Natural COVID-19 immunity is powerful — but kind of irrelevant

Over 43 million Americans have reported cases of COVID-19. Many of them likely have some amount of natural immunity, and this kind of immunity can be quite protective, even without vaccination. Why does it seem that scientists are ignoring natural immunity in the national discussion of vaccine mandates and vaccine passports?

Natural immunity can, indeed, be powerful. Even before vaccines were available, individuals who recovered from COVID-19 had detectable T-cell responses, and reinfections were rare, at least prior to the emergence of the aggressive Delta variant.

However, the scientific community strongly recommends vaccination even in people who had COVID-19 infection. There are very good reasons for this. Every component of the immune response to the SARS-CoV-2 virus improves after vaccination, including antibodies and T-cells. In those with prior COVID-19 infection, vaccination can elicit important cross-variant neutralizing antibodies. And clinical protection improves after vaccination in people who had prior infection: In a recent study, people with prior COVID-19 who received even one vaccine dose had half the risk of a breakthrough infection than unvaccinated people with prior COVID-19. So, vaccination even helps those with prior COVID-19 (and everyone they interact with). 

Not everyone who has a case of COVID-19 will have natural immunity. In a recent Centers for Disease Control and Prevention (CDC) study of those with prior COVID-19 infection, 36 percent did not form any antibodies against the virus. This is in stark contrast to antibody formation in 100 percent of (non-immunocompromised) people who receive even one dose of an mRNA vaccine (Pfizer or Moderna), as impressively reported in the large vaccine trials. So, from a practical perspective, if a business or school is trying to figure out if someone is safe to be around, they can rest quite assured that someone who shows them vaccine proof is safe, but it would be nearly impossible to determine if someone with prior COVID-19 is safe. Beyond the logistical issues of proving that a person had prior COVID-19, how can they prove they’re in the 64 percent who have some natural immunity?

It is possible that antibody testing could eventually play a role in providing “immunity passes” for those with natural immunity who have not been vaccinated. Antibody levels do seem to correlate with neutralization assays and even clinical protection: more antibodies means more protection. However, there are currently no commercially available antibody tests that are fully, reliably quantitative; even if we could quantify antibody levels, different antibody tests report different ranges, and our understanding of what different levels mean is far from mature enough for clinical decisions. If experienced scientists and medical providers cannot make sense of this, certainly a business or school cannot take this on.

Finally, all immunity wanes — especially antibody immunity, which is the first-line attack against the virus and critically important for early responses to the virus, preventing infection that can impact others around you, reducing the time that someone is shedding virus and contagious, and reducing the risk of a more prolonged infection. Waning natural immunity, and associated increase in breakthrough infections, has been recently reported. Everyone who has received a vaccine will ultimately need a booster, and for the same reasons everyone who has developed natural immunity will ultimately need a booster.

Without a booster, people remain at risk of being a COVID-19 conduit — even if they do not develop severe disease, they can still acquire the disease and unknowingly spread it to others, some of whom may develop severe disease because they are immunocompromised, have underlying medical conditions or just get unlucky.  Of course, a breakthrough COVID-19 infection can function as a “booster,” but this is a very risky way to rekindle the immune system, both for the person who gets the infection as well as everyone around them.

So, why does it seem that scientists are ignoring natural immunity in the national discussion of vaccine mandates and vaccine passports? Anyone with prior COVID-19 will still benefit personally from vaccination, given the wide variation of natural immunity and the substantial improvement in all aspects of immunity associated with vaccination after infection.

More importantly, vaccine mandates and vaccine passports are about population health, about everyone around us, about determining if it is safe to be around someone. Since many who had prior COVID-19 will not mount a strong natural immune response, since natural immunity will ultimately wane — and given the challenges in testing for immunity — it is not possible to determine if it is safe to be around someone with natural immunity. As such, regardless of how powerful natural immunity might or might not be, vaccination is the only reliable indicator that a person has reduced risks of spreading or suffering from COVID-19.

Dorry Segev, MD, Ph.D., is a professor of surgery at Johns Hopkins University School of Medicine and Professor of Epidemiology at Johns Hopkins Bloomberg School of Public Health. Segev has been leading an observational study of COVID-19 vaccine responses in immunosuppressed people since December 2020 and is the principal investigator of the NIH/NIAID-funded interventional trial “COVID-19 Protection After Transplantation (CPAT).” Follow him on Twitter: @dorry_segev