There's human data on the Moderna vaccines (minimal, but it's there) and fairly extensive data from animal trials on both the Pfizer and Johnson & Johnson (as well as AstraZeneca) vaccines that clearly show little sterilizing immunity from any of the vaccines.
Not even close. The fraction of the population that needs to be vaccinated for herd immunity is equal to 1-1/R0. The low-range of R0 for SarsCoV2 is 3.5 so this implies 70% to 80% vaccination levels for herd immunity.
And that's before taking into account the new UK variant that's 50% to 70% more contagious and will drive the needed vaccination levels to ~90%.
Here's the other tidbit of data out of the AstraZeneca study. People in the placebo arm were getting infected at just 30% of the rate of the general population during the same time period. And this is AFTER adjusting for age, gender, race, geography, nationality, and co-morbidities.
The sort of people who volunteered for these trials did NOT mirror the general population in terms of their levels of personal mask-wearing and mitigation.
That means the 60% protection from infection is some combination of vaccine-related protection PLUS abnormally high levels of personal mitigation.
If we drop mitigation efforts, the actual level of protection from infection is certain to be significantly lower than 60%
One last thing...that 60% are ASYMPTOMATIC infection. There was a 3rd category of "symptomatic infection, but below the level of the study's definition of symptomatic disease". That pushes the rate of infection after vaccination even higher.
Excellent explanation,thank you ! I was quite baffled by the low rate of illness as well and wondered why no company reported level of mitigation in each group ,? How many health care workers for instance ,knowing most of us are really serious about public mitigation ..
What do you think will be the immunologic consequence of letting virus spread with no ability to cause serious disease?( if vaccine stops serious disease )
And another question : pfizer reports 3400 cases of covid like illness with negative PCR , noted equal in both groups b/n shot 1 and 2 and near double in vaccinated group after shot 2 , specifically notconsidered sude effect (page 49 from fda review?)
Thanks again for this very non bias and science driven discussion !
Right now current mitigation efforts has keep R-effective down to the 0.9 to 1.2 range...from it's potential 3.5 to 5.0 range.
We're seeing 5-7 million cases a week...which is comparable to a typical flu season with about 4-5 million flu cases a week. (And seasonal influenza has an R0 of ~1.2 so these numbers all make sense).
If we make a few extremely optimistic assumptions just to set up a model:
1. Vaccine confers a 10x reduction in mortality and severe disease
2. 50% effective at reducing infection
3. 100% vaccination rate
4. ZERO mitigation (back to 2019 levels)
5. 12-months of protective disease immunity
You would see the virus go fully endemic with about 50% of the population catching it annually or ~165M cases a year or ~3 million cases a week.
Btw...that compares to the common cold (R0 ~2.0) where we see 1-billion colds a year or about 25-million colds a week during the 8-month cold season. With each person catching on average 3 colds a year.
So if we have 165M infections (mostly mild or asymptomatic) with a 0.1% IFR (essentially equal to seasonal influenza)...that would mean 165,000 deaths a year or about the 3rd leading cause of death in the US.
Now those are massively unrealistic assumptions. If we start to back off those assumptions a bit, say 60% vaccination rate and zero mitigation you would see:
200M people vaccinate with 100M infections and 200K deaths
...plus...
132M people walking around buck naked with no vaccination with closer to 50M-to-100M infections possible at 10x the death rate...so 500,000 deaths on the low end.
Now we have 700,000 deaths making Covid the leading cause of death exceeding even heart disease.
Reality is likely somewhere between those two brackets...UNLESS significant levels of mitigation are maintained (80% mask usage, 50% capacity in public venues, etc.)
I just don't think things will be getting better unless we continue to focus on heavy mitigation along with high vaccine compliance rates.
200M people vaccinate with 100M infections and ~100K deaths
...plus...
132M people walking around buck naked with no vaccination with closer to 50M-to-100M infections possible at 10x the death rate...so ~500,000 deaths on the low end.
Now we have 600,000 deaths making Covid the leading cause of death exceeding even heart disease.
This was the most detailed and interesting article (and podcast with Mark Hyman) that I have seen and was hugely helpful. I only listened to it yesterday, just before my partner received the AstraZeneca vaccine. His doctor said that it was 95% effective against ALL covid infections and asymptomatic transmission, even when I checked with her. I saw that there has been another very recent study coming out of Israel in the last day or so, suggesting these type of results. How can there be such a disparity between the same vaccine studies? If we take this latest data, it would suggest no reason for many mitigation practices, which living here in the UK with the new variant, concerns me hugely.
Great article! But your conclusion about reinfection of seropositive patients seems to be at odds with the study reported by Oxford U researchers in the this NEJM paper:
The results in their study shows very low (asymptomatic) re-infection rates over several months compared with the non-seropositive population, indicating that "natural" infection does provide significant sterilizing immunity, at least before significant mutations come into play.
This particular article is based entirely on the AstraZeneca Phase III study results submitted for regulatory review.
It's not clear how strong the results of the NEJM paper are. They have an awfully small sample size (N=2) for seropositives who later showed re-infection.
The AZ study is significantly larger and has a sample size of N=27 in the group of seropositives who later showed re-infection.
Clearly, more work needed to be done...these are extremely small sample sets to be drawing and sort of definite conclusions at this point.
It would...but it has proven to be quite difficult to develop an effective one. There have been 30 years of research on ones for seasonal influenza...including two that made it to market.
Both were withdrawn due to ineffectiveness and there are currently none in trials. So conceptually it's possible, but practically it's so far not been feasible.
Thanks for this, maybe the replication, incubation, and transmission dynamics of SARS-CoV-2 are more favourable to the efficacy of a nasal vaccine (mucosal IGA antibodies etc) than influenza? I really hope people get on the case quickly if there's anyone you can write to to lobby for researching this. Sterilizing immunity may be our only permanent solution to vaccine-escape mutants and you might see higher uptake for people afraid of needles. It may not need to be one or the other either it could be adjunct to intra-muscular delivery. To me it feels almost like a wasted year already that we haven't developed one. Vincent Racaniello provides an article on the subject here: https://www.virology.ws/2020/09/03/the-route-matters/
The very best and focused data review I've seen so far , I strongly believe in vaccinations but don't understand why the transparency now is so low in the US on pointing out the data you summarized and not talking about other good vaccines coming (Janssen, Novavax,Astra Z ). Also, where is the ongoing data from Pfizer and Moderna , now 2 months after Pfizer coming out , what happened to both groups ,impossible to find, why ? I thought FDA wants to know that ?
Pfizer, Moderna, and AstraZeneca data has been published. Multiple animal trials have been published for those three plus the Johnson & Johnson single-dose vaccine.
I have read that the Moderna Vaccine does not elicit a strong Killer T-cell response (CD8+) while the Pfizer vaccine does that. Is there any evaluation of what that actually means in terms of vaccine efficacy?
Do you have any sources? That seems a bit counter-intuitive given that the Pfizer and Moderna vaccines are nearly identical in absolutely every respect.
It would be less surprising to see such a difference between say Pfizer vs AstraZeneca given the more substantial difference between those vaccines.
I think you might be being a bit overly pessimistic here. First, the evidence seems to be that the primary cause of spread is *presymptomatic transmission* rather than truly asymptomatic transmission (i.e., cases where patients never experience symptoms). Although there is evidence that totally asymptomatic patients do have health effects (and this ought to be studied carefully - did the ones that tested positive have ground glass opacities, etc.?), there is also evidence that the viral load is lower and therefore they may be at significantly reduced risk of transmission to others. So the fact that the vaccines suppress symptomatic disease might well end up reducing R(t) to below 1 which is really the only real thing needed to suppress the virus.
Secondly, the "reinfection" -- do we know these cases were actual reinfection as opposed to redirection? Did they sequence the virus and confirm novel reinfection?
Perhaps...although the correlation between viral load, being asymptomatic, and level of contagiousness is largely in the realm of pure speculation at this point.
It's not at all clear how to make a connection between what's on swab and any of these other attributes. Every molecular diagnostics company in existence would die for a test of "infectiousness" or test that could identify a super-spreader.
At this point NO ONE knows how to design such a test...the data just isn't there.
In terms of re-infection...there's an active project in the Netherlands tracking re-infection cases using NGS to confirm unique genotypes between the initial on subsequent infections.
But among contact tracing groups, it's now being seen on a daily basis and is increasingly commonplace.
That's been my primary concern so far it likely will be about 6 months are the early rounds of mass vaccinations are complete before we'll know for certain.
But if were a high prevalence event, some indication would absolutely have shown up in the data by now. So things are looking fairly positive so far (albeit early still).
The most useful explanation I have read in newspapers or on media. I certainly will be taking the AstaZeneca vaccine when available. The risk is that after so much orchestrated bad mouthing from US scientific commentators it will be much delayed.
Of course their trials were more informative than others because in fact designed by Oxford academics rather than Big Pharma but unfortunately not tailored to the demands of the regulators.
All the major vaccines seem to be very effective and equally good choices. People just need to understand what the vaccines can and cannot be expected to do. I will certainly be taking whichever one is available first.
I’ve seen this posted on social media as a reason to not trust the vaccines. Can you clarify your stance for the general public regarding receiving the vaccines?
These are highly effective vaccines with no major safety issues. Any short-term reactions are trivial compared with the risks posed by Covid-19.
There have now been about 1-million man-days of post-vaccination observation. So any safety issues are going to be very low prevalence.
And that's in spite of the recent reports of allergic reactions. An allergic reaction is short-term and easily treated...not one has ever been put on an ECMO for an allergic reaction.
I intend to be vaccinated once it becomes available for my age group...
Your "1-million-man-days" is a false way to quote vaccine safety observation. Vaccines are tested in long-term trials to discover adverse long-term effects... and giving it to more people is not a replacement for long-term observation (https://www.history.com/news/swine-flu-rush-vaccine-election-year-1976)
The FDA is allowing these vaccines for emergency use, because the adverse effects of the vaccine on at-risk individuals are lower than the effects of COVID-19.
However, before the FDA will approve them for widespread use, the same needs to be true for not-at-risk individuals, and over a longer-time period. We'll see when the vaccines get widespread use approval.
There's a trade-off there in study design. A far larger test group can turn up low-probability events in a shorter trial. But you're right, there are ALSO effects that require some minimal period of calendar-time to pass before they'll show up.
Very much like the linkage between HPV and Cervical cancer that requires 25+ years between infection and onset of cancer.
I think the calculus made here was that with the current death rates, it's too risky to push the trial out over a multi-year period. But we know that the vaccine is dramatically less risky than acquiring the disease...even if all the risk won't be fully known for years.
Sounds like some people have been giving you a hard time for expressing yourself. Please ignore them and keep writing. I’ve been following your views since this started and I find them very helpful, thoughtful and intelligent and I know others do too.
I would disagree with you on one point. Ignorant or badly educated people aren’t necessarily stupid, but they are very distrustful - for good reason as they have history of being duped - and they often live by simple rules of thumb (which is what behavioural economics is all about). Problem is, once you’re caught in a perceived lie with them, there no come back. Getting through to these people the nuance of vaccines will be a massive challenge .
While I do not disagree with your general conclusions, this and some other websites have misinterpreted the results from the Astra-Zeneca Phase 3 COVID vaccine trial report you mention with respect to estimating its sterilizing immunity efficacy. This efficacy is not determined just by the ratio of asymptomatic infections from the vaccinated group relative to placebo, because symptomatic cases are clearly also infectious and therefore need to be included in this efficacy calculation. A more meaningful measure is the sum of the symptomatic (adjusted to include both primary and non-primary cases) and asymptomatic cases (in other words: all PCR positive tests) for the vaccinated group relative to same sum in placebo group, with appropriate weighting to account for slight differences in the total participant numbers in the symptomatic and asymptomatic counts (presumably because not all participants were tested for asymptomatic infection). For the SD/SD standard regimen, the sterilizing immunity calculated using this method is 35%, which is certainly not sufficient to achieve herd immunity but is definitely better than “zero”. More importantly the results from the LD/SD trial data yields a sterilizing immunity of 77% for this protocol, definitely better than the 59% figure for the asymptomatic ratio in the Astra Zeneca table.
Furthermore, in terms of determining the effect of vaccine on the reproduction number R, you need to take into account that carriers with asymptomatic infections are less contagious than symptomatic ones, as has been measured in a published study: Infectivity of asymptomatic versus symptomatic COVID-19 - The Lancet . This shows that asymptomatic carriers are 3.85 times less infectious than symptomatic ones (per contact). Allowing that asymptomatic carriers will likely have more contacts while they are infectious than symptomatic carriers do (say about 54% more), the effective ratio for disease reproduction would reduce to 2.5. Hence you can estimate the reproduction mitigation efficacy of the vaccine by further weighting of the vaccinated and placebo asymptomatic cases by a factor of 1 /2.5 in the summations discussed above. This yields efficacies of 45% and 83% for the SD/SD and LD/SD regimens, respectively. A follow-up paper to the above Astra-Zeneca report has been submitted which includes data from an extra month of observation: (https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3777268). These results point towards slightly higher sterilizing immunity efficacy for the SD/SD regimen (39%), lower efficacy of the LD/SD regimen (67%), and reproduction mitigation efficacies of 48% and 72% for SD/SD and LD/SD regimens, respectively.
But as you say, lower vaccine effectiveness in the general population coupled with less than 100% acceptance will lead to significantly lower protection levels, so it does not change the conclusion that herd immunity is not reachable and the disease will be endemic for years to come. Nevertheless, starting with a reproduction mitigation efficacy over 70% can be of significant help in relaxing mitigation measures while keeping infection levels in check, allowing a higher degree of “normality” to return to people’s lives.
So,vaccination with current available vaccine is not confer sterilization, only protects against severe disease reducing mortality what is the use of vaccinating everybody if they still can get infected and spread the disease and Not Just vaccinate the vulnerable
A 10x reduction in the risk of severe disease leading to hospitalization or death.
The analogy is this. If I'm going into a gunfight and my choice is a bullet-proof vest that's 70% effective or a snarky t-shirt...I'm opting for the less-than-perfect bullet-proof vest because I'm not an idiot.
The choice to take the vaccine is a similar trade-off.
Current data suggests 80% of the USA is going to be exposed to COVID-19 before the end of April, but widespread vaccines won't be delivered until summer at the very earliest (and possibly later). So why get all fear-mongery about vaccine results, when most people will be "innoculated" by the actual virus?
The purpose of our emergency vaccine distribution is to vaccinate the most at-risk individuals, because they disproportionally represent the severe-illness cases and deaths.
thanks for the piece. is the pfizer/moderna vaccine that is out in the US protect from asymptomatic contraction/illness?
There's human data on the Moderna vaccines (minimal, but it's there) and fairly extensive data from animal trials on both the Pfizer and Johnson & Johnson (as well as AstraZeneca) vaccines that clearly show little sterilizing immunity from any of the vaccines.
Correct me if I understand this wrong but seems like Astra zeneca gives 60 % protection from asymptomatic infection ?
This is not that bad after all ,sure not good enough fir herd immunity ?
Thank you!
Not even close. The fraction of the population that needs to be vaccinated for herd immunity is equal to 1-1/R0. The low-range of R0 for SarsCoV2 is 3.5 so this implies 70% to 80% vaccination levels for herd immunity.
And that's before taking into account the new UK variant that's 50% to 70% more contagious and will drive the needed vaccination levels to ~90%.
Here's the other tidbit of data out of the AstraZeneca study. People in the placebo arm were getting infected at just 30% of the rate of the general population during the same time period. And this is AFTER adjusting for age, gender, race, geography, nationality, and co-morbidities.
The sort of people who volunteered for these trials did NOT mirror the general population in terms of their levels of personal mask-wearing and mitigation.
That means the 60% protection from infection is some combination of vaccine-related protection PLUS abnormally high levels of personal mitigation.
If we drop mitigation efforts, the actual level of protection from infection is certain to be significantly lower than 60%
One last thing...that 60% are ASYMPTOMATIC infection. There was a 3rd category of "symptomatic infection, but below the level of the study's definition of symptomatic disease". That pushes the rate of infection after vaccination even higher.
Excellent explanation,thank you ! I was quite baffled by the low rate of illness as well and wondered why no company reported level of mitigation in each group ,? How many health care workers for instance ,knowing most of us are really serious about public mitigation ..
What do you think will be the immunologic consequence of letting virus spread with no ability to cause serious disease?( if vaccine stops serious disease )
And another question : pfizer reports 3400 cases of covid like illness with negative PCR , noted equal in both groups b/n shot 1 and 2 and near double in vaccinated group after shot 2 , specifically notconsidered sude effect (page 49 from fda review?)
Thanks again for this very non bias and science driven discussion !
Right now current mitigation efforts has keep R-effective down to the 0.9 to 1.2 range...from it's potential 3.5 to 5.0 range.
We're seeing 5-7 million cases a week...which is comparable to a typical flu season with about 4-5 million flu cases a week. (And seasonal influenza has an R0 of ~1.2 so these numbers all make sense).
If we make a few extremely optimistic assumptions just to set up a model:
1. Vaccine confers a 10x reduction in mortality and severe disease
2. 50% effective at reducing infection
3. 100% vaccination rate
4. ZERO mitigation (back to 2019 levels)
5. 12-months of protective disease immunity
You would see the virus go fully endemic with about 50% of the population catching it annually or ~165M cases a year or ~3 million cases a week.
Btw...that compares to the common cold (R0 ~2.0) where we see 1-billion colds a year or about 25-million colds a week during the 8-month cold season. With each person catching on average 3 colds a year.
So if we have 165M infections (mostly mild or asymptomatic) with a 0.1% IFR (essentially equal to seasonal influenza)...that would mean 165,000 deaths a year or about the 3rd leading cause of death in the US.
Now those are massively unrealistic assumptions. If we start to back off those assumptions a bit, say 60% vaccination rate and zero mitigation you would see:
200M people vaccinate with 100M infections and 200K deaths
...plus...
132M people walking around buck naked with no vaccination with closer to 50M-to-100M infections possible at 10x the death rate...so 500,000 deaths on the low end.
Now we have 700,000 deaths making Covid the leading cause of death exceeding even heart disease.
Reality is likely somewhere between those two brackets...UNLESS significant levels of mitigation are maintained (80% mask usage, 50% capacity in public venues, etc.)
I just don't think things will be getting better unless we continue to focus on heavy mitigation along with high vaccine compliance rates.
Sorry...wrong math, same outcome though:
200M people vaccinate with 100M infections and ~100K deaths
...plus...
132M people walking around buck naked with no vaccination with closer to 50M-to-100M infections possible at 10x the death rate...so ~500,000 deaths on the low end.
Now we have 600,000 deaths making Covid the leading cause of death exceeding even heart disease.
This was the most detailed and interesting article (and podcast with Mark Hyman) that I have seen and was hugely helpful. I only listened to it yesterday, just before my partner received the AstraZeneca vaccine. His doctor said that it was 95% effective against ALL covid infections and asymptomatic transmission, even when I checked with her. I saw that there has been another very recent study coming out of Israel in the last day or so, suggesting these type of results. How can there be such a disparity between the same vaccine studies? If we take this latest data, it would suggest no reason for many mitigation practices, which living here in the UK with the new variant, concerns me hugely.
Great article! But your conclusion about reinfection of seropositive patients seems to be at odds with the study reported by Oxford U researchers in the this NEJM paper:
https://www.nejm.org/doi/full/10.1056/NEJMoa2034545
The results in their study shows very low (asymptomatic) re-infection rates over several months compared with the non-seropositive population, indicating that "natural" infection does provide significant sterilizing immunity, at least before significant mutations come into play.
Thanks...I'd not seen that study.
This particular article is based entirely on the AstraZeneca Phase III study results submitted for regulatory review.
It's not clear how strong the results of the NEJM paper are. They have an awfully small sample size (N=2) for seropositives who later showed re-infection.
The AZ study is significantly larger and has a sample size of N=27 in the group of seropositives who later showed re-infection.
Clearly, more work needed to be done...these are extremely small sample sets to be drawing and sort of definite conclusions at this point.
Wouldn't a nasal-administered vaccine elicit better sterilizing immunity? Why isn't anyone working on one?
It would...but it has proven to be quite difficult to develop an effective one. There have been 30 years of research on ones for seasonal influenza...including two that made it to market.
Both were withdrawn due to ineffectiveness and there are currently none in trials. So conceptually it's possible, but practically it's so far not been feasible.
Thanks for this, maybe the replication, incubation, and transmission dynamics of SARS-CoV-2 are more favourable to the efficacy of a nasal vaccine (mucosal IGA antibodies etc) than influenza? I really hope people get on the case quickly if there's anyone you can write to to lobby for researching this. Sterilizing immunity may be our only permanent solution to vaccine-escape mutants and you might see higher uptake for people afraid of needles. It may not need to be one or the other either it could be adjunct to intra-muscular delivery. To me it feels almost like a wasted year already that we haven't developed one. Vincent Racaniello provides an article on the subject here: https://www.virology.ws/2020/09/03/the-route-matters/
I think the influenza vaccine nasal spray is being used in the U.K. on children
Please excuse the typos in my post and thank you for this discussion
The very best and focused data review I've seen so far , I strongly believe in vaccinations but don't understand why the transparency now is so low in the US on pointing out the data you summarized and not talking about other good vaccines coming (Janssen, Novavax,Astra Z ). Also, where is the ongoing data from Pfizer and Moderna , now 2 months after Pfizer coming out , what happened to both groups ,impossible to find, why ? I thought FDA wants to know that ?
Pfizer, Moderna, and AstraZeneca data has been published. Multiple animal trials have been published for those three plus the Johnson & Johnson single-dose vaccine.
Please, advise where could I find data after Nov 14 th on Pfizer? Thanks
I have read that the Moderna Vaccine does not elicit a strong Killer T-cell response (CD8+) while the Pfizer vaccine does that. Is there any evaluation of what that actually means in terms of vaccine efficacy?
Do you have any sources? That seems a bit counter-intuitive given that the Pfizer and Moderna vaccines are nearly identical in absolutely every respect.
It would be less surprising to see such a difference between say Pfizer vs AstraZeneca given the more substantial difference between those vaccines.
https://www.fiercebiotech.com/biotech/pfizer-reports-strong-t-cell-response-to-covid-19-vaccine
"CD8 T-cell responses to S-2P were observed only at low levels after the second vaccination among the participants in the two age subgroups who received the 100-μg dose". Also click on Supplementary appendix and see table S14 on page 36 - https://www.nejm.org/doi/full/10.1056/NEJMoa2028436?source=nejmtwitter&medium=organic-social
I think you might be being a bit overly pessimistic here. First, the evidence seems to be that the primary cause of spread is *presymptomatic transmission* rather than truly asymptomatic transmission (i.e., cases where patients never experience symptoms). Although there is evidence that totally asymptomatic patients do have health effects (and this ought to be studied carefully - did the ones that tested positive have ground glass opacities, etc.?), there is also evidence that the viral load is lower and therefore they may be at significantly reduced risk of transmission to others. So the fact that the vaccines suppress symptomatic disease might well end up reducing R(t) to below 1 which is really the only real thing needed to suppress the virus.
Secondly, the "reinfection" -- do we know these cases were actual reinfection as opposed to redirection? Did they sequence the virus and confirm novel reinfection?
Perhaps...although the correlation between viral load, being asymptomatic, and level of contagiousness is largely in the realm of pure speculation at this point.
It's not at all clear how to make a connection between what's on swab and any of these other attributes. Every molecular diagnostics company in existence would die for a test of "infectiousness" or test that could identify a super-spreader.
At this point NO ONE knows how to design such a test...the data just isn't there.
In terms of re-infection...there's an active project in the Netherlands tracking re-infection cases using NGS to confirm unique genotypes between the initial on subsequent infections.
But among contact tracing groups, it's now being seen on a daily basis and is increasingly commonplace.
Given that there were 69 cases, how confident can we be that there is no risk of antibody-dependent enhancement?
That's been my primary concern so far it likely will be about 6 months are the early rounds of mass vaccinations are complete before we'll know for certain.
But if were a high prevalence event, some indication would absolutely have shown up in the data by now. So things are looking fairly positive so far (albeit early still).
The most useful explanation I have read in newspapers or on media. I certainly will be taking the AstaZeneca vaccine when available. The risk is that after so much orchestrated bad mouthing from US scientific commentators it will be much delayed.
Of course their trials were more informative than others because in fact designed by Oxford academics rather than Big Pharma but unfortunately not tailored to the demands of the regulators.
All the major vaccines seem to be very effective and equally good choices. People just need to understand what the vaccines can and cannot be expected to do. I will certainly be taking whichever one is available first.
I’ve seen this posted on social media as a reason to not trust the vaccines. Can you clarify your stance for the general public regarding receiving the vaccines?
These are highly effective vaccines with no major safety issues. Any short-term reactions are trivial compared with the risks posed by Covid-19.
There have now been about 1-million man-days of post-vaccination observation. So any safety issues are going to be very low prevalence.
And that's in spite of the recent reports of allergic reactions. An allergic reaction is short-term and easily treated...not one has ever been put on an ECMO for an allergic reaction.
I intend to be vaccinated once it becomes available for my age group...
I trust the FDA process and vaccines.
Your "1-million-man-days" is a false way to quote vaccine safety observation. Vaccines are tested in long-term trials to discover adverse long-term effects... and giving it to more people is not a replacement for long-term observation (https://www.history.com/news/swine-flu-rush-vaccine-election-year-1976)
The FDA is allowing these vaccines for emergency use, because the adverse effects of the vaccine on at-risk individuals are lower than the effects of COVID-19.
However, before the FDA will approve them for widespread use, the same needs to be true for not-at-risk individuals, and over a longer-time period. We'll see when the vaccines get widespread use approval.
There's a trade-off there in study design. A far larger test group can turn up low-probability events in a shorter trial. But you're right, there are ALSO effects that require some minimal period of calendar-time to pass before they'll show up.
Very much like the linkage between HPV and Cervical cancer that requires 25+ years between infection and onset of cancer.
I think the calculus made here was that with the current death rates, it's too risky to push the trial out over a multi-year period. But we know that the vaccine is dramatically less risky than acquiring the disease...even if all the risk won't be fully known for years.
Sounds like some people have been giving you a hard time for expressing yourself. Please ignore them and keep writing. I’ve been following your views since this started and I find them very helpful, thoughtful and intelligent and I know others do too.
I would disagree with you on one point. Ignorant or badly educated people aren’t necessarily stupid, but they are very distrustful - for good reason as they have history of being duped - and they often live by simple rules of thumb (which is what behavioural economics is all about). Problem is, once you’re caught in a perceived lie with them, there no come back. Getting through to these people the nuance of vaccines will be a massive challenge .
While I do not disagree with your general conclusions, this and some other websites have misinterpreted the results from the Astra-Zeneca Phase 3 COVID vaccine trial report you mention with respect to estimating its sterilizing immunity efficacy. This efficacy is not determined just by the ratio of asymptomatic infections from the vaccinated group relative to placebo, because symptomatic cases are clearly also infectious and therefore need to be included in this efficacy calculation. A more meaningful measure is the sum of the symptomatic (adjusted to include both primary and non-primary cases) and asymptomatic cases (in other words: all PCR positive tests) for the vaccinated group relative to same sum in placebo group, with appropriate weighting to account for slight differences in the total participant numbers in the symptomatic and asymptomatic counts (presumably because not all participants were tested for asymptomatic infection). For the SD/SD standard regimen, the sterilizing immunity calculated using this method is 35%, which is certainly not sufficient to achieve herd immunity but is definitely better than “zero”. More importantly the results from the LD/SD trial data yields a sterilizing immunity of 77% for this protocol, definitely better than the 59% figure for the asymptomatic ratio in the Astra Zeneca table.
Furthermore, in terms of determining the effect of vaccine on the reproduction number R, you need to take into account that carriers with asymptomatic infections are less contagious than symptomatic ones, as has been measured in a published study: Infectivity of asymptomatic versus symptomatic COVID-19 - The Lancet . This shows that asymptomatic carriers are 3.85 times less infectious than symptomatic ones (per contact). Allowing that asymptomatic carriers will likely have more contacts while they are infectious than symptomatic carriers do (say about 54% more), the effective ratio for disease reproduction would reduce to 2.5. Hence you can estimate the reproduction mitigation efficacy of the vaccine by further weighting of the vaccinated and placebo asymptomatic cases by a factor of 1 /2.5 in the summations discussed above. This yields efficacies of 45% and 83% for the SD/SD and LD/SD regimens, respectively. A follow-up paper to the above Astra-Zeneca report has been submitted which includes data from an extra month of observation: (https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3777268). These results point towards slightly higher sterilizing immunity efficacy for the SD/SD regimen (39%), lower efficacy of the LD/SD regimen (67%), and reproduction mitigation efficacies of 48% and 72% for SD/SD and LD/SD regimens, respectively.
But as you say, lower vaccine effectiveness in the general population coupled with less than 100% acceptance will lead to significantly lower protection levels, so it does not change the conclusion that herd immunity is not reachable and the disease will be endemic for years to come. Nevertheless, starting with a reproduction mitigation efficacy over 70% can be of significant help in relaxing mitigation measures while keeping infection levels in check, allowing a higher degree of “normality” to return to people’s lives.
So,vaccination with current available vaccine is not confer sterilization, only protects against severe disease reducing mortality what is the use of vaccinating everybody if they still can get infected and spread the disease and Not Just vaccinate the vulnerable
A 10x reduction in the risk of severe disease leading to hospitalization or death.
The analogy is this. If I'm going into a gunfight and my choice is a bullet-proof vest that's 70% effective or a snarky t-shirt...I'm opting for the less-than-perfect bullet-proof vest because I'm not an idiot.
The choice to take the vaccine is a similar trade-off.
Sorry, it still would apply to high risk people not to the majority population of which most are asymptomatic or have mild symptoms.
We've known everything in this article since April.
We've never expected COVID immunity to be sterilizing. Research over the last few years suggests all known human coronavirus immunity is non-sterilizing. (https://www.technologyreview.com/2020/04/27/1000569/how-long-are-people-immune-to-covid-19/amp/)
Current data suggests 80% of the USA is going to be exposed to COVID-19 before the end of April, but widespread vaccines won't be delivered until summer at the very earliest (and possibly later). So why get all fear-mongery about vaccine results, when most people will be "innoculated" by the actual virus?
The purpose of our emergency vaccine distribution is to vaccinate the most at-risk individuals, because they disproportionally represent the severe-illness cases and deaths.