Effectiveness of a third dose of the BNT162b2 mRNA COVID-19 vaccine for preventing severe outcomes in Israel: an observational study

Author(s): Noam Barda , MD ^a ^, ^b ^, ^d ^, ^e ^, ^* , Noa Dagan , MD ^a ^, ^b ^, ^d ^, ^e ^, ^* , Cyrille Cohen , Prof, PhD ^f , Miguel A Hernán , Prof, MD ^g ^, ^h ^, ^j , Marc Lipsitch , Prof, DPhil ^g ^, ⁱ ^, ^k , Isaac S Kohane , Prof, MD ^d ^, ^e ^, ^m , Ben Y Reis , PhD ^e ^, ^l ^, ^m ^, ^† , Ran D Balicer , Prof, MD ^a ^, ^c ^, ^e ^, ^† ^, ^*

Publication date (Electronic): 29 October 2021

Journal: Lancet (London, England)

Publisher: Elsevier Ltd.

Read this article at

ScienceOpenPublisher PMC

Bookmark

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Background

Many countries are experiencing a resurgence of COVID-19, driven predominantly by the delta (B.1.617.2) variant of SARS-CoV-2. In response, these countries are considering the administration of a third dose of mRNA COVID-19 vaccine as a booster dose to address potential waning immunity over time and reduced effectiveness against the delta variant. We aimed to use the data repositories of Israel's largest health-care organisation to evaluate the effectiveness of a third dose of the BNT162b2 mRNA vaccine for preventing severe COVID-19 outcomes.

Methods

Using data from Clalit Health Services, which provides mandatory health-care coverage for over half of the Israeli population, individuals receiving a third vaccine dose between July 30, 2020, and Sept 23, 2021, were matched (1:1) to demographically and clinically similar controls who did not receive a third dose. Eligible participants had received the second vaccine dose at least 5 months before the recruitment date, had no previous documented SARS-CoV-2 infection, and had no contact with the health-care system in the 3 days before recruitment. Individuals who are health-care workers, live in long-term care facilities, or are medically confined to their homes were excluded. Primary outcomes were COVID-19-related admission to hospital, severe disease, and COVID-19-related death. The third dose effectiveness for each outcome was estimated as 1 – risk ratio using the Kaplan-Meier estimator.

Findings

1 158 269 individuals were eligible to be included in the third dose group. Following matching, the third dose and control groups each included 728 321 individuals. Participants had a median age of 52 years (IQR 37–68) and 51% were female. The median follow-up time was 13 days (IQR 6–21) in both groups. Vaccine effectiveness evaluated at least 7 days after receipt of the third dose, compared with receiving only two doses at least 5 months ago, was estimated to be 93% (231 events for two doses vs 29 events for three doses; 95% CI 88–97) for admission to hospital, 92% (157 vs 17 events; 82–97) for severe disease, and 81% (44 vs seven events; 59–97) for COVID-19-related death.

Interpretation

Our findings suggest that a third dose of the BNT162b2 mRNA vaccine is effective in protecting individuals against severe COVID-19-related outcomes, compared with receiving only two doses at least 5 months ago.

Funding

The Ivan and Francesca Berkowitz Family Living Laboratory Collaboration at Harvard Medical School and Clalit Research Institute.

Related collections

Most cited references 28

Record: found
Abstract: found
Article: not found

Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine

Fernando P Polack, Stephen J. Thomas, Nicholas R.E. Kitchin … (2023)

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (Covid-19) have afflicted tens of millions of people in a worldwide pandemic. Safe and effective vaccines are needed urgently. Methods In an ongoing multinational, placebo-controlled, observer-blinded, pivotal efficacy trial, we randomly assigned persons 16 years of age or older in a 1:1 ratio to receive two doses, 21 days apart, of either placebo or the BNT162b2 vaccine candidate (30 μg per dose). BNT162b2 is a lipid nanoparticle–formulated, nucleoside-modified RNA vaccine that encodes a prefusion stabilized, membrane-anchored SARS-CoV-2 full-length spike protein. The primary end points were efficacy of the vaccine against laboratory-confirmed Covid-19 and safety. Results A total of 43,548 participants underwent randomization, of whom 43,448 received injections: 21,720 with BNT162b2 and 21,728 with placebo. There were 8 cases of Covid-19 with onset at least 7 days after the second dose among participants assigned to receive BNT162b2 and 162 cases among those assigned to placebo; BNT162b2 was 95% effective in preventing Covid-19 (95% credible interval, 90.3 to 97.6). Similar vaccine efficacy (generally 90 to 100%) was observed across subgroups defined by age, sex, race, ethnicity, baseline body-mass index, and the presence of coexisting conditions. Among 10 cases of severe Covid-19 with onset after the first dose, 9 occurred in placebo recipients and 1 in a BNT162b2 recipient. The safety profile of BNT162b2 was characterized by short-term, mild-to-moderate pain at the injection site, fatigue, and headache. The incidence of serious adverse events was low and was similar in the vaccine and placebo groups. Conclusions A two-dose regimen of BNT162b2 conferred 95% protection against Covid-19 in persons 16 years of age or older. Safety over a median of 2 months was similar to that of other viral vaccines. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04368728.)

0 comments Cited 7023 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Effectiveness of Covid-19 Vaccines against the B.1.617.2 (Delta) Variant

Jamie Lopez Bernal, Nick Andrews, Charlotte Gower … (2021)

Background The B.1.617.2 (delta) variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (Covid-19), has contributed to a surge in cases in India and has now been detected across the globe, including a notable increase in cases in the United Kingdom. The effectiveness of the BNT162b2 and ChAdOx1 nCoV-19 vaccines against this variant has been unclear. Methods We used a test-negative case–control design to estimate the effectiveness of vaccination against symptomatic disease caused by the delta variant or the predominant strain (B.1.1.7, or alpha variant) over the period that the delta variant began circulating. Variants were identified with the use of sequencing and on the basis of the spike ( S ) gene status. Data on all symptomatic sequenced cases of Covid-19 in England were used to estimate the proportion of cases with either variant according to the patients’ vaccination status. Results Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) was notably lower among persons with the delta variant (30.7%; 95% confidence interval [CI], 25.2 to 35.7) than among those with the alpha variant (48.7%; 95% CI, 45.5 to 51.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 93.7% (95% CI, 91.6 to 95.3) among persons with the alpha variant and 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 74.5% (95% CI, 68.4 to 79.4) among persons with the alpha variant and 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant. Conclusions Only modest differences in vaccine effectiveness were noted with the delta variant as compared with the alpha variant after the receipt of two vaccine doses. Absolute differences in vaccine effectiveness were more marked after the receipt of the first dose. This finding would support efforts to maximize vaccine uptake with two doses among vulnerable populations. (Funded by Public Health England.)

0 comments Cited 1391 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Mass Vaccination Setting

Noa Dagan, Noam Barda, Eldad Kepten … (2021)

Abstract Background As mass vaccination campaigns against coronavirus disease 2019 (Covid-19) commence worldwide, vaccine effectiveness needs to be assessed for a range of outcomes across diverse populations in a noncontrolled setting. In this study, data from Israel’s largest health care organization were used to evaluate the effectiveness of the BNT162b2 mRNA vaccine. Methods All persons who were newly vaccinated during the period from December 20, 2020, to February 1, 2021, were matched to unvaccinated controls in a 1:1 ratio according to demographic and clinical characteristics. Study outcomes included documented infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), symptomatic Covid-19, Covid-19–related hospitalization, severe illness, and death. We estimated vaccine effectiveness for each outcome as one minus the risk ratio, using the Kaplan–Meier estimator. Results Each study group included 596,618 persons. 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 to 98); for hospitalization, 74% (95% CI, 56 to 86) and 87% (95% CI, 55 to 100); and for severe disease, 62% (95% CI, 39 to 80) and 92% (95% CI, 75 to 100), respectively. Estimated effectiveness in preventing death from Covid-19 was 72% (95% CI, 19 to 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. Conclusions This study in a nationwide mass vaccination setting suggests that the BNT162b2 mRNA vaccine is effective for a wide range of Covid-19–related outcomes, a finding consistent with that of the randomized trial.

0 comments Cited 1280 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-ta): Lancet

Journal ID (iso-abbrev): Lancet

Title: Lancet (London, England)

Publisher: Elsevier Ltd.

ISSN (Print): 0140-6736

ISSN (Electronic): 1474-547X

Publication date PMC-release: 29 October 2021

Publication date (Electronic): 29 October 2021

Affiliations

[a ]Clalit Research Institute, Innovation Division, Clalit Health Services, Tel Aviv, Israel

[b ]Software and Information Systems Engineering, Ben Gurion University of the Negev, Be'er Sheva, Israel

[c ]School of Public Health, Faculty of Health Sciences, Ben Gurion University of the Negev, Be'er Sheva, Israel

[d ]Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA

[e ]The Ivan and Francesca Berkowitz Family Living Laboratory Collaboration at Harvard Medical School and Clalit Research Institute, Boston, MA, USA

[f ]The Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel

[g ]Department of Epidemiology, Harvard T H Chan School of Public Health, Boston, MA, USA

[h ]Department of Biostatistics, Harvard T H Chan School of Public Health, Boston, MA, USA

[i ]Department of Immunology and Infectious Diseases, Harvard T H Chan School of Public Health, Boston, MA, USA

[j ]CAUSALab, Harvard T H Chan School of Public Health, Boston, MA, USA

[k ]Center for Communicable Disease Dynamics, Harvard T H Chan School of Public Health, Boston, MA, USA

[l ]Predictive Medicine Group, Computational Health Informatics Program, Boston Children's Hospital, Boston, MA, USA

[m ]Harvard Medical School, Boston, MA, USA

Author notes

[* ]Correspondence to: Prof Ran D Balicer, Clalit Research Institute, Innovation Division, Clalit Health Services, Tel Aviv 6209804, Israel

[*]

Joint first authors

[†]

Contributed equally

Article

Publisher Item ID: S0140-6736(21)02249-2

DOI: 10.1016/S0140-6736(21)02249-2

PMC ID: 8555967

PubMed ID: 34756184

SO-VID: e5537b6f-149a-4b59-9089-62ff5114a543

License:

Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

Effectiveness of a third dose of the BNT162b2 mRNA COVID-19 vaccine for preventing severe outcomes in Israel: an observational study

Read this article at

Abstract

Background

Methods

Findings

Interpretation

Funding

Related collections

Novel Coronavirus Disease COVID-19

Most cited references 28

Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine

Effectiveness of Covid-19 Vaccines against the B.1.617.2 (Delta) Variant

BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Mass Vaccination Setting

Author and article information

Journal

Affiliations

Author notes

Article

History

Categories

Comments

Comment on this article

Similar content 278

Cited by 455

Most referenced authors 663