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Pfizer/BioNTech's COVID-19 vaccine appeared to prevent not only symptomatic disease, but asymptomatic infection as well, a real-world review of Israeli health records showed.

A large case-control study comprising over one million people found that the estimated vaccine effectiveness for "documented infection" was 46% (95% CI 40-51%) at days 14-20 following one dose of vaccine, and was 92% (95% CI 88-95%) at least 7 days following the second dose, reported Ran Balicer, MD, PhD, of Clalit Health Services in Tel Aviv, and colleagues.

Using a proxy for asymptomatic infection, they estimated 29% vaccine efficacy (95% CI 17-39%) at days 14-20 following the first dose and 90% (95% CI 83-94%) at 7 or more days after the second dose, as noted in the

Study authors defined asymptomatic infection as "a PCR-confirmed infection with no report of symptoms during referral and initial physician questioning." They included these data in a supplemental appendix, with a caveat: "In the absence of systematic periodic testing of SARS-CoV-2 among asymptomatic people in Israel, documented asymptomatic infections do not account for all asymptomatic infections, and likely cannot capture vaccine effectiveness for this outcome," Balicer and colleagues wrote.

The Pfizer vaccine is authorized in the U.S. to prevent symptomatic COVID-19 illness, which was the primary endpoint in the product's phase III trial. Prevention of overall coronavirus infection was not addressed directly in the trial, though Pfizer promised to examine it later through antibody testing.

Balicer's group also sought to address the vaccine's efficacy against the B.1.1.7 "U.K." coronavirus variant, which they said accounted for up to 80% of SARS-CoV-2 isolates in Israel in the days before data extraction. "Although we cannot provide an effectiveness estimate for the B.1.1.7 variant, the plateau observed during the later periods in the cumulative incidence curve for vaccinated persons suggests that the [Pfizer] vaccine is effective for this variant."

Balicer and colleagues examined data from Clalit Health Services, which ensures almost 5 million patients, about half of Israel's population. They attempted to include a population similar to the Pfizer trial: individuals ages 16 and older with no prior positive RT-PCR test for SARS-CoV-2. They excluded healthcare workers, nursing home residents, those medically confined to the home, and those who accessed the healthcare system in the prior 3 days, which may have indicated the start of symptomatic disease.

From December 20, 2020 to February 1, 2021, all newly vaccinated individuals were matched with unvaccinated controls based on variables associated with probability of vaccination or severity of COVID-19.

Overall, 596,618 individuals were matched to unvaccinated controls, who tended to be younger and have fewer chronic conditions. Participants' median age was 45, with an even split between men and women. About 57% had no risk factors according to CDC criteria. About a third were overweight, 17% had hypertension, and 5% had asthma.

Estimated vaccine effectiveness at least 7 days after the second dose was 94% for symptomatic COVID-19 illness, 87% for hospitalization, and 92% for severe COVID-19. For COVID-19-related death, estimated vaccine effectiveness was 72% at 14 to 20 days after the first dose.

Researchers said their large sample size allowed them to estimate vaccine effectiveness in subpopulations that the randomized trial "was not sufficiently powered to evaluate." Across age groups, they found that the estimated efficacy of the COVID-19 vaccine was 94%-96% 7 days or more after the second dose, with similar effectiveness for adults ages 70 and older and younger age groups during the same time period. They also found that vaccine effectiveness may be "slightly lower" among individuals with multiple comorbidities.

They noted limitations to their study, such as excluding healthcare workers and nursing home residents; Pfizer's trial did not exclude healthcare workers. In addition, the date of onset of symptoms was not available, so the date of swab collection was used, though they noted this may be an underestimate of the vaccine effectiveness, since this estimate "reflects a narrower window for the vaccine to be active."

Balicer and colleagues also said the South African virus variant, B.1.351, was rare in Israel during the study period; hence, they were unable to assess vaccine efficacy against it.

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