The CDC is finally recognizing ‘natural immunity’ — legislators should follow suit

There are now more than 65 million people who have recovered from COVID-19 in the United States. While vaccination for COVID-19 has been critically important to protect us against severe disease, hospitalizations and death, the U.S. Centers for Disease Control and Prevention (CDC) are finally acknowledging the strong protection provided from immunity after a SARS-CoV-2 infection: so-called “natural immunity.”  

In the CDC report, which analyzed COVID-19 cases in California and New York in 2021 from May 30 to November 20, the scientists compared the risk of new SARS-CoV-2 infection among four groups of people: those who were unvaccinated without a prior case of COVID-19; those vaccinated without prior COVID-19; those unvaccinated with prior COVID-19 and those vaccinated with prior COVID-19.   

The authors explain that before the emergence of the delta variant of SARS-CoV-2, recent vaccination was more protective against new infection than natural immunity (in California during June, for example, 20.9-fold vs 8.2-fold). However, after delta became prevalent, natural immunity was more protective against infection than vaccination (in California during September, 8.3-fold vs 35.0-fold).  

During the delta wave of COVID-19, the incidence of SARS-CoV-2 infection among those with “enhanced” immunity due to both vaccination and prior infection, was 32.5-fold lower in California and 19.8-fold lower in New York, whereas rates among those vaccinated alone (without prior COVID-19) were only 6.2-fold lower in California and 4.5-fold lower in New York. The rates among those with natural immunity were 29.0-fold lower in California and 14.7-fold lower in New York. The authors note that hospitalization rates followed a similar pattern.  

The report finally acknowledges what many have suspected for a long time — that surviving COVID-19 provides excellent natural immunity not only repeat infection but also to hospitalization and death for the delta variant of COVID-19.  

The pattern of improved protection after natural infection makes sense. It always has. That’s how immunity against infections works. That is why vaccines work. The COVID-19 vaccines were developed to mimic a natural infection based on the original virus that was identified in 2019, what biologists call the “wildtype” strain of SARS-CoV-2. The vaccines, especially the commonest mRNA-based ones, use the spike protein of SARS-CoV-2, the protein that acts as a key to enter cells and cause infection. By blocking that entry with vaccine-induced antibodies, infection is prevented.   

In contrast, during a natural infection, the human body is exposed to all parts of the virus, including the spike protein. When the immune system responds to enable recovery from the infection, it is broader and more diverse, with a greater ability to defend against any future SARS-CoV-2 virus variants. Therefore, while mutations naturally form in the SARS-CoV-2 spike protein through the process of viral evolution, the targeted vaccine-based approach to attack the spike protein, while still effective, is not as robust as the armamentarium created from surviving a true infection, and most effective in combination with vaccination.  

What is clear from the new CDC report over all periods is this — the worst group to be in is the nonvaccinated group without prior COVID-19. That group is the most likely to be infected, and if also at risk for severe disease — older 65 years of age, obese, chronically ill or immunocompromised — the most likely to die from an infection. Therefore, if you are in this group, please get vaccinated!  

Vaccination is superior to natural infection because the risks of death or severe long-term symptoms are astronomically lower. One limitation of the CDC study was that we must await new data and research to see if there are differences in immunity due to vaccination or prior infections during this current period of the highly infectious omicron variant of SARS-CoV-2. We have observed that those vaccinated, while not protected from infection, are much less likely to be hospitalized. Similarly, those who had a previous infection and remain unvaccinated are also highly protected against serious omicron disease.  

Given now that CDC recognizes the protective effect of prior infection, it is time to update vaccination policies and school or work-entry requirements across federal and state or county governments. Those with natural immunity should have equal status as those vaccinated. Demonstrating a prior infection is no more difficult than demonstrating vaccination. Many European countries recognize that immunity due to prior infection is equal to vaccination.  

Not exempting those with prior infection was always unfair; now it is unscientific as well. 

Jeffrey Klausner, MD, MPH, is a clinical professor of Medicine, Population and Public Health Sciences at the Keck School of Medicine of the University of Southern California. Twitter: @DrKlausner. Noah Kojima is a senior resident in internal medicine at UCLA Health.