Tag: informed consent

Hello. Regarding the mandate for all employees. I have several questions on behalf of myself and colleagues that I trust you should be able to answer. If you cannot answer, please simply state such. I hold informed consent and education in high regard and strive to be vigilant of industry-biased and corporation funded “science” that has tarnished aspects and the history of western medicine; therefore, I appreciate the opportunity to address some global concerns. I have also attached references to peer-reviewed articles to add the breadth of data to my inquiry.

The below questions are based on the August 23, 2021 Summary Basis for Regulatory Action – Comirnaty (SBRA) found at https://www.fda.gov/media/151733/download as well as the Prescribing Information (PI) found at https://www.fda.gov/media/151707/download (a) or https://www.fda.gov/media/144413/download (b). Additional supporting documents from the FDA are found at: https://www.fda.gov/vacines-blood-biologics/qa-comirnaty-covid-19-vaccine-mrna

First and foremost, as [[this employer]] moves into requiring COVID-19 vaccines for staff, is there a plan to explicitly carry Comirnaty once it is in production? There are currently two vaccines produced by Pfizer. The EUA authorization explicitly states that “As the vaccination provider, you must communicate to the recipient or their caregiver, information consistent with the “Vaccine Information Fact Sheet for Recipients and Caregivers” (and provide a copy or direct the individual to the website www.cvdvaccine.com to obtain the Vaccine Information Fact Sheet) prior to the individual receiving each dose of Pfizer-BioNTech COVID-19 Vaccine, including: FDA has authorized the emergency use of the Pfizer-BioNTech COVID-19 Vaccine, which is not an FDA-approved vaccine. The recipient or their caregiver has the option to accept or refuse Pfizer-BioNTech COVID-19 Vaccine. The significant known and potential risks and benefits of Pfizer-BioNTech COVID-19 Vaccine, and the extent to which such risks and benefits are unknown (PI(b), p.9-10).”

Next, I’d like to understand your clinical study methodology. It appears that safety and immunogenicity (BNT162-01) was based off a 24-patient sample in Germany (SBRA, p. 15, Table 6). It also states that no control group was used in the same table. Do we believe this methodology was sound and the sample size is adequate in representing our employees? Can you shed some light on how so? I am specifically interested in how a control group doesn’t apply here and how 24 participants from Germany is an adequate sample size for our target population. Again, this was the safety and immunogenicity study, so my concern is that safety took a backseat.

You will also find that study ID C4591001 to evaluate efficacy is ongoing and notes it had a placebo group that was first a dose-finding study, then stratified to include participates at high risk of acquiring COVID-19 for a duration of up to 7 days after the second dose without evidence of prior COVID-19 infection (SBRA, p.16; PI, p.18). I would like some clarity about this 7-day window after the 2nd dose as we have all been told people are not “fully vaccinated” until two weeks after the 2nd dose. I struggle to understand why we adopted 14 days when their efficacy study does not extend past 7 days. How does this short efficacy period justify the unknown risks thereafter?

Further, this study (C4591001) is no longer using a gold-standard placebo as it became unblinded December 14, 2020 and placebo groups were offered the EUA vaccine (SBRA, p.17). Does [[this employer]] find this approach worrisome? The PI(a) has a conflicting timeline and states that the participants were unblinded on December 11, 2020 (p.7). Is this study acceptable to validate the concerns of safety in the short-term for all employees? I can only see that it provides up to 6 months of data, nothing more. According to Peter Doshi, the editor of the BMJ, only 7% of the control group was still considered true placebo at the cutoff of the study by March 13, 2021 yet they were still counted in the placebo arm (https://blogs.bmj.com/bmj/2021/08/23/does-the-fda-think-these-data-justify-the-first-full-approval-of-a-covid-19-vaccine/).

The plan for Comirnaty’s “risk and associated uncertainties” mitigation is through labeling and postmarketing studies (SBRA, p.24). From what I can tell, this means that data is still unclear and mandating this product is an ethical challenge as people in studies should always be provided with fully informed consent free of coercion. I am sure you are aware that long-term safety data will not be known for several years from any of these products and the safety clinical trials are yet to start for COMIRNATY with an end goal for December 2022 based on the registry: https://clinicaltrials.gov/ct2/show/NCT04815031. Emergency department employees provide individualized care to our patients, should we also be afforded the same treatment based on our individual health status and our willingness to consent to these yet known risks?

Section 13.1 of the PI(a) states that “Comirnaty has not been evaluated for the potential to cause carcinogenicity, genotoxicity, or impairment of male fertility” (p.15). With the use of a new mRNA technology in humans, one would postulate that genotoxicity and carcinogenicity are important factors to understand or at least evaluate prior to forcing it upon otherwise healthy people? Am I missing something?

My biggest concern is what is looming in the upcoming cold/flu season. We have no data on whether this product will cause antibody-dependent enhancement or “vaccine-associated enhanced disease” or “vaccine-associated enhanced respiratory disease” (SBRA, p.25) as acknowledged in all previous coronavirus and similar pathogen animal trials:

1. A Double-Inactivated Severe Acute Respiratory Syndrome Coronavirus Vaccine Provides Incomplete Protection in Mice and Induces Increased Eosinophilic Proinflammatory Pulmonary Response upon Challenge (https://doi.org/10.1128/JVI.06048-11)
2. Cellular Immune Responses to Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) Infection in Senescent BALB/c Mice: CD4+ T Cells Are Important in Control of SARS-CoV Infection (https://doi.org/10.1128/JVI.01281-09)
3. Evasion by Stealth: Inefficient Immune Activation Underlies Poor T Cell Response and Severe Disease in SARS-CoV-Infected Mice (https://doi.org/10.1371/journal.ppat.1000636)
4. Immunization with inactivated Middle East Respiratory Syndrome coronavirus vaccine leads to lung immunopathology on challenge with live virus (https://doi.org/10.1080/21645515.2016.1177688)
5. Immunization with Modified Vaccinia Virus Ankara-Based Recombinant Vaccine against Severe Acute Respiratory Syndrome Is Associated with Enhanced Hepatitis in Ferrets (https://doi.org/10.1128/JVI.78.22.12672-12676.2004)
6. Immunization with SARS Coronavirus Vaccines Leads to Pulmonary Immunopathology on Challenge with the SARS Virus (https://doi.org/10.1371/journal.pone.0035421)
7. Pathogenic priming likely contributes to serious and critical illness and mortality in COVID-19 via autoimmunity (https://doi.org/10.1016/j.jtauto.2020.100051)
8. Structural Basis of SARS-CoV-2 and SARS-CoV Antibody Interactions (https://doi.org/10.1016/j.it.2020.09.004)
9. Two Different Antibody-Dependent Enhancement (ADE) Risks for SARS-CoV-2 Antibodies (https://doi.org/10.3389/fimmu.2021.640093)
10. Vaccine Efficacy in Senescent Mice Challenged with Recombinant SARS-CoV Bearing Epidemic and Zoonotic Spike Variants (https://doi.org/10.1371/journal.pmed.0040080)

Was [[this employer]] aware of the problems in these trials prior to this policy change? I fear this outcome for staffing burdens this winter when challenged with similar respiratory pathogens. When faced with increased rates of infection, is it wise to add selective pressures onto these viruses to mutate around our interventions? Can you explain how these biologics do not contribute to immune escape nor cause an explosion of variants? Several world renown virologists hold these concerns forefront and are trying to sound the alarm. I know that [[this employer]] cares about mitigating risk for their employees, so I am wondering if these concerns were addressed or if you can share your position on these matters.

1. Antibody-dependent enhancement of coronavirus (https://doi.org/10.1016/j.ijid.2020.09.015)
2. Two Different Antibody-Dependent Enhancement (ADE) Risks for SARS-CoV-2 Antibodies (https://doi.org/10.3389/fimmu.2021.640093)
3. COVID-19 Tragic Pandemic: Concerns over Unintentional “Directed Accelerated Evolution” of Novel Coronavirus (SARS-CoV-2) and Introducing a Modified Treatment Method for ARDS (https://doi.org/10.1002/ctm2.284)
4. Out of the frying pan and into the fire? Due diligence warranted for ADE in COVID-19 (https://doi.org/10.1016/j.micinf.2020.06.006)
5. Antigenic Evolution on a Global Scale Reveals the Potential Natural Selection of Severe Acute Respiratory Syndrome-Coronavirus 2 by Pre-existing Cross-Reactive T-Cell Immunity (https://doi.org/10.3389/fmicb.2021.599562)
6. Structural Basis of SARS-CoV-2 and SARS-CoV Antibody Interactions (https://doi.org/10.1016/j.it.2020.09.004)
7. Health Care Policy Makers’ Response to COVID-19 Pandemic; Pros and Cons of “Flattening the Curve” from the “Selective Pressure” Point of View: A Review (https://doi.org/10.18502/ijph.v49i6.3356)
8. Antibody Dependent Enhancement Due to Original Antigenic Sin and the Development of SARS (https://doi.org/10.3389/fimmu.2020.01120)
9. Review of COVID-19 Variants and COVID-19 Vaccine Efficacy: What the Clinician Should Know? (https://doi.org/10.14740/jocmr4518)
10. Is COVID-19 receiving ADE from other coronaviruses? (https://doi.org/10.1016/j.micinf.2020.02.006)
11. Vaccine-associated enhanced disease: Case definition and guidelines for data collection, analysis, and presentation of immunization safety data (https://doi.org/10.1016/j.vaccine.2021.01.055)
12. Role of antibody-dependent enhancement (ADE) in the virulence of SARS-CoV-2 and its mitigation strategies for the development of vaccines and immunotherapies to counter COVID-19 (https://doi.org/10.1080/21645515.2020.1796425)
13. What are the roles of antibodies versus a durable, high quality T-cell response in protective immunity against SARS-CoV-2? (https://doi.org/10.1016/j.jvacx.2020.100076)
14. The SARS-CoV-2 Delta variant is poised to acquire complete resistance to wild-type spike vaccines (https://doi.org/10.1101/2021.08.22.457114)
15. Epitope profiling reveals binding signatures of SARS-CoV-2 immune response in natural infection and cross-reactivity with endemic human CoVs (https://doi.org/10.1016/j.celrep.2021.109164)
16. Vaccine- and natural infection-induced mechanisms that could modulate vaccine safety (https://doi.org/10.1016/j.toxrep.2020.10.016)
17. Risk of rapid evolutionary escape from biomedical interventions targeting SARS-CoV2 spike protein (https://doi.org/10.1371/journal.pone.0250780)

With the clinical trial data cutoff date of March 13, 2021, there was no evaluation of this vaccination against this evolving “Delta” or subsequent variants. We lack supporting evidence to suggest that the biologics modeled off the old mutation has any effect on Delta, as that was not the dominant variant during the study period per the CDC’s own website (https://covid.cdc.gov/covid-data-tracker/#variant-proportions). Could you provide me with the studies to support a decreased risk of infection for those previously vaccinated in light of the “breakthrough” infections? What is the take on current trends that show vaccinated can contract and spread disease? If this is so, can you clarify how this would be of benefit to [[this employer’s]] staff? We all work with these patients. We have seen the previously vaccinated COVID-positive ICU patient and fear that for ourselves as our risks are greater than the general population. Our risks will always be higher for potential ADE because we work in an environment that is not lacking in respiratory pathogens.

With the initiation of COVID-19 EUA products, have [[this employer’s]] staff had training on the use of VAERS to report adverse events surrounding vaccine administration or “breakthrough” infections that has now shifted to a health department data collection? This is mandated by the CDC and FDA, but I have met several providers and nurses that have never heard the term “VAERS” or Vaccine Adverse Events Reporting System, much less input any data into it. VAERS has been inundated with data that is unmonitored and ill organized since the use of the COVID-19 EUA products (https://vaers.hhs.gov/data/datasets.html?). If [[this employer]] evaluated these tools prior to the policy change, can this be shared with fellow employees? Since this is a policy mandate, will [[this employer]] accept any responsibility for negative health outcomes of those they mandated to take these products? As this policy seemingly removes personal choice, I was also wondering if there were any arbitration or mediation clauses that would impede a formal litigation process.

As far as efficacy, Comirnaty’s package insert explicitly states in Section 5.5 that it “may not protect all vaccine recipients” (PI(a), p.6) which is also reiterated on the FDA website. Since the US has not provided transparent data, we must use the United Kingdom’s data as it is organized by age, vaccination status, genomic sequencing of variant, and deaths in each group. The most recent is found here: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1012644/Technical_Briefing_21.pdf, though there should be an additional update soon.

The groups suffering the most are above age 50. Delta is shown to be very contagious; however, the case-fatality rate for the Delta variant, of most concern currently, is the most interesting portion (p. 22-23). Fully vaccinated more than 14 days has 679 total deaths in a population of 73,372 total cases. This is a case-fatality rate of 0.93%. Compared to the unvaccinated that have a total death toll of 390 in a population of 183,133 which is a 0.21% case-fatality. So, with this data in mind, who is at more risk of adverse outcome? While unvaccinated have contracted more disease, the severity of the outcome (death) is not as high as those previously vaccinated. Is this data indicating vaccine-associated enhanced disease or am I mistaken? I have not seen any convincing arguments to the contrary and was hoping you held a different perspective on this data because its implications are grave.

Update: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1014926/Technical_Briefing_22_21_09_02.pdf The update follows the same trend with the following:
Vaccinated 14 days post-dose 2: Cases 113,823 with Deaths 1,091 (calculated case-fatality rate of 0.96%)
Unvaccinated: Cases 219,716 with Deaths: 536 (calculated case-fatality rate of 0.24%)

I am concerned that healthcare organizations are rushing to place these policies on their staff without solid scientific evidence, as it is not yet available. Why has mandating become acceptable when, even as nurses and providers, we are to give informed consent to our patients? Is our consent inferior to that of our patients? Can personal responsibility apply to these health choices? The following studies are a warning of the risks outweighing the benefits of vaccination and considerations for natural immunity. The great news is that your employees have spent countless hours in the presence of COVID-19 patients and may already have superior protection.

1. The Safety of COVID-19 Vaccinations—We Should Rethink the Policy (https://doi.org/10.3390/vaccines9070693)
2. Longitudinal analysis shows durable and broad immune memory after SARS-CoV-2 infection with persisting antibody responses and memory B and T cells (https://doi.org/10.1016/j.xcrm.2021.100354)
3. SARS-CoV-2 infection induces long-lived bone marrow plasma cells in humans (https://doi.org/10.1038/s41586-021-03647-4)
4. Longitudinal observation of antibody responses for 14 months after SARS-CoV-2 infection (https://doi.org/10.1016/j.clim.2021.108814)
5. Is a COVID-19 vaccine developed by nature already at work? (https://doi.org/10.1016/j.mehy.2020.110335)
6. What are the roles of antibodies versus a durable, high quality T-cell response in protective immunity against SARS-CoV-2? (https://doi.org/10.1016/j.jvacx.2020.100076)
7. Risk of SARS-CoV-2 reinfection after natural infection (https://doi.org/10.1016/S0140-6736(21)00662-0)

I do not know all the details surrounding or informing this policy, but things are not adding up. Please do your best to support counterpoints with references like I have provided for you here. This is a serious discussion and has major implications for the individual and we need these answers.

Thank you for your time,

“just a nurse”