Israel Data Show Real-World Efficacy with Pfizer COVID-19 Vaccine

Real-world observation of mass coronavirus 2019 (COVID-19) vaccination in Israel shows Pfizer-BioNTech vaccine BNT162b2 is effective across a spectrum of preventive outcomes in the weeks after administration.

The data from investigators at Clalit Research Institute in Tel Aviv and the Ben Gurion University of the Negev in Be’er Sheva provide the most extensive nationwide outlook on a COVID-19 vaccine’s efficacy and safety to date, as Israel has paced well ahead all countries in national COVID-19 immunizations per capita.

Led by Noa Dagan, MD, and Noam Barda, MD, of Clalit, investigators sought to compare the outcome of real-world residents vaccinated with BNT162b2 in 1:1 control matches according to demographic and clinical characteristics. Their study outcomes included documented infection with SARS-CoV-2, symptomatic COVID-19, hospitalization related to COVID-19, severe illness, and death.

The vaccine’s effectiveness for each outcome was estimated in a risk ratio conducted via the Kaplan-Meier estimator. Observed individuals were vaccinated between December 20, 2020 and February 1, 2021.

Of the 1,163,534 vaccinated individuals eligible for the trial, 596,618 were matched to unvaccinated controls. Median patient age in both arms was 45 (IQR, 35-62), with patients predominately aged 16-39 years old (35.7%). Patients aged 60 years and older made up approximately 28% of the population.

Another 43.3% of participants had ≥1 risk factor for COVID-19 based on US Centers for Disease Control and Prevention (CDC) criteria. The most prominent risk factors included smoking (19.9% in the vaccination arm), obesity (16.9%), and type 2 diabetes mellitus (11.1%).

Investigators reported vaccine efficacy outcomes versus placebo at 3 different time points:

• 14-20 days after first dose
• 21-27 days after first dose
• 7 days after second dose to end of follow-up

At 14-20 days, documented SARS-CoV-2 infection risk reduction was 46% among vaccinated persons. At 21-27 days, risk reduction reached 60%. At 7 days after second dose and beyond, risk reduction was 92%.

Symptomatic COVID-19 illness risk reduction was 57%, 66%, and 94% at the observed time points. Hospitalization risk reduction was 74%, 78%, and 87%, respectively. Severe disease risk reduction was 62%, 80%, and 92%, respectively. Risk of death reduced 72% and 84% at the respective times after first dose, and was not calculable after 7 days post-second dose.

Overall, the assessment observed 229 total cases of severe COVID-19—55 in the vaccinated group, and 174 in the control group.

What’s more, the assessment came at a time when an increasing rate of SARS-CoV-2 isolates in Israel included the B.1.1.7 variant, a byproduct of virus mutation that has been associated with greater transmission risk. Up to 80% of all the nation’s virus isolates were identified as the concerning variant in the days prior to data extraction, investigators wrote.

Additionally, the B.1.351 variant has been estimated to be rare in Israel at the time of data extraction.

“Thus, this study estimates an average effectiveness of the vaccine over multiple strains,” investigators wrote. “Although we cannot provide a specific 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 BNT162b2 vaccine is also effective for this variant, an observation consistent with previous reports that showed preserved neutralizing antibody titers.”

Dagan and Barda wrote that, given the likely time gap between COVID-19 symptom onset and PCR test collection, the comparative divergence of incidence between vaccinated persons and control may be slightly delayed.

“In parallel, there might be an underestimation of the vaccine effectiveness at each time window, since the estimate actually reflects a narrower window for the vaccine to be active,” they explained. “Because SARS-CoV-2 PCR testing is highly accessible in Israel and can be done without referral in a matter of hours, we estimate this potential time gap and thus the vaccine effectiveness underestimation to be small.”

The team concluded that the new data show a high real-world effectiveness with BNT162b2 for preventing symptomatic COVID-19 in an uncontrolled setting—data similar to that observed in the controlled phase 3 trial. They also observed strong efficacy in the more severe outcome risks associated with the pandemic virus.

“Furthermore, the estimated benefit increases in magnitude as time passes,” investigators wrote. “These results strengthen the expectation that newly approved vaccines can help to mitigate the profound global effects of the COVID-19 pandemic.”