To evaluate the effectiveness of the BNT162b2 messenger RNA vaccine in pregnant women, we conducted an observational cohort study of pregnant women aged 16 years or older, with no history of SARS-CoV-2, who were vaccinated between 20 December 2020 and 3 June 2021. A total of 10,861 vaccinated pregnant women were matched to 10,861 unvaccinated pregnant controls using demographic and clinical characteristics. Study outcomes included documented infection with SARS-CoV-2, symptomatic COVID-19, COVID-19-related hospitalization, severe illness and death. Estimated vaccine effectiveness from 7 through to 56 d after the second dose was 96% (95% confidence interval 89-100%) for any documented infection, 97% (91-100%) for infections with documented symptoms and 89% (43-100%) for COVID-19-related hospitalization. Only one event of severe illness was observed in the unvaccinated group and no deaths were observed in either group. In summary, the BNT162b2 mRNA vaccine was estimated to have high vaccine effectiveness in pregnant women, which is similar to the effectiveness estimated in the general population.

To evaluate the effectiveness of the BNT162b2 messenger RNA vaccine in pregnant women, we conducted an observational cohort study of pregnant women aged 16 years or older, with no history of SARS-CoV-2, who were vaccinated between 20 December 2020 and 3 June 2021. A total of 10,861 vaccinated pregnant women were matched to 10,861 unvaccinated pregnant controls using demographic and clinical characteristics. Study outcomes included documented infection with SARS-CoV-2, symptomatic COVID-19, COVID-19-related hospitalization, severe illness and death. Estimated vaccine effectiveness from 7 through to 56 d after the second dose was 96% (95% confidence interval 89-100%) for any documented infection, 97% (91-100%) for infections with documented symptoms and 89% (43-100%) for COVID-19-related hospitalization. Only one event of severe illness was observed in the unvaccinated group and no deaths were observed in either group. In summary, the BNT162b2 mRNA vaccine was estimated to have high vaccine effectiveness in pregnant women, which is similar to the effectiveness estimated in the general population.

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.

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.

BACKGROUND: Preapproval trials showed that messenger RNA (mRNA)-based vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had a good safety profile, yet these trials were subject to size and patient-mix limitations. An evaluation of the safety of the BNT162b2 mRNA vaccine with respect to a broad range of potential adverse events is needed.

METHODS: We used data from the largest health care organization in Israel to evaluate the safety of the BNT162b2 mRNA vaccine. For each potential adverse event, in a population of persons with no previous diagnosis of that event, we individually matched vaccinated persons to unvaccinated persons according to sociodemographic and clinical variables. Risk ratios and risk differences at 42 days after vaccination were derived with the use of the Kaplan-Meier estimator. To place these results in context, we performed a similar analysis involving SARS-CoV-2-infected persons matched to uninfected persons. The same adverse events were studied in the vaccination and SARS-CoV-2 infection analyses.

RESULTS: In the vaccination analysis, the vaccinated and control groups each included a mean of 884,828 persons. Vaccination was most strongly associated with an elevated risk of myocarditis (risk ratio, 3.24; 95% confidence interval [CI], 1.55 to 12.44; risk difference, 2.7 events per 100,000 persons; 95% CI, 1.0 to 4.6), lymphadenopathy (risk ratio, 2.43; 95% CI, 2.05 to 2.78; risk difference, 78.4 events per 100,000 persons; 95% CI, 64.1 to 89.3), appendicitis (risk ratio, 1.40; 95% CI, 1.02 to 2.01; risk difference, 5.0 events per 100,000 persons; 95% CI, 0.3 to 9.9), and herpes zoster infection (risk ratio, 1.43; 95% CI, 1.20 to 1.73; risk difference, 15.8 events per 100,000 persons; 95% CI, 8.2 to 24.2). SARS-CoV-2 infection was associated with a substantially increased risk of myocarditis (risk ratio, 18.28; 95% CI, 3.95 to 25.12; risk difference, 11.0 events per 100,000 persons; 95% CI, 5.6 to 15.8) and of additional serious adverse events, including pericarditis, arrhythmia, deep-vein thrombosis, pulmonary embolism, myocardial infarction, intracranial hemorrhage, and thrombocytopenia.

CONCLUSIONS: In this study in a nationwide mass vaccination setting, the BNT162b2 vaccine was not associated with an elevated risk of most of the adverse events examined. The vaccine was associated with an excess risk of myocarditis (1 to 5 events per 100,000 persons). The risk of this potentially serious adverse event and of many other serious adverse events was substantially increased after SARS-CoV-2 infection. (Funded by the Ivan and Francesca Berkowitz Family Living Laboratory Collaboration at Harvard Medical School and Clalit Research Institute.).

BACKGROUND: Preapproval trials showed that messenger RNA (mRNA)-based vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had a good safety profile, yet these trials were subject to size and patient-mix limitations. An evaluation of the safety of the BNT162b2 mRNA vaccine with respect to a broad range of potential adverse events is needed.

METHODS: We used data from the largest health care organization in Israel to evaluate the safety of the BNT162b2 mRNA vaccine. For each potential adverse event, in a population of persons with no previous diagnosis of that event, we individually matched vaccinated persons to unvaccinated persons according to sociodemographic and clinical variables. Risk ratios and risk differences at 42 days after vaccination were derived with the use of the Kaplan-Meier estimator. To place these results in context, we performed a similar analysis involving SARS-CoV-2-infected persons matched to uninfected persons. The same adverse events were studied in the vaccination and SARS-CoV-2 infection analyses.

RESULTS: In the vaccination analysis, the vaccinated and control groups each included a mean of 884,828 persons. Vaccination was most strongly associated with an elevated risk of myocarditis (risk ratio, 3.24; 95% confidence interval [CI], 1.55 to 12.44; risk difference, 2.7 events per 100,000 persons; 95% CI, 1.0 to 4.6), lymphadenopathy (risk ratio, 2.43; 95% CI, 2.05 to 2.78; risk difference, 78.4 events per 100,000 persons; 95% CI, 64.1 to 89.3), appendicitis (risk ratio, 1.40; 95% CI, 1.02 to 2.01; risk difference, 5.0 events per 100,000 persons; 95% CI, 0.3 to 9.9), and herpes zoster infection (risk ratio, 1.43; 95% CI, 1.20 to 1.73; risk difference, 15.8 events per 100,000 persons; 95% CI, 8.2 to 24.2). SARS-CoV-2 infection was associated with a substantially increased risk of myocarditis (risk ratio, 18.28; 95% CI, 3.95 to 25.12; risk difference, 11.0 events per 100,000 persons; 95% CI, 5.6 to 15.8) and of additional serious adverse events, including pericarditis, arrhythmia, deep-vein thrombosis, pulmonary embolism, myocardial infarction, intracranial hemorrhage, and thrombocytopenia.

CONCLUSIONS: In this study in a nationwide mass vaccination setting, the BNT162b2 vaccine was not associated with an elevated risk of most of the adverse events examined. The vaccine was associated with an excess risk of myocarditis (1 to 5 events per 100,000 persons). The risk of this potentially serious adverse event and of many other serious adverse events was substantially increased after SARS-CoV-2 infection. (Funded by the Ivan and Francesca Berkowitz Family Living Laboratory Collaboration at Harvard Medical School and Clalit Research Institute.).

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.

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.