An observational study from Israel confirmed that BNT162b2, an mRNA Covid-19 vaccine, is highly effective in preventing symptomatic disease, severe disease, hospitalization, and death related to SARS-CoV-2 infection — and estimated benefits increased over time, researchers reported.
BNT162b2 — manufactured by Pfizer, Inc. and BioNTech — was authorized for emergency use in the U.S. in December 2020, along with another mRNA vaccine, Moderna’s mRNA-1273. The Israeli government also approved BNT162b2 in December, and the vaccine became a major component of the nation’s mass vaccination campaign. For their analysis, Noa Dagan, MD, of Clalit Health Services in Tel Aviv, Israel, and colleagues assessed data on newly vaccinated individuals from Dec. 20, 2020 through Feb. 1, 2021 to evaluate the vaccine’s effectiveness over time for five key outcomes: documented SARS-CoV-2 infection, symptomatic Covid-19, hospitalization, severe illness, and death.
“This study estimates a high effectiveness of the BNT162b2 vaccine for preventing symptomatic Covid-19 in a non-controlled setting, similar to the vaccine efficacy reported in the randomized trial [by Polack et al],” Dagan and colleagues reported in The New England Journal of Medicine — the study by Polack et al was also published in the New England Journal of Medicine, on Dec. 31, 2020. “Our study also suggests that effectiveness is high for the more serious outcomes: hospitalization, severe illness, and death. Furthermore, the estimated benefit increases in magnitude as time passes. These results strengthen the expectation that newly approved vaccines can help to mitigate the profound global effects of the Covid-19 pandemic.”
These results are consistent with a report from Leshem et al, also conducted in Israel, which found that vaccination with BNT162b2 led to substantial early reductions in SARS-CoV-2 infections and symptomatic Covid cases after the first vaccine dose among a cohort of over 9,000 healthcare workers — Leshem and colleagues published their findings in a Lancet Correspondence earlier this month, as previously reported by BreakingMED.
For this analysis, Dagan and colleagues pulled data from Clalit Health Services, the largest integrated health care organization in Israel, which insures more than half of the nation’s population. Patients were eligible for inclusion if they were 16 years of age or older, did not have a previously documented positive SARS-CoV-2 polymerase-chain-reaction test, and were a member of Clalit Health Services during the previous 12 months. Those excluded were persons who did not have a documented geostatistical living area, those who had interactions with the health care system during the preceding three days that may indicate the start of symptomatic disease and may preclude vaccination, nursing home residents, persons medically confined to the home, and health care workers.
Newly vaccinated patients were matched to unvaccinated controls in a 1:1 ratio according to demographic and clinical characteristics, with the final study cohort consisting of 596,618 participants in each group for a total of 1,193,236.
The study outcomes included documented infection with SARS-CoV-2, symptomatic Covid-19, Covid-19-related hospitalization, severe illness, and death — vaccine effectiveness for each outcome was estimated as one minus the risk ratio, using the Kaplan-Meier estimator, the study authors explained.
“Estimated vaccine effectiveness for the study outcomes at days 14 through 20 after the first dose and at 7 or more days after the second dose was as follows: for documented infection, 46% (95% confidence interval [CI], 40 to 51) and 92% (95% CI, 88 to 95); for symptomatic Covid-19, 57% (95% CI, 50 to 63) and 94% (95% CI, 87-98); for hospitalization, 74% (95% CI, 56-86) and 87% (95% CI, 55-100); and for severe disease, 62% (95% CI, 39-80) and 92% (95% CI, 75-100), respectively,” Dagan and colleagues reported. “Estimated effectiveness in preventing death from Covid-19 was 72% (95% CI, 19-100) for days 14 through 20 after the first dose. Estimated effectiveness in specific subpopulations assessed for documented infection and symptomatic Covid-19 was consistent across age groups, with potentially slightly lower effectiveness in persons with multiple coexisting conditions.”
The study authors added that the large sample size for their study allowed them to estimate vaccine efficacy in specific subpopulations that the randomized trial by Polack et al was unable to assess.
“In the trial, the estimated efficacy for Covid-19 among persons up to 55 years of age, older than 55 years, and 65 years or older 7 days after the second dose was 94 to 96%,” they wrote. “We were able to study more granular age groups, and we estimated that the vaccine effectiveness was similar for adults 70 years of age or older and for younger age groups for the same time period.”
Dagan and colleagues also noted that the B.1.1.7 Covid-19 variant from the U.K. was particularly active in Israel at the time of data extraction and, while their study cannot provide a specific effectiveness estimate for that strain, “the plateau observed during the later periods in the cumulative incidence curve for vaccinated persons suggests that the BNT162b2 vaccine is also effective for this variant, an observation consistent with previous reports that showed preserved neutralizing antibody titers.” The B.1.351 variant from South Africa was rare in Israel during the study period, they added.
The study authors pointed to the potential of residual confounding — resulting from differences between vaccinated individuals and unvaccinated controls, “especially in terms of health-seeking behavior” — as a limitation of their study. Other limitations included the exclusion of groups with high internal variability in the probability of vaccination or disease outcome, possible selection bias stemming from informative censoring, and a lack of data regarding date of symptom onset among patients with Covid-19.
- Results from an observational trial in Israel found that the mRNA-based BNT162b2 Covid-19 vaccine was highly effective in reducing symptomatic SARS-CoV-2 infections, cases of severe disease, hospitalizations, and deaths.
- These findings are consistent with past literature and confirm the efficacy of BNT162b2 in combating the Covid-19 pandemic.
John McKenna, Associate Editor, BreakingMED™
Dagan reports grants from Pfizer outside the submitted work.
Cat ID: 190
Topic ID: 79,190,730,933,190,926,192,927,925,934
