Covid Vaccination One Dose or Two iV
I didn’t expect this to be a series of posts, but there is news since I wrote post number III.
There is a partial change of subject, because the news concerns the Oxford/AstraZeneca adenovirus based vaccine and not the mRNA based vaccines which I discussed before.
In the UK they decided to delay the second dose for 3 months in order to get a first dose in as many people as possible as quickly as possible. This is roughly what I proposed in post I. Since then, Israeli HMOs have noted a significant rate of infection (detected by PCR screening) two to three weeks after the first dose the Pfizer/BioNTech vaccine (link to same post number III and post number II). After 3 weeks, they injected the second dose, so they can’t follow further.
Now the UK has new data. As in Israel, these are comparisons of vaccinated people to the general population not a randomized trial with a control group. The evidence strongly supports the UK approach of delaying the second dose.
First the estimated effectiveness of one dose is 75%, which actually slightly above the estimate of effectiveness of two doses in the phase III trial (62%). Second, the estimated effectiveness of two doses 3 months apart is even higher (82.4%). This suggests that the delay increases the effectiveness of the booster shot (the three week delay is due to the fact that, for other viruses, it has long been known that booster shots before 3 weeks have passed are not effective — 3 weeks was the shortest reasonable interval).
I think the similarity of 75% and 82.4% provides relatively solid evidence that it is not important to give the second shot quickly. There are many possible biases in a study of case vs general population, but it is much harder to see how they bias the estimate of the relative magnitude of the effects of first and second doses. Clearly the estimated benefit per dose is vastly greater for the first dose, so it is hard to argue against delaying the second.
Importantly, there was no clear evidence that protection from one dose waned during the 3 months.
Finally, in addition to the headline data on symptomatic cases, there are estimates of the probability of conversion to a positive result by PCR (this is not the primary outcome measure for any phase III trial but is the outcome measured in Israel which helps explain the difference from phase III trials). In the UK AstraZeneca case, the probability of PCR detected virus decline 67%. This is close to the decline in symptomatic disease. This is reassuring as it would be very bad for herd immunity to give people a vaccine which made them become asymptomatic carriers.
Obviously UK authorities are claiming that the new data prove they made the right choice (authorities always claim that). But this time, they might have a point.
Hi Robert;
Something more than The Guardian; “Single-Dose Oxford COVID Vax Data Bolsters Prime-Boost Strategy,” MedScape Today, February 2, 2021.
“One standard dose of the AstraZeneca/Oxford COVID-19 vaccine was highly effective against symptomatic disease up to 3 months later, lending support to a prime-boost vaccination strategy, additional analyses of phase III vaccine trial data found.
Vaccine efficacy was 76% (95% CI 59%-86%) from 22 days following the first dose of vaccine to the next dose 90 days later, reported Andrew Pollard, PhD, of the University of Oxford in England, and colleagues.”
I am off for a second dose of Pfizer Monday at U of M in Ann Arbor.
To me the big question of one dose has always been: Does one dose protect from serious illness and/or death? What brings this to mind is reports that among two dose patients nobody who gets infected (the 5%) dies (zero). So if one dose reduces the illness to something akin to the flu, then, getting twice as many vaccinated with one dose initially would make a lot of sense — and whatever the results might indicate in between.
One caveat: whether one dose affects mutation rate.
As of Thursday, only 254 individuals out of the 416,900 who were already a week after the second Pfizer shot – the time where the immunity is considered to kick in – got infected with the virus, the organization reported. Moreover, those who were found to be positive only had light symptoms, with just four of them being hospitalized, all of them in light condition.
https://www.jpost.com/health-science/covid-just-006-percent-israelis-sick-after-two-shots-no-one-serious-study-657871
After all front line workers, healthcare, first responders, and school teachers have obtained the maximum protection, then I don’t care if the rest only have protection from serious infection. Remember that sick people are still carriers even if they do not die and that logistics still will mean that 70% of the population reaching any level of protection is still a long way off. Big problem in winter is increased risk of herd contamination flocking together to obtain immunity. VA schools have been pressure to stage back to in-person before all teachers have been given immunization. Never discount stupid for what it is.
Ron:
In Michigan the cry is to let kids play sports besides reopen schools. I guess they could if there are no spectators or cheer leaders and just keep it to a game. That is risky too. No one will care if someone gets ill and dies or is incapacitated. It just takes one, everyone will pray, and the ill will be forgotten. All for a scholarship where only a few will actually play. Is it worth the risk ?
Run,
What a risk is worth depends upon who bears the risk and who obtains the benefit.
There were several pre-existing online infrastructures for K-12, but few states chose to use them instead of rolling their own substandard custom effort. Too many interests are served by failing virtual classrooms. School district partnerships with K-12 or Khan Academy are so effective that they would be retained beyond the pandemic effectively raising the quality of public education in general, but more importantly standardizing public education across school districts. School boards and text book publishers would take a huge hit from such progress. It would be a great aid to teachers on the one hand and a great inducement for thinning the herd of the least effective teachers on the other hand.
So, I would be in favor of fewer teachers with better pay and the best possible tools for learning. An AI never loses its patience and by definition presents ideal individual attention to each student, which is to say an AI is the best possible assistant instructor that a teacher can have.
Ron:
I thought I was discussing high school sports like basketball?
The term AI used to bother me, but I have come to accept the terminology of artificial intelligence as a development in semantics, since no such development in technology is conceivably possible. Living things have an innate sense of value judgements backing the development of their learning that machines cannot reasonably be expected to ever have of their own. Perhaps a programmer might imprint his own idea of those value judgements on a machine, but they are unlikely to ever be innate natural value systems. Machines do not suffer hunger nor have a libido nor fear death. Life learns from its pains and wants and fears. Intelligence is the means by which life makes choices according to its understanding of consequences. Life cannot make intelligent choices without consequences.
BTW, what we call AI is actually about the fifth generation of advancement in expert systems. Expert systems developed memory of experiences and algorithms from which to value those experiences in about their 3rd gen. Algorithms are neither innate nor natural regardless of how sophisticated that they become and the underlying value judgements were entirely contrived by the developers. It is that contrived part that is the subject of disastrous AI sci-fi dramas. Since humans typically do not understand how their own values developed, then it is simple enough to project them into circumstances in which they would be entirely inappropriate.
Run,
High school sports are so important to people trying to grab that brass ring that there is no better misdirection away from online schooling. No physical schools equals no sports. They are just throwing the dog a bone wrapped in bacon.
And I am discussing the chances of spreading Covid if this expansion is not done right. No spectators, cheer leaders, and just players.
Make undergraduate college free for all and then watch high school sports injuries disappear.
Of course then there are those that want to be one of the 18K professional athletes in the US, a great occupation for 0.005% of the population. Kids that are bad at math maybe, but parents want to send their kids to college without having to pay for it. Without college athletic scholarships, then all that is left is to impress the chicks.
BTW, if it is not clear, then “they” are the elites of the public school political-economic complex (PSPEC) and the “dog” is parents with school age children. Neither really cares about the quality of education that kids get as long as it is cheap for parents and makes PSPEC elites wealthier and/or more powerful.
Run,
Virginia has been having high school sports on a somewhat abbreviated and delayed schedule with frequent game cancellations this winter. It is a given that such activity will increase the spread of Covid-19 even if attendance is severely restricted. Individual activities before and after games is not controlled. People are willing to take the risk anyway. Why?
High school athletes are more popular than high school mathletes. Rational choice cannot survive in such an environment.
Hyde County NC has had 597 confirmed cases of Covid-19 to date and only six deaths and no, you cannot go there to Hyde. NC state has had 791,457 confirmed cases to date and 9,880. Covid-19 is not an equal opportunity deployer.
9,880 deaths in NC state-wide that is.
So, another hypothesis bites the dust. Hyde County constitutes 0.05% of NC state’s total population, but 0.06% of NC state’s total Covid-19 deaths. Remoteness in and of itself does not always lead to a better pandemic bottom line. Better healthcare in remote areas will be limited to only certain high income resort areas. Hyde County being remote, but also coastal, probably gets more thru traffic than depressed remote areas in Appalachia.
Yet, Covid-19 spread is unevenly dispersed. Remoteness plays into the variability, but is not the controlling factor.
[These guys seem entirely content that R0 explains all of the local variances and I will never have enough data to second guess them with any authority. Besides that then contact rate does explain about everything except that the assumption that population density can be considered an effective proxy for contact rate can in many cases be deeply flawed.]
Estimating and explaining the spread of COVID-19 at the county level in the USA | Communications Biology (nature.com)
Abstract
The basic reproduction number, R0, determines the rate of spread of a communicable disease and therefore gives fundamental information needed to plan public health interventions. Using mortality records, we estimated the rate of spread of COVID-19 among 160 counties and county-aggregates in the USA at the start of the epidemic. We show that most of the high among-county variance is explained by four factors (R2 = 0.70): the timing of outbreak, population size, population density, and spatial location. For predictions of future spread, population density and spatial location are important, and for the latter we show that SARS-CoV-2 strains containing the G614 mutation to the spike gene are associated with higher rates of spread. Finally, the high predictability of R0 allows extending estimates to all 3109 counties in the conterminous 48 states. The high variation of R0 argues for public health policies enacted at the county level for controlling COVID-19…
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[The most valuable part of this exercise may have been the confirmation that copy and paste function is browser dependent. I switched from Firefox to Edge this week.]
The first law of mathematical modeling is that one cannot model what one cannot measure. Transient rates and specific local population density anomalies such as institutionalized residences with high contact caretakers are far better understood than they are measured.