By author Timothy Cardozo, MD-PhD. January 31, 2021
This statement is my personal and professional opinion and in no way represents the views of my employer, NYU Langone Health or any other entity. No conclusion may be drawn about the opinions, practices, policies or intentions of NYU Langone Health or any other entity from this statement.
Thank you for your interest in this published article. This statement is intended to respond to non-scientific or clinical questions and comments about the article. If you have scientific or clinical academic questions or comments specifically about the evidence presented in the article or about the conclusions drawn from that evidence, please feel free to email me at the author contact email address with your questions/comments. Otherwise, for non-scientific/clinical points of discussion, I provide the following statement and request no further contact about these topics.
The article provides evidence to support informing COVID-19 clinical trial vaccine recipients of the risk of worsened disease due to vaccine priming prior to encounter with the virus in the community. With regard to vaccine recipients in the community who are not clinical trial subjects, my opinion is that there is no position that would reasonably support NOT informing vaccine recipients specifically of this of this risk and making sure each person comprehends this risk before making a decision about whether to receive the vaccine or not. Personally, I believe that is common sense.
The published article makes no statement whatsoever about whether COVID-19 vaccines are good or bad or whether they should be taken or avoided.
That being said, the PRELIMINARY data on the Pfizer and Moderna vaccine trial results, which came out after the article was published, are as good as could possibly be hoped from an efficacy and safety point of view, greatly reducing my concern about antibody dependent enhancement of disease (ADE) with these vaccines and greatly increasing my perception of the benefits of these vaccines. Indeed, I believe these results apply to all the vaccines that use the "2P" design of the CoV-2 viral spike invented by Drs. Graham, Corbett, Kwong, Mclellan and others at the NIH's Vaccine Research Center. It was unknown, prior to the Pfizer and Moderna clinical trial results whether this "2P" design "trick" would work to shield the ADE epitopes in the viral spike that are cited in my article as plaguing prior SARS and MERS vaccines. The absence of adverse effects in the vaccine groups representative of ADE or one of its concerning flavors, vaccine associated hypersensitivity (VAH), so far with Pfizer and Moderna vaccines give me hope that, in fact, the "trick" succeeded and that these dangerous elements in the viral spike, though present in these vaccines, are shielded from immune responses and might not pose a danger. The vaccines that use this viral protein design, to my knowledge are Pfizer, Moderna, Novavax and Johnson and Johnson. I do not believe that the AstraZeneca vaccine uses this design and have no knowledge of the other vaccine candidates in this respect.
However, the Pfizer and Moderna vaccines are early, 2-months follow up results, so, while the results are encouraging and reduce my concern, they do not eliminate it. A good example of that is that no mortality benefit is seen so far from the vaccines: e.g. there was one death each in the Moderna vaccine and placebo groups of 15,000 subjects. Clearly, that is not reflective of the real situation, where one would expect a safe and effective vaccine to reduce the number of deaths significantly as compared to placebo, if COVID-19 is indeed as deadly a disease as it seems to be. I do not believe that the "you may experience adverse effects that we do not know about yet" informed consent clause is sufficient because this clause does not reach the level of patient comphrension of the risk of ADE, which likely remains the most significant risk of this vaccine. My opinion is that the clinical trial results absolutely warrant emergency use authorization of these vaccines and suggest far greater benefit than risk for these vaccines, but proper disclosure prominently and specifically of the risk of ADE/VAH should be provided to vaccine recipients in their informed consent procedure until ADE/VAH is ruled out.
The statement in the above paragraph applies only to the Pfizer and Moderna vaccines. I am reasonably confident that the Novavax vaccine is equivalent in safety and efficacy to the Pfizer and Moderna vaccines and, once that data is available, the above statement will apply to that vaccine as well. I am hopeful about the Johnson and Johnson vaccine, but as it is expressed as an Adenovirus, I am concerned that there may be alterations in the "2P" design that reduce its effectiveness a bit. Nevertheless, the press release on the Johnson and Johnson vaccine states that deaths were eliminated in the vaccinated: if they were not eliminated in the placebo group and were numerous, that would be a mortality benefit that might support eliminating the specific disclosure of ADE in informed consent for these vaccines. I hope that is the case when the official published results are released.
Bottom line: my opinion is that the Pfizer and Moderna vaccine data DOES support that you will nearly 100% protect your family and community from transmission of the virus through you if you are vaccinated, but at some as yet unknown, but likely small, health risk to yourself from antibody-mediated tissue damage, not from the vaccine, but from later exposure to the virus. You should understand this risk in the process of making your choice to receive the vaccine.
I will try to post any changes to my views or opinions on this page over time if new information becomes available.
Timothy Cardozo MD PhD
Corresponding author of the above article
Feb 5, 2021 Clarifications
If a statistically significant reduction in death from all causes in the vaccine group is observed as compared to the placebo group in any clinical trial that uses the "2P" design, then I would consider ADE/VAH ruled out as a significant risk for those vaccines (or at least remote enough that the blanket "unknown risk" statement would apply).
"nearly 100% protect your family and community" is my interpretation of the Pfizer and Moderna results that 162 laboratory confirmed SARS-CoV-2 infections were seen out of ~22,000 Pfizer placebo subjects and only 8 out of ~22,000 Pfizer vaccinated subjects, while the numbers were 90/15,000 placebo and 5/15000 Moderna vaccinated. Despite this dramatic difference in detectable infections, essentially no difference in deaths from all causes was seen between the two groups in both studies. My article describes prior research in which ADE tissue damage occurs in the absence of detectable virus (and the laboratory test itself has many false negatives for a variety of reasons), meaning that subjects severely affected or killed by virus-elicited ADE would not be included as COVID-19 subjects in these clinical trials, but WOULD appear as deaths in the vaccine group. However, they would still not be able to transmit the virus. Thus, the clinical trials clearly show that vaccination will reduce or eliminate transmission of the virus through you to your family or community, most likely by preventing infection in the first place, but even in the perhaps rare event of you experiencing ADE, severe disease or death.
April 15, 2021
I have confirmed that the AstraZeneca vaccine does NOT use the 2P design, and therefore is most susceptible to eliciting ADE. It is also clear that the AstraZeneca vaccine is experiencing significantly more adverse events and lower efficacy than Pfizer, Moderna or J&J. Therefore, I believe that the AstraZeneca experience confirms that ADE can and does happen with COVID-19 vaccines, but that the risk of enhancement of ADE of infection by vaccination with Pfizer and Moderna is much lower and still has a chance to be actually absent. J&J vaccine appears to be in between, but J&J definitely uses the 2P design so while there might be a slightly higher risk of ADE phenomena, I would be comfortable concluding that the risk of ADE enhancement of infection by J&J vaccine is still quite low...however I am less certain and more concerned about J&J than Pfizer and Moderna. And very concerned about AstraZeneca (and probably Sputnik and Chinese vaccines as well).
June 1, 2021
There are reports that the CDC is investigating myocarditis resulting from Pfizer and Moderna vaccines. The current reports are that these incidents are very, very rare, however, myocarditis is a possible outcome of ADE/VAH, and myocarditis was clearly prevalent in those experiencing severe disease from COVID-19, suggesting that it may indeed by an antibody-mediated phenomenon in COVID-19 infection and vaccination. Therefore, my conclusion remains that there is a very low, but real, risk of ADE/VAH from the Pfizer and Moderna vaccines, likely a similar risk from the Novavax vaccine (although there is very little data on this), a slightly higher, but still very low risk of ADE/VAH from Johnson and Johnson and potentially significant risk from Astra Zeneca and other vaccines.
July 30, 2021
At this point, sufficient data has accumulated on millions of people vaccinated with Pfizer and Moderna vaccines to re-emphasize that the risk of ADE/VAH is very low, very rare and when not rare, mild in intensity. Again, based on the above, I would expect similar safety profile with Novavax. I remain cautious, as do many others about the Johnson and Johnson vaccine, although the data remains unclear as to whether some of the problems with that vaccine are due the adenovirus or with ADE/VAH. The risk of ADE/VAH should be seriously considered by all individuals taking the AstraZeneca, Chinese, Indian or Russian vaccines, HOWEVER my assessment is that, even for these potentially problematic COVID-19 vaccines, the benefits greatly outweigh the risks.
December 14, 2021
I would expect Pfizer and Moderna boosters containing the Omicron sequence to be equally safe with respect to ADE/VAH, as these new versions will use the 2P protein design. This conclusion has nothing to do with whether or not Omicron evades current vaccines, and/or whether one should get the current Pfizer/Moderna booster or a future Omicron booster.