Things that went whizzing by that I want to remember: So Friday morning I woke up with the sniffles in Carbon County, Montana—east northeast of the Yellowstone-Grand Teton National Park complex. No fever. Full senses of smell and taste. No coughing or perceived shortness of breath (after accounting for the altitude: I was at 5,500 feet instead of the sea level I am used to).... Hope is not a plan. The Delta plague wave will brush relatively lightly past Teton County, Wyoming. I fear what it will do to Carbon County, Montana.
The Canadian study done in long-term care homes found full vaccine efficacy to last five months. The CDC is getting six to nine months on a more general population.
It really is a coronavirus; the Uncommon Cold. You get a cold every year. There's no reason to suppose this is different in that respect, and the emerging data says it's not. (Various optimism about T-cells versus antibody counts notwithstanding.)
The way forward here is to make and apply enough effective vaccines to everyone on earth in a single three month period. Actually logistically doable, but the political will could be considered lacking.
Also, the morbidity doesn't get _enough_ better with vaccination. We're still looking at a debate about whether case severity correlates with degree of cognitive impairment (UK data says yes, US data says no) from the pre-vaccinated cases; we haven't got anybody (there hasn't been time!) publishing on whether vaccination reduces cognitive impairment or any other morbidity.
Given the correlation between age and comorbidities on the one hand and early vaccination on the other, it is proving very difficult to precisely pin down the vaccine immunity-erosion effect...
Which in turn means that "when do we put all the infection control mandates back?" and "when do we start booster shots?" is a delicate and difficult judgement call, where waiting too long is likely to have a high cost.
Bergstrom appears to argue the reason that we see purported efficacy declines in Israel and lack of staying power for 2x mRNA is due to population differences and relative age / efficacy.
The recent NEJM paper seems to indicate continued efficacy. Yes, the examples Eric Topol cites (Qatar / others) do not, but aren’t there significant problems extrapolating out from those? (Can’t really say the same with REACT though).
"The 2SLS estimates are often much bigger than the OLS estimates. Their discrepancy is negatively correlated with the strength of the IVs…"
Well that *could* be a violation of the exclusion restriction, as Xu suggests. But might it not alternatively be interpreted as "method hacking"? That is, a 2SLS analysis was selected for publication because it gave the most publishable results? That *could* be due to correlation between the instrument and the error term in the underlying probability generating process, but it could also just be spurious. Either way, I would put the blame on the selection effect.
One thing I'm confused about is the recent insistence that dropoff of Covid antibodies after a few months is a reason to get a 3rd, booster, shot. I seem to recall reading a few months ago that 'not to worry, antibodies always drop off, the important thing is that your killer-T cells have been trained and will trash Covid anyhow if it shows up in your body', or something to that effect.
Also, here in Southern Oregon, well-vaxxed in some spots and not in others, I'm waiting for the ICU's, now full, to overflow, and maybe get some antivaxxers to belatedly mask up.
Booster recommenders have several concerns they have to deal with. Do they just care about preventing severe cases? Do they just care about hospitalizations, or symptomatic cases, or the odds of simply testing positive? Preventing severe infection is not the same as preventing transmission. I saw another study that said that viral load doesn't correlate well with transmission, and note viral load is why we are concerned about transmission from fully vaxed. So we are still substantially in the dark.
That paper finds that you get meaningful mutation _during transmission_. Part of the goal has to be to minimize transmission because we don't want the virus exploring any more of its potential space than we can possibly avoid.
I saw a paper last week, that claimed that viral load doesn't correlate with transmissibility. If this is true, then we are in the dark about an important aspect of the effect of the vaccines on contageousness.
The estimates for wild type were about a thousand virions; there, how much is being shed, how fast, and how close you are standing, would be dominant factors. With Delta, if the threshold of infection is one to three (or one to eight) virions, you can catch the disease if you come into contact with one (1) inert virus particle in the air. At that point, sheer dumb luck -- you happen to be the person on the street who inhaled at the wrong time, fifty metres away from the infectious individual -- starts to play a significant role in transmission, and the correlation between viral load and how many people you infect breaks down.
Yes. The other authors thought the range was 1 to 8. I didn't see anything about the reasoning behind those numbers. I suspect only epidemiologic data will be a reliable way to tell, and that takes a while to get.
The Canadian study done in long-term care homes found full vaccine efficacy to last five months. The CDC is getting six to nine months on a more general population.
It really is a coronavirus; the Uncommon Cold. You get a cold every year. There's no reason to suppose this is different in that respect, and the emerging data says it's not. (Various optimism about T-cells versus antibody counts notwithstanding.)
The way forward here is to make and apply enough effective vaccines to everyone on earth in a single three month period. Actually logistically doable, but the political will could be considered lacking.
Also, the morbidity doesn't get _enough_ better with vaccination. We're still looking at a debate about whether case severity correlates with degree of cognitive impairment (UK data says yes, US data says no) from the pre-vaccinated cases; we haven't got anybody (there hasn't been time!) publishing on whether vaccination reduces cognitive impairment or any other morbidity.
Given the correlation between age and comorbidities on the one hand and early vaccination on the other, it is proving very difficult to precisely pin down the vaccine immunity-erosion effect...
Indeed.
Which in turn means that "when do we put all the infection control mandates back?" and "when do we start booster shots?" is a delicate and difficult judgement call, where waiting too long is likely to have a high cost.
Bergstrom appears to argue the reason that we see purported efficacy declines in Israel and lack of staying power for 2x mRNA is due to population differences and relative age / efficacy.
https://twitter.com/ct_bergstrom/status/1427767356600688646?s=21
The recent NEJM paper seems to indicate continued efficacy. Yes, the examples Eric Topol cites (Qatar / others) do not, but aren’t there significant problems extrapolating out from those? (Can’t really say the same with REACT though).
Yes. We should be comparing old and young people vaccinated late and early, with four boxes...
"The 2SLS estimates are often much bigger than the OLS estimates. Their discrepancy is negatively correlated with the strength of the IVs…"
Well that *could* be a violation of the exclusion restriction, as Xu suggests. But might it not alternatively be interpreted as "method hacking"? That is, a 2SLS analysis was selected for publication because it gave the most publishable results? That *could* be due to correlation between the instrument and the error term in the underlying probability generating process, but it could also just be spurious. Either way, I would put the blame on the selection effect.
One thing I'm confused about is the recent insistence that dropoff of Covid antibodies after a few months is a reason to get a 3rd, booster, shot. I seem to recall reading a few months ago that 'not to worry, antibodies always drop off, the important thing is that your killer-T cells have been trained and will trash Covid anyhow if it shows up in your body', or something to that effect.
Also, here in Southern Oregon, well-vaxxed in some spots and not in others, I'm waiting for the ICU's, now full, to overflow, and maybe get some antivaxxers to belatedly mask up.
So sorry you had to go through that in Montana!
It's not so much the drop-off in antibodies: it's the number of cases in Israel...
This is the first paper I've come across that tries to measure T-cells:
https://medicalxpress.com/news/2021-08-robust-t-cell-response-mrna-covid-.html
Booster recommenders have several concerns they have to deal with. Do they just care about preventing severe cases? Do they just care about hospitalizations, or symptomatic cases, or the odds of simply testing positive? Preventing severe infection is not the same as preventing transmission. I saw another study that said that viral load doesn't correlate well with transmission, and note viral load is why we are concerned about transmission from fully vaxed. So we are still substantially in the dark.
Remember that "Delta produces a thousand times the virus load" factoid?
It comes from this paper: https://virological.org/t/viral-infection-and-transmission-in-a-large-well-traced-outbreak-caused-by-the-delta-sars-cov-2-variant/724
That paper finds that you get meaningful mutation _during transmission_. Part of the goal has to be to minimize transmission because we don't want the virus exploring any more of its potential space than we can possibly avoid.
I saw a paper last week, that claimed that viral load doesn't correlate with transmissibility. If this is true, then we are in the dark about an important aspect of the effect of the vaccines on contageousness.
How could viral load not correlate with transmissibility?
Thats what the paper imp[lied. It is a counterintuitive result if true.
The estimates for wild type were about a thousand virions; there, how much is being shed, how fast, and how close you are standing, would be dominant factors. With Delta, if the threshold of infection is one to three (or one to eight) virions, you can catch the disease if you come into contact with one (1) inert virus particle in the air. At that point, sheer dumb luck -- you happen to be the person on the street who inhaled at the wrong time, fifty metres away from the infectious individual -- starts to play a significant role in transmission, and the correlation between viral load and how many people you infect breaks down.
If the "one to three virions" results (for example, https://www.biorxiv.org/content/10.1101/2021.02.22.432096v1, discussed in https://www.news-medical.net/news/20210224/SARS-CoV-2-transmission-bottleneck-is-of-the-order-of-one-to-three-virions.aspx) are correct, you would expect there to be no correlation. Dumb luck will have a lot to do with it.
Yes. The other authors thought the range was 1 to 8. I didn't see anything about the reasoning behind those numbers. I suspect only epidemiologic data will be a reliable way to tell, and that takes a while to get.