More Pfizer Documents and More Misinterpretations
The gist: The FDA has been ordered to comply with a FOIA request regarding the documents it used to make the judgments to approve the Pfizer/BioNTech vaccine. For background on what that means, I strongly recommend Professor Reiss’s explanation here. The request is the result of motivated anti-vaccine lobbyists seeking to distort any information in those documents to seem incriminating about the safety or effectiveness of the vaccines, as they do constantly when they misrepresent package inserts. The documents in question are written in the specialized language of pharmaceutical regulation, and as such are prone to misinterpretation by those who lack specific training in the pertinent fields because they use terms that do not necessarily mean what they sound like they do. I have previously discussed one such document from these requests which caused an uproar when many were misinformed to believe it contained 9 pages of horrific side effects, when in reality these were adverse events of special interest- things that Pfizer stated that it wanted to be informed about immediately IF they occurred, not events that actually happened (which might have been obvious if people had bothered to read the list which includes things like “exposure to communicable disease"). This month, more documents were released, and with them came more false claims, this time by Kim Iversen and Laura Ingraham. They both claim that these documents demonstrate that pharmaceutical companies know that infection confers superior immunity, COVID-19 vaccines weaken the immune system, and that the vaccines are dangerous for younger people. Iversen also has several additional claims about antibody-dependent enhancement and infertility. While these claims are all demonstrably false (detailed below), what is especially galling about them is not simply that the documents do not at any point make any of these claims or present data suggestive of them, but that at several points they even include explicit passages that tell you WHY what Iversen and Ingraham are claiming is untrue. This suggests that they either did not read the documents, or deliberately misrepresented them for an agenda to discourage vaccination. That is not supporting autonomy. That is not a promotion of informed consent.
Recently, more internal pharmacovigilance documents from Pfizer have been released; it’s been reported to be 11,043 pages. Simply put, I am not going to read through all of them because it would be an enormous waste of time and no one would have the patience to read through my explanation of what they actually say, so instead I’ll keep this discussion more focused. Despite the highly specialized nature of the documents and the jargon in them that I’ve explained before, some people have a strong desire to read through these documents and “judge for themselves.” The intent is noble, but the execution is lacking, because it’s not exactly valuable to read something, not understand it, and then invent the meaning you think applies as some seem to have elected to do with them. In this installment the following claims are levied:
Pharmaceutical companies (I am guessing in this case Pfizer) know infection confers superior immunity
COVID-19 vaccines weaken the immune system
The vaccines are more dangerous for younger people, who have worse reactions
The vaccines cause infertility and ADE
Truthfully, these claims are so far outside the scope of what these documents say that I can’t even see how someone could misinterpret them to mean these things unless they were deliberately lying, and unfortunately in this subject that is well within the scope of what is possible, so let’s examine what the documents actually say, as well as consider any relevant data we have on the subject.
Claim: Infection-acquired immunity is superior
Clip here: https://twitter.com/Christy1Gaga/status/1510104480993497089?s=20&t=wcBCpbYhvt3sujfBa4-JXg
As it happens, I have written extensively on this point before, but let’s focus on these documents for the moment. When I read through the documents, I could not find anything in them that said something remotely similar. When I probed further, I was able to find Laura Ingraham’s discussion (she was not the only one to discuss it, but I couldn’t find anyone else to provide the quote). She argues that the screenshotted quote (from her broadcast) indicates that SARS-CoV-2 infection provides 100% protection against reinfection.
If we go to the actual document for the full quote (she actually does us the service of giving it to us, which I sincerely appreciate), it reads (bolded part is what is in the screenshot):
Among participants without evidence of SARS-CoV-2 infection before and during the vaccination regimen (evaluable efficacy population), the estimated VE against CDC-defined severe COVID-19 occurring at least 7 days after Dose 2 was 100.0% (2-sided 95% CI: 88.1%, 100.0%), with 0 and 32 cases in the BNT162b2 and placebo groups, respectively. Similarly, the estimated VE was also 100.0% (2-sided 95% CI: 88.0%, 100.0%) among participants with or without evidence of SARS-CoV-2 infection before and during the vaccination regimen, also with 0 and 32 cases in the BNT162b2 and placebo groups, respectively.
In other words, the vaccine had 100% efficacy against severe COVID-19 as defined by the CDC whether or not the vaccinees had evidence of prior COVID-19 infection, meaning it performed equally well among those who had survived COVID-19 and those who had the good fortune of never having experienced it. Beyond this however, in Pfizer’s phase 3 clinical trial 6-month paper (which is essentially a much shorter summary of the information within this document), the protection of prior infection is evaluated:
Covid-19 was less common among the placebo recipients with positive N-binding antibodies at trial entry (7 of 542 participants, for an incidence of 1.3%) than among those without evidence of infection at trial entry (1015 of 21,521, for an incidence of 4.7%); these findings indicate that previous infection conferred approximately 72.6% protection.
72.6% isn’t terrible but that number is a far cry from the 100% effectiveness claimed. It’s worth noting that the design of this study did not have random sampling of individuals for PCR testing to check for infection- participants had to develop symptoms to be counted. I make this point to emphasize that the individuals who survived their first bout with COVID-19 had to actually get sick to be counted in the effectiveness calculation quoted. Additionally, while the comparison can’t be made in this way, it’s worth pointing out that at the end of the 6-month analysis period this study examines, the effectiveness of the vaccine against symptomatic COVID-19 was still 83.7% (74.7 to 89.9), which is higher than the value computed for infection. It is therefore especially puzzling to claim that pharmaceutical companies know that prior infection confers superior immunity to the Pfizer/BioNTech vaccine when their own data do not support that.
Ingraham argues that this proves the manufacturers therefore knew that SARS-CoV-2 infection conferred immunity and this was still taboo to discuss. Several issues with that line of thinking. The first is, this quoted section does not show a difference in the protection against severe COVID-19 in those who had infection compared with those who hadn’t, meaning it is possible (if we consider this quote in a vacuum as she seemingly wants to) that the entirety of protection from severe disease is the result of vaccination, if we work from this statement alone. Another matter is that whether or not infection confers protection is irrelevant to public health policy because infection will never be an appropriate public health policy. We are continuously learning more about how SARS-CoV-2 can be devastating to immunologically naive individuals, even if mild. Just recently, several extremely robust analyses have demonstrated that if immunologically naive to SARS-CoV-2 and infected, patients have an increased risk of multiple forms of heart disease, diabetes, and blood clots for, at least, months after that infection- which is really the tip of the iceberg given how many complications can arise from PASC. Until relatively recently, effective treatment options for COVID-19 have been extremely limited. Remdesivir is extremely effective, but requires a 3-day infusion that makes it very inaccessible, and must be given early on in infection, not to mention its prohibitive cost. Paxlovid is also fantastically effective and can even be given orally but also has to be given within 5 days of symptom onset (but ideally 3) for effectiveness, requires good compliance with the twice daily x 5 days medication regimen (which can be difficult because it causes unpleasant taste disturbances), and has an extensive list of complex drug interactions because it contains ritonavir, which is required for it to work. Dexamethasone and other corticosteroids are an older therapy long known to us (in pandemic time, anyway) but it must be given later on in the course of disease, and unfortunately are not as effective the antivirals. You get the idea. The point being, arguments to recognize infection have always been a red herring, and benefits for vaccinating patients who have survived infection are well-established.
Claim: COVID-19 vaccines weaken the immune system
As absurd as the previous claim is, this one I cannot possibly bring myself to believe to be the result of anything other than dishonesty, and you’ll see why in a moment. The adjacent screenshot is how Iversen presents a section of the request for priority review.
She highlighted a portion of the text that says there was a temporary drop in white blood cells for about 1 week after dose 1, explicitly leaving out the part immediately after the highlighted text about how this transient decrease was not associated with any health issues and not considered to be clinically relevant. Iversen claims that this means the vaccine is leaving the person with a weakened immune system for a week and this is information that the general public should have been made aware of in advance of vaccination. If you actually bother to go to the document in full (emphasis mine; italicized is Iversen’s quote):
Clinical laboratory evaluations showed a transient decrease in lymphocytes that was observed in all age and dose groups after Dose 1, which resolved within approximately 1 week, were not associated with any other clinical sequelae, and were not considered clinically relevant.
Ribonucleic acid (RNA) vaccines are known to induce type I interferon,10 and type I interferons regulate lymphocyte recirculation and are associated with transient migration and/or redistribution of lymphocytes.11 This rapid rebound of lymphocytes supports that the lymphocytes are not depleted, but temporarily migrated out of the peripheral blood, and subsequently re-entered the bloodstream by the time of the next assessment
In other words, this transient decline in the levels of lymphocytes does not in any way represent immunosuppression. What is actually happening is that they are migrating out of the blood and into the lymph nodes, which is why some people develop swelling at their lymph nodes (called lymphadenopathy). This same claim was made months ago by Alex Berenson and expertly rebutted by Professor Shane Crotty:
Berenson wrote in an email that “the first dose of the mRNA vaccine temporarily suppresses the immune system.” He has claimed on Twitter that the mRNA vaccines “transiently suppress lymphocytes,” or our white blood cells, and suggested that this might lead to “post-vaccination deaths.”
Scientists tore this one to shreds. “The claim he is making is simply fearmongering, connecting a simple physiological event with bogus claims of deaths,” Shane Crotty, a researcher at the Center for Infectious Disease and Vaccine Research at the La Jolla Institute for Immunology, told me. “The observation of lymphocyte numbers temporarily dropping in blood is actually a common phenomenon in immune responses.”
There is no difference in the incidence of COVID-19 for the vaccine or placebo group in the first week following immunization with the Pfizer/BioNTech COVID-19 vaccine. N Engl J Med 2021; 385:1761-1773 DOI: 10.1056/NEJMoa2110345
Now, I suppose you could ignore Professor Crotty as he discusses the exact thing that he is one of the world’s leading experts in, but there’s another very basic point that argues against there being immunosuppression. The trial was measuring the incidence of COVID-19 in each group. If there were significant immunosuppression during that 1-week period, given that they were following more than 44,000 people, surely there should be evidence of more COVID-19 in the vaccinated group during that first week than in the placebo group. I’m afraid those hoping for such results will be disappointed. There is no difference.
I find it very hard to believe that this was an error of ignorance on the part of people like Iversen who are making the claim after having claimed to have read the documents given that they explicitly tell you that this does not represent immunosuppression.
Claim: The Vaccines are Dangerous for Younger People, who Have Worse Reactions
The document reads:
Reactogenicity and AEs were generally milder and less frequent in participants in the older group compared with the younger group and overall tended to increase with increasing BNT162b2 dose. Reactogenicity was mostly mild to moderate and short-lived after dosing, and the AE profile did not suggest any safety concerns, including up to approximately 6 months after Dose 2 for BNT162b2 30 µg groups.
…
Based on Phase 2/3 data from approximately 44,000 participants ≥16 years of age with up to at least 6 months of follow-up after Dose 2 in Study C4591001, BNT162b2 at 30 µg was safe and well-tolerated across age groups. Reactogenicity and AEs were generally milder and less frequent in participants in the older group (>55 years of age) compared with the younger group (≤55 years of age). Reactogenicity was mostly mild to moderate and short-lived after dosing for both younger and older age groups (ie, median onset between 1 to 4 days after dosing and resolution within 1 to 2 days after onset), and the AE profile did not suggest any serious safety concerns. The incidence of serious adverse events (SAEs) and deaths were low in the context of the number of participants enrolled and comparable between BNT162b2 and placebo. The incidence of discontinuations due to AEs was also generally low and similar between BNT162b2 and placebo groups.
The claim is not technically untrue but is very misleading because of imprecise language. Reactogenicity refers to the expected set of side effects that arise due to inflammation from the immune response elicited by the vaccine. These can include things like headache, body aches, fever, swelling at the injection site or nearby lymph nodes, redness, pain, nausea, vomiting, etc. They are transient and do not represent safety concerns in and of themselves. Because they are unpleasant, however, it is desirable to try to minimize reactogenicity, and medications can generally be taken to help relieve the unpleasantness as needed. The problem is that it tends to be the case that the most effective vaccines are the most reactogenic at the population level, and we also want to maximize the effectiveness of the vaccines we administer. Younger people have more robust immune systems than the elderly, and so, as a group, are more likely to have more intense reactogenicity than elderly individuals are. Sometimes this can be modulated by adjusting the doses of the vaccine (for instance, the elderly receive a high-dose influenza vaccine that contains 4 times as much antigen) or tinkering with the adjuvants, if the vaccines have any. Regardless, as the document states, no serious safety concerns were identified. You could say “I don’t trust Pfizer to make that judgment” (though that does beg the question of why you are reading this if you fall into that group), but as I discussed before, this conclusion has been the one literally every regulatory body on the planet has come to through analysis of the pharmacovigilance data for the Bnt162b2 vaccine.
Claim: The vaccines cause infertility, myocarditis, and ADE
Kim Iversen raises this argument in her discussion of the documents. Iversen claims that the documents note that they cannot rule out the possibility of antibody-dependent enhancement (ADE) from vaccination. In the broadest sense, antibody-dependent enhancement describes a situation in which the presence of antibodies worsens the severity of an infectious disease and it is best characterized in Dengue, but has been observed experimentally in animal models with some coronaviruses. Importantly, ADE is a distinct phenomenon from vaccine-associated enhanced respiratory disease (VAERD) which was seen in a doubly-inactivated SARS-CoV-1 vaccine in an animal model and infamously, in a human trial of an inactivated, alum-adjuvanted RSV vaccine. VAERD is classically associated with what is known as type 2/type 17 inflammation (alternatively written as Th1/Th17, referring to the type of helper T cells that orchestrate the response), which refers to a pattern of inflammation we evolved principally to deal with parasites, and extracellular bacteria or fungi respectively. Under some now-outdated models, there are just two types of inflammation. Type 1 targets intracellular pathogens like viruses and some bacteria. Type 2 targets extracellular pathogens like some bacteria, fungi, and parasites. Because of the history of VAERD with some respiratory viruses, a major focal point in the design of COVID-19 vaccines was to create those that would emphasize type 1 inflammation, which is classically what is required for control of viral infections like SARS-CoV-2, and viewed very coarsely, inhibits the type of type 2 inflammation that is associated with VAERD and poor outcomes in COVID-19. As it happens, the Pfizer/BioNTech vaccine, and mRNA vaccines in general, give a very strong type 1 inflammatory response with minimal type 2 inflammation, as shown by the cytokine profile of vaccinees. Per the request for priority review document:
Nonclinical studies in mice and NHP demonstrate that BNT162b2 elicits a rapid antibody response with measurable SARS-CoV-2 neutralizing titers after a single dose and substantial increases in titers after a second dose that exceed titers in sera from SARS-CoV- 2/ COVID-19- recovered individuals. A Th1-dominant T cell response was evident in both mice and NHPs. S-specific CD8+ T cell responses were also detectable in BNT162b2-immunized animals. The strongly Th1-biased CD4+ T cell response and interferon-γ (IFNγ)+ CD8+ T cell response after immunization with BNT162b2 is a pattern favored for vaccine safety and efficacy and provided added reassurance for clinical safety.8 In a SARS-CoV-2 rhesus challenge model, BNT162b2 provided complete protection from the presence of detectable viral RNA in the lungs compared to the saline control with no clinical, radiological, or histopathological evidence of vaccine-elicited disease enhancement.9
…
The confinement of severe cases of COVID-19 predominantly to the placebo group versus the BNT162b2 group suggests no evidence of vaccine-associated enhanced disease (VAED). Post-authorization safety review reinforces that BNT162b2 is safe and tolerable.
So in short the documents say that there is no evidence of enhanced disease in vaccinated individuals in the studies, and no evidence of ADE is observed either. However, in science, when it comes to empirical phenomena, you cannot prove a negative, meaning it is hypothetically possible that VAED/ADE are occurring but too rarely to be detected. However, given the size of this trial and the data accumulated to date on the matter, that’s also a reassuring comment on safety. As it happens though, on the question of ADE, some fascinating data were recently published that further vindicate the vaccine. A recent study finds that among COVID-19 patients, there was evidence of antibody-dependent enhancement of infection into monocytes and macrophages, critical cells of the immune system. Now, notably, while the virus was aided in entering the cells, this ADE is slightly different from the classic forms associated with dengue. In Dengue, enhancing antibodies do create new susceptible cells (also monocytes and macrophages), and Dengue’s replication massively increases within them (about 300 times if you combine the contributions of intrinsic and extrinsic ADE). In SARS-CoV-2, while they may promote entry, monocytes are not permissive to SARS-CoV-2 infection. The infection is not productive (it does not result in production of new viral particles) because in response, the monocytes and macrophages die by a process called pyroptosis. In fact, when the team attempted to do a plaque assay to look for infectious virus within the macrophages and monocytes, no plaques formed, and viable virus could only be detected by ultrasensitive methods. Pyroptosis is an extremely inflammatory mode of cell death that results in massive activation of the immune system, and it can in fact be harnessed with vaccination to promote vaccine responses. The problem is: too much of a good thing is not good. While this pyroptosis does effectively stop viral replication within the monocytes and activate the immune system, it seems to make the immune system overactivated, which may be driving fatal COVID-19. In fact, autopsies of the lungs of patients who died of COVID-19 showed that alveolar macrophages had structures called inflammasomes present within them, which are the machinery that induces pyroptosis. So- if the infection does it, surely the vaccine must, right? As it happens, no. The monocytes that are infected by SARS-CoV-2 all express a protein called CD16, which is a receptor that recognizes antibodies and in effect mediates antibody-dependent enhancement of infection into the monocytes. However, CD16 has an exceptional affinity for afucosylated antibodies- those lacking the sugar fucose from their core glycan. Afucosylated antibodies are elicited by infections of enveloped viruses, like SARS-CoV-2, though the mechanism is not well understood. In contrast, mRNA vaccines elicit antibodies that are only very rarely afucosylated, and instead highly sialylated and promote anti-inflammatory actions that limit tissue damage. The explicit proof came when SARS-CoV-2 was incubated with CD16-expressing monocytes in the presence of vaccinee antibodies: no infection occurred. In other words, the vaccines definitively do not cause antibody-dependent enhancement.
Iversen also references an informed consent form for parents considering enrolling their children, stating that it mentions the risk of myocarditis (adding that the mainstream media has denied this risk, which is patently false, e.g). This form, I will add, however, was not one I could find in the most recent set of documents released per the FOIA request via PHMPT, which is what I presume the source to be. In the background, there does appear to be a form titled Cincinnati Children’s Hospital Medical Center Parental Permission Form (Sub Study B) and Iversen states it is dated December 2021. Anyway, the form says more or less the same exact things as have always been said about COVID-19 vaccine-associated myocarditis: it occurs predominantly in younger males after dose 2, is rare, usually manifests in the first week after vaccination, and usually shows rapid functional resolution with longer term outcomes still incompletely understood. It also states that if the participant develops signs and symptoms consistent with myocarditis, they should seek care immediately and inform the study doctors. I’m not sure what the smoking gun here is- that’s literally what every single major medical organization relevant to the question has been saying about the condition for months. Compare this to the AHA statement also issued in December 2021- the salient themes and message are identical, with this consent form basically adding that the study doctors need to be informed if it happens.
Iversen also proceeds to engage in an appeal to ignorance about the effects of the vaccines on fertility, in reference to this document which she states notes that the effects are unknown. As she did not provide any way to find the document anywhere, I can’t verify what it does or does not say, but I can discuss the evidence base regarding the vaccines and their effects on fertility. Firstly, in the request for priority review there is explicit mention of the DART (developmental and reproductive toxicity) study, which reads (emphasis mine):
In a DART study, 0.06 mL of a vaccine formulation containing the same quantity of nucleoside-modified mRNA (30 µg) and other ingredients included in a single human dose of BNT162b2 was administered to female rats by the IM route on four occasions: 21 and 14 days prior to mating, and on gestation days 9 and 20. No vaccine-related adverse effects on female fertility, fetal development, or postnatal development were reported in the study.
This has been known since EUA was first filed for by Pfizer and BioNTech and is in the FDA briefing documents publicly available from VRBPAC. However, since this time, a great deal has been uncovered regarding the vaccines and their effects on fertility: there isn’t any. There’s a massive amount of literature on the matter at this point, but rather than go through it all, I will instead direct you to reproductive immunologist Dr. Victoria Male’s google doc summarizing those studies and providing you the references should you want to verify them yourself. Dr. Male has also written a number of publications in peer-reviewed journals about the effects of the vaccines on reproductive health and their use in pregnancy. Most of the fertility concerns raised are related to female fertility, and the bulk of the literature focuses on that. Ironically, as Dr. Male’s document notes, there is data showing that having COVID-19 can temporarily harm male fertility, and similarly data showed that following vaccination, 45 men being treated for male factor infertility actually had significant improvements in their sperm parameters (the paper reports this as simply not worsening, which is accurate, but the statistics suggest an improvement in the quality, although I do think that could be artifactual as I can’t think of any reason the mRNA vaccines might enhance male sperm parameters and the sample is fairly limited). Despite this, in an indirect way, vaccination may improve male fertility by preventing COVID-19 which appears to reliably cause a transient reduction. I will furthermore add that claiming that vaccines reduce fertility is among the oldest tactics in the anti-vaccine handbook and it has been claimed for every single vaccine and it has been wrong every single time.
As I was writing this I came upon a surprise: Kim Iversen’s discussion on youtube includes a description which actually says this:
There is currently no evidence that any vaccines, including COVID-19 vaccines, cause fertility problems (problems trying to get pregnant) in women or men.
There is limited research on COVID-19 vaccination and the menstrual cycle. However, research to date has found no meaningful change in menstrual cycle length associated with COVID-19 vaccination.
Currently, no evidence shows that any vaccines, including COVID-19 vaccines, cause male fertility problems. A recent small study of 45 healthy men who received an mRNA COVID-19 vaccine looked at sperm characteristics, like quantity and movement, before and after vaccination. Researchers found no significant changes in these sperm characteristics after vaccination. However, one study found that COVID-19 infection may be associated with a decline in fertility for men for up to 60 days after infection.
This is quite different from the tone of her own words, which is curious.
I understand the desire to get information directly from its source, in this case the FDA/Pfizer/BioNTech and think about the information independently to make your own choices. That’s a form of autonomy and it’s empowering. It’s an excellent and important goal. However, this FOIA request has predictably been abused by bad-faith actors or people who simply do not understand what they are reading to spread false claims about what they actually say- and not just a little false, but in some cases the exact opposite of what the data indicate. My most sincere helpful advice for anyone seeking to understand more about the vaccines and make a decision about whether or not to get vaccinated is to speak to a qualified expert about your concerns, like your primary care physician. You will not gain anything useful from listening to journalists who have no background in any field relevant to this inventing the meaning they want from cherry-picked snippets of the documents. Talk to an expert.
