A breakthrough Covid-19 coronavirus infection may not be “super” to have. But can it actually give you what’s being called “super immunity” on social media? In other words, can a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection after being fully vaccinated against Covid-19 bring you even greater protection? Well, a research letter just published in JAMA offered a small window into this “super” possibility.
Monica Gandhi MD, MPH, a Professor of Medicine at the University of California, San Francisco (UCSF) and HIV researcher, used the terms “hybrid immunity” and “super immunity” when tweeting about the study described in the JAMA research letter:
She called it “hybrid immunity,” because the potentially boosted immune protection may come from a combination of vaccination and then subsequent infection. Gandhi also referenced another study described in a pre-print uploaded to MedRxiv that drew blood from 35 vaccinated individuals Provincetown, Massachusetts, 14 of whom had had subsequent breakthrough infections. This pre-print described how the blood of the breakthrough infection group had 28-fold higher levels of binding antibodies and 34-fold higher levels of neutralizing antibodies against the SARS-CoV-2 Delta variant than the blood of the rest. This study also looked at another measure of immune protection, how the individual’s T cells responded to the virus, a measure that I described previously for Forbes. Those with breakthrough infections had a 4.4-fold higher Spike protein-specific CD8+ T cell responses against the Delta variant than the rest of the study participants. Take all the results from this pre-print with a Ugg boot full of salt though. Anyone with a laptop, an Internet connection, and opposable thumbs can upload a pre-print. It is not the same as a peer-reviewed study published in a reputable scientific journal.
JAMA, of course, is a reputable scientific journal that puts research letter submissions through peer review. The study described by this JAMA research letter though was not perfect either. So take all findings from the study with at least 52 grains of salt. The study had 52 study participants total, comparing the blood from 26 fully-vaccinated health care workers who subsequently had breakthrough SARS-CoV-2 infections with the blood from a control group of 26 fully health care workers who didn’t. A team from Oregon Health and Science University (Timothy A. Bates, Savannah K. McBride, Bradie Winders, Devin Schoen, Lydie Trautmann, EngD, PhD, Marcel E. Curlin, MD, and Fikadu G. Tafesse, PhD) conducted the study.
The research team recruited study participants from January 31, 2021, through August 18, 2021. Nearly all, 24 out of 26, of the fully vaccinated folks in the breakthrough group had received the Pfizer-BioNTech Covid-19 vaccine. Ten of the breakthrough infections were due to the Delta variant, nine to non-Delta versions of the virus, and seven were unknown. These 26 study participants weren’t super old, with an average age 38 years. The majority (77%) were women. Most (81%) ended up having mild symptoms from their breakthrough infection.
For the control group, the team selected 26 health care workers who were fully vaccinated with the Pfizer-BioNTech vaccine but did not have any breakthrough infections. The control group had a similar average age (39 years) and a similar distribution of women (81%) as the breakthrough infection group. One key difference between the groups was how long after vaccination blood was drawn from the participants: a median of 213.5 days after receiving their last vaccine dose for the breakthrough group and 28 days for the control group. More on this later.
After the research team obtained blood samples from all of the study participants, they checked the blood sera for different antibodies, IgG, IgA, and IgM, against the SARS-CoV-2 spike protein. Then they mixed the serum samples with different samples of the virus, including the original SARS-CoV-2 strain and four current variants of concern (Alpha, Beta, Gamma, and Delta) to determine how well the antibodies in the sera could neutralize the viruses.
The results from the breakthrough infection group seemed “super” compared to those from the control group. Those who had had breakthrough infections had significantly higher levels of IgA and IgG antibodies, especially IgA, than the control group members. Moreover, the sera from the breakthrough group demonstrated increased ability to cross-neutralize the different variants compared to the sera from the control group. This ability was even more enhanced for those who had breakthrough infections from the Delta variant.
Again, this was a limited study. Size does matter in such cases. While 26 may seem like a large number when it comes to bowling balls in your pants, it is rather small for a clinical study. Such a small sample size can’t account for the variation that may be seen among different people and circumstances.
Furthermore, as mentioned earlier, there was a big difference in how long after vaccination the blood sera was collected between the breakthrough and control groups. Your level of immune protection can vary the longer you go after getting vaccinated. Plus, this study checked just one aspect of immune protection: antibody protection. That’s like focusing on whether a guy is holding a fish on his Tinder profile picture. Sure, they’re important measures, since antibodies do play a significant role and you could always end up fishing on a date. But neither should be the only measure.
Nevertheless, the results from this study shouldn’t be too super surprising since the more your immune system gets to know the SARS-CoV-2 and all its spikes, the better prepared it can be. Prior to being exposed to the spike protein via vaccination or infection, your immune system can be like you entering college. It can start off rather naïve, being unprepared to handle the SARS-CoV-2 and having a really bad haircut. However, every bad experience can make it stronger, presuming that none of the experiences end up in permanent damage or death. So one might expect your immune system to be even more prepared each time it sees that darn spike protein.
The road to the end of the Covid-19 coronavirus pandemic should go through repeated exposure to the spike protein. Rather than disappear completely, the virus is probably going to transition into becoming a more seasonal “endemic” pathogen that’s not as harmful as it’s been. It could eventually more resemble other seasonal respiratory viruses like the flu. This transition may happen once enough of the population becomes “used to” the SARS-CoV-2 and nearly everyone’s immune systems can finally say, “oh, that virus again.” When will this happen? This coming year, 2022, could see a significant shift. Vaccination can help facilitate and accelerate this shift. Indeed, someone who’s been exposed to the spike protein twice through vaccination can already fend off a Covid-19 coronavirus infection better than someone who’s gone unvaccinated. Why shouldn’t three exposures be better than two?
The term “super immunity” may not be that appropriate, though. It implies that there are only two types of immunity: regular immunity and super immunity. Your immune protection is not like a packet of French Fries or a cup of soda. You can’t just say, “oh, yes, I’ll take the super immunity with a side of sexiness.” Instead, immune protection is more of a continuous and dynamic thing that can change over time, sort of like life experience and your propensity to doing something stupid.
Arbitrarily calling a level of immune protection “super immunity” now won’t allow for varying levels of immunity in the future. Will there eventually be “super duper immunity”, “super OMG immunity”, “Venti immunity”, “almost super immunity”, “not quite super immunity”, “Venti immunity”, or something else like that?
Ultimately, this study provides further evidence that breakthrough infections doesn’t mean that the Covid-19 vaccine is not working. Each vaccine dose help your immune system “get more used to” the spike protein and in turn the SARS-CoV-2. Sure, getting infected with the SARS-CoV-2 may help you “get “used to” the virus as well. But then there’s that whole “might die, might get hospitalized, or might get long Covid” thing with natural infection. Why not use a vaccine first instead to teach your immune system? After all, wouldn’t you rather be told how to avoid getting smacked in the face with an oar than experiencing it yourself first?
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