Journal name: The New England Journal of Medicine

Publishing date: May 25, 2022

Author: Yair Goldberg, PhD et.al

Protection against SARS-CoV-2 decreased as the time increased since the last immunity-conferring event (infection or vaccination). Protection was found to be higher after infection than after vaccination. A single dose of vaccine after infection reinforced protection against reinfection.

Why does this study matter?

Although a decline in protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection after two doses of BNT162b2 vaccine (Pfizer–BioNTech) has been observed in several studies, the level of protection remains unclear, as does the presence or extent of the waning of natural immunity. Several studies have shown that 6 or more months after infection, persons still have substantial natural immunity against SARS-CoV-2.  However, one recent study showed that messenger RNA (mRNA)–based vaccines confer a level of protection against hospitalisation that is five times as high as that provided by the previous infection.

Study Design

Data was extracted using the Israeli Ministry of Health database, for August and September 2021, when the B.1.617.2 (delta) variant was predominant, on all persons who had been previously infected with SARS-CoV-2 or who had received coronavirus 2019 vaccine. Using Poisson regression with adjustment for confounding factors they compared the rates of infection as a function of time since the last immunity-conferring event. They estimated the incidence of confirmed SARS-CoV-2 infection in the following cohorts: previously infected, unvaccinated persons; previously infected persons who had also received the BNT162b2 vaccine; and vaccinated persons who had not been previously infected. For each cohort, they quantified the association between the time that had passed since infection or vaccination and the rate of confirmed infection. By comparing the rates of infection among these groups, they were able to assess the level of protection afforded by hybrid immunity as compared with that afforded by natural immunity or immunity conferred by vaccination.

The number of cases of SARS-CoV-2 infection per 100,000 person-days at risk (adjusted rate) increased with the time that had elapsed since vaccination with BNT162b2 or since the previous infection. Among unvaccinated persons who had recovered from the infection, this rate increased from 10.5 among those who had been infected 4 to less than 6 months previously to 30.2 among those who had been infected 1 year or more previously.

Among persons who had received a single dose of vaccine after a previous infection, the adjusted rate was low (3.7) among those who had been vaccinated less than 2 months previously but increased to 11.6 among those who had been vaccinated at least 6 months previously. Among previously uninfected persons who had received two doses of vaccine, the adjusted rate increased from 21.1 among those who had been vaccinated less than 2 months previously to 88.9 among those who had been vaccinated at least 6 months previously.

Results and Conclusion

Among persons who had been previously infected with SARS-CoV-2 (regardless of whether they had received any dose of vaccine or whether they had received one dose before or after infection), protection against reinfection decreased as the time increased since the last immunity-conferring event; however, this protection was higher than that conferred after the same time had elapsed since receipt of the second dose of the vaccine among previously uninfected persons. A single dose of vaccine after infection reinforced protection against reinfection.

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