A pair of studies yesterday in the New England Journal of Medicine (NEJM) suggest good, durable protection of COVID-19 vaccines against recurrent infection.
Fewer reinfections among older participants
Researchers from Clalit Health Services in Tel Aviv, Israel, retrospectively analyzed the electronic health records of 83,356 recipients of at least one dose of the Pfizer/BioNTech COVID-19 vaccine after recovery from infection and 65,676 unvaccinated survivors.
The observational study began on Mar 1, 2021, after the Israeli Ministry of Health approved COVID-19 vaccination for all patients who had recovered from COVID-19 3 or more months before. All participants had recovered from a primary SARS-CoV-2 infection from Aug 23, 2020 (190 days before the study period), to May 31, 2021 (90 days after study initiation). Average patient age was 39.3 years (range, 16 to 110).
COVID-19 reinfection occurred in 354 of 83,356 vaccinated participants (0.4%; 2.5 cases per 100,000 person-days) and in 2,168 of 65,676 of their unvaccinated peers (3.3%; 10.2 per 100,000).
In the 16- to 64-year age-group, 326 of 73,972 vaccinated participants (0.4%; 2.6 cases per 100,000 person-days) were reinfected, compared with 2,120 of 60,877 of their unvaccinated counterparts (3.5%; 10.8 per 100,000).
Among patients 65 years and older, reinfection occurred in 28 of 9,384 vaccinated (0.3%; 1.5 cases per 100,000 person-days) and 48 of 4,799 unvaccinated participants (1.0%; 3.0 per 100,000). The study authors said that the difference between the two age-groups may be explained by an assumption that older COVID-19 survivors would have taken more precautions against reinfection than younger people.
According to a Cox proportional-hazards regression model analysis, the adjusted hazard ratio (aHR) for reinfection in the vaccinated group, relative to the unvaccinated, among 16- to 64-year-olds was 0.18. Among those 65 and older, the aHR was 0.40. Estimated vaccine effectiveness in the younger age-group was 82%, compared with 60% in the older group.
A secondary analysis showed that the aHR for reinfection among the 67,560 participants who received one COVID-19 vaccine dose, compared with 15,251 who received two doses, was 0.98. "Given the previous exposure to the virus, it seems that the primary vaccine dose in recovered patients provided a more robust and longer immunogenic response than the first dose alone in patients without previous Covid-19," the researchers wrote.
The authors said that the study, which spanned the Delta variant surge in Israel, "supports a public health policy of vaccinating patients who have recovered from Covid-19, particularly in places where the delta variant is still of concern."
Sustained 90% protection when vaccine follows infection
A prospective study led by UK Health Security Agency researchers evaluated the effectiveness and duration of COVID-19 vaccination in a group of asymptomatic UK healthcare workers who underwent testing for infection every 2 weeks, as well as monthly antibody testing.
The team compared the time to SARS-CoV-2 infection among unvaccinated participants and those who received the Pfizer or AstraZeneca/Oxford COVID-19 vaccine up to 10 months before, stratified by whether they had been previously infected. Median age was 46 years, and 84% were women.
Among 35,768 participants, 27% had recovered from COVID-19, as evidenced by the presence of SARS-CoV-2 antibodies. Nearly all participants (97%) had received two vaccine doses; 78% of them had received the Pfizer vaccine with a long interval (6 weeks or more) between doses, while 9% received the same vaccine with a short interval (less than 6 weeks) between doses, and 8% had received the AstraZeneca vaccine.
From Dec 7, 2020, to Sep 21, 2021, there were 2,747 primary SARS-CoV-2 infections and 210 reinfections. Among COVID-19–naïve participants in the long-interval Pfizer group, adjusted vaccine effectiveness fell from 85% 14 to 73 days after the second dose to 51% at a median of 201 days. Effectiveness was not significantly different between the long- and short-interval groups.
Among AstraZeneca vaccine recipients, adjusted vaccine effectiveness was 58% after the second dose, much lower than among Pfizer vaccinees.
Unvaccinated participants saw waning of infection-acquired immunity after 1 year, although efficacy stayed higher than 90% in those who were vaccinated after infection, even in those infected more than 18 months before.
Overall, 357 participants (13%) with primary infection reported a hospital visit for COVID-19, compared with 18 (9%) of those with reinfection.
"Two doses of BNT162b2 vaccine were associated with high short-term protection against SARS-CoV-2 infection; this protection waned considerably after 6 months," amid the UK Delta surge, the authors said. "Infection-acquired immunity boosted with vaccination remained high more than 1 year after infection."
They conclude, "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."
Sequence of infection, vaccination may matter
In an audio interview in the same issue on both studies, as well as another on the antiviral combination nirmatrelvir-ritonavir in COVID-19 patients, Eric Rubin, MD, PhD, NEJM editor-in-chief, and Deputy Editor Lindsey Baden, MD, said that immune response can vary depending on which SARS-CoV-2 strain caused natural infection and whether natural infection or vaccination occurred first.
"The sequence of these events—vaccination followed by natural infection or natural infection followed by vaccination—may have very different consequences and implications for the immune increasing and then the subsequent immune boosting," Rubin said.
He said that COVID-19 survivors can still benefit from subsequent vaccination, although the ideal time to vaccinate is yet unknown: "There is an advantage, and although the absolute risk difference may be small, it's real. Also, there doesn't appear to be a safety issue with getting boosted."
