Initial report of decreased SARS-CoV-2 viral load after inoculation with the BNT162b2 vaccine

[mayku-T-meelo]

Initial report of decreased SARS-CoV-2 viral load after inoculation with the BNT162b2 vaccine - Nature Medicine

Breakthrough infections of SARS-CoV-2 occurring 12 or more days after the first dose of the BNT162b2 mRNA vaccine were associated with lower viral loads than those found in unvaccinated individuals, suggesting that the vaccine might reduce infectiousness.

www.nature.com

So the study found that the viral load after taking the Pfizer vaccine is apparently substantially reduced, that claim or similar ones will be definitely be pushed and used to show the efficacy and purpose for vaccinating people.

What they say is:

When we calculated the mean Ct for post-vaccination infections identified on each day after vaccination, we found that the Ct values of positive samples collected 12–37 d after vaccination with the first dose (a second dose having been given on day 21 for all samples taken after day 21) were higher than the Ct values of positive samples taken during the first 11 d after vaccination for the RdRp gene (Fig. 1) and for the genes N and E (Extended Data Fig. 2) (P < 10−19 for the three genes, Mann–Whitney U-test). Differences in mean Ct calculated for these two time periods ranged from 1.7 ± 0.2 for RdRp to 1.6 ± 0.2 for gene E and 1.4 ± 0.2 for gene N.
[...]
We next compared the Ct values of these post-vaccination infections with Ct values of positive tests of unvaccinated patients.

What mean of Ct values are they even measuring here, how do they come up with those values? From the perspective on senselessness of PCR tests I grasped that those values of tests were pre-set by the manufacturer of the test. And that the "hot potato" of the story was that the too high of a value (that multiplies or potentiates the whatever viral load there is) is then producing the abundant false positives.

I know some of you are far better informed than I am. Does anyone understands this more in depth?

 

[Perry Staltic]

The Ct is fixed for routine tests, but it sounds like for this study they used the lowest Ct that proteins were detected. In other words, as soon as fluorescence was detected the Ct was recorded. Increased Ct means decreased "viral" load.

 

[mayku-T-meelo]

The Ct is fixed for routine tests, but it sounds like for this study they used the lowest Ct that proteins were detected. In other words, as soon as fluorescence was detected the Ct was recorded. Increased Ct means decreased "viral" load.

Thank you. Do you (or anyone else) have any idea what possible underlying sequence of biological events would result in those higher values? The study is not very strictly experimentally controlled, so I imagine some of it is open for interpretation. But they nevertheless show some decrease of the load that they measure (with regard to the unvaccinated), so I am wondering what would be the most sensible explanation.

 

[Perry Staltic]

The higher the Ct it takes to detect anything, the lower the amount of material being detected. If a lot of virus exists, the Ct will be low, and vice versa. Anything above Ct 34 it's only detecting viral fragments, not whole, infectious virus. They typically run tests at around 40.

 

[mayku-T-meelo]

The higher the Ct it takes to detect anything, the lower the amount of material being detected. If a lot of virus exists, the Ct will be low, and vice versa. Anything above Ct 34 it's only detecting viral fragments, not whole, infectious virus. They typically run tests at around 40.

Thanks again. I understood that vaguelly, but what I meant was how the values get higher in the context of the study. And what would be the mechanism that lowers those detected deactivated fragments then. Does the vaccination somehow forcefully mobilizes the cleanup of the debris?

 

[Perry Staltic]

Thanks again. I understood that vaguelly, but what I meant was how the values get higher in the context of the study. And what would be the mechanism that lowers those detected deactivated fragments then. Does the vaccination somehow forcefully mobilizes the cleanup of the debris?

I have no idea how what they claim is happening works.

 

[Giraffe]

Patients were excluded if they had a positive sample before vaccination; if they had a positive sample more than 21 d after the first dose of the vaccine but did not receive the second dose on day 21; or if they were over the age of 90 years (28 patients older than 90 were not included because it was not possible to match them with unvaccinated controls).

How many patients were excluded because they did not receive the second dose on day 21? Why did they not receive the second dose? Were they too ill? What was the CT value of the excluded ones? -- If viral load corresponds with severity of the disease, and if people were excluded because they were too ill to get the second jab, this could be a major source of bias.

When we calculated the mean Ct for post-vaccination infections identified on each day after vaccination, we found that the Ct values of positive samples collected 12–37 d after vaccination with the first dose (a second dose having been given on day 21 for all samples taken after day 21) were higher than the Ct values of positive samples taken during the first 11 d after vaccination [...]

For patients with multiple positive post-vaccination tests, only the first test was included.

If you check in figure 2 (see below) the number of patients you see that the numbers raised sharply until day 7 and then slowly decreased. 37% have been tested positive within the first week. 75% have been tested positive within the first two weeks. 92% have been tested positive within the first three weeks. -- This is to give an idea of the numbers. The dots to the right side of the dashed gray line represent only 8% of the patients.

Now why did they choose the intervals 1-11 days and 12-37 days? Why not 1-10 and 11-37?

The CT value on day 11 is equal to or higher than that of day 17, 19, 22 and 26. The number of patients on day 11 is 277, this is enough to offset all data points which I marked with the red square. I think, it's easy to see that the green line would come down quite a bit if day 11 would be counted there. There wouldn't be much left of the "lower viral load".

 

[mayku-T-meelo]

How many patients were excluded because they did not receive the second dose on day 21? Why did they not receive the second dose? Were they too ill? What was the CT value of the excluded ones? -- If viral load corresponds with severity of the disease, and if people were excluded because they were too ill to get the second jab, this could be a major source of bias.






If you check in figure 2 (see below) the number of patients you see that the numbers raised sharply until day 7 and then slowly decreased. 37% have been tested positive within the first week. 75% have been tested positive within the first two weeks. 92% have been tested positive within the first three weeks. -- This is to give an idea of the numbers. The dots to the right side of the dashed gray line represent only 8% of the patients.

Now why did they choose the intervals 1-11 days and 12-37 days? Why not 1-10 and 11-37?

The CT value on day 11 is equal to or higher than that of day 17, 19, 22 and 26. The number of patients on day 11 is 277, this is enough to offset all data points which I marked with the red square. I think, it's easy to see that the green line would come down quite a bit if day 11 would be counted there. There wouldn't be much left of the "lower viral load".

View attachment 22501

Wow, you're good Giraffe, I didn't even notice those small numbers. I'm still confused every time I start re-reading the text, but the slowly falling numbers of tests taken into account speak for themselves.

 

[Giraffe]

Wow, you're good Giraffe, I didn't even notice those small numbers. I'm still confused every time I start re-reading the text, but the slowly falling numbers of tests taken into account speak for themselves.

Yeah, these data points on the right side look more important than they are.

The really curious part though is the patients that were excluded because they have not received the second jab. If you want to show viral loads after the first shot, there is no reason to exclude the patients who have only received the first one. Furthermore, if they had been included, the researchers could have tested, if the second shot made a difference or not. It was not investigated in the phase 1 to phase 3 trials if the second shot is necessary.

 

[mayku-T-meelo]

Right, in a sense yes, but just from the presented figure it could be argued that the number of positive tests is falling with each day, which then seems to speak in favor of the vaccine, but then again who knows how many of those that initially received the vaccine were afterwards excluded. So it could be that the strong made it till the end, no matter the obstacles, kind of real battle of the fittest scenario, but then again who knows.

I was breaking my head with this one for a while, but I succumb:

Interim Estimates of Vaccine Effectiveness of BNT162b2 and mRNA

mRNA COVID-19 vaccine effectiveness against SARS-CoV-2 infection

www.cdc.gov

I guess a lot could be speculated trying to answer and both of these studies are operating under open uncertainty, just observationally, so it's hard to pinpoint anything with any confidence.

 

[Giraffe]

Right, in a sense yes, but just from the presented figure it could be argued that the number of positive tests is falling with each day, which then seems to speak in favor of the vaccine, but then again who knows how many of those that initially received the vaccine were afterwards excluded. So it could be that the strong made it till the end, no matter the obstacles, kind of real battle of the fittest scenario, but then again who knows.

If you think of the countless cases of huge outbreaks in nursing homes just days after vaccination, you could interpret the data in a different way. You could theorize that the vaccination triggers SARS-CoV-2 infections and/or positive PCR tests and that the peak occurs one week after the vaccination.

 

[mayku-T-meelo]

If you think of the countless cases of huge outbreaks in nursing homes just days after vaccination, you could interpret the data in a different way. You could theorize that the vaccination triggers SARS-CoV-2 infections and/or positive PCR tests and that the peak occurs one week after the vaccination.

Yes, I see your point. But then again, this could be brushed off, since they didn't show any difference with demographically matched control group for the first period. Which I don't find very convincing, I suppose you can strip and prune the data however you wish as long as they match demographically, if you have a huge dataset. Even if they didn't bother to adjust this control group, they probably left out people who had really bad reactions and we don't know how many, so only people who were resilient enough to the inflammatory effect of the vaccine stayed in the group, and nobody knows and noone is responsible, nothing conclusive can be said either way, except that if you argue against it and hint that it's basically marketing and nudging, you will be considered an enemy of the state and science.

 

[Giraffe]

was breaking my head with this one for a while, but I succumb:

Interim Estimates of Vaccine Effectiveness of BNT162b2 and mRNA

mRNA COVID-19 vaccine effectiveness against SARS-CoV-2 infection

www.cdc.gov

I guess a lot could be speculated trying to answer and both of these studies are operating under open uncertainty, just observationally, so it's hard to pinpoint anything with any confidence.

• 279 participants were excluded because of low participation, and in total there were 205 PCR-confirmed infections. The data came from eight different sites. No information about Ct is given.
• 161 PCR-confirmed infections happened before participants had a chance to get the vaccine or in participants that didn't get vaccinated at all.
• There were 44 PCR-confirmed infections after the participants got vaccinated of which 75% (33/44) were excluded from the efficiency calculation because they occurred in the first two weeks after vaccination "when immune status was considered indeterminate".
• An unknown number of participants with prior PCR-confirmed infection got vaccinated later (see below).
• The numbers do not add up (see below)
• Something is strange about how the J&J vaccine was treated in the study (see below).

The results must have been truly destroying!

205 PCR-confirmed infections vs 279 participants that were excluded: this is completely disproportionate. Researchers could at best have concluded that their data are not sufficient to prove efficiency of the vaccine. -- And we know that often in the "excluded because of protocol deviations" group most of the disturbing adverse events are hidden.

.....

Participants with prior PCR-confirmed infection were later vaccinated. Weren't they immune already?

During the 116,657 person-days when participants were unvaccinated, 161 PCR-confirmed infections were identified (incidence rate = 1.38/1,000 person-days).

989 participants were not vaccinated, and the study lasted 13 weeks. So the unvaccinated participants can only account for 77% (989*13*7/116,657) of the 116,657 person-days.

Another way to look at it is the following:

Here the immune status "unvaccinated" (= no vaccination or before vaccination) accounts for 38% of the person-days while only 25% of the participants did not get vaccinated. So only 66% of the "unvaccinated" person-days have been contributed by the participants that have not been vaccinated.

Numbers do not add up.

One way I calculated 77% and another way I calculated 66%. There is something weird with the data. They say that they have included 3,950 participants in the efficiency analysis. According to my math this is 359,450 person-days.

Why was Johnson & Johnson treated differently?

Five who have received J&J "contribute unvaccinated person-days until their vaccination date and then no longer contribute to the analysis." They don't explain why they do so. They should be included in "fully immunized".

By the way, this is not enough to explain the difference above.

 

[Giraffe]

Yes, I see your point. But then again, this could be brushed off, since they didn't show any difference with demographically matched control group for the first period. Which I don't find very convincing, I suppose you can strip and prune the data however you wish as long as they match demographically, if you have a huge dataset. Even if they didn't bother to adjust this control group, they probably left out people who had really bad reactions and we don't know how many, so only people who were resilient enough to the inflammatory effect of the vaccine stayed in the group, and nobody knows and noone is responsible, nothing conclusive can be said either way, except that if you argue against it and hint that it's basically marketing and nudging, you will be considered an enemy of the state and science.

I would avoid any discussion about the efficiency of the vaccines. The studies have shown that they reduce the risk of getting infected only minimally. In the Pfizer trial it was a reduction from 0.88% down to 0.04% (see Antony Colpo's article). And we talk about an illness with a survival rate above 99%. It's not worth the risk of taking a vaccine. It's better to ensure that your vitamin D levels are OK. This will protect you from all sorts of bacteria and virusses.

 

[mayku-T-meelo]

Thank you again. It's important to know the weak points, if someone brings the efficacy up, because more and more "ecologically valid" studies will pop up, I imagine more and more data is being and going to be gathered and then skewed to show use for the vaccines. Reading those studies is most of the time way over my head and assessing their non-validity is yet another thing, but it seems that the main recurring theme is that just from the beginning back in summer they were always leaving out all susceptible people that would make the results vulnerable.

 

[Giraffe]

Thank you again. It's important to know the weak points, if someone brings the efficacy up, because more and more "ecologically valid" studies will pop up, I imagine more and more data is being and going to be gathered and then skewed to show use for the vaccines. Reading those studies is most of the time way over my head and assessing their non-validity is yet another thing, but it seems that the main recurring theme is that just from the beginning back in summer they were always leaving out all susceptible people that would make the results vulnerable.

It's always telling when certain information is missing. For example, when I read that 279 were excluded because of low participation, I wonder whether they came from the vaccinated or the unvaccinated group. The information is missing in the study. -- I bet that 90 % of them had been vaccinated.

Or when they write:

Only 22.9% of PCR-confirmed infections were medically attended, including two hospitalizations; no deaths occurred.

How many of those who needed medical attention and/or were hospitalized were vaccinated? This information is missing.