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.
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 ?
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?
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?
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.
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?
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
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?
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.
Wouldn't a nasal-administered vaccine elicit better sterilizing immunity? Why isn't anyone working on one?
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 ?
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?
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?
Given that there were 69 cases, how confident can we be that there is no risk of antibody-dependent enhancement?
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.
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?
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
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.