As the Delta variant ravages the Southeast and threatens similarly dire outcomes in broad swaths of the country, businesses, government bodies, health groups, and schools have begun mandating employees prove they are vaccinated against COVID-19. Workplace vaccination mandates are a legal, ethical and necessary means to increase population-level immunity and protection against infection.
But such mandates beg the question: What about people who already had the coronavirus? Before vaccines for COVID-19 were available, many scientists suspected that prior infection protected against re-infection, as shown in experiments in animals or from studies of human outbreaks.
More recently, a not-yet-peer-reviewed study conducted this year among 52,238 employees of the Cleveland Clinic Health System in Ohio found that of 1,359 unvaccinated people, zero previously-infected employees developed COVID-19. Meanwhile, among those unvaccinated without prior SARS-CoV-2 infection, there was a steady rate of new infection.
ADVERTISEMENT
Another not-yet-peer-reviewed study that followed employees in a clinical SARS-CoV-2 testing laboratory who were screened daily for infection also found that the rates of new infection were equally low among those with prior infection and those who were vaccinated.
There is growing evidence, in other words, that past COVID-19 infection is equally as protective as vaccination.
This matters as the unvaccinated—and the country paying a price for their resistance—may have a safe way ahead if such people can prove that they have had prior infection. Recognizing that some Americans, even without shots, may have equal immunity due to past infection as those vaccinated would help us feel more confident that we are moving faster on the road towards herd immunity—the sought-after-state where infections are uncommon and the non-immune population is protected from infection or disease.
Much like vaccines, natural infection stimulates potent antibody and T cell immune response. Concentrations of anti-spike IgG antibodies peak and decline similarly among people with prior SARS-CoV-2 infection and people who have been vaccinated. Interestingly, people with prior SARS-CoV-2 infection who had symptoms tend to have stronger antibody response than people who were asymptomatic.
In a large study in the United Kingdom, where over 30,000 participants were tested for the presence of antibodies due to natural infection, those with antibodies had an 84 percent lower risk of a new repeat infection compared to those without antibodies. Among the few who were infected, the rates of serious disease, hospitalization, and death were very low.
That frequency of protection against infection, 84 percent, is identical to very recent (not yet peer-reviewed) findings that protection with the Moderna vaccine against Delta variant infection is also 84 percent.
The reason natural infection and vaccination may produce similar levels of infection could involve similar immunity due to the concentration of antibodies that are produced. A study conducted in Italy found no significant difference in the concentration of circulating anti-spike IgG antibodies when comparing the serum antibody response between people with prior SARS-CoV-2 infection and those who had taken a SARS-CoV-2 vaccine.
Current recommendations in the United States suggest that people with prior infection should get vaccinated. After all, the risk of safe and effective vaccines backfiring on such individuals is virtually zero. The vaccines are very safe.
As for whether vaccines make previously infected people all the safer, the evidence is still coming in.
While a recent CDC study in Kentucky suggested that there might be additional benefit from vaccination in those with prior infection, that study had several limitations. The study was small, and might have been biased by the selection of the control or comparison group that took extra efforts to protect themselves.
The question then arises: Should people who have recovered from COVID-19 be required to be vaccinated in the New Normal? If the patient requests, should doctors offer them a medical exemption?
If some previously sick people are to be exempt from vaccination requirements, one measure to determine whether prior infection still produces adequate protection over time is the amount of antibody in that individual. As of early July, there was an FDA-authorized antibody test that provides a reliable measure of antibody quantity.
Because what exact quantity of antibody confers protection is not yet exactly known, the FDA does not recommend using such tests to predict protection. Physicians may, however, use the results to confirm prior infection. And if we accept the fact that prior infection protects against re-infection in similar potency and durability as vaccination, that might suffice for a physician to counsel a patient that their risk for reinfection is low.
The European Union and Israel include evidence of prior infection in their “Green Pass,” the certificate that enables people to travel and access events. With that certificate, documentation of a prior infection is considered equal to vaccination, allowing travel or entry into various venues including restaurants. The WHO also describes natural immunity as protective for at least 6 to 8 months after infection in their Scientific Brief on COVID-19 on Natural Immunity.
Physicians can continue to recommend vaccination for those with prior infection willing to be vaccinated. There is unlikely to be any substantial harm. However, in those unwilling or unable—in the United States, this is a large share of the population, however much it might annoy us—there should be an option for medical exemption.
In the current epidemic of the Delta variant, some might be concerned that prior infection with other variants might not confer similar protection. The evidence is mixed, but newer studies suggest the previous infection indeed protects against infection and severe disease with the Delta variant. The absence of public-health reports describing increases in new cases currently among those with prior infection further supports that conclusion.
It is time for the U.S. to get up to speed and align its guidance with other expert groups on the protective effect of prior infection. One way to do that is to acknowledge that natural immunity exists, and is protective. Accepting medical exemptions for mandated vaccination based on the evidence of prior infection would be a logical step in that direction.
