Infection + vaccination = The best protection against COVID-19?

Individuals with a prior COVID-19 infection and who are fully vaccinated against COVID-19 appear to have the greatest immunity to the virus, according to the SIREN* study.

“Vaccination after previous infection appeared to boost and extend immunity, and we found no indication of waning of this immunity even more than 1 year after primary infection,” the authors commented.

The ongoing, multicentre, prospective study involved 35,768 asymptomatic healthcare workers (median age 46 years, 84 percent female) in the UK who underwent routine PCR testing** every 2 weeks. Of these, 27 percent had a previous SARS-CoV-2 infection. Ninety-five percent of participants had received two doses of the COVID-19 vaccine (ChAdOx1 nCoV-19 or BNT162b2 vaccine). About 79 and 9 percent received the BNT162b2 vaccine with a long and short interval between doses, respectively (≥6 or <6 months since previous dose, respectively), while 7.8 percent received the ChAdOx1 nCoV-19 vaccine.

A total of 2,747 primary infections and 210 reinfections were recorded in this cohort between December 7, 2020 and September 21, 2021.

At 14 days before or after the date of the positive PCR test, 61 percent of patients with primary infections reported COVID-19–related symptoms compared with 34 percent of those with reinfections. Thirteen percent of patients with primary infections required a hospital visit due to COVID-19–related symptoms compared with 9 percent of those with reinfections.

Among previously uninfected participants, adjusted vaccine effectiveness among those who received the BNT162b2 vaccine with a long interval between the two doses reduced from 85 percent at 14–73 days after the second vaccine dose, to 68 percent 134–193 days after the second dose, to 51 percent at a median 201 days after the second dose. [N Engl J Med 2022;386:1207-1220]

Similarly, adjusted vaccine effectiveness was 89 and 53 percent at 14–73 days and a median 238 days after the second vaccine dose among those who received the BNT162b2 vaccine with a short interval between doses.

“We found no significant difference between the BNT162b2 vaccine participants who had a long interval and those who had a short interval between doses with respect to protection after the second dose [hazard ratio, 1.34 at 14–73 days vs the short interval group],” the authors noted.

Adjusted vaccine effectiveness was 58 percent 14–73 days after the second dose of the ChAdOx1 nCoV-19 vaccine.

“At 14–73 days after the second dose, the BNT162b2 vaccine with a short interval between doses was 74 percent more effective and the BNT162b2 vaccine with a long interval between doses was 65 percent more effective than the ChAdOx1 nCoV-19 vaccine,” said the authors.

In the subgroup of participants with previous SARS-CoV-2 infection (n=6,169), the risk of reinfection was 86 percent lower than the risk of primary infection among unvaccinated participants without a previous infection. Protection reduced to 69 percent >1-year post-infection, with protection 54 percent higher during the first year post-infection compared with >1 year post-infection.

Infection-acquired immunity reduced after 1 year in unvaccinated participants (69 percent) but was consistently higher than 90 percent in vaccinated participants (94 and 95 percent at 14–73 and 194–262 days after the second dose, respectively).   

 

The impact of waning protection

“[A] reduction in vaccine effectiveness against infection will increase transmission to and the risk of infection among high-risk persons, some of whom may have progression to severe disease,” the authors cautioned.

“[In this study,] the period of waning of protection coincided with the period when the Delta variant was the predominant circulating strain,” they said, noting that previous reports have hinted at decreased vaccine effectiveness with the Delta strain.

“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,” they continued.

 

More research needed

Seeing as how the participants were relatively young and healthy and the incidence of severe outcomes low, the SIREN findings cannot be used to assess the impact of protection of vaccination and infection on severe outcomes, the authors said. The length of immune protection following infection is also unknown due to the short follow-up period, as is the reduction in vaccine effectiveness in ChAdOx1 nCoV-19 vaccine recipients and BNT162b2 vaccine recipients with a short between-dose interval.

The findings may also not necessarily translate to the wider population as “it is possible that the sustained infection-acquired protection in our cohort was affected by repeated low-dose occupational exposure to COVID-19,” they suggested.

“It is also possible that sustained protection results from a broader diversity of T-cell immunity against different SARS-CoV-2 spike protein epitopes that emerges after infection, enhancing protection against variants and inducing long-lasting memory T-cell populations,” they added.