cases in this trial. I'd be curious if they
| are similar shape / relative magnitude, or if there's
| dramatically more cases in the US in general than the
| laboratory-confirmed cases in the trial.
|
| I couldn't actually find an actual case definition (maybe
| it's in the supplement?) but I found this under the
| Efficacy subheading in the main text: > BNT162b2 efficacy
| against laboratory-confirmed COVID-19 with onset >=7 days
| post-dose 2 was assessed descriptively in participants
| without serological or virological evidence of SARS-
| CoV-2 infection <=7 days post-dose 2, and in participants
| with and without evidence of prior infection. Efficacy
| against severe COVID-19 was also assessed.
|
| So I think that means when calculating their overall VE
| number, they don't "start counting" lab-confirmed
| COVID-19 until it's been at least a week post second
| dose. I do know in general in these trials they like to
| play that game (ignoring infections before the "fully
| vaccinated" cutoff to get a better-looking VE number).
| Although Figure 2 seems to provide numbers starting
| immediately after dose #1 so I suppose those numbers tell
| us that while VE is quite bad immediately after the first
| dose, its expected value doesn't seem to be negative (at
| least in this cohort)
|
| As an aside, I'd note that they blew up the control arm
| after 6 months, so this is basically the only clean data
| we're ever going to get. Which should be very concerning
| to people considering the enormous push to mandate
| vaccination for an intervention that has never been shown
| to reduce all-cause mortality in the studied populations.
|
| > So, it's possible that the beneficial effect of the
| vaccine is still hidden in the statistical noise since
| there have been so few infections in the placebo group.
| It's also possible that some people _were_ harmed by
| receiving the vaccine (see table S4 [2]), so there's a
| fixed harm upfront to the vaccine group, which may
| eventually be surpassed once more of the placebo group
| gets infected.
|
| Unless the data is doctored or has some flaw that I'm not
| seeing, I agree that a much higher base rate of COVID
| infection would probably have shown a positive effect on
| mortality. Which brings us back to #1 of the 3 positive
| explanations I gave in my original comment. I find it
| very interesting that actual COVID mortality (or even bad
| outcomes) were so rare in this cohort of >44,000 people,
| that a well-over-90-percent-effective-in-reducing-COVID-
| mortality intervention literally did not make a
| detectable effect on net mortality. I think from a
| societal perspective it's quite interesting because
| during the time this trial was running, people were (and
| still are btw) getting bombarded by fearmongering, giant
| red eternally-incrementing "live" death tickers, etc.
|
| It doesn't take some grand conspiracy to see why that
| might be, but I think it's something interesting to
| reflect on. It's a large part of why COVID took me from
| kind of libertarian leaning to full-blown
| anarchocapitalist, because I am personally so disgusted
| by what the media, the public health "authorities", and
| "polite society" at large did in terms of catalyzing such
| tremendous suffering on a worldwide scale (via the
| hysteria, global supply chain disruption, missed medical
| appointments, cancelled elective surgeries, and outright
| authoritarian/totalitarian public policy), for something
| that for _most_ people, they would literally never notice
| if not bombarded about its existence.
| nekt wrote:
| I am not making any claims of any of these substances
| effectiveness in treating covid. I'm just pointing out that
| this substance claims to block the same human protein
| ivermectin does. We can all make of that what we will.
| ashtonkem wrote:
| In political discussions we call this the "anti-anti"
| position. If you're not making any claims that Ivermectin
| works, why are you wasting so much energy and karma
| attacking those that think it doesn't work?
| space_fountain wrote:
| Some quick googling doesn't back this up and my understanding
| is that ivermectin has only shown itself to be effective at
| doses that are higher then are remotely safe. It also just
| isn't the sort of thing there would be incentive to lie about.
| Probably then the straightforward story is true no it's only
| effective as prescribed as treatment for parasites. If you'd
| like to provide some sources though or more explanation that
| would be great.
|
| Note that TMPRSS2 has been a potential target for treating
| covid basically since the beginning, so some one lying and
| claiming it as a mechanism of action isn't surprising
| ralusek wrote:
| I have no opinion whatsoever regarding whether or not
| ivermectin's purported mechanism of action against COVID is
| valid.
|
| However, this:
|
| > It also just isn't the sort of thing there would be
| incentive to lie about
|
| is not true.
|
| There are two incentives to lie about this, if you are in any
| way associated with drug or vaccine manufacturers.
|
| 1.) Ivermectin is out of patent and dirt cheap; basically not
| profitable at all
|
| 2.) Emergency use authorization for the vaccines relied on
| there being no available alternative treatment
|
| Again, I have no opinion regarding whether or not ivermectin
| is remotely useful for COVID. But there are plenty of
| incentives aimed against any older generic being repurposed.
| space_fountain wrote:
| You're discussing incentives that maybe some major drug
| companies might have, but they aren't the only ones around.
| I guess, the more accurate position is that there are
| strong upper bounds to how effective a secretly suppressed
| drug could be. Imagine that ivermectin just cured covid for
| a minute. The would be incredibly easy to prove in a study.
| I mean just observational studies would be glaringly
| obvious. What ambitious young scientist wouldn't want
| curing covid on their resume? So you have to believe,
| either the vast majority of scientists, the press, or
| government are complicit in this conspiracy and I don't see
| strong incentives for any of those groups.
| ralusek wrote:
| Well that's the thing, is that there are literally
| millions of people in entire countries being prescribed
| it. India has dished out millions of doses for COVID, and
| there are many doctors and researchers completely
| convinced by clinical evidence. It's not as if there are
| no people picking up a signal, or that no studies are
| showing utility, it's that the available studies are
| methodologically questionable. But as you are aware,
| there are more formal studies taking place at the moment,
| and the official scientific consensus is that we don't
| yet know.
|
| Again, my argument against you was that you said that
| there was no motivation against it, and I said that
| wasn't true.
| weaksauce wrote:
| > 2.) Emergency use authorization for the vaccines relied
| on there being no available alternative treatment
|
| That's simply so factually wrong it's tough to take it as
| serious. having a treatment that might lessen the severity
| of some percentage of the people that get covid has
| absolutely nothing to do with a prophylactic EUA for a
| vaccine that is wildly efficacious against mild and severe
| covid cases and stop you from getting it in the first
| place. Let's do a thought experiment even if that were
| true... that would mean the other vaccines that are under
| an EUA would have been revoked the moment Pfizer got their
| full approval which didn't happen. This is "there are naval
| insignias on the flags therefore we are not a
| constitutional democracy" level of conspiratorial thinking.
|
| > 1.) Ivermectin is out of patent and dirt cheap; basically
| not profitable at all
|
| that's the reason they threw it at the virus in the first
| place. They were looking for anything that might help.
| nekt wrote:
| Well you're wrong.
|
| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996102/
|
| "Ivermectin was found as a blocker of viral replicase,
| protease and human TMPRSS2."
| analyte123 wrote:
| Computer docking simulations don't prove anything and are
| only possibly useful for initial drug screening.
| nekt wrote:
| He said ivermectin was not found to block TMPRSS2. I
| linked a nih study that said it did.
|
| Now its about proving its efficacy against sars-cov-2?
|
| I believe this is called "moving the goalposts".
|
| And there we have it - in silico is fine for this new
| substance that will likely have a huge price tag. Not
| fine for an existing generic.
|
| Far fewer people are buying this nonsense these days.
| capnrefsmmat wrote:
| For what it's worth, that is not an NIH study; it may be
| listed on PubMed but it appears to be conducted by
| researchers at the Integrative Biochemistry & Immunology
| Laboratory, Department of Animal Science, Kazi Nazrul
| University. PubMed indexes most biomedical literature,
| not just research conducted by the NIH.
|
| And again, computer simulations suggesting that
| ivermectin may interact with a specific protein is not
| the same as saying that it indeed does do so in human
| tissue.
| nekt wrote:
| Im unsure of what you are trying to say. Are you trying
| to say ivermectin has no impact on TMPRSS2? Ok here is
| another the google machine gave me.
|
| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7372205/
|
| What is most telling about all of this is that there is
| no honest discussion. My only initial comment was that
| this blocks the same protein that ivermectin does.
| Multiple studies confirm this, its easy to search for
| them, and it has been the hypothesized mechanism by which
| ivermectin may show some efficacy.
|
| Does ivermectin block TMPRSS2 or not?
| unanswered wrote:
| No, no. You have to give a _source_! Like CNN, or
| MotherJones! Until then there 's no way to know the truth
| about whether ivermectin blocks this protein or not. I
| mean there isn't even really a right answer to that
| question, until we hear it from reliable sources!
| nekt wrote:
| All of this was flagged. Unbelievable. Welp chalk this
| site up as another disgusting hive of censorship.
| Dylan16807 wrote:
| Because you're waving around a study that did not test
| _Ivermectin_.
| space_fountain wrote:
| He's saying that none of these studies have shown in the
| real world that ivermectin effects TMPRSS2. And I've been
| trying to have an honest discussion from the beginning. I
| said I'd failed to find what you were claiming, but tried
| to make it clear that I was listening if you did have
| some evidence. Luckily you did, but analyte123 pointed
| out it was weak.
|
| This paper seems to to be a survey of other papers so
| doesn't actually provide any new evidence itself. It also
| has a few grammar issues which makes me more skeptical of
| it, but whatever. The claim made as I understand it is
| that there is only very weak evidence that `ivermectin`
| might effect `TMPRSS2` (aka computer models). Since we've
| done randomized controlled trials we can be fairly
| confident that ivermectin doesn't work to treat covid.
| The best evidence I've heard of for it working came from
| cell cultures where at very high concentrations it was
| able to prevent covid from entering cells so maybe the
| mechanism there even is related to TMPRSS2, but I'm just
| not really sure of what discussion you were expecting.
|
| Your comment read to me like you see this as vindication
| that ivermectin is likely to be an effective drug, when
| it sounds like TMPRSS2 has been consistently targeted as
| a treatment for covid by a number of different drugs and
| you've still only shown at best weak evidence that
| ivermectin even effects it
| [deleted]
| analyte123 wrote:
| As far as I can tell ivermectin has only been "studied"
| against TMPRSS2 _in silico_. The better-studied purported
| mechanism of ivermectin against SARS-CoV-2 involves something
| called importin [1]. On the other hand, bromhexine, which is
| a cough medicine used OTC around the world does inhibit
| TMPRSS2 and may have action against SARS-Cov-2 [2].
| Bromhexine is a prodrug for ambroxol, which is also an OTC
| cold medicine in much of the world.
|
| [1] https://pubmed.ncbi.nlm.nih.gov/32251768/ [2]
| https://pubmed.ncbi.nlm.nih.gov/32983936/
| abecedarius wrote:
| Already in 2020 (I forget just how early), __ice9 on
| twitter was pointing out bromhexine and stressing the
| importance of blocking both ACE2 and TMPRSS2 binding
| ("dual-entry inhibition"). This is not an area I personally
| know about, but it's worth bringing up for the enthusiasts
| for censorship.
|
| https://twitter.com/__ice9/status/1368634545717788677
|
| If it works, the OTC nature is important. Hard for any drug
| to be very effective if the get-an-appointment-see-a-
| doctor-get-a-prescription-get-it-filled system takes you
| well past peak viral load before you even start using it.
| WithinReason wrote:
| > in silico
|
| you mean they only studied it in a computer simulation?
| weaksauce wrote:
| correct
| thehappypm wrote:
| "some quick googling"? Do better than this.
| space_fountain wrote:
| I mean it really isn't on me to source someone else's
| claim. That's why I ask them to provide a source.
| newbamboo wrote:
| From the featured article "Janetka co-founded a biotechnology
| startup company called ProteXase Therapeutics"
|
| I guess you could see what their business plan is?
| space_fountain wrote:
| But that doesn't incentive say a PHD candidate at Harvard
| to agree right? They're not making any money from this new
| startup and they'd probably get a lot of positive news
| coverage if they could show a cheap cure to covid.
| Certainly now things are a bit locked in place so it would
| be harder, there would be some repetitional damage at
| stake, but I'm just very unconvinced a cabal of biotech
| startups really has the power to keep a lid on something
| like this
| vfclists wrote:
| I can't believe it's not Ivermectin
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