COVID-19 mRNA Vaccines: Lessons Learned from the Registrational Trials and Global Vaccination Campaign

Abstract

Our understanding of COVID-19 vaccinations and their impact on health and mortality has evolved substantially since the first vaccine rollouts. Published reports from the original randomized phase 3 trials concluded that the COVID-19 mRNA vaccines could greatly reduce COVID-19 symptoms. In the interim, problems with the methods, execution, and reporting of these pivotal trials have emerged. Re-analysis of the Pfizer trial data identified statistically significant increases in serious adverse events (SAEs) in the vaccine group. Numerous SAEs were identified following the Emergency Use Authorization (EUA), including death, cancer, cardiac events, and various autoimmune, hematological, reproductive, and neurological disorders. Furthermore, these products never underwent adequate safety and toxicological testing in accordance with previously established scientific standards. Among the other major topics addressed in this narrative review are the published analyses of serious harms to humans, quality control issues and process-related impurities, mechanisms underlying adverse events (AEs), the immunologic basis for vaccine inefficacy, and concerning mortality trends based on the registrational trial data. The risk-benefit imbalance substantiated by the evidence to date contraindicates further booster injections and suggests that, at a minimum, the mRNA injections should be removed from the childhood immunization program until proper safety and toxicological studies are conducted. Federal agency approval of the COVID-19 mRNA vaccines on a blanket-coverage population-wide basis had no support from an honest assessment of all relevant registrational data and commensurate consideration of risks versus benefits. Given the extensive, well-documented SAEs and unacceptably high harm-to-reward ratio, we urge governments to endorse a global moratorium on the modified mRNA products until all relevant questions pertaining to causality, residual DNA, and aberrant protein production are answered.

Keywords: autoimmune; cardiovascular; covid-19 mrna vaccines; gene therapy products; immunity; mortality; registrational trials; risk-benefit assessment; sars-cov-2 (severe acute respiratory syndrome coronavirus -2); serious adverse events.

Figure 1. Analysis of Pfizer trial’s weekly mortality over a 33-week period

This representation of the Pfizer trial by Michels et al. [54] showcases the weekly count of subject deaths from July 27, 2020, to March 13, 2021. Solid bars denote BNT162b2 recipients, gray bars signify the placebo group, and hatched bars represent previously unblinded placebo subjects who later received BNT162b2. The solid line represents the cumulative death count for the BNT162b2 group and the dotted line for the placebo group. Image Source: Michels et al., 2023 [54]; Published with permission by authors under CC BY-NC-ND 4.0 Deed (Attribution-NonCommercial-NoDerivs 4.0 International)

Figure 2. Charts illustrating Pfizer trial irregularities in reporting of COVID-19 cases and humoral immune responses (antibody titers)

This  indicates an unusual pattern post day 12 following the BNT162b2 injection. While the placebo group continued experiencing cases, the BNT162b2 group showed a sudden decline in infection rates, suggesting unexpected immediate immunity. Image source: Palmer M, et al., 2023 [82];  Reproduced under Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License (CC BY-NC-SA 4.0). Data was extracted from the European Medicines Agency (EMA) report, referencing Figures 9 (A) and 7 (B) [83].

Figure 3. Cleveland Clinic study showing increasing COVID-19 cases with increasing mRNA vaccinations

Cleveland Clinic study demonstrating COVID-19 incidence among participants based on the number of prior mRNA vaccine doses received. The study shows rising case rates associated with increased COVID-19 mRNA vaccine doses. Image Source: Shrestha et al., 2023 [99]; Open Access article with public sector information, licensed under the Open Government Licence v3.0 (http://www.nationalarchives.gov.uk/doc/open- government-licence/version/3/)

Figure 4. Cleveland Clinic study showing increased COVID-19 cases for subjects most "up to date" with mRNA vaccinations

Cleveland Clinic study comparing cumulative COVID-19 incidence between "up-to-date" and "not up-to-date" individuals based on CDC-defined vaccination status. The plot includes point estimates and 95% confidence intervals along the x-axis. Image Credit: Shrestha et al., 2023 [100]; Open access, licensed under CC BY 4.0 Deed (Attribution 4.0 International)

Figure 5. VAERS reports of autoimmune disease per million doses of COVID-19 mRNA (2021-2023) compared to Influenza (2018-2020) vaccinations

Based on a VAERS query (https://vaers.hhs.gov/) using the MedDRA code “Autoimmune disorder”, there was an 803% increase in reporting rate per million doses administered when comparing Influenza vaccines administered from 2018 through 2020 to COVID-19 mRNA injections administered from 2021 through 2023. Notably, the reports exclude individuals with a history of an autoimmune disorder. Image credit: Jessica Rose (coauthor), [173]

Figure 6. Factors contributing to COVID-19 mRNA vaccine inefficacy

COVID-19 vaccines may lose efficacy in part by inducing SARS-CoV-2 mutations that lead to new immune escape variants, thus ultimately limiting vaccine-related protection against subsequent coronavirus infections. Periodic COVID-19 mRNA injections could elicit a diverse range of mechanisms associated with immune dysfunction (mostly due to subversion of innate immunity), resulting in a heightened risk of cancers, infections, and autoimmune disorders. Image Credit: Majumder and Razzaque, 2022 [247]; adapted with permission from authors.

Figure 7. Myocarditis reports in VAERS Domestic Data as of September 29, 2023, plotted by age and dose

Dose 1: pink, Dose 2: green, Dose 3: blue Data indicates a five-fold rise in myocarditis cases after the second COVID-19 shot for 15-year-old males, and overall, second doses were linked to more myocarditis cases [263]. VAERS: Vaccine Adverse Event Reporting System; COVID-19: coronavirus disease 2019 Image Credit: Jessica Rose (coauthor).

Figure 8. Registrational trial for Pfizer, projected three-year mortality If the six-month Pfizer trial had continued, the risk difference would reach statistical significance at 34 months, with a 31% higher mortality risk in the vaccine group compared to the placebo group

This is a transparent, quantifiable, and simple illustration of how small death rates might become statistically significantly different over time within the three-year duration originally planned for the trials. Hypothetically, if the six-month Pfizer trial had continued, assuming the relative risk of 1.31 remained constant and deaths accrued at the same rates as during the trial, then the lower limit of the 95% confidence interval would exceed one at 34 months. Stated another way, the relative risk would exhibit statistical significance (p<0.05) at this time, with a 31% increased mortality risk in the mRNA vaccine vs placebo groups.  This calculation assumes death rates are held constant in each group and mortality is measured at six-month intervals, with p-values monotonically declining over time. Thus, assuming the mortality rates continued unchanged in both groups as observed in the initial six months, the all-cause mortality difference would have become statistically significant (p<0.05) around 2.8 years (34 months). At 2.5 years, the p-value was at 0.065, decreasing to 0.053 by 2.75 years. Chart generated by biostatistician Russ Wolfinger (coauthor).