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Conspiracy theories about antibody-dependent enhancement (ADE) with COVID-19 vaccines are swirling yet again, apparently due to a letter to the editor and a controversial talk by a physician at a school board meeting.

That's despite the fact that there's absolutely no evidence of the condition occurring as hundreds of millions of people around the world have been vaccinated.

"If COVID-19 vaccines caused ADE, people who are vaccinated against COVID-19 would have more severe disease," Nada Fadul, MD, an infectious diseases physician with Nebraska Medicine, . "This is not happening. On the contrary, people who are vaccinated typically have very mild disease or none at all. In fact, the majority of COVID-19 deaths in the U.S. are people who aren't fully vaccinated."

Dan Stock, MD, a physician in Indiana, 2 weeks ago that the summer surge of infections was due to ADE resulting from vaccination (essentially, the idea with ADE is that certain antibodies actually make it easier for viruses to get inside cells). Around the same time, a was published in the Journal of Infection that proposed the Delta variant was posing new challenges with ADE.

Derek Lowe, a biotech blogger for , noted that the letter by Nouara Yahi, PhD, of Aix-Marseille University in France, and colleagues, is purely theoretical, with no experimental evidence to support their molecular modeling.

Yahi and colleagues theorized a new potential mechanism for binding enhancement with the Delta variant, but the idea wasn't even tested in vitro, Lowe warned, noting that their work does attempt to build on a reputable paper by Dapeng Li, PhD, of the Duke Human Vaccine Institute, and colleagues published as a preprint in February, and .

The Li paper demonstrated some in vitro evidence of ADE with both neutralizing and non-neutralizing antibodies against the receptor-binding domain and the N-terminal domain of the original strain of the virus, Lowe said. However, Li and colleagues did not see any evidence of ADE in animal models with these antibodies.

"Indeed, antibodies that showed ADE in the cell culture models still protected primates from viral replication when they were challenged by the actual virus," Lowe wrote.

He said the Yahi paper "is not aligned with reality," and that any such theory would "have to be confirmed by experimental data before [it] can be taken seriously."

"There are a great number of things that look plausible in such simulations that do not translate to reality," Lowe said.

He cautioned that -- also computational, with no experimental data -- offered an explanation of how the debunked treatments azithromycin and hydroxychloroquine work together in synthesis against COVID-19.

Edward Nirenberg, a , also noted that the Yahi letter (B.1.617.2) with the Kappa variant (B.1.617.1), which have "very different properties as far as antibody neutralization (based on significant differences in the spike protein mutations each bears) and very different prevalences around the world (Kappa has nearly disappeared from much of the world and appeared to have substantially greater antibody evasion than Delta)."

The Yahi model is based on the Kappa variant spike protein, Nirenberg said.

Lowe concluded that there's no evidence of ADE in vaccinated people, and in fact the clinical data show the opposite: vaccinated people are less likely to be infected with Delta, and if they do get sick, they are less likely to develop serious illness.

"If the mechanism proposed by Yahi et al. were happening in the real world, then we should see higher Delta infection rates among vaccinated people, with more severe disease," he wrote. "We are not. We are seeing the reverse. The vaccines simply to not appear to be causing ADE, no matter how many reasons one might be able to spin for them to do so."

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