Superhuman: People with "hybrid immunity" can best all six COVID variants -- plus the original SARS virus

AP Photo/LM Otero

Read this and for the first time you’ll find yourself (slightly) jealous of people who’ve caught the virus. Alternate headline: “Donald Trump basically indestructible by COVID now.”

We’ve been over this ground before, actually. Back in May studies were already beginning to show that while natural immunity is powerful and vaccine immunity is powerful, having natural immunity and then getting vaccinated creates an extremely robust, almost superhuman immune response to the virus. My layman’s understanding is that when you’re infected, your immune system gets a look at the complete virus and begins fashioning antibodies to neutralize it. That’s different from a vaccinated person, whose system gets a look only at the spike protein. Immunity to COVID continues to evolve over time in both groups, generating more complex antibodies, but they’re especially complex in people with natural immunity because they saw more of the virus than the vaccinated did. Which may explain why people with natural immunity do much better against Delta.

When you take someone who has that more complex immune memory from infection and dose them with the vaccine, you generate an enormous surge of antibodies and prompt that person’s already sophisticated response to the virus to become even more sophisticated from a second look at the spike protein. Result: Not only are they extremely protected from illness, the antibodies they produce are capable of handling all known strains of the virus and unknown respiratory viruses as well.

Super-immunity: Catch the fever. Literally!

In a study published online last month, Bieniasz and his colleagues found antibodies in these individuals that can strongly neutralize the six variants of concern tested, including delta and beta, as well as several other viruses related to SARS-CoV-2, including one in bats, two in pangolins and the one that caused the first coronavirus pandemic, SARS-CoV-1.

“This is being a bit more speculative, but I would also suspect that they would have some degree of protection against the SARS-like viruses that have yet to infect humans,” Bieniasz says…

In fact, these antibodies were even able to deactivate a virus engineered, on purpose, to be highly resistant to neutralization. This virus contained 20 mutations that are known to prevent SARS-CoV-2 antibodies from binding to it. Antibodies from people who were only vaccinated or who only had prior coronavirus infections were essentially useless against this mutant virus. But antibodies in people with the “hybrid immunity” could neutralize it.

Granted, the sample size for the studies was small at just 14 people, but researchers saw similar super-immune responses in every one of them. It appears that if you have hybrid immunity, the pandemic is essentially over for you. Not even the Wuhan Institute of Virology could cook up a virus capable of laying you low.

Why is hybrid immunity so potent? Virologist Shane Crotty explained in a piece published in June:

Memory B cells are a primary reason. They have two major functions: one is to produce identical antibodies upon reinfection with the same virus, and the other is to encode a library of antibody mutations, a stockpile of immunological variants. These diverse memory B cells, created in response to the original infection, appear to be preemptive guesses by the immune system as to what viral variants may emerge in the future. This brilliant evolutionary strategy is observed clearly for immunity to SARS-CoV-2: A substantial proportion of memory B cells encode antibodies that are capable of binding or neutralizing [variants of concern], and the quality of those memory B cells increases over time. Thus, the increase in variant-neutralizing antibodies after vaccination of previously SARS-CoV-2–infected persons reflects recall of diverse and high-quality memory B cells generated after the original infection…

Memory B cells are increased 5- to 10-fold in hybrid immunity compared with natural infection or vaccination alone.

Read the first excerpt above again. Scientists engineered a super-virus designed to overcome standard COVID immunity — but people with hybrid immunity had gained such a complex repertoire of potential antibody responses that they had already evolved a way to beat it by the time it was ready. Not only that, says Crotty, they also had massively more antibodies against the immune-resistant strain B.1.351 (the South African variant) relative to people with just natural immunity (100 times more) or just vaccine immunity (25 times more). “[A] long-standing rule of thumb is that repeated exposures are recognized as an increased threat” by the body, he writes, so when your body is infected by SARS-CoV-2 and then “reinfected” by the spike protein in vaccination, it perceives a durable risk of infection and evolves a more durable immune response to fend it off. “Hence the success of vaccine regimens split into two or three immunizations,” Crotty notes.

Speaking of which, given that logic, to what degree might people with vaccine immunity gain some measure of super-protection from a third dose? One immunologist told NPR that he expects the same fundamentals of the process will hold with booster shots, with the vaccinated evolving more sophisticated antibodies after they get a third look at the spike protein. Whether their antibodies will be *as* complex as those of someone who’s encountered the full virus is another matter. But that raises another intriguing question, one with lots of momentary resonance: What happens when a vaccinated person ends up with a breakthrough infection? Their immune system is seeing the full virus at last; how will that affect the sophistication of the antibodies they evolve after recovering? Will theirs be more sophisticated than someone with traditional hybrid immunity (i.e. infected first, then vaccinated) or less? Should people mix-and-match their boosters in order to nudge their bodies to produce a more complex set of antibodies?

It would have been nice to have these questions answered before the start of booster season 12 days from now but you go to war with the public-health bureaucracy you have.

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