COVID-19 vaccine impact in Israel and a way out of the pandemic
Authors: Eyal Leshem, Annelies Wilder-Smith
Journal: The Lancet (2021)

In December, 2020, Israel initiated a national campaign to vaccinate its population with Pfizer–BioNTech's mRNA COVID-19 vaccine BNT162b2 (tozinameran). Israel's Ministry of Health recommended a two-dose schedule with a 21-day interval between doses. Israel delivered more than 10 million doses within 4 months; by April 19, 2021, 54% of the entire population of 9·1 million people, and 88% of people aged 50 years or older, had received two doses.1Israel Ministry of HealthCOVID-19 daily situation report.https://datadashboard.health.gov.il/COVID-19/generalDate accessed: April 20, 2021Google Scholar Factors contributing to Israel's rapid roll-out include its small geographical and population sizes; advanced information technology that allowed prioritisation, allocation, and documentation of vaccines for eligible individuals; effective cooperation between government and community-based health funds, which were charged with providing vaccines to those they insured; and experience in rapid large-scale emergency responses.2Rosen B Waitzberg R Israeli A Israel's rapid rollout of vaccinations for COVID-19.Isr J Health Policy Res. 2021; 10: 6Crossref PubMed Scopus (184) Google Scholar Vaccines were rolled out around the time of Israel's third and largest wave of SARS-CoV-2 infections, with a peak 7-day moving average of 8328 new infections per day, which resulted in a 2-month national lockdown. Thus, Israel's setting provided a robust platform on which to examine vaccine effectiveness and the impact of high vaccine coverage in real-life conditions at a national level. From March, 2021, onwards, Israel reported a rapid decline in COVID-19 cases across all age groups, despite the easing of lockdown restrictions and reopening of education and commerce. By April 19, 2021, the 7-day moving average of new cases dropped to 149 per day, indicating effective control of the pandemic within the country's borders.1Israel Ministry of HealthCOVID-19 daily situation report.https://datadashboard.health.gov.il/COVID-19/generalDate accessed: April 20, 2021Google Scholar, 3Haas JE Angulo FJ McLaughlin JM et al.Impact and effectiveness of mRNA BNT162b2 vaccine against SARS-CoV-2 infections and COVID-19 cases, hospitalisations, and deaths following a nationwide vaccination campaign in Israel: an observational study using national surveillance data.Lancet. 2021; (published online May 5.)https://doi.org/10.1016/S0140-6736(21)00947-8Summary Full Text Full Text PDF PubMed Scopus (1103) Google Scholar The marked reduction in new cases prompted the Israeli Government to ease nationwide restrictions, including the discontinuation of face covering use in open spaces. In The Lancet, Eric Haas and colleagues report on a nationwide observational study of the impact and vaccine effectiveness of BNT162b2 in Israel.3Haas JE Angulo FJ McLaughlin JM et al.Impact and effectiveness of mRNA BNT162b2 vaccine against SARS-CoV-2 infections and COVID-19 cases, hospitalisations, and deaths following a nationwide vaccination campaign in Israel: an observational study using national surveillance data.Lancet. 2021; (published online May 5.)https://doi.org/10.1016/S0140-6736(21)00947-8Summary Full Text Full Text PDF PubMed Scopus (1103) Google Scholar Israel's Ministry of Health used aggregated data from the national SARS-CoV-2 surveillance and vaccination programme dataset to compare infection and disease incidence between vaccinated and unvaccinated people. Overall, of 232 268 SARS-CoV-2 infections during the study period (Jan 24 to April 3, 2021), 154 648 (66·6%) occurred in people aged 16 years or older and were included in the analyses (of which 20·4% were in the Arab sector, 15·7% in the ultra-Orthodox sector, and 63·9% in the general Jewish [non-ultra-Orthodox] sector). Adjusted estimates of vaccine effectiveness at 7 days or longer after the second dose were 95·3% (95% CI 94·9–95·7) against SARS-CoV-2 infection, 91·5% (90·7–92·2) against asymptomatic SARS-CoV-2 infection, 97·0% (96·7–97·2) against symptomatic SARS-CoV-2 infection, 97·2% (96·8–97·5) against COVID-19-related hospitalisation, 97·5% (97·1–97·8) against severe or critical COVID-19-related hospitalisation, and 96·7% (96·0–97·3) against COVID-19-related death. Vaccine effectiveness against symptomatic SARS-CoV-2 infection, COVID-19-related hospitalisation, and COVID-19-related death exceeded 96% across all age groups, including older adults (aged ≥75 years and ≥85 years). These results closely mirror the efficacy estimates of the BNT162b2 vaccine reported in the phase 3 trial.4Polack FP Thomas SJ Kitchin N et al.Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine.N Engl J Med. 2020; 383: 2603-2615Crossref PubMed Scopus (9742) Google Scholar The strengths of the study include its nationwide design, mandatory routine reporting of new infections and of vaccination status to the national dataset, large sample size, exclusive use of BNT162b2, and occurrence of a highly efficient vaccine roll-out during peak transmission of SARS-CoV-2, which resulted in high vaccination coverage of most of the adult population. However, several limitations should be considered when interpreting the results. First, social desirability bias affecting symptom questionnaire respondents and presymptomatic infections at the time of questioning could have contributed to an overestimation of vaccine effectiveness against asymptomatic infection. Additionally, patients with COVID-19 who reported symptoms were defined as asymptomatic if they did not report fever or respiratory symptoms. This unorthodox case definition might have resulted in a substantial overestimation of vaccine effectiveness against asymptomatic SARS-CoV-2 infection.5Hall VJ Foulkes S Saei A et al.COVID-19 vaccine coverage in health-care workers in England and effectiveness of BNT162b2 mRNA vaccine against infection (SIREN): a prospective, multicentre, cohort study.Lancet. 2021; (published online April 23.)https://doi.org/10.1016/S0140-6736(21)00790-XSummary Full Text Full Text PDF PubMed Scopus (435) Google Scholar Second, during early 2021, the B.1.1.7 variant of SARS-CoV-2 was estimated to account for 95% of cases in Israel, and the results thus indicate that the vaccine was effective against this variant of concern. However, the study did not report on effectiveness against other variants of concern, such as B.1.351 and P.1. Concerns regarding breakthrough infections were recently raised as a case-cohort study from Israel reported a disproportionally high infection rate with the B.1.351 variant in fully vaccinated compared with unvaccinated individuals.6Kustin T Harel N Finkel U et al.Evidence for increased breakthrough rates of SARS-CoV-2 variants of concern in BNT162b2 mRNA vaccinated individuals.medRxiv. 2021; (published online April 9.) (preprint).https://doi.org/10.1101/2021.04.06.21254882Google Scholar Nevertheless, the incidence of B.1.351 infection in Israel to date remains low. Rapid mass vaccination coupled with non-pharmaceutical interventions7Wilder-Smith A Freedman DO Isolation, quarantine, social distancing and community containment: pivotal role for old-style public health measures in the novel coronavirus (2019-nCoV) outbreak.J Travel Med. 2020; 27: 27Crossref Scopus (1469) Google Scholar might have successfully controlled its spread. Haas and colleagues' findings from Israel suggest that high vaccine coverage rates could offer a way out of the pandemic.5Hall VJ Foulkes S Saei A et al.COVID-19 vaccine coverage in health-care workers in England and effectiveness of BNT162b2 mRNA vaccine against infection (SIREN): a prospective, multicentre, cohort study.Lancet. 2021; (published online April 23.)https://doi.org/10.1016/S0140-6736(21)00790-XSummary Full Text Full Text PDF PubMed Scopus (435) Google Scholar, 8Leshem E Lopman BA Population immunity and vaccine protection against infection.Lancet. 2021; (published online April 23.)https://doi.org/10.1016/s0140-6736(21)00870-9Summary Full Text Full Text PDF Scopus (24) Google Scholar Regrettably, rapid population level coverage cannot be easily replicated in many other countries. The global use of the BNT162b2 vaccine is limited by supply issues, high costs, and ultra-cold chain storage requirements. Global COVID-19 vaccine roll-out has been sluggish, and vaccine distribution is inequitable despite the achievements of COVAX, mainly due to the lack of adequate manufacturing scalability.9Wouters OJ Shadlen KC Salcher-Konrad M et al.Challenges in ensuring global access to COVID-19 vaccines: production, affordability, allocation, and deployment.Lancet. 2021; 397: 1023-1034Summary Full Text Full Text PDF PubMed Scopus (785) Google Scholar, 10The LancetAccess to COVID-19 vaccines: looking beyond COVAX.Lancet. 2021; 397: 941Summary Full Text Full Text PDF PubMed Scopus (44) Google Scholar Rapid expansion of deployment of other effective vaccines with more achievable cold chain storage requirements remains an urgent global priority.9Wouters OJ Shadlen KC Salcher-Konrad M et al.Challenges in ensuring global access to COVID-19 vaccines: production, affordability, allocation, and deployment.Lancet. 2021; 397: 1023-1034Summary Full Text Full Text PDF PubMed Scopus (785) Google Scholar Facing such challenges, alternative approaches must be considered to allow rapid protection of at-risk populations against severe COVID-19. One such approach is deferring the second dose to accelerate and maximise coverage of the first dose in the population. Indeed, the situation in Scotland looks promising: the first dose of BNT162b2 was associated with a vaccine effectiveness of 91% (85–94) for COVID-19-related hospitalisation at 28–34 days post-vaccination.11Vasileiou E Simpson CR Shi T et al.Interim findings from first-dose mass COVID-19 vaccination roll-out and COVID-19 hospital admissions in Scotland: a national prospective cohort study.Lancet. 2021; 397: 1646-1657Summary Full Text Full Text PDF PubMed Scopus (381) Google Scholar Israel's robust dataset could allow further assessment and corroboration of first-dose short-term effectiveness and lead other countries to considering deferring the second vaccine dose.3Haas JE Angulo FJ McLaughlin JM et al.Impact and effectiveness of mRNA BNT162b2 vaccine against SARS-CoV-2 infections and COVID-19 cases, hospitalisations, and deaths following a nationwide vaccination campaign in Israel: an observational study using national surveillance data.Lancet. 2021; (published online May 5.)https://doi.org/10.1016/S0140-6736(21)00947-8Summary Full Text Full Text PDF PubMed Scopus (1103) Google Scholar Post-introduction vaccine effectiveness studies such as those from Israel3Haas JE Angulo FJ McLaughlin JM et al.Impact and effectiveness of mRNA BNT162b2 vaccine against SARS-CoV-2 infections and COVID-19 cases, hospitalisations, and deaths following a nationwide vaccination campaign in Israel: an observational study using national surveillance data.Lancet. 2021; (published online May 5.)https://doi.org/10.1016/S0140-6736(21)00947-8Summary Full Text Full Text PDF PubMed Scopus (1103) Google Scholar and the UK5Hall VJ Foulkes S Saei A et al.COVID-19 vaccine coverage in health-care workers in England and effectiveness of BNT162b2 mRNA vaccine against infection (SIREN): a prospective, multicentre, cohort study.Lancet. 2021; (published online April 23.)https://doi.org/10.1016/S0140-6736(21)00790-XSummary Full Text Full Text PDF PubMed Scopus (435) Google Scholar, 11Vasileiou E Simpson CR Shi T et al.Interim findings from first-dose mass COVID-19 vaccination roll-out and COVID-19 hospital admissions in Scotland: a national prospective cohort study.Lancet. 2021; 397: 1646-1657Summary Full Text Full Text PDF PubMed Scopus (381) Google Scholar will gain increasing importance in augmenting the current evidence, which has so far been based only on data from phase 3 efficacy trials. WHO has published a best practice guidance document on how to conduct vaccine effectiveness assessments using observational study designs.12WHOEvaluation of COVID-19 vaccine effectiveness—interim guidance.https://www.who.int/publications/i/item/WHO-2019-nCoV-vaccine_effectiveness-measurement-2021.1Date accessed: April 19, 2021Google Scholar Israel's experience provides impetus for countries to proactively pursue high vaccine coverage to protect the population;8Leshem E Lopman BA Population immunity and vaccine protection against infection.Lancet. 2021; (published online April 23.)https://doi.org/10.1016/s0140-6736(21)00870-9Summary Full Text Full Text PDF Scopus (24) Google Scholar however, rollout would need to follow the WHO prioritisation roadmap to maximise the public health impact, in light of vaccine supply constraints. More post-introduction vaccine effectiveness studies will be required. Timely reporting of vaccine effectiveness against variants of concern, the duration of protection across age groups and geographical settings, and the effectiveness of alternative dosing regimens is crucial to provide data-driven immunisation policies.12WHOEvaluation of COVID-19 vaccine effectiveness—interim guidance.https://www.who.int/publications/i/item/WHO-2019-nCoV-vaccine_effectiveness-measurement-2021.1Date accessed: April 19, 2021Google Scholar EL reports personal fees from Sanofi Pasteur for participation in a global advisory board of influenza vaccination, outside the area of work commented on here. AW-S serves as a consultant to WHO's Immunization and Vaccination Department. The authors alone are responsible for the views expressed in this Comment, and they do not necessarily represent the decisions or policies of WHO. Impact and effectiveness of mRNA BNT162b2 vaccine against SARS-CoV-2 infections and COVID-19 cases, hospitalisations, and deaths following a nationwide vaccination campaign in Israel: an observational study using national surveillance dataTwo doses of BNT162b2 are highly effective across all age groups (≥16 years, including older adults aged ≥85 years) in preventing symptomatic and asymptomatic SARS-CoV-2 infections and COVID-19-related hospitalisations, severe disease, and death, including those caused by the B.1.1.7 SARS-CoV-2 variant. There were marked and sustained declines in SARS-CoV-2 incidence corresponding to increasing vaccine coverage. These findings suggest that COVID-19 vaccination can help to control the pandemic. Full-Text PDF