Sunday, April 21, 2024

Japanese Real-World Observational Study: mRNA Vaccines how Low efectiveness

From February 1 to March 17, 2022, Epidemiological, public health and health economic researchers representing Hiroshima University in Japan along with Japan’s Ministry of Health, Labor and Welfare, Health Insurance Bureau, Medical Economics Division conducted a test-negative case-control study using a dataset of 117,335 individuals, collected through the COVID-19 J-SPEED form in the PCR center at Hiroshima Prefecture, Japan.

The study team, represented by corresponding author Yui Yumiya, Ph.D., MPH, Assistant Professor in the Graduate School of Biomedical and Health Sciences (Medical), estimated a propensity score matching for vaccine status based on participants’ demographic characteristics. Thereafter, the team calculated the odds ratio from logistic regression to determine any association between COVID-19 vaccination status and test positivity rate adjusting for symptoms, exposure to close contact, as well as previous history.

The Hiroshima University-led team of researchers established vaccine effectiveness as a formula (1 –aORs) ×100%). The team concluded that the data generated points to the protective effect of the COVID-19 vaccines against the Omicron strain. However, that’s interpreted in such a way because more unvaccinated are infected than vaccinated. If measured against the World Health Organization standard for vaccine approval, the mRNA vaccines as assessed in this study would fail the WHO 50% vaccine effectiveness test, as even boosted vaccine effectiveness equaled 26.4%.

The results of this AMED-funded observational study were published in PLOS, Global Public Health.

The authors of this study emphasize some strengths, such as the comprehensive data collection conducted across all PCR centers in collaboration with the Hiroshima prefectural office. Considered an “extensive and unique epidemiological survey,” it represents a material contribution, “with no comparable large-scale study conducted in other prefectures of Japan.”

Of course, many limitations with such a study exist (and are mentioned below), but the authors promote their use of detailed information representing occupation and various risk factors (likelihood of close contact and pre-existing conditions) that they articulate enhancing the study’s robustness. Such factors, adjusted within the model, account for potential confounding influence.

PCR Positivity Rates by Vaccination Status: the X axis represents the study period; y axis represents the test positivity rate. The figure displays PCR positive rates for three distinct groups: non-vaccinated, vaccinated with two doses and vaccinated with three doses (booster).


Reporting PCR test positivity rates were 7.9%, 4.5%, and 2.8% for the non-vaccinated (non-vaccinated, vaccinated with a single dose, and vaccinated with two doses less than 14 days ago), vaccinated with two doses (vaccinated over 14 days ago), and three doses, respectively.

Presenting both unadjusted and adjusted analyses, vaccine effectiveness of two doses against infection were 38.5% (95% confidence interval [CI]: 32.8%–43.8%) and 34.7% (95%CI: 28.4%–40.4%), respectively, compared to the non-vaccinated group. Vaccine effectiveness of three doses was 33.8% (95%CI: 25.0%–41.5%) and 26.4% (95%CI: 16.4%–35.2%), respectively, compared to those vaccinated with two doses.

While the authors cite these results in the positive (vaccine affords protection), not only should the actual vaccination effectiveness rate be questioned, but also noted that three dose rates is lower than the VE for two jabs. The authors emphasize the protective influence of the vaccine countermeasures.


All observational studies fall short in terms of evidentiary strength as compared to randomized controlled trials. Consequently, the team’s findings should be interpreted with caution and consideration of such inherent limitations, which include:

No specified estimation of VE for individual vaccine types, booster types (heterologous or homologous), time-sensitive effectiveness (effectiveness at different intervals post-vaccination), or the interval between vaccine doses.
The generalizability of our results may be affected due to the nature of this study population. For example, PCR test recipients who visited a PCR center may have a higher level of health consciousness compared to those who didn’t visit a PCR center.


Another finding of low vaccine effectiveness

How durable was the original monovalent mRNA vaccine when measured against prevention of COVID-19 Omicron-associated hospitalization involving children and adolescents? The Overcoming COVID-19 investigator network recently reported on this data between 2020 and 2023.

The results are challenging, evidencing rapidly waning vaccine effectiveness (VE) based on the known confluence of factors from mutating viral pathogens to the possibility of immunological imprinting (antigenic sin), and frankly, vaccines not engineered for breadth or durability results.

How severe is the waning VE? It is significant. For example, when measuring against hospitalization, VE should be substantially high, as the threshold is different for this class of product than preventing transmission. When the hospitalization incidence occurs a mere four months or more after the hospitalization event the VE rate equals 19% and ranges from as low as 2% to up to 32%. This is a remarkably weak rate evidencing serious concern about the longer-term viability of the COVID-19 countermeasures. The targeted threshold of effectiveness needs to be significantly higher for our children and adolescents.


Authoring this study paper was the Overcoming COVID-19 investigators, part of a study seeking to characterize the development of COVID-19 complications in children and young adults as a consequence of exposure to COVID-19 including the Multisystem Inflammatory Syndrome in Children (MSI-C).

MIS-C emerged as a significant concern during the SARS-CoV-2 delta surge but waned during Omicron.

A real-time surveillance and observational study, the investigation included prospective enrollment of study participants with collection of blood and respiratory samples. What were the risk factors and outcomes of COVID-19 critical illness in the pediatric population? What defined complications in this young vulnerable court and linked to SARS-CoV-2? What about predictive markers of these complications? Finally, what characterized the development and maintenance of adaptive immunity? The Overcoming COVID-19 investigators sought to answer these, and other questions.

How durable is pediatric vacation with use of mRNA COVID-19 vaccine countermeasures? This was a central question driving this investigation. Overall, parents have increasingly opted to keep their children away from the COVID-19 countermeasures.

The authors, represented by corresponding author Laura Zambrano, Ph.D., M.D., senior epidemiologist at the Centers for Disease Control and Prevention (CDC), report that during December 19, 2021–October 29, 2023, the Overcoming COVID-19 Network evaluated vaccine effectiveness (VE) of ≥2 original monovalent COVID-19 mRNA vaccine doses against COVID-19–related hospitalization and critical illness among U.S. children and adolescents aged 5–18 years, using a case-control design.

The authors report, “Too few children and adolescents received bivalent or updated monovalent vaccines to separately evaluate their effectiveness” which most certainly is a telling data point as to the reality of demand for COVID-19 vaccines among parents and their children and adolescents.

For this particular study, the authors led by Zambrano point out that a majority of individuals tested positive for SARS-CoV-2 fell in the unvaccinated category, “despite the high frequency of reported underlying conditions associated with severe COVID-19.”


So, what was the vaccine effectiveness of the original monovalent vaccine against COVID-19–related hospitalizations?

According to the findings here, VE equaled 52% (95% CI = 33%–66%) when the most recent dose was administered <120 days before hospitalization, and 19% (95% CI = 2%–32%) if the interval was 120–364 days. TrialSite suggests the rate of 19% VE in preventing hospitalization 4 months and on represents an incredibly weak record.

Another measure, or slice of the data, was a vaccine administered any time within the previous year, which looks at least somewhat better than the pathetic 19% figure, especially for this category of the original monovalent vaccine against COVID-19–related hospitalization was 31% (95% CI = 18%–43%).

When looking at the definition of hospitalization with more granularity, diffident VE rates emerge. For example, looking at the category “COVID-19-related illness” defined as receipt of noninvasive or invasive mechanical ventilation, vasoactive infusions, extracorporeal membrane oxygenation, and illness resulting in death and VE rates equaled the following:

VE Scenario

VE was similar after excluding children and adolescents with documented immunocompromising conditions.

The CDC authors emphasize that the receiver of ≥2 monovalent mRNA COVID-19 vaccines are associated with fewer COVID-19 hospitalizations during the Omicron period in children and adolescents aged 5–18 years. But this
“protection from original vaccines was not sustained over time, necessitating increased coverage with updated vaccines.”

A majority of hospitalized kids were unvaccinated, and few had received updated vaccine doses despite a high prevalence of underlying comorbidities associated with more severe disease.

The social determinants of health continue to be a factor in vaccination trends, with vaccination rate decline associated with social vulnerability.

The authors acknowledge carefully the overall dismal VE rates, stating:

“VE of original monovalent doses against COVID-19–related pediatric hospitalizations were lower than previous VE estimates reported by the Overcoming COVID-19 Network before Omicron emergence.”

The CDC does not include any risk-benefit analysis within its recommendations, e.g., avoids discussion of myocarditis/pericarditis risk to young adolescent males and avoids the topic of natural immunity when recommending that “all children and adolescents receive updated COVID-19 vaccines to protect against severe COVID-19.”


Not surprisingly, many limitations suggest any interpretation done so with caution. Dr. Zambrano and team identify four major limitations including:

SARS-CoV-2 infection-induced immunity was not assessed

Limited viral sequencing data prevented consideration of subvariant-attributed immune evasion

Limited coverage with bivalent vaccines and currently recommended updated monovalent vaccines precluded the estimation of VE of these formulations

Previously healthy children and adolescents accounted for <20% of case-patients, limiting generalizability




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