Earlier this year, Korean epidemiological researchers led by a group at Samsung Medical Center, Sungkyunkwan University, School of Medicine and other academic medical centers reported on deaths occurring within close temporal proximity to COVID vaccination, with various attempts to assign causality or comorbidities as linked to the deaths. But success has been limited to date. Unless another comparable study has been published since the start of this year, the authors claim this is the first investigation to provide a comprehensive insight into the fatality rate of individual adverse event (AE) causes and the potential risk factors for mortality in patients with severe serious adverse events (SAE) following COVID-19 jabs. Of particular concern to TrialSite are the death reports linked to vaccine-induced neoplasms including acute myeloid leukemia, a blood cancer. Of course, while all of these deaths are temporally proximate to either the mRNA or viral-vector vaccinations, this doesn’t mean causality is proven.

COVID-19 Vaccination in South Korea

Four vaccines were approved by 2021 in South Korea including: 1) viral vector-based ChAdOx1-S/nCoV-19 (Oxford–AstraZeneca) and Ad.26. COV2.S (Janssen) vaccines and 2) mRNA-based BNT162b2 (Pfizer-BioNTech), and mRNA-1273 (Moderna) vaccines.

The location of this study is Gyeonggi Province, one of the largest local government bodies in South Korea, inhabited by approximately 13 million people, which is almost one-third of the nation’s population. As of March 2022, 85.9 % of its residents had been fully vaccinated, and 86.8 % had been vaccinated at least once against SARS-CoV-2

The Korean authors are adamant about the growing risk of mortality associated with the COVID-19 vaccines. For example:

“Despite mounting evidence on disease-specific mortality following SARS-CoV-2 vaccination, only a few studies have systematically analyzed the risk factors and case fatality rate (CFR) in patients already experiencing serious AEs (SAEs)."

The authors raise the specter of alarm, suggesting this critical information is “important for clinicians because some AEs may require timely medical attention to avoid poor outcomes.”

Study Context

In this study the medical researchers sought to (1) identify differences in patient-specific and external factors in patients with severe SAEs who died within 42 days of SARS-CoV-2 vaccine administration versus those who survived beyond 42 days; (2) evaluate how vaccine dose, vaccine mechanism, comorbidities, age, and sex may affect survival in patients with severe SAEs; and (3) explore the CFR in different types of severe SAEs.

The authors represented by Jinyoung Youn, Jin Myoung Seok, Kunhee Park and colleagues articulate that their study is the first to elucidate mortality in this group of patients.

The Study

A retrospective cohort study of physician- or self-reported severe SAEs temporally associated with SARS-CoV-2 vaccination in Gyeonggi Province, the most populated province in South Korea from February 26, 2021, to March 15, 2022.

The team evaluated patient-specific and external factors contributing to mortality within 42 days of the last vaccination and the causes of severe SAEs that resulted in fatal outcomes.

Study Method

AEs, Rates—‘Rare but Real’

Out of a total of 38,828,691 SARS-CoV-2 vaccine doses administered from February 26, 2021, to March 15, 2022, 105,409 AEs were reported equaling a total adverse reaction rate of 0.271% fitting in the range TrialSite has estimated from 0.2% to 0.8%.

Out of that total 687 patients were reported to have severe SAEs temporally associated with SARS-CoV-2 vaccination. The authors point out however that the causality between SARS-CoV-2 vaccines and the reported SAEs is still under investigation.

Excluded from this analysis were cases that did not require ICU admission, were not life-threatening or fatal, and were not associated with long-term sequelae (N = 23). In total, 664 cases of severe SAEs resulted in significant morbidity or mortality.

The authors in a survival analysis segmented patients into two groups: the “death” group, which included 291 deaths that occurred during the follow-up period within 42 days of vaccination, and the “censored” group, which included 373 patients who survived beyond 42 days from vaccination.

Adverse Events

Source: Vaccine X

The outcomes here derive from a retrospective cohort study involving 687 cases of reported severe SAEs that resulted in significant morbidity or mortality following SARS-CoV-2 vaccination.

What were the key findings?

The viral vector-based vaccines were associated with a lower risk of mortality than the mRNA-based vaccines—or put another way mRNA vaccines are more deadly
Vaccinations performed at nursing hospitals and facilities were associated with a higher risk of mortality, whereas vaccinations performed at government-supported vaccination centers were associated with a lower risk
Age, but not Charlson comorbidity index (CCI), was associated with a slightly increased risk of mortality
The case fatality rate (CFR) was variable according to different causes of severe SAEs, and an apparent mismatch was found between the frequency and CFRs.

So, does this mean that at least in this populated region of Korean when it comes to mortality the viral vector-based vaccines had fewer deaths than the mRNA vaccines?

Yes.

The authors report that a large proportion of adverse event following immunization (AEFI) could be explained by unwanted immune responses occasionally triggered by molecular mimicry?

Yes. This implied that it would be prudent to understand the differences in survival outcomes ensuing mRNA-based and viral vector-based vaccination. This could include differences in immunological traits that should be identified.

Molecular mimicry is a theoretical possibility that foreign and self-peptides can have similar sequences, which can lead to the cross-activation of autoreactive T or B cells by pathogen-derived peptides. This can cause an immune response to an environmental agent to cross-react with a host antigen, which can result in disease.

The authors' analyses point to a stronger and broader immune response with multiple doses of mRNA-based vaccines as compared with viral vector-based vaccines, and this might possibly boost the probability of immunological complications.

What were the most common causes of severe SAEs with fatal outcomes?

Diseases of the circulatory system. Importantly the case fatality rate was at 39.1%, lower than they anticipated, meaning that these circulatory system diseases were “monitored and treated relatively well.”

What was the most severe critical SAE with a fatal outcome in this study?

Neoplasms, involving a case fatality rate of 85.7%. Disturbingly, the most frequently reported neoplasm was acute myeloid leukemia, a blood cancer.

But should we apply caution to this data?

Yes. The temporal link does not equate to causality.

Did sudden deaths occur among patients in the unidentifiable diagnoses cohort?

Yes. 86 patients with unidentifiable diagnoses died within 42 days from the last vaccination in our study, and the diagnoses were inconclusive in 17 patients, even with autopsies. These patients experienced sudden death due to unclear causes and were labeled arbitrarily with sudden cardiac death, acute respiratory failure, or unclassified.

Can we imply causality with the above deaths?

No. More research is required.

What are some key limitations of this study?

An observational study meaning the findings are inherently discovered are only associations and not causations. However, the authors do believe that the temporal association suggested in our study may provide valuable insights into causality assessments.
Passive surveillance using the Korean data stores is vulnerable to under-reporting bias. However, to increase sensitivity, the authors undertook efforts to overcome this limitation, plus a robust follow-up was performed on each patient with severe SAEs to ensure that only a negligible amount of bias was driven by dropout.
The number of deaths associated with SARS-CoV-2 infection during the follow-up period was not entirely accounted for.
The denominator for the case fatality rate in this study was patients with severe SAEs and not the total population. Caution should be taken when generalizing the outcomes to the rest of the public.
The authors did not account for the differences in immunogenicity and reactogenicity between homologous and heterologous vaccination strategies.

Summary

The authors report that “older people receiving mRNA-based vaccines in nursing hospitals and facilities who reportedly develop severe SAEs with a high CFR (e.g., neoplastic, respiratory, and digestive disorders) may have an increased risk of 42-day mortality.”

Of paramount importance according to the Korean medical researchers is a “Timely government-led public surveillance and guidance in these groups of vaccine recipients who develop severe SAEs should be implemented to avoid unnecessary fatalities.”

A follow-up study is underway to investigate the differential effects of sequential dosing schemes on mortality in patients with severe SAEs.

Participating Institutions

Infectious Disease Control Center, Gyeonggi Provincial Government, Suwon, Korea
Department of Biostatistics, Soonchunhyang University Seoul Hospital, Seoul, Korea
Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
Neuroscience Center, Samsung Medical Center, Seoul, Korea
Department of Neurology, Soonchunhyang University Hospital Cheonan, Soonchunhyang University College of Medicine, Cheonan, Korea
Department of Applied Statistics, Chung-Ang University, Seoul, Korea

Jinyoung Youn, MD, PhD, Corresponding Author

Lead Research/Investigator

Jongmok Ha, Min Cheol Song, Suyeon Park, Hyunwook Kang, Taeeun Kyung, Namoh Kim , Dong Kyu Kim, Kihoon Bae, Kwang June Lee, Euiho Lee. Beom Seuk Hwang

Jinyoung Youn, MD, PhD Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine; Neuroscience Center, Samsung Medical Center, Seoul; Corresponding Author

Jin Myoung Seok, PhD, Department of Neurology, Soonchunhyang University Hospital Cheonan, Soonchunhyang University College of Medicine, Cheonan; Corresponding Author

Kunhee Park, Infectious Disease Control Center, Gyeonggi Provincial Government, Suwon, Korea, Corresponding Author

https://www.trialsitenews.com/a/major-korean-study-investigators-covid-19-vaccine-deathscancers-mortality-a-concern-rare-and-realcausation-remains-unsettled-37062f09