Natural Immunity vs. Super Immunity: Only a COVID-19 Vaccination Away

For many who are concerned about the dismal rate of full vaccinations in the United States, as compared to even some third-world countries, such as Cambodia, the new study from the Centers for Disease Control and Prevention (CDC) regarding vaccine efficacy was welcomed news. The study observed over five times the efficacy in the prevention of COVID-19 hospitalizations in those who were vaccinated as opposed to those who had a previous infection.

The CDC’s study had an unusual design. It evaluated patients being admitted to the hospital with COVID-19 like symptoms and then determined how many actually had COVID-19. The study also adjusted for sociodemographic and health characteristics. The study was able to identify 6382 individuals who were fully vaccinated with 2 doses of an mRNA vaccine and admitted with COVID-19 like illness, and another 1020 individuals who had a previous laboratory documented

Kevin Kavanagh, MD

COVID-19 infection and later admitted to the hospital with another infection with COVID-19 like symptoms. The number of individuals in our society who are vaccinated without a previous SARS-CoV-2 infection is far greater than the number of unvaccinated individuals who had a previous COVID-19 infection which had documentation of a previous SARS-CoV-2 molecular test. (Unlike other countries, the US does not have a unified national health care record system to allow easy availability of a patient’s medical history.)

The CDC’s study found that the unvaccinated, but previously infected group had 5.49 times more infections than the vaccinated group (adjusted odds ratio of 5.49). And comparable results were obtained pre and post Delta variant. Similar to the Mayo study, the Moderna vaccine was found to have a higher protection effect than the Pfizer/BioNTech vaccine (7.3 versus 5.11 adjusted odds ratio, p = 0.02). Also, individuals 65 years and older received more benefit from vaccination (19.57 versus 2.57 adjusted odds ratio, p = 0.05).

In addition, there is a large psychological overlay in reinfections versus vaccination breakthrough studies. Those vaccinated may lead a less cautious life, feeling that they are impervious to the virus; and those who have had a previous COVID-19 infection have often been through hell and may be more cautious, not wanting to be reinfected and wishing to safeguard their loved ones. Thus, the behavior may be much different between these 2 groups. In a pandemic, following public health advice matters and can lessen infections. Despite these concerns, the CDC study still observed less of a chance of becoming infected in those who were vaccinated versus those with “natural immunity.”

This finding is in stark contrast, to the Israeli study which reported that those vaccinated with the Pfizer/BioNTech were 13.06 times more likely to have an infection than those who were previously infected. It should be remembered tha the Pfizer/BioNTech vaccine’s protection wanes faster than Moderna’s and this efficacy is during a time period greater than 3 months to 5.5 months post vaccination. When the analysis included infections that occurred at any time after vaccination, there was a 5.96-fold increased risk of reinfection, a 7.13 increased risk of symptomatic infection and a 7 to 8 times increase risk of hospitalization. The study eliminated those patients who received a third dose of Pfizer/BioNtech booster. Importantly, the authors noted that the study suggested waning of natural immunity against the Delta variant and that “individuals who were both previously infected with SARS-CoV-2 and given a single dose of the vaccine gained additional protection against the Delta variant.”

Cavanaugh, et al. also reported that those who were unvaccinated and had a SARS-CoV-2 infection were 2.34 times less likely to have another infection if they became vaccinated. Another study by Assis, et al. documented the types of antibodies produced in SARS-CoV-1 infections. In that study, 3347 specimens were analyzed, and the authors concluded that the “anti-receptor binding domain (RBD) reactivity was low and there was no cross-reactivity against SARS S1 or SARS RBD.” RBD is the portion of the virus which needs to be deactivated in order to prevent replication and spread of the virus. The authors also concluded that once vaccinated, previously infected individuals develop higher antibody levels than those not previously infected and that mRNA vaccination induces a stronger and broader antibody response than SARS-CoV-2 infection.

All of the above has led up to the discovery of “super immunity.” Many now believe that super immunity can develop in those who have had SARS-CoV-2 infections and have become vaccinated. They develop a much more robust and diverse antibody response which should be “effective to any future variant that SARS-CoV-2 throws against them.”

Finally, after all of these mental gymnastics, one realizes that of course vaccines are better than being infected with SARS-CoV-2, besides virtually avoiding the risk of disability and death from the infection, you can also obtain boosters if your immunity wanes.

The CDC is currently considering changing the definition of fully vaccinated to 3 doses of the mRNA vaccine. Greater than 2 vaccine doses in a vaccination schedule is very common. Diphtheria, tetanus, polio, H. influenza, S. pneumoniae, pertussis and Hepatitis B all require 3 to 4 doses in the first year and a half of life. No one is advocating becoming reinfected with COVID-19 to maintain your immunity.

SARS-CoV-2 hits some very hard with a life-threatening disease which will augment their immunity. Other patients will have a less severe illness and will achieve a less durable immune response. Vaccines build up durable immunity more slowly with repeated vaccinations. This mitigates side effects and allows for the attainment of immunity with almost no risk as compared to natural infection.

The bottom line is that all need to be vaccinated, even those who have had previous infections. The definition of fully vaccinated for mRNA vaccines needs to be changed to 3 doses, making previous comparisons of infection versus 2 doses of a vaccine moot. In addition, those previously infected should also become vaccinated. How many doses and the exact vaccination schedule is still under investigation. But for now, those receiving 2 doses of an mRNA vaccine should obtain a booster and those with a previous infection should become “super-immune” with a vaccination.