The Clalit Research Institute, in collaboration with researchers from Harvard University, analyzed one of the world's largest integrated health record databases to examine the effectiveness of the Pfizer vaccine against COVID-19. The study provides the first large-scale peer-reviewed evaluation of the effectiveness of a COVID-19 vaccine in a nationwide mass-vaccination setting. The study was conducted in Israel, which currently leads the world in COVID-19 vaccination rates.

The results of this study validate and complement the previously reported findings of the Pfizer/BioNTech Phase-III randomized clinical trial, which focused on symptomatic infections, and which, with 21,720 vaccinated individuals, could not precisely assess vaccine effectiveness against severe disease in the fully vaccinated. The present study's large size allows a more detailed assessment of the vaccine's effectiveness in preventing a wider range of outcomes, across different time periods and population sub-groups.

The study took place from December 20, 2020, the launch of Israel's national vaccination drive to Feb. 1, 2021. It coincided with Israel's third and largest wave of coronavirus infection and illness, during which the B.1.1.7 variant gradually became the dominant strain in the country for new infections.

Researchers reviewed data from 596,618 vaccinated individuals aged 16 and over (of whom approximately 170,000 were aged 60+). These individuals were carefully matched with 596,618 unvaccinated individuals based on an extensive set of demographic, geographic and health-related attributes associated with risk of infection, risk of severe disease, health status and health seeking behavior. Individuals were assigned to each group dynamically based on their changing vaccination status (approximately 85,000 individuals moved from the unvaccinated cohort into the vaccinated cohort during the study). Multiple sensitivity analyses were conducted to ensure that the estimated vaccine effectiveness was robust to potential biases.

The results show that in fully vaccinated individuals (7 or more days after the second dose), the risk of symptomatic COVID-19 decreased by 94% compared with the unvaccinated, while the risk of severe disease decreased by 92%. In the period immediately preceding the second dose (days 14-20 after the first dose), vaccine effectiveness was lower, but still substantial -- the risk of symptomatic COVID-19 decreased by 57% in vaccinated individuals, and the risk of severe disease by 62%. While there was insufficient data to provide an estimate on the reduction in mortality in those who received two doses, data from 21-27 days after the first dose points to a substantial reduction in mortality as well.

As an observational study conducted in a mass-vaccination setting, this study was not designed to systematically assess viral transmission or asymptomatic infections. With the careful matching procedures, multiple outcomes assessed and multiple sensitivity analyses performed, the large sample size in this study also allowed the estimation of vaccine effectiveness in a number of specific subpopulations. The vaccine effectiveness for preventing symptomatic COVID-19 proved consistent across age groups, including adults aged 70+. The study also evaluated subpopulations with different numbers of comorbidities and found indications that vaccine effectiveness for preventing symptomatic COVID-19 may be slightly lower for individuals with a higher number of comorbidities, although the difference was not statistically significant.

The research was conducted by Dr. Noa Dagan, Dr. Noam Barda, Dr. Eldad Kepten, Oren Miron, Shai Perchik, Dr. Mark Katz and Prof. Ran Balicer from the Clalit Research Institute, as well as Prof. Miguel Hernán and Prof. Marc Lipsitch of the Harvard T.H. Chan School of Public Health, and Prof. Ben Reis of Boston Children's Hospital and Harvard Medical School.

Source: Clalit Research Institute