Sputnik V vaccine-neutralization escape by SARS-CoV-2 Spike variants(medrxiv.org)
medrxiv.org
Sputnik V vaccine-neutralization escape by SARS-CoV-2 Spike variants
https://www.medrxiv.org/content/10.1101/2021.03.31.21254660v1
73 comments
SARS-2 was always destined to become yet another endemic seasonal respiratory virus, just to be clear.
Also, it basically is a cold virus already. For the majority of the population it’s a mild respiratory virus. For the very elderly it is quite deadly. I wish more people appreciated this fact.
Interestingly OC43, one of the already-extant human CoVs, seems pretty comparable in mortality for the elderly last time I checked.
Also, it basically is a cold virus already. For the majority of the population it’s a mild respiratory virus. For the very elderly it is quite deadly. I wish more people appreciated this fact.
Interestingly OC43, one of the already-extant human CoVs, seems pretty comparable in mortality for the elderly last time I checked.
There is strong circumstantial evidence that OC43 caused the 1889 pandemic, which killed about 0.06% of the world population. It's still endemic today, but most of us get infected as youths which provides some immunity later in life.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7252012/
So far COVID-19 has killed about 0.04% of the world population.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7252012/
So far COVID-19 has killed about 0.04% of the world population.
Thanks for the link. (As an aside, the usage of the phrase "COVID-19 virus" in the paper really triggers me :P) Not sure if you were just sharing information or if there was an implication that it's at odds with what I said, but just to be explicit I consider that to confirm what I said above.
> It's still endemic today, but most of us get infected as youths which provides some immunity later in life.
Right! That's why it's really a great analogy for SARS-2. I've been trying to get people to understand for awhile now that unlike say a really bad flu pandemic [flu has a bi-modal death distribution], SARS-2 kills the very elderly and the very sickly, but doesn't touch the very young. That means that once it's more-or-less fully spread through the population (as it has been doing the last 1.5 years or so), we're basically done with COVID-19 mortality forever.
Why? Because of exactly that reason: children will get exposed to SARS-2 young the same way they get exposed to the other circulating non-SARS hCoVs. And like any infection, once infected and recovered immunological memory persists for decades upon decades. Memory B/T cells hang around, ready and waiting to respond to the characteristic antigen when presented with them in the future.
> It's still endemic today, but most of us get infected as youths which provides some immunity later in life.
Right! That's why it's really a great analogy for SARS-2. I've been trying to get people to understand for awhile now that unlike say a really bad flu pandemic [flu has a bi-modal death distribution], SARS-2 kills the very elderly and the very sickly, but doesn't touch the very young. That means that once it's more-or-less fully spread through the population (as it has been doing the last 1.5 years or so), we're basically done with COVID-19 mortality forever.
Why? Because of exactly that reason: children will get exposed to SARS-2 young the same way they get exposed to the other circulating non-SARS hCoVs. And like any infection, once infected and recovered immunological memory persists for decades upon decades. Memory B/T cells hang around, ready and waiting to respond to the characteristic antigen when presented with them in the future.
3 months ago, a friend of mine got it and he couldn't even walk the stairs.
He's 34 and does a lot of sports. So, i wouldn't say that it's a cold virus already... Not deadly for younger people, doesn't mean it has no consequences.
He's 34 and does a lot of sports. So, i wouldn't say that it's a cold virus already... Not deadly for younger people, doesn't mean it has no consequences.
Okay, I had PCR and serology confirmed SARS-2 that was completely asymptomatic. I'm in my late 20's.
Numbers vary but most studies have the rate of asymptomaticity quite high. I've seen anything from 10% to 60%. And then you have the people that are "paucisymptomatic" (mild symptoms). And then you have a more traditional flu-type response, and then you have the subset of people who have a severe response that seems comparable to a SARS-1 infection (read: quite bad).
I didn't say that SARS-2 was never dangerous for anyone. So-called "cold" viruses can cause serious illness too. I'm not downplaying SARS-2, rather everyone else is downplaying what a normal cold virus can be capable of.
Sorry to hear about your friend's illness BTW.
Numbers vary but most studies have the rate of asymptomaticity quite high. I've seen anything from 10% to 60%. And then you have the people that are "paucisymptomatic" (mild symptoms). And then you have a more traditional flu-type response, and then you have the subset of people who have a severe response that seems comparable to a SARS-1 infection (read: quite bad).
I didn't say that SARS-2 was never dangerous for anyone. So-called "cold" viruses can cause serious illness too. I'm not downplaying SARS-2, rather everyone else is downplaying what a normal cold virus can be capable of.
Sorry to hear about your friend's illness BTW.
As anecdotal as it can be, I also know people in their mid-thirties workout complicating pathologies and in good shape that ended up being treated in ICUs and on ventilation (one with a collapsed lung, pneumonia and a bacterial infection).
Well, i did mention it because it's not the only one I know.
A friend of mine is a nurse and she also mentioned lots of young and fit collegues getting it pretty bad.
But correct, no research. But mostly people i know they got infected. Sure, some have nothing or only lose smell and taste.
A friend of mine is a nurse and she also mentioned lots of young and fit collegues getting it pretty bad.
But correct, no research. But mostly people i know they got infected. Sure, some have nothing or only lose smell and taste.
As someone who suffered long haul, I don’t know anyone in my social circle who came down with long symptoms besides me. So maybe it’s not as common as the medical journals describe?
Basically any viral infection bears the risk of extended symptoms of fatigue/malaise - see the whole ME/CFS literature (note: there's considerable controversy as to whether it's "real" or not - I don't take a side in that fight).
Almost all "research" I've seen of so-called "long COVID" has been self-reported surveys from self-select internet populations; hopefully it's obvious why such "research" will end up dramatically overstating the prevalence. (Edit: Re-reading this the tone doesn't come across quite how I want it so to be clear I'm criticizing the research itself not denying that anyone experiences these symptoms)
Lastly, I do very much worry that the widespread culture of fear and stress - which has been actively encouraged rather than calmed down by health "experts" around the globe - is contributing to a type of psychogenic / psychosomatic illness. To be explicit, psychosomatic illness is a real illness, but it does mean that the underlying mechanism is not of physiological origin but rather psychoemotional stress/belief systems that ultimately culminate in physical symptoms.
Very sorry to hear that you're actively suffering from long COVID. I hope things get better for you. I struggle with a sort of chronic fatigue myself (not anywhere as severe as the ME/CFS type horror stories I hear about, but still) so I know how shitty it can be. I've always got a bunch of ideas bouncing around my head of new research directions, articles I want to write, etc, and it many times feels out of my control whether I'm going to have the energy to pursue those goals or not.
Almost all "research" I've seen of so-called "long COVID" has been self-reported surveys from self-select internet populations; hopefully it's obvious why such "research" will end up dramatically overstating the prevalence. (Edit: Re-reading this the tone doesn't come across quite how I want it so to be clear I'm criticizing the research itself not denying that anyone experiences these symptoms)
Lastly, I do very much worry that the widespread culture of fear and stress - which has been actively encouraged rather than calmed down by health "experts" around the globe - is contributing to a type of psychogenic / psychosomatic illness. To be explicit, psychosomatic illness is a real illness, but it does mean that the underlying mechanism is not of physiological origin but rather psychoemotional stress/belief systems that ultimately culminate in physical symptoms.
Very sorry to hear that you're actively suffering from long COVID. I hope things get better for you. I struggle with a sort of chronic fatigue myself (not anywhere as severe as the ME/CFS type horror stories I hear about, but still) so I know how shitty it can be. I've always got a bunch of ideas bouncing around my head of new research directions, articles I want to write, etc, and it many times feels out of my control whether I'm going to have the energy to pursue those goals or not.
WHO had research about long haulers, including the biggest hospitals in italy.
Not that "self reported", i suppose...
Not that "self reported", i suppose...
My social circle seems to be similar to what the research says about covid long haul.
Which claims that 1/3rd who got it has covid-19 long term problems ( WHO ), my circle doesn't seem to be needing an differentiator for age. Since I don't know any elderly who got it.
So my perception is more pessimistic about the research, but I could have a more pessimistic circle, while you had a more optimistic one.
( Except for you ofc, that sucks. I wish you a speedy recovery)
Which claims that 1/3rd who got it has covid-19 long term problems ( WHO ), my circle doesn't seem to be needing an differentiator for age. Since I don't know any elderly who got it.
So my perception is more pessimistic about the research, but I could have a more pessimistic circle, while you had a more optimistic one.
( Except for you ofc, that sucks. I wish you a speedy recovery)
One of the most unfortunate aspects of containment-type policies (or the type of mitigation-but-with-all-the-downsides-of-containment like in my state of California), is that they put people into a physiological (and psychological) state where they are more vulnerable to disease:
- Vitamin D is a critical pro-hormone for immunoregulatory function in general and respiratory pathology specifically. In many ways severe COVID-19 is a disorder of immunoregulation. Vitamin D deficiency is already very widespread, and telling people to stay inside / not go out, and when going out to cover some exposed skin with a mask, is very obviously going to negatively impact Vitamin D as well as nitric oxide production/release respectively. Both are really important for respiratory pathology although Vitamin D is by far more important
- Decreased sleep, increased stress/fear, decreased exercise: all of these put the body into a pro-inflammatory state as well as a state in which immunoregulatory processes start to break down. Some stress/fear/sleep is unavoidable during a pandemic or epidemic but the vast majority of it is disproportionate to the reality of the situation and is a direct result of fear-based messaging from public health "experts", politicians, and the media.
(Remember when beaches were closed down? In many places gyms are still closed, etc)
- Improper wearing of masks (read: how literally every community member wears a mask) very plausibly increases the risk of bacterial pneumonia due to having a warm, moist cloth bacterial reservoir attached to both of one's breathing holes for long periods of time. This was a concern which was identified after the "Spanish" Flu of 1918 where the scientific consensus after the fact was that such usage of masking was both completely unfounded and likely contributed to bacterial pneumonia and other worsened outcomes. So many of the interventions (universal masking) we're advised or mandated to undertake increase a lot of these risks, which is doubly ironic when the wealth of research literature around masking for community transmission of respiratory viruses is at best inconclusive.
- Vitamin D is a critical pro-hormone for immunoregulatory function in general and respiratory pathology specifically. In many ways severe COVID-19 is a disorder of immunoregulation. Vitamin D deficiency is already very widespread, and telling people to stay inside / not go out, and when going out to cover some exposed skin with a mask, is very obviously going to negatively impact Vitamin D as well as nitric oxide production/release respectively. Both are really important for respiratory pathology although Vitamin D is by far more important
- Decreased sleep, increased stress/fear, decreased exercise: all of these put the body into a pro-inflammatory state as well as a state in which immunoregulatory processes start to break down. Some stress/fear/sleep is unavoidable during a pandemic or epidemic but the vast majority of it is disproportionate to the reality of the situation and is a direct result of fear-based messaging from public health "experts", politicians, and the media.
(Remember when beaches were closed down? In many places gyms are still closed, etc)
- Improper wearing of masks (read: how literally every community member wears a mask) very plausibly increases the risk of bacterial pneumonia due to having a warm, moist cloth bacterial reservoir attached to both of one's breathing holes for long periods of time. This was a concern which was identified after the "Spanish" Flu of 1918 where the scientific consensus after the fact was that such usage of masking was both completely unfounded and likely contributed to bacterial pneumonia and other worsened outcomes. So many of the interventions (universal masking) we're advised or mandated to undertake increase a lot of these risks, which is doubly ironic when the wealth of research literature around masking for community transmission of respiratory viruses is at best inconclusive.
The "mild respiratory flu" description is utter bullshit.
There was an analysis a couple of days ago about a very high percentage of people having to return to ICU 3 months after going in for covid. And another high percentage dying after the 3 months.
That's not anecdotal, that's statistics.
There was an analysis a couple of days ago about a very high percentage of people having to return to ICU 3 months after going in for covid. And another high percentage dying after the 3 months.
That's not anecdotal, that's statistics.
>For the majority of the population it’s a mild respiratory virus
I know someone in her 40s who got it and is not overweight. She said it was terrible and that she's definitely getting the vaccine because she never wants to get it again.
What exactly would you consider a non-mild respiratory virus?
I know someone in her 40s who got it and is not overweight. She said it was terrible and that she's definitely getting the vaccine because she never wants to get it again.
What exactly would you consider a non-mild respiratory virus?
> What exactly would you consider a non-mild respiratory virus?
SARS-1 is an example of a non-mild respiratory virus. We don't know quite as much about it since it never became a massive global phenomenon the way SARS-2 did, but the research I've read basically indicates that a "run-of-the-mill" SARS-1 infection is much like a severe COVID-19 case.
People seem to really be taking issue with my statement, and I think it comes down to them conflating "mild respiratory virus for the majority of the population" with "mild respiratory virus for everyone". Here's one simple way to put it: if "asymptomatic COVID-19" (which is an oxymoron but I'll spare you that rant) is as common as they say it is, that's an indication that it is a mild respiratory virus in many people.
SARS-1 is an example of a non-mild respiratory virus. We don't know quite as much about it since it never became a massive global phenomenon the way SARS-2 did, but the research I've read basically indicates that a "run-of-the-mill" SARS-1 infection is much like a severe COVID-19 case.
People seem to really be taking issue with my statement, and I think it comes down to them conflating "mild respiratory virus for the majority of the population" with "mild respiratory virus for everyone". Here's one simple way to put it: if "asymptomatic COVID-19" (which is an oxymoron but I'll spare you that rant) is as common as they say it is, that's an indication that it is a mild respiratory virus in many people.
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That is just speculation I'm afraid. There is much evidence that newer variants are more contagious, more virulent, and affect younger people more severely. Brazil's experience is instructive.
Thankfully the fantastic results of the mRNA vaccines mean that we should be able to suppress Covid down to the levels of measles, if not eradicate it like smallpox.
Thankfully the fantastic results of the mRNA vaccines mean that we should be able to suppress Covid down to the levels of measles, if not eradicate it like smallpox.
But it looks like none of those variants are going to be able to evade T-cells generated by existing vaccines or previous strains, thats my point.
The studies seem to suggest the existing antibodies produced by some vaccine are not effextive against some strains, is there any evidence T-cells will do better given the variant looks like a completely new virus to the immune system?
Yes, lots of evidence. Look at my comment above.
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Ok, I saw your twitter links, I just took the SA study regarding prior infection or AZ vaccination as a contrary proof, perhaps the fact that they didn't include any severe cases mean that both findings can be reconciled and that vaccines won't eradicate COVID-19 but rather it will become less severe over time.
> […], we determined that 8 out of 12 (75%) of serum samples from 12 recipients […] showed dose response curve slopes indicative of failure to neutralize rcVSV-CoV2-S: B.1.351.
I may be misreading this, as English is not my native language, but 8/12 is 66 % and not 75 %, no? Or does the “(75 %)” refer to something else?
I may be misreading this, as English is not my native language, but 8/12 is 66 % and not 75 %, no? Or does the “(75 %)” refer to something else?
Off-by-one errors, they’re not just for programmers anymore.
This study is not particularly interesting as a measurement of vaccine effectiveness (because of the extremely low sample count of 12 patients). So don't read too much into the particular numbers. Instead, there's two useful and valuable results in it:
1. It gives us information on the mechanism that the variants are using for vaccine evasion - the E484K substitution which was the suspected mechanism for B.1.351 ("south african variant") was tested on its own and did not evade the vaccine-induced antibodies as effectively as the full B.1.351 mutation set. This tells us that there is some other mechanism in B.1.351 that makes it more successful at evading antibodies. This is important and valuable information.
2. It demonstrates a really fast, safe, and clever method of testing vaccine effectiveness against a new variant - what they did was to take an entirely unrelated virus, graft a modified S protein on it, expose it to blood serum from vaccinated patients, and then try to infect a cell culture with it. By counting infected cells compared to the same count without the serum exposure, you can measure how effective the neutralization is, without having to measure infection counts in a large population. This is awesome and can easily be done with other vaccines and any new variant that shows up, as long as it's sequenced, even if it doesn't have much prevalence in the population. In fact, you can use this method to test hypothetical variants that only exist in animal viruses or not at all, and be able to redeploy vaccines that are particularly effective against those in regions where they happen to emerge. This, to me, is the absolute highlight of this paper, and I suspect it will be extremely useful.
1. It gives us information on the mechanism that the variants are using for vaccine evasion - the E484K substitution which was the suspected mechanism for B.1.351 ("south african variant") was tested on its own and did not evade the vaccine-induced antibodies as effectively as the full B.1.351 mutation set. This tells us that there is some other mechanism in B.1.351 that makes it more successful at evading antibodies. This is important and valuable information.
2. It demonstrates a really fast, safe, and clever method of testing vaccine effectiveness against a new variant - what they did was to take an entirely unrelated virus, graft a modified S protein on it, expose it to blood serum from vaccinated patients, and then try to infect a cell culture with it. By counting infected cells compared to the same count without the serum exposure, you can measure how effective the neutralization is, without having to measure infection counts in a large population. This is awesome and can easily be done with other vaccines and any new variant that shows up, as long as it's sequenced, even if it doesn't have much prevalence in the population. In fact, you can use this method to test hypothetical variants that only exist in animal viruses or not at all, and be able to redeploy vaccines that are particularly effective against those in regions where they happen to emerge. This, to me, is the absolute highlight of this paper, and I suspect it will be extremely useful.
So essentially Sputnik is most likely useless against the South African variant?
Useless? No. Less efficient? Likely.
I guess they will have to produce an updated version in nearest future.
I guess they will have to produce an updated version in nearest future.
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My amateur reading of the paper: They say that there's a chance still it can reduce some of the symptoms and reduce the need for hospitalization of the South African variant (B.1.351), but it doesn't do a great job at preventing infections in the first place.
> we determined that 8 out of 12 (75%) of serum samples from 12 recipients of the Russian Sputnik V Ad26 / Ad5 vaccine showed dose response curve slopes indicative of failure to neutralize rcVSV-CoV2-S: B.1.351.
> Furthermore, we acknowledge that in vivo protective efficacy can be derived from Fc effector functions of antibodies that bind but do not neutralize.
> we determined that 8 out of 12 (75%) of serum samples from 12 recipients of the Russian Sputnik V Ad26 / Ad5 vaccine showed dose response curve slopes indicative of failure to neutralize rcVSV-CoV2-S: B.1.351.
> Furthermore, we acknowledge that in vivo protective efficacy can be derived from Fc effector functions of antibodies that bind but do not neutralize.
More commentary on reddit:
https://www.reddit.com/r/COVID19/comments/milxvy/qualitative...
It basically echoes comments here, that there's a significant reduction in neutralization (and paper says several instances of no neutralization in some sera). Comments also says that the pre-fusion spike stabilization used on the mRNA vaccine and J&J (which otherwise similar to Sputnik as both use Adenovirus vector) seems to be the difference.
If you're interested in a fairly long discussion with the(?!) guy who developed the stabilized spike protein substitutions. Have a look at this TWiV.
https://www.youtube.com/watch?v=P9S28_5AqUA
What is the effect of taking multiple vaccines, with a few months of gap? Sputnik is available to me starting yesterday. If I take it now, will taking a different vaccine that is effective against the variants later on, give me immunity? Or will the new vaccines not do anything because the immune response has already happened?
It’s unknown. There is a phenomenon called “original antigenic sin” that may or may not apply.
There’s also a potential issue with immunity to the vector.
There’s also a potential issue with immunity to the vector.
The only issue could be if you take Sputnik now and Sputnik V2 too soon, if they use the same viral vector in the future (you could develop antibodies to the adenovirus itself, afik Sputnik uses 2 adenoviruses for dose 1 and dose 2 for this exact reason) if the vector is different, they will both work(in the case of mRNA the vector is not an issue, afik).
So if you're allowed to get another vaccine in a couple of months, take Sputnik now.
So if you're allowed to get another vaccine in a couple of months, take Sputnik now.
Multiple vaccines have not been tested, but immunology suggests they would be safe (using the same adeno-virus would likely be less effective since your body would pre-empt spike production). One possible hypothesis for why Sputnik (which it self is a succession of two different adeno-virus laden spike protein generators) is less effective is that it (unlike Moderna, Pfizer, J&J) does not appear to use a stabilized Spike protein, which makes the immune response it generates more susceptible to this substitution. They key is what parts of the artificial vaccine spike you develop antibodies for, as to how effective the vaccine is for a variant since much of the active portion of the protein is unchanged.
However, since both Moderna and Pfizer are testing mRNA "booster" vaccines specifically for the SA variant, you might just wait for that. They don't have an adeno-virus vector that could be pre-empted by immune response.
However, since both Moderna and Pfizer are testing mRNA "booster" vaccines specifically for the SA variant, you might just wait for that. They don't have an adeno-virus vector that could be pre-empted by immune response.
No one knows, it hasn’t happened before and it would probably be hard in the past to just test continuous vaccinations indefinitely.
Flu shots are taken every year, so we do know the effects of those (it's okay). In this case it depends what kind of vaccine each one is.
How bad is this result and the similar result on the AstraZeneca vaccine?
Does it mean that the South African variant will almost certainly cause another pandemic in countries vaccinated with those (thus requiring a revaccination with an mRNA vaccine) or is there somehow a chance that the variant won't be prevalent?
Does it mean that the South African variant will almost certainly cause another pandemic in countries vaccinated with those (thus requiring a revaccination with an mRNA vaccine) or is there somehow a chance that the variant won't be prevalent?
I believe az had similar (bad) results which caused south africa to pause the rollout.
Yup, except none of the recipients in the AZ study had severe cases.
IIRC no one in either arm of that study had a serious case. The study was nearly useless.
the problem is of course that even if that's true, if the virus spreads asymptomatically the same mutation risk applies to the variant itself and at some point then we might up with something that again completely escapes immunity and vaccination.
It's just evolution in action. Any variant that dodges the vaccine starts a new game of dice.
It's just evolution in action. Any variant that dodges the vaccine starts a new game of dice.
Well, what's the alternative? Get covid19 and risk death or life long ill effects? The virus mutates anyway in healty individuals that develop mild cases. There's enough of a scadal with the AZ vaccine in the EU, people don't want to get vaccinated with it because of blood clots with in DIC 0.35/1M and CVST in 0.9/1M individuals[1] and fever for a day, the company has rebdand it as Vaxzevria in an attempt to reduce the fallout. The vaccination rollout is not going well in the EU, it was even criticised by the WHO as being too slow. Yet this vaccine works and can probably stop the pandemic and save lives along with the others. I took my chanches and got vaccinated with it a week and a half ago, instead of waiting for something better and risk getting covid in the meantime. I might have taken Sputnik V as well if nothing else was available. AZ at least seems to work, was proven at least on 1/4 of the UK population. Their cases seem to go down. I guess we'll see.
1. https://www.ema.europa.eu/en/news/covid-19-vaccine-astrazene...
1. https://www.ema.europa.eu/en/news/covid-19-vaccine-astrazene...
I don’t think it is the vaccine technology rather what part of the virus the vaccine causes the immune system to react on.
If I may point to a comment of mine that got heavily downvoted:
https://news.ycombinator.com/item?id=26664839
Someone needs to do exactly the same study (same methods, ideally same lab) on sera from people vaccinated with all the major vaccines. The lack of a valid comparison study is ridiculous.
I wouldn't say it's ridiculous. This is generally how a scientific study is done. One "object" per study. An article like this is not made to stand alone and should in general not be used for non-science purposes, such as policy-making. First order comparative studies (such as experiments) of course exists, but comparisons are generally done to my knowledge in meta-studies.
For laypeople and policy makers we of course need comparisons and validations before we let them guide our choices.
For laypeople and policy makers we of course need comparisons and validations before we let them guide our choices.
I disagree. There is no way this can be meta-analyzed in a way that can reliably inform policy, and waiting until we discover (or not) which vaccines remain effective in the face of variants due to an outbreak in a vaccination is horrible public health and economic policy.
To the contrary, the policy makers have access to insane amounts of money. The US has spent trillions overall due to Covid and billions on vaccine development. Paying the researchers or a different lab $1M to run an important study is a no-brainer. Or do it DARPA/DoD style: announce a list of studies that need doing, let people apply for grants to do them, and keep the list updated!
The fact that researchers are bumbling around doing good quality science, getting nice publications, and failing to answer the right questions is an abject failure of science policy.
edit: here’s your meta-analysis: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7654888/
This sucks. As the authors note, the individual studies were not usefully standardized and mostly can’t be compared. At the very least, the FDA could have said, as part of the initial Covid vaccination trial goals, that a specific set of identical measurements were required, and that all candidates were expected to make those particular measurements. Additional measurements would, of course, be welcome. This would have cost the public a grand total of $0. Maybe $500k for someone to write the thing down and take some feedback to make sure the list made sense, but that seems high.
To the contrary, the policy makers have access to insane amounts of money. The US has spent trillions overall due to Covid and billions on vaccine development. Paying the researchers or a different lab $1M to run an important study is a no-brainer. Or do it DARPA/DoD style: announce a list of studies that need doing, let people apply for grants to do them, and keep the list updated!
The fact that researchers are bumbling around doing good quality science, getting nice publications, and failing to answer the right questions is an abject failure of science policy.
edit: here’s your meta-analysis: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7654888/
This sucks. As the authors note, the individual studies were not usefully standardized and mostly can’t be compared. At the very least, the FDA could have said, as part of the initial Covid vaccination trial goals, that a specific set of identical measurements were required, and that all candidates were expected to make those particular measurements. Additional measurements would, of course, be welcome. This would have cost the public a grand total of $0. Maybe $500k for someone to write the thing down and take some feedback to make sure the list made sense, but that seems high.
At this point, what is the cost-benefit of further vaccine development versus heavier investment in drugs and other therapies to reduce the severity of disease?
There are a couple doctors in the US (particularly Peter McCullough) who make a case that we haven't invested enough in the latter and too much in the former. Naturally the anti-vax people seem to love these guys, so it's hard to find any kind of balanced analysis on it.
Or do the numbers still work out to be "more pandemic, more full hospitals, many more dead" no matter how good the drug treatment gets?
There are a couple doctors in the US (particularly Peter McCullough) who make a case that we haven't invested enough in the latter and too much in the former. Naturally the anti-vax people seem to love these guys, so it's hard to find any kind of balanced analysis on it.
Or do the numbers still work out to be "more pandemic, more full hospitals, many more dead" no matter how good the drug treatment gets?
The cost vs benefit analysis is: do all of the above. The total amount spent on biotech related to Covid is negligible compared to the cost of Covid. Israel seems to understand this. Many other countries are orders of magnitude off in their analysis.
This is true, but this is not Israel's calculation, far from it.
They are playing a zero-sum game of outbidding others so that they are 1st, no matter what.
Countries like the UK that invested in supply chain efficiencies well ahead of vaccine validation, even as there was risk of the investment failing ... this was acting ahead.
Almost every nation failed at this: we should have all been investing 10x what we did in anything to get the vaccines ready, even for those that ultimately failed because the $20B wasted on unneeded prep would have been less than the amount wasted in our current lock downs that could have been avoided were we already to have been vaccinated.
They are playing a zero-sum game of outbidding others so that they are 1st, no matter what.
Countries like the UK that invested in supply chain efficiencies well ahead of vaccine validation, even as there was risk of the investment failing ... this was acting ahead.
Almost every nation failed at this: we should have all been investing 10x what we did in anything to get the vaccines ready, even for those that ultimately failed because the $20B wasted on unneeded prep would have been less than the amount wasted in our current lock downs that could have been avoided were we already to have been vaccinated.
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A lot has been invested in drugs. Most of them don't work. The best that was found was Dexamethasone, which reduces mortality in severe cases significantly.
Generally medication for viral infections seems to be hard. There isn't much good medication for other respiratory viral diseases. It doesn't look like a major breakthrough in drug treatment will happen.
A vaccine can make the difference between "you get the disease" and "you don't get the disease and can't spread it to others". No drug comes remotely close to that.
Generally medication for viral infections seems to be hard. There isn't much good medication for other respiratory viral diseases. It doesn't look like a major breakthrough in drug treatment will happen.
A vaccine can make the difference between "you get the disease" and "you don't get the disease and can't spread it to others". No drug comes remotely close to that.
A lot of very competent coordinated studies of drugs have been done. Oh wait, no it hasn’t.
We had a mishmash of variously competent and incompetent studies of AZ/HCQ. We have anecdotal data on ivermectin. We have some preliminary studies of fluvoxamine (excellent results, needs follow up); the large scale expedited follow up is MIA. It’s been over six months from the original study — there is no fundamental reason it should take more than two months to test it on a few tens of thousands of people. Ditto for anti-androgens. Camistat ought to have at least some effect (famous last words); this has been known for something like a year with no meaningful followup.
What’s needed here is IMO public health department coordination on studies, which isn’t quite the same thing as money.
We had a mishmash of variously competent and incompetent studies of AZ/HCQ. We have anecdotal data on ivermectin. We have some preliminary studies of fluvoxamine (excellent results, needs follow up); the large scale expedited follow up is MIA. It’s been over six months from the original study — there is no fundamental reason it should take more than two months to test it on a few tens of thousands of people. Ditto for anti-androgens. Camistat ought to have at least some effect (famous last words); this has been known for something like a year with no meaningful followup.
What’s needed here is IMO public health department coordination on studies, which isn’t quite the same thing as money.
To be clear, almost all of these studies showed very small effect sizes. The best therapeutics we have are remdesevir (small but real effect on severity, unclear effect on hospitalization and death), dexamethosone (moderate to large effect on death when hospitalized), and antibody drugs for which Lilly’s has already been remove because ineffective against variants though Regeneron’s cocktail seems quite good. Fluvoxamine is I’m sure under investigation, we’ll get a readout eventually but that’s a relatively new result.
The best drugs we have are either:
1.) treat the virus with a novel entity (Regeneron, the other antibodies)
2.) treat the inflammation (dexamethosone, possibly eventually fluvoxamine)
The repurposing and general antivirals (including remdesevir) have little effect and likely won’t make a difference. There are novel drugs being developed (Pfizer just started a protease inhibitor trial) but that’s the only place I’d expect to see real impact, with fluvoxamine as a treat the symptoms wildcard. People have been trying to find drugs or repurpose, and academic medical centers have been working on it. It’s that almost nothing works when subjected to the hard trials.
The best drugs we have are either:
1.) treat the virus with a novel entity (Regeneron, the other antibodies)
2.) treat the inflammation (dexamethosone, possibly eventually fluvoxamine)
The repurposing and general antivirals (including remdesevir) have little effect and likely won’t make a difference. There are novel drugs being developed (Pfizer just started a protease inhibitor trial) but that’s the only place I’d expect to see real impact, with fluvoxamine as a treat the symptoms wildcard. People have been trying to find drugs or repurpose, and academic medical centers have been working on it. It’s that almost nothing works when subjected to the hard trials.
There's likely room to pick better monoclonal antibodies to use. There was an antibody identified that smashed variants, for instance.
https://www.medrxiv.org/content/10.1101/2021.01.26.21250224v...
Some contextualization at https://twitter.com/K_G_Andersen/status/1367592606641704961
https://www.medrxiv.org/content/10.1101/2021.01.26.21250224v...
Some contextualization at https://twitter.com/K_G_Andersen/status/1367592606641704961
Is the Regeneron drug an example of the "monoclonal antibodies" that I keep hearing about?
Yes. Monoclonal antibodies are single antibodies that are produced at scale. Regeneron has 2 mABs that they mix to create a cocktail. Your immune system generated a polyclonal antibody response, which is to say it creates a multitude of different antibodies against the virus. If most aren’t great, that’s fine as long as one is good enough. If a few work together to neutralize the virus, that’s also fine. If you can identify one of those antibodies as especially good, you can then clone it and make a bunch of it artificially, hence “monoclonal”.
There is now a lot more than just anecdotal data on ivermectin. This site has an index of the latest studies. Some show positive results, others show no effect or were inconclusive. Research continues.
https://c19ivermectin.com/
https://c19ivermectin.com/
This is actually McCullough's main thesis as far as I can tell ("we didn't study drugs enough and jumped straight to vaccine"), so it's interesting to hear it corroborated.
Dexamethasone is no longer considered the best. The latest research indicates better results with methylprednisolone, which has a similar mechanism of action.
https://pubmed.ncbi.nlm.nih.gov/33632000/
https://pubmed.ncbi.nlm.nih.gov/33632000/
There's lots of work on anti-virals and other drugs, but unless you happen to hit a pre-approved drug showing both efficacy and safety will take so long that it probably won't matter until the next epidemic. Drug treatments are much harder to develop without significant side-effects and also likely less effective than a well targeted vaccine.
Watch around 1hr into this TWiV, if you're interested in what targets there are for anti-virals, who's working on them, and why they're hard.
https://www.youtube.com/watch?v=7dL-ll8dSmY
Watch around 1hr into this TWiV, if you're interested in what targets there are for anti-virals, who's working on them, and why they're hard.
https://www.youtube.com/watch?v=7dL-ll8dSmY
How recent are these arguments?
Deploying the vaccines is very cheap compared to hospitalization.
And like a sibling comment has already said, we should just be spending money anywhere it even seems to make sense.
Deploying the vaccines is very cheap compared to hospitalization.
And like a sibling comment has already said, we should just be spending money anywhere it even seems to make sense.
McCullough recently testified before the Texas state senate: https://youtu.be/QAHi3lX3oGM
He argued that drugs can and do significantly reduce hospitalization. He also claimed that literally nobody was stuffing drugs to reduce hospitalization, which is a strong claim but alarming if true.
He argued that drugs can and do significantly reduce hospitalization. He also claimed that literally nobody was stuffing drugs to reduce hospitalization, which is a strong claim but alarming if true.
His narrative is a bit cartoonish. He complains that communication was silenced starting in May 2020 and is testifying there because of a paper published in August 2020 in one of the most prominent journals in the US. An alternative explanation about the lack of ambulatory care is that most protocols don't really move the needle...
I also don't understand why he thinks the vaccine doesn't make sense for people under 50 (he says there is no scientific rationale for it). I'm in my early 40s and have a chance of dying of greater than 1/10,000 if I get infected. The vaccines cost very little and carry much less risk than that!
I also don't understand why he thinks the vaccine doesn't make sense for people under 50 (he says there is no scientific rationale for it). I'm in my early 40s and have a chance of dying of greater than 1/10,000 if I get infected. The vaccines cost very little and carry much less risk than that!
Indeed, this is why I wanted to get some feedback. It definitely seemed exaggerated and I'm not sure what his point was supposed to be by the end of it.
I also found it odd that somehow his practice was seeing incredible results with drug combinations in keeping people out of hospitals, but somehow this effect wasn't noticed by any other medical professionals or researchers anywhere else in the world. Are combination protocols really that under-studied?
I also found it odd that somehow his practice was seeing incredible results with drug combinations in keeping people out of hospitals, but somehow this effect wasn't noticed by any other medical professionals or researchers anywhere else in the world. Are combination protocols really that under-studied?
The president of Argentina has just been diagnosed with Covid, with mild symptoms, after being vaccinated with both doses of Sputnik for over a month or two.
Completely expected. That's why the efficacy is not 100%.
We have people in hospital after 2 rounds of Pfizer.
We have people in hospital after 2 rounds of Pfizer.
There is speculation that Argentina may have failed to keep Sputnik V cold enough during distribution, so it is quite possible that the president and others recently vaccinated received degraded vaccine.
No, that’s just speculation or fake news [1]: the Sputnik V boxes can last up to 60hs without refrigeration
1: https://factual.afp.com/las-cajas-con-vacunas-sputnik-v-mant...
1: https://factual.afp.com/las-cajas-con-vacunas-sputnik-v-mant...
So how we should know is vaccine good or is it degraded? Any way of testing?
Not all batches should or could be tested but you could do random sample testing.
Not all batches should or could be tested but you could do random sample testing.
So covid will try and evolve to keep spreading but it will become less deadly as vaccination and natural immunity increase. So its destiny is to become a cold virus like the other human coronaviruses.
https://twitter.com/Coronavirusgoo1/status/13769286914738135...
https://twitter.com/Coronavirusgoo1/status/13667086756797644...
https://twitter.com/profshanecrotty/status/13552620195622092...