Informed consent disclosure to vaccine trial

Informed consent disclosure to vaccine trial subjects of risk of COVID-19 vaccines worsening clinical disease


Robert Gorter, MD, PhD.

January 10th, 2021

Cardozo T, Veazey R. Informed consent disclosure to vaccine trial subjects of risk of COVID-19 vaccines worsening clinical disease. Int J Clin Pract. 2020 Oct 28:e13795. doi: 10.1111/ijcp.13795. Epub ahead of print. PMID: 33113270; PMCID: PMC7645850.


Aims of the study: Patient comprehension is a critical part of meeting medical ethics standards of informed consent in study designs. The aim of the study was to determine if sufficient literature exists to require clinicians to disclose the specific risk that COVID-19 vaccines could worsen disease upon exposure to challenge or circulating virus.

Methods: Published literature was reviewed to identify preclinical and clinical evidence that COVID-19 (SARS-CoV-2) vaccines could worsen disease upon exposure to challenge or circulating virus. Clinical trial protocols for COVID-19 vaccines were reviewed to determine if risks were properly disclosed.

Results: COVID-19 vaccines designed to elicit neutralizing antibodies may likely sensitize vaccine recipients to more severe disease than if they were not vaccinated. Vaccines for SARS, MERS and RSV have never been approved, and the data generated in the development and testing of these vaccines suggest a serious mechanistic concern: that vaccines designed empirically using the traditional approach (consisting of the unmodified or minimally modified coronavirus viral spike to elicit neutralizing antibodies), be they composed of protein, viral vector, DNA or RNA and irrespective of delivery method, may worsen COVID-19 disease via antibody-dependent enhancement (ADE). This risk is sufficiently obscured in clinical trial protocols and consent forms for ongoing COVID-19 vaccine trials that adequate patient comprehension of this risk is unlikely to occur, obviating truly informed consent by subjects in these trials.

Conclusions and clinical implications: The specific and significant COVID-19 risk of ADE should have been and should be prominently and independently disclosed to research subjects currently in mRNA vaccine trials, as well as those being recruited for the trials and future patients after vaccine approval, in order to meet the medical ethics standard of patient comprehension for informed consent.

Cardozo T*, Veazey R**. Informed consent disclosure to vaccine trial subjects of risk of COVID-19 vaccines worsening clinical disease. Int J Clin Pract. 2020 Oct 28:e13795. doi: 10.1111/ijcp.13795. Epub ahead of print. PMID: 33113270; PMCID: PMC7645850.

*Department of Biochemistry and Molecular Pharmacology, NYU Langone Health, New York, NY, USA.

**Division of Comparative Pathology, Department of Pathology and Laboratory Medicine, Tulane University School of Medicine, Tulane National Primate Research Center, Covington, LA, USA.


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Boyoglu-Barnum S, Chirkova T, Anderson LJ. Biology of infection and disease pathogenesis to guide RSV vaccine development. Front Immunol. 2019;10:1675.

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Dr. Robert Gorter:

Already from April 2020 on, several colleagues in the Netherlands, Germany, Italy and my team noticed that those patients with symptomatic COVID-19 infection who did much worse and needed ventilation and other interventions, all had been vaccinated during the previous year(s) against the flu (“flu jab”) which included components against Corona infections. Approx. 30% of all flu epidemics are caused by the Corona virus family of which COVID-19 is a member.

In the peer-reviewed medical literature, there are many studies showing that repeated exposure to an infection or to a slightly different antigen, caused by a mutation or strain, a more severe and fatal disease progression can take place. A very good example is the re-infection by the mosquito-born Dengue fever.

Thus; all volunteers in all current studies with mRNA vaccines should be informed about this real risk.

robert gorter

One bout with Dengue fever, transmitted by the Aedes aegypti mosquito, is usually bearable, but a second can lead to life-threatening autoimmune diseases, like hemorrhagic fever (ITP)

Armies can be overpowered when they fail to adapt to a new enemy. The immune system makes the same mistake when battling repeated bouts of dengue fever, according to a new study. The results could help researchers develop a much-needed vaccine to protect against the widespread mosquito-borne tropical disease.

Most of the more than 50 million people sickened by dengue virus each year develop dengue fever, a weeklong bout of joint and muscle pain. But many who suffer repeated infections have it much worse. They come down with Dengue hemorrhagic fever and suffer massive internal bleeding and liver damage. Oddly, the virus causing Dengue fever comes in four strains, and immunity to one seems to make infection by a second strain more dangerous. There is significant proof that antibodies generated by a first bout with Dengue bind to a second strain, which helps it multiply in the immune cells does not account for the internal bleeding and tissue damage, says Juthathip Mongkolsapaya of Mahidol University in Bangkok, Thailand. So Mongkolsapaya, Gavin Screaton of the University of Oxford, and their colleagues asked whether dengue was also causing T-cells, which ordinarily kill virus-infected cells, to alter and malfunction.

To find out, they studied T-cells from blood samples from 71 children with dengue fever or dengue hemorrhagic fever. In test tube experiments, they linked virus fragments to human cell proteins; adding this complex to the T-cells provoked them to fight the virus. By studying how the T-cells responded, the group learned that the cells were primed to fight a different strain than the one attacking them. What is more, the Dengue-specific T-cells were rapidly self-destructing; a response that leads to tissue damage, according to results reported in the July 2020 issue of Nature Medicine. The immune misfiring and resulting cell suicide, Mongkolsapaya says, is very likely a primary cause of Dengue hemorrhagic fever. Similar experiments might now be able to find other Dengue virus fragments which together could make up a vaccine that provokes a protective immune response.

The work is “very important,” says infectious-disease physician Wellington Sun of the Walter Reed Army Institute of Research in Silver Spring, Maryland, USA. Although it still doesn’t explain how infants sometimes develop dengue hemorrhagic fever the first time when they are infected, he says, it “underscores that T cells could be just as important as antibodies” when ordinary cases of dengue fever turn ugly.

The same principle is taking place in COVID-19 (SARS-CoV-2) infection. The mRNA vaccine will affect T-cell populations and hopefully stimulate the immune system to antibody production against COVID-19 which can also trigger the same autoimmune reactions as in a re-infection with Dengue fever.

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