Prior infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was associated with high rates of durable protection from subsequent coronavirus infection in a prospective cohort of more than 35,000 asymptomatic health care workers in the U.K., who took part in the SARS-CoV-2 Immunity and Reinfection Evaluation (SIREN) study-the world's largest study of COVID-19 antibodies-reported in the New England Journal of Medicine (2022; https://www.nejm.org/doi/full/10.1056/NEJMoa2118691).
Around a quarter of the cohort had a previous SARS-CoV-2 infection. The onset of waning natural immunity from around a year after prior infection in unvaccinated individuals was found to be halted by subsequent vaccination-showing that vaccination had been valuable-even in people with natural immunity from prior infection.
Study participants who had not previously been infected with SARS-CoV-2 were found to derive similarly good protection purely from vaccination (delivered in two separated doses). For them, risk-reduction was as good as with immunity derived from natural infection. But the risk benefit from vaccination had halved around 6 months after the second of two vaccinations. The study found, however, that third "booster" vaccinations could maintain high immunity beyond this period.
"This research demonstrates why it is crucial to get vaccinated, as it provides a significantly greater level of protection against infection from COVID-19, whether or not you have been previously infected," said Susan Hopkins, FRCP, SIREN's leader and Chief Medical Advisor at the UK Health Security Agency.
Study Details
The SIREN group investigated the duration and effectiveness of immunity in a prospective cohort of asymptomatic health care workers in the U.K. who had routine PCR testing and were enrolled between June 18, 2020, and April 23, 2021, from 135 sites across the U.K. A total of 35,768 met the inclusion criteria. Most participants were women (84%) and the median age was 46 years.
Vaccine effectiveness up to 10 months after the first dose of vaccine and infection-acquired immunity were assessed by comparing the time to PCR-confirmed infection in vaccinated individuals with the unvaccinated. The study analyzed the effect of previous SARS-CoV-2 infection status, vaccine type, and dosing interval.
By the end of the analysis, 94.9 percent of the participants had received two doses of vaccine, 78.5 percent received the BNT162b2 vaccine (Pfizer BioNTech) with a long interval between doses, 8.6 percent received the BNT162b2 vaccine with a short interval between doses, and 7.8 percent had the ChAdOx1 nCoV-19 vaccine (AstraZeneca).
The primary outcome was a PCR-confirmed SARS-CoV-2 infection, irrespective of the participant's symptom status. This was either a primary infection in the previously uninfected cohort or a reinfection in the previously infected cohort.
Main Findings
Of 35,768 participants, 9,488 had a previous SARS-CoV-2 infection. More than three-quarters of the cohort had the BNT162b2 vaccine with a long interval between doses (more than 6 weeks). Most of the others had the same Pfizer vaccine with a short dose interval (fewer than 6 weeks), received the ChAdOx1 nCoV-19 vaccine, or were unvaccinated. There was a total of 2,747 primary infections and 210 reinfections between December 7, 2020, and September 21, 2021.
Two doses of BNT162b2 vaccine were found to be associated with high short-term protection against SARS-CoV-2 infection that waned "considerably" after around 6 months. At a median of 201 days after the second dose of the Pfizer vaccine (given with a long-dose interval), the study found the "adjusted" vaccine effectiveness had waned to 51 percent.
A year after infection, natural immunity waned to 69 percent in participants who continued to be unvaccinated, but was maintained above 90 percent in those who were subsequently vaccinated-even in those infected more than 18 months previously. No waning of protection was observed more than 1 year after infection or more than 6 months after vaccination following the infection.
Looking specifically at vaccination with the Pfizer product (which outperformed the AstraZeneca vaccine in the SIREN study), Hopkins said that immunity had been unaffected by the interval of time between first and second doses. In study subjects who had their second doses 6 weeks or more after the first ones, protection from coronavirus infection had been 85 percent up to 73 days after the second dose and had fallen to 51 percent at 6 months. When the dosing interval had been 6 weeks or less, the protection was of the same order: 89 percent out to 73 days after the second injection, falling to 53 percent after 6 months.
"To avoid infection and illness, it is vital that everyone eligible takes up the offer of a booster [vaccine] as soon as it is offered," Hopkins said.
Although the study had contributed granular data on immunity, some of the remaining difficulties of drawing clear conclusions were highlighted in a comment by the authors that the period of waning immunity had coincided with the period when the delta variant had become the predominant circulating strain. This may have resulted in more pronounced waning of protection, researchers noted. Also, the SIREN study had not been able to shed light on the effectiveness of vaccination or previous infection against severe outcomes. This was because the relatively young, fit cohort encountered few cases of severe disease.
The investigators concluded that vaccinations were highly protective both in people who had already been infected with SARS-CoV-2 and those with no prior infection. "Two doses of BNT162b2 vaccine were associated with high short-term protection against SARS-CoV-2 infection; this protection waned considerably after 6 months. Infection-acquired immunity boosted with vaccination remained high more than 1 year after infection," they wrote.
"The highest and most durable protection was observed in participants who received one or two doses of vaccine after a primary infection. Strategic use of booster doses of vaccine to avert waning of protection (particularly in double-vaccinated, previously uninfected persons) may reduce infection and transmission in the ongoing response to COVID-19."
Peter M. Goodwin is a contributing writer.