Reinfection Redux — 3 Comments

  1. I’ve been keeping an eye on antibody-dependent enhancement (ADE), because it’s sort of a bogeyman. It’s very probably not a factor, but if it does turn out to be a factor, it might be a huge problem. In other diseases, it’s mainly been noted when a person has been vaccinated for one strain of a virus, then encounters a slightly different strain in the wild. There seem to be a number of gating conditions, such as the new strain being different enough but not too different, and the person having enough antibodies to the old strain but not too many.

    Since few people have yet been vaccinated against SARS-CoV-2, the reports of multiple-infection so far are from people who developed antibodies from a wild-caught strain, not from a vaccine. It may turn out that the vaccines are less prone to triggering ADE than a natural infection, because all of the vaccine candidates of immediate interest (Operation Warp Speed/BARDA) are only using the Spike protein — that being the protein that triggers neutralizing antibodies. There are indications that ADE might be triggered mainly by antibodies to the Nucleocapsid protein, which isn’t in the vaccine but of course is present in the wild virus (and any vaccines using inactivated or attenuated whole virus).

    Despite all of that “really really not likely at all” stuff, I remain a bit jittery about plans to widely vaccinate certain groups (particularly nursing home residents) prior to the Phase III trials having run for maybe five or six months without signs of ADE. Fortunately, someone else will make that decision, not me.

    • If ADE depends on mutations to get a foothold, we might not be in such bad shape with SARS-CoV-2. It’s a coronavirus and those are at the top of the viral pack in terms of the size of its RNA load. That’s one reason coronaviruses mutate relatively slowly, unlike e.g. influenza. Another reason is that the family packs proofreading machinery for transcribing RNA. I have not heard about ADE with any coronavirus: common cold (3x), SARS, or MERS. It does occur apparently in dengue, but that is from a different family, a flavivirus.

  2. I’m very definitely not an expert on this stuff, so I’ll refer you to an article in Nature magazine about a month ago. “ADE and ERD [enhanced respiratory disease] has been reported for SARS-CoV and MERS-CoV both in vitro and in vivo… Available data suggest that the most probable ADE mechanism relevant to COVID-19 pathology is the formation of antibody–antigen immune complexes that leads to excessive activation of the immune cascade in lung tissue.”

    However, reports and a credible mechanism aren’t proof, so the article also notes, “No definitive role for ADE in human coronavirus diseases has been established.”

    Also on the positive side, “Vaccines that elicit neutralizing antibodies against the S protein reliably protect animals from SARS-CoV challenge without evidence of enhancement of infection or disease. These data suggest that human immunization strategies for SARS-CoV-2 that elicit high neutralizing antibody titres have a high chance of success with minimal risk of ADE.”

    From the article’s conclusion: “Clinical data has not yet fully established a role for ADE in human COVID-19 pathology. … Ongoing animal and human clinical studies will provide important insights into the mechanisms of ADE in COVID-19. Such evidence is sorely needed to ensure product safety in the large-scale medical interventions that are likely required to reduce the global burden of COVID-19.”


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