The unraveling theory of severe-COVID vaccine efficacy
The pandemic is over. However, the controversies surrounding the pandemic continue unabated. A central question that faces health authorities is why they mandated and coerced the population into undergoing experimental medical interventions; COVID-19 vaccination. An equally troubling question is why those same authorities demonized, threatened, and censored those who questioned that policy. For those reasons, the debate about the medical value or harm of COVID-19 vaccination continues with some intensity.
The original intent of COVID-19 vaccination was the prevention of disease transmission. But, as “break-through” infections became the norm more than the exception, that justification lost credibility. The remaining justification for COVID-19 vaccination was that it prevented severe disease. In fact, this justification for COVID-19 vaccination became a virtual mantra for those who got infected despite vaccination.
The following is representative evidence supporting the theory of vaccine prevention of severe COVID. It has been obtained from randomized and observational trials.
Efficacy of “approximately 90%” against severe-critical disease in a randomized controlled trial of Ad26.COV2.S manufactured by Johnson & Johnson-Janssen.
Efficacy of 96.7% (95% CI, 80.3 to 99.9) against severe disease in a randomized controlled trial of BNT162b2 manufactured by Pfizer-BioNTech.
Efficacy of 98.2% (95% CI, 92.8 to 99.6) in a randomized controlled trial of mRNA-1273 manufactured by Moderna.
Odds ratio of hospitalization with COVID-19 of 0.4 for unvaccinated vs. vaccinated in an observational study.
Odds ratio of hospitalization with COVID-19 of 0.34 [95% CI 0.32 - 0.36] for unvaccinated vs. vaccinated in an observational study with case-control matching and risk-factor adjustment.
Efficacy of mRNA against hospitalization with COVID-19 of 86.9% (95% CI: 80.4 to 91.2%) in an observational study with test-negative case-control matching.
Those findings are based on problematic methodologies. Specifically:
The randomized controlled trials did not consider the outcome of COVID-19 hospitalization. As a result, some have claimed that those trials had “limited power to assess efficacy among persons with underlying illnesses who are at high risk for severe Covid-19.”
The randomized controlled trials involved widespread planned unblinding of study personnel. The COVID-19 vaccines were distributed and prepared differently from the placebo. This required that personnel at each site were unblinded.
Maintaining the blind for other personnel was challenging in the randomized controlled trials. The blind could be broken indirectly due to physical differences between the placebo and the vaccines, differences in the side-effect profiles and differences in laboratory findings including immunogenicity studies.
The COVID-19 case definition protocol was not standardized, nor universal, in the randomized controlled trials. This includes variability in the location at which the COVID-19 testing was done. For the trial of BNT162b2, the protocol specifies that the locations of testing were performed at the central laboratory “… unless no result is available from the central laboratory”. There is also variability in the type of COVID-19 testing. In the trial of Ad26.COV2.S, the protocol gives the COVID-19 case definition is based on “molecularly confirmed” disease defined as: “… a positive SARS-CoV-2 viral RNA result using a PCR-based or other molecular diagnostic test.” The other “molecular diagnostic test” is not defined in the protocol. Most importantly, testing details are not standardized. In another trial, for example, a standardized “cycle threshold” was reported.
The conflict-of-interest in clinical trials sponsored by the manufacturer could not be greater. Notwithstanding the promotion of these trials by the manufacturers and the recognition accorded to these trials by the US federal regulatory agencies these trials are highly prone to bias and thus provide low-quality evidence of the value of the pharmaceutical.
US observational trials such as Havers et al failed to validate the integration of clinical and public immunization records. Observational trials of COVID-19 vaccine efficacy are challenging to carry out in the United States. Records of hospitalization and COVID-19 vaccination are typically physically independent and are not designed for integration. Cross referencing the clinical outcome with the vaccination status is impeded by regulatory and technical hurdles as discussed by Kohane and Omenn. Inaccuracy in cross-referencing between the clinical and vaccination records can affect the accuracy of the trial. Failure to properly cross-reference a clinical outcome with a vaccination record can lead to misclassification bias; a COVID-19 outcome is improperly attributed to the lack of vaccination. Numerous other trials rely on a similar data model.
The matched case-control study of Piernas et al failed to include cancer as a risk factor for hospitalization with COVID. The study estimated the odds of hospitalization with COVID after adjusting for risk factors such as diabetes, hypertension, and cardiovascular disease. Cancer is likely to be a risk factor for hospitalization with COVID, and that risk may not be balanced between the vaccinated and unvaccinated groups. The exclusion of cancer as a risk factor in the statistical model raises questions about the validity of the results.
The test-negative case-control study of Tenforde et al failed to fully disclose the criteria for the selection of subjects. The inclusion and exclusion criteria are described in a cited article. The trial ultimately enrolled 4906 COVID-19 test-positive and 5172 COVID-19 test-negative subjects from among patients at participating hospitals. Patients were identified from reviews of the medical records. It is unlikely that that balance in the two study groups would be obtained using the given inclusion/exclusion criteria. Thus, other factors are involved in patient selection that were not disclosed.
In summary, evidence for the theory of severe-COVID vaccine efficacy has always been of low quality. The evidence for this theory consists of studies with every sort of blatant or potential flaw or bias. No matter how many times this theory is recited by the COVID vaccination advocates, it is a dubious proposition.