The claim that COVID-19 vaccines will cause more severe disease through antibody-dependent enhancement is not supported

Social media posts claiming that the COVID-19 vaccine will lead to more severe disease went viral on social media platforms (examples here and here). The claim is based on the observation of more severe disease occurring in individuals who received vaccines such as the one for dengue fever.  In a 2018 study, scientists showed that newborn mouse pups harboring anti-Zika antibodies were more vulnerable to death from dengue exposure than mice that lacked anti-Zika antibodies. This likely due to a phenomenon known as antibody-dependent enhancement (ADE), however ADE has not been shown to occur in individuals that received COVID-19 vaccines to date. 

As reported by Flora Teoh at Health Feedback

Health Feedback reached out to experts to find out how ADE works and whether the claim is supported by scientific evidence [See scientists’ feedback in full].

Angeline Rouers, a research fellow at the Singapore Immunology Network, explained, “ADE is a well-known mechanism which was described for the first time in dengue patients. It occurs when antibodies do not neutralize the virus to prevent its entry into the target cells, for example, but instead facilitate the infection of other cells, such as macrophages (a type of immune cell).” However, Rouers added that there is “no clear evidence” showing that the virus which causes COVID-19, SARS-CoV-2, can infect macrophages.

Walter Orenstein, a professor at Emory University’s School of Medicine and associate director of the Emory Vaccine Center, said, “Vaccine-enhanced disease is theoretically possible with SARS-CoV-2 vaccines, but it has not been seen as of yet in the clinical trials reported.”

Sanjay Mishra, a staff scientist and project coordinator at Vanderbilt University Medical Center who is also working in the COVID-19 and Cancer Consortium, concurred. “The major vaccine candidates that have so far progressed in the large-scale Phase 3 trials, such as the ones by Moderna, Pfizer, and AstraZeneca, have all ruled out any serious safety concerns,” he said.

Overall, all three scientists agreed that close monitoring of vaccinated people is important to ensure that ADE can be safely ruled out as a side effect of COVID-19 vaccines, but for the moment, the evidence has not shown the vaccines to have such an effect.

Indeed, preliminary findings released by frontrunners Moderna, Pfizer, and AstraZeneca have shown that among the trial participants who did develop COVID-19, those who received the vaccine did not show higher rates of severe disease compared to those who received the placebo. The vaccines were also able to prevent COVID-19 at a high efficacy. However, an important caveat of these findings is that these trials are still underway, and the number of people included in these interim analyses is relatively small.

Apart from the post’s unsupported claim linking ADE with COVID-19 vaccines, its suggestion that non-neutralizing antibodies are always ineffective for protection is inaccurate. The immune system has several ways to deal with viruses, and “Antibody-dependent cellular cytotoxicity, which can involve non-neutralizing antibodies, is another mechanism that is distinct from neutralization, that is also important for a protective immune response,” Rouers pointed out.

And contradicting Everly’s claim that “no one is concerned about it,” Health Feedback was able to find multiple articles published over the course of 2020 that discussed concerns about ADE with respect to the COVID-19 vaccine. Some examples are this article in The Scientist, this article in PNAS and these two articles in Nature[1,2], the latter two being highly respected journals in the scientific community.

Overall, while ADE is a theoretical possibility with a COVID-19 vaccine, clinical trials in people so far have not shown that participants who received the vaccine have a higher rate of severe illness compared to participants who did not receive the vaccine. Given the paramount importance of vaccine safety, scientists continue to encourage rigorous safety monitoring so as to completely rule out ADE as a potential side effect.