BACKGROUND: Methodologically rigorous studies on Covid-19 vaccine effectiveness (VE) in preventing SARS-CoV-2 infection are critically needed to inform national and global policy on Covid-19 vaccine use. In Israel, healthcare personnel (HCP) were initially prioritized for Covid-19 vaccination, creating an ideal setting to evaluate early real-world VE in a closely monitored population.

METHODS: We conducted a prospective study among HCP in 6 hospitals to estimate the effectiveness of the BNT162b2 mRNA Covid-19 vaccine in preventing SARS-CoV-2 infection. Participants filled out weekly symptom questionnaires, provided weekly nasal specimens, and three serology samples - at enrollment, 30 days and 90 days. We estimated VE against PCR-confirmed SARS-CoV-2 infection using the Cox Proportional Hazards model and against a combined PCR/serology endpoint using Fisher's exact test.

RESULTS: Of the 1567 HCP enrolled between December 27, 2020 and February 15, 2021, 1250 previously uninfected participants were included in the primary analysis; 998 (79.8%) were vaccinated with their first dose prior to or at enrollment, all with Pfizer BNT162b2 mRNA vaccine. There were four PCR-positive events among vaccinated participants, and nine among unvaccinated participants. Adjusted two-dose VE against any PCR-confirmed infection was 94.5% (95% CI: 82.6%-98.2%); adjusted two-dose VE against a combined endpoint of PCR and seroconversion for a 60-day follow-up period was 94.5% (95% CI: 63.0%-99.0%). Five PCR-positive samples from study participants were sequenced; all were alpha variant.

CONCLUSIONS: Our prospective VE study of HCP in Israel with rigorous weekly surveillance found very high VE for two doses of Pfizer BNT162b2 mRNA vaccine against SARS-CoV-2 infection in recently vaccinated HCP during a period of predominant alpha variant circulation.

FUNDING: Clalit Health Services.

BACKGROUND: Methodologically rigorous studies on Covid-19 vaccine effectiveness (VE) in preventing SARS-CoV-2 infection are critically needed to inform national and global policy on Covid-19 vaccine use. In Israel, healthcare personnel (HCP) were initially prioritized for Covid-19 vaccination, creating an ideal setting to evaluate early real-world VE in a closely monitored population.

METHODS: We conducted a prospective study among HCP in 6 hospitals to estimate the effectiveness of the BNT162b2 mRNA Covid-19 vaccine in preventing SARS-CoV-2 infection. Participants filled out weekly symptom questionnaires, provided weekly nasal specimens, and three serology samples - at enrollment, 30 days and 90 days. We estimated VE against PCR-confirmed SARS-CoV-2 infection using the Cox Proportional Hazards model and against a combined PCR/serology endpoint using Fisher's exact test.

RESULTS: Of the 1567 HCP enrolled between December 27, 2020 and February 15, 2021, 1250 previously uninfected participants were included in the primary analysis; 998 (79.8%) were vaccinated with their first dose prior to or at enrollment, all with Pfizer BNT162b2 mRNA vaccine. There were four PCR-positive events among vaccinated participants, and nine among unvaccinated participants. Adjusted two-dose VE against any PCR-confirmed infection was 94.5% (95% CI: 82.6%-98.2%); adjusted two-dose VE against a combined endpoint of PCR and seroconversion for a 60-day follow-up period was 94.5% (95% CI: 63.0%-99.0%). Five PCR-positive samples from study participants were sequenced; all were alpha variant.

CONCLUSIONS: Our prospective VE study of HCP in Israel with rigorous weekly surveillance found very high VE for two doses of Pfizer BNT162b2 mRNA vaccine against SARS-CoV-2 infection in recently vaccinated HCP during a period of predominant alpha variant circulation.

FUNDING: Clalit Health Services.

At the COVID-19 pandemic onset, when individual-level data of COVID-19 patients were not yet available, there was already a need for risk predictors to support prevention and treatment decisions. Here, we report a hybrid strategy to create such a predictor, combining the development of a baseline severe respiratory infection risk predictor and a post-processing method to calibrate the predictions to reported COVID-19 case-fatality rates. With the accumulation of a COVID-19 patient cohort, this predictor is validated to have good discrimination (area under the receiver-operating characteristics curve of 0.943) and calibration (markedly improved compared to that of the baseline predictor). At a 5% risk threshold, 15% of patients are marked as high-risk, achieving a sensitivity of 88%. We thus demonstrate that even at the onset of a pandemic, shrouded in epidemiologic fog of war, it is possible to provide a useful risk predictor, now widely used in a large healthcare organization.

At the COVID-19 pandemic onset, when individual-level data of COVID-19 patients were not yet available, there was already a need for risk predictors to support prevention and treatment decisions. Here, we report a hybrid strategy to create such a predictor, combining the development of a baseline severe respiratory infection risk predictor and a post-processing method to calibrate the predictions to reported COVID-19 case-fatality rates. With the accumulation of a COVID-19 patient cohort, this predictor is validated to have good discrimination (area under the receiver-operating characteristics curve of 0.943) and calibration (markedly improved compared to that of the baseline predictor). At a 5% risk threshold, 15% of patients are marked as high-risk, achieving a sensitivity of 88%. We thus demonstrate that even at the onset of a pandemic, shrouded in epidemiologic fog of war, it is possible to provide a useful risk predictor, now widely used in a large healthcare organization.