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SUMMARY
Comirnaty induces potentially life-threatening, apparently transient, blood cell problems. The two old geezers cannot match the numbers from the eight regulatory and publication sources consulted. If you do not want to be confused, don't read any further.
In the phase I trial of the Pfizer/BioNTech mRNA vaccine, lymphopenia was reported in the vaccine group. The company reported the vaccine’s mechanism of action is expected to induce lymphopenia—all the lymphopenia events in phase I were reported as transient and resolved. However, TTE was surprised that testing for lymphopenia was omitted in the phase II/III trial.
If it's an expected event, we might find it in the Package Insert, but there's nothing to see.
Two studies started running in April 2020. The first is BNT16201, divided into b1 and b2—abbreviated to BNT162b1 (120 participants) and BNT 162b2.
The two vaccine candidates share the same modRNA platform, RNA production and purification processes, and formulation of lipid nanoparticles. They differ in the nucleotide sequences that encode the vaccine antigens and in the overall size of the RNA constructs, which results in several RNA molecules in 30 μg of BNT162b1 that is approximately 5 times as high as that in 30 μg of BNT162b2.
Nature published the “Phase I/II study of COVID-19 RNA vaccine” BNT162b1 on 12 August 2020 and reported on the laboratory changes.
The largest reported decreases in lymphocyte count after the first dose were seen in 8% (1/12), 46% (5/11), and 50% (6/12) of those who received the 10 μg, 30 μg, and 100 doses, respectively. Six participants had grade 3 decreases in the lymphocyte count. These decreases were transient and reported to return to normal 6–8 days after vaccination.
On 10 December 2020, questions about lymphopenia were raised at the US FDA’s 162nd Meeting of Vaccines and Related Biological Products Advisory Committee.
‘For Dr. Jansen, one regarding mechanism of action. RNAs, in principle, can be recognized via the innate immune system. Specifically, potential RNA boost activation of Toll-like receptor and could induce interferons, which may explain the transient lymphocytopenia.’
Not for the first time, TTE finds the figures don’t match up.
The meeting transcript reported the same line that a lymphocyte decrease occurred one to three days after the first dose and generally normalised within six to eight days. This time, transient decreases occurred in 5/12 participants in the 18 to 55-year-old group and 4/12 participants in the 65 to 85-year-old group. We now have nine participants, not the 12 reported in the Nature publication.
Severity was reported to the FDA as “mostly grade one to two.” The six reported in the Nature publication, with grade 3 decreases in lymphocyte count, weren’t mentioned.
The two trials were republished in the New England Journal of Medicine on October 14, 2020: “Safety and Immunogenicity of Two RNA-Based COVID-19 Vaccine Candidates” to make this analysis even more complex.
Here, we learn that ‘The largest changes from baseline in laboratory values were transient decreases in lymphocyte counts, which resolved within 1 week after vaccination.’
In April 2021, Nature published again on the SARS-CoV-2 BNT162b1 mRNA vaccine in 144 healthy SARS-CoV-2-naive Chinese participants. In line with the German studies, the most common laboratory abnormality was a transient lymphocyte decrease.
We now learn that platelet counts decreased, and C-reactive protein (CRP) levels were increased.
Surprisingly, we should have known this all along. The triallist reported the data aligned with the results of the German study. Oddly, we can’t find any mention of CRP or platelets in the August 2020 publication. All this seemingly bypassed the UK’s EWG.
You might be asking why all this matters.
Lymphopenia occurs when the level of lymphocytes in your blood are abnormally low. Lymphocytes play a pivotal role in the immune system. Low levels are associated with an increased risk of infection-related death, which increases when lymphopenia is combined with abnormal CRP levels.
Moreover, Thrombocytopenia, or low platelet count, increases the risk of death during sepsis. Platelet activation can suppress infection; however, their role in active infection is not fully understood.
Over at the TTE office we are still unsure how many participants in the trials had lymphopenia and for how long. More mental gymnastics are required.
Pfizer’s own Clinical Study Results, published on their own website in November 2023, report the number of participants in each age group who had a drop in lymphocyte count after receiving Dose 1 of BNT162b1 (Figure 4A) or BNT162b2 (Figure 4B).
So, for BNT162b1, 11/36 (31%) participants in the 18 to 55-year-old group and 6/36 (17%) in the 65 to 85-year-old group had lymphopenia, and 2/36 (5.6%) and 3/36 (8.3%), respectively, in the BNT162b2 study group.
This may be the number of participants with lymphopenia, but the numbers don't add up, which concerns us. BNT162b1 was supposed to have 120 participants, and BNT 162b2 96—however, the above reports 180 participants (90 in each study). The study reports that a total of 195 participants underwent randomisation - Where did 15 go then?
Also, the Biological Licensing Application (BLA) to the FDA only mentions 18-55-year-old participants in the b1 trial.
Feeling confused? We are.
So, we looked at the EU trial register entry to clear up the matter. For BNT162b1, we now found seven doses (compared to the three reported in the Pfizer trial report) in the age 18 to 55-year group (n=72) and three doses (same number as the Pfizer trial report) in the 56 to 85-year group (n=36).
This gives 108 participants for BNT162b1 Part A (there is no Part B), or 126 if we assume there are 18 placebo participants (there is no report of placebo participants in the entry).
Still with us? Feeling more confused? We are.
For BNT162b2, the trial register reports five arms (two less) in the age 18 to 55-year group (n=60) and three doses (the same) in the 56 to 85-year group (n=36). Giving 96 or 114 if we again assume 18 placebo participants for BNT162b2. Again, there is no part B.
To say we are bewildered is an underestimate.
So, we went to the clinical study reports on the Public Health and Medical Professionals for Transparency Documents site.
We started with study report R-20-0254, which analysed neutralising antibody titers in the BNT162-01 trial. Note the name change to puzzle the TTE office further: The report is like picking from a deck of cards, including BNT 162b1 and b2 arms of differing follow-up lengths. Data for b2 seem to start from pdf page 4319.
For BNT162b1, 48 participants aged 18 to 55 received a primer and booster for one of four doses (1,10, 30 and 50 ug), and 12 participants received just the primer dose of 60ug. Oops, we've now lost the older age group, as reported by Pfizer.
In the BNT162b2 study, 60 participants given one of five doses (1, 3, 10, 20 or 30 ug), aged 18 to 55, and 12 (20 ug dose) aged 56 to 85 were evaluated. In reality, as you will see in the following post, number 4 in the series, trial b1 participants were only 18-55-year-olds.
Further searching the PHMPT database we found the protocol.
The trial design is stated to be in two parts: Part A and Part B. However, due to changes in the overall clinical development plan, the protocol states that ‘Part B will no longer be conducted.‘
Note that we discovered on page 200 of the protocol why Part B was never done.
‘Part B will use a randomized, placebo-controlled design in the likely target population (e.g., higher risker populations such as elderly and/or immunocompromised populations). Part B may employ a surrogate marker as a measure of vaccine efficacy.’
Table 9 (page 40 ) in the protocol reports the number dosed at least once with the BNT162 vaccine as of 24 Sep 2020.
Notice anything strange? Now, we have a c2 candidate trial.
The fact we can't find any numbers to match is beyond disconcerting.
No formal sample size calculations were performed. Including 12 participants per dose group was considered adequate for a safety assessment. In the study synopsis, we learn that 120 younger and older participants were treated with BNT162b1 and included in the Safety Set, and 96 were included in the BNT162b2 Safety Set.
Many more people were given vaccines in phase 1 of the BNT162-1 trials than appeared in the safety outcomes (the synopsis makes no mention of the lymphopenia outcomes). Safety data is based on a subset of those who received the vaccine, but it is anyone's guess as to how those who appeared in the safety subset were chosen.
The question on our minds is whether all of this confusion is deliberate.
Two confused, dizzy and disconcerted old Geezers wrote this post.
As a humble dentist, I wonder if the same trials are available for the Moderna product and does it also show leucopenia? Or have the UK authorities ditched Moderna and bought bucket loads of Cominarty as it will kill off all those flu-ey pensioners hogging the corridors of the East Surrey Hospital???
Confusing and alarming. Such work makes one ask questions, as did Dr Daniel Armstrong, who has been struck off the Medical Register for suggesting, perhaps both intemperately and correctly, that COVID vaccines were harmful (worth looking at the Medical Tribunal report which is online). A number of US physicians have lost their jobs because of their Galilean stand against Settled Science. Has the same phenomenon now appeared here in the UK?