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Following the emergency use authorisation of the Pfizer–BioNTech mRNA COVID-19 vaccine BNT162b2 (international non-proprietary name tozinameran) in Israel, the Ministry of Health (MoH) launched a campaign to immunise the 6·5 million residents of Israel aged 16 years and older. We estimated the real-world effectiveness of two doses of BNT162b2 against a range of SARS-CoV-2 outcomes and to evaluate the nationwide public-health impact following the widespread introduction of the vaccine.
We used national surveillance data from the first 4 months of the nationwide vaccination campaign to ascertain incident cases of laboratory-confirmed SARS-CoV-2 infections and outcomes, as well as vaccine uptake in residents of Israel aged 16 years and older. Vaccine effectiveness against SARS-CoV-2 outcomes (asymptomatic infection, symptomatic infection, and COVID-19-related hospitalisation, severe or critical hospitalisation, and death) was calculated on the basis of incidence rates in fully vaccinated individuals (defined as those for whom 7 days had passed since receiving the second dose of vaccine) compared with rates in unvaccinated individuals (who had not received any doses of the vaccine), with use of a negative binomial regression model adjusted for age group (16–24, 25–34, 35–44, 45–54, 55–64, 65–74, 75–84, and ≥85 years), sex, and calendar week. The proportion of spike gene target failures on PCR test among a nationwide convenience-sample of SARS-CoV-2-positive specimens was used to estimate the prevelance of the B.1.1.7 variant.
During the analysis period (Jan 24 to April 3, 2021), there were 232 268 SARS-CoV-2 infections, 7694 COVID-19 hospitalisations, 4481 severe or critical COVID-19 hospitalisations, and 1113 COVID-19 deaths in people aged 16 years or older. By April 3, 2021, 4 714 932 (72·1%) of 6 538 911 people aged 16 years and older were fully vaccinated with two doses of BNT162b2. Adjusted estimates of vaccine effectiveness at 7 days or longer after the second dose were 95·3% (95% CI 94·9–95·7; incidence rate 91·5 per 100 000 person-days in unvaccinated vs 3·1 per 100 000 person-days in fully vaccinated individuals) against SARS-CoV-2 infection, 91·5% (90·7–92·2; 40·9 vs 1·8 per 100 000 person-days) against asymptomatic SARS-CoV-2 infection, 97·0% (96·7–97·2; 32·5 vs 0·8 per 100 000 person-days) against symptomatic COVID-19, 97·2% (96·8–97·5; 4·6 vs 0·3 per 100 000 person-days) against COVID-19-related hospitalisation, 97·5% (97·1–97·8; 2·7 vs 0·2 per 100 000 person-days) against severe or critical COVID-19-related hospitalisation, and 96·7% (96·0–97·3; 0·6 vs 0·1 per 100 000 person-days) against COVID-19-related death. In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined. 8006 of 8472 samples tested showed a spike gene target failure, giving an estimated prevalence of the B.1.1.7 variant of 94·5% among SARS-CoV-2 infections.
Two 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.
including 821 748 cases and 6236 deaths in Israel
(population 9·1 million). Among the SARS-CoV-2 strains characterised globally in 2020, the D614G variant was dominant.
More recently, the SARS-CoV-2 variant B.1.1.7, first identified in the UK and associated with increased transmissibility, has emerged in several countries.
B.1.1.7 was first reported in Israel on Dec 23, 2020.
The Pfizer–BioNTech mRNA COVID-19 vaccine BNT162b2, administered as two doses 21 days apart, was authorised for emergency use in Israel in December, 2020, after it was shown to have high efficacy against symptomatic laboratory-confirmed COVID-19 in a randomised controlled trial of individuals aged 16 years and older. Since the initiation of vaccine rollout, we have been closely monitoring the scientific literature (including preprint servers) and press coverage to identify reports of BNT162b2 vaccine effectiveness. Although observational studies have estimated the effectiveness of BNT162b2, precise nationwide effectiveness estimates of two doses of BNT162b2 against SARS-CoV-2 outcomes are lacking. More data are particularly needed regarding the vaccine’s effectiveness against severe disease and deaths, and effectiveness in older adults. Finally, no country has yet described the nationwide public health impact of a national COVID-19 vaccination campaign.
This analysis of nationwide surveillance data, done in a period when SARS-CoV-2 variant B.1.1.7 was the dominant strain, provides precise real-world estimates of the high effectiveness of two doses of BNT162b2 against a range of SARS-CoV-2 outcomes, including symptomatic and asymptomatic infection and hospitalisation or death due to COVID-19. The median follow-up time of 7 weeks after the second dose for vaccinated individuals was longer than that in previous reports. Marked and sustained declines in the incidence of SARS-CoV-2 infections were observed in all age groups as the percentage of individuals vaccinated with two BNT162b2 doses began to rise, thereby showing, at a national level, the beneficial public health impact of a nationwide vaccination campaign.
Vaccination with two doses of BNT162b2 has high efficacy and effectiveness against a range of SARS-CoV-2 outcomes, including among older adults (aged ≥85 years), offering hope that COVID-19 vaccination will eventually control the pandemic. These findings are of international importance as vaccination programmes ramp up across the rest of the world, suggesting that other countries can similarly achieve marked and sustained declines in SARS-CoV-2 incidence if they can achieve high vaccine uptake.
In a randomised controlled trial (RCT), two doses of the Pfizer–BioNTech mRNA COVID-19 vaccine BNT162b2 (international non-proprietary name tozinameran) had 95% efficacy against symptomatic laboratory-confirmed COVID-19 at least 7 days after the second dose in people aged 16 years or older with no evidence of existing or previous SARS-CoV-2 infection.
After emergency use authorisation of BNT162b2 in Israel on Dec 6, 2020, the Ministry of Health (MoH) launched a nationwide vaccination campaign to administer two doses of BNT162b2 to the 6·5 million people aged 16 years and older (71% of the population). On April 3, 2021, 61% of the population of Israel had received at least one dose of a COVID-19 vaccine, a proportion higher than that of any other country in the world.
Preliminary estimates of the effectiveness of one dose of BNT162b2 have been reported from Denmark, Israel, the UK, and the USA, and estimates for two doses of BNT162b2 have been described for a subset of the Israeli population enrolled in a health maintenance organisation.
However, no estimates of the effectiveness of two doses of BNT162b2 against a range of SARS-CoV-2 outcomes, including among older adults, have been reported. Furthermore, population-level estimates of the impact of a COVID-19 vaccine on the incidence of SARS-CoV-2 infections have not been reported.
In this study, we provide nationwide estimates of the effectiveness of two doses of BNT162b2 against a range of SARS-CoV-2 outcomes and to evaluate the nationwide public-health impact following the widespread introduction of the vaccine.
Study design and population
In this observational study, we analysed nationwide surveillance data from Jan 24 to April 3, 2021, to assess the effectiveness of the BNT162b2 vaccine against various SARS-CoV-2 outcomes. The study population consisted of residents of Israel (ie, the census population) aged 16 years and older. The start of the study period corresponded to 14 days after the first individuals received their second BNT162b2 dose.
Clalit (in which 54% of the population are enrolled), Maccabi (26%), Meuhedet (12%), and Leumit (8%).
All Israeli residents are assigned a unique identification number that enables data linkage in the national medical records database.
The Israel MoH planned, organised, and continues to lead the nationwide vaccination campaign, which began on Dec 20, 2020, and was initially targeted at people aged 65 years and older, health-care workers, and residents of long-term care facilities. Vaccine availability was subsequently expanded, approximately weekly, to younger age cohorts in 5-year intervals. Until Feb 28, 2021, because of an insufficient vaccine supply, individuals with a previous diagnosis of laboratory-confirmed SARS-CoV-2 infection were instructed to not seek vaccination, unless they were a resident of a long-term care facility. However, an unknown number of previously diagnosed people received vaccine. Immunisations were given at around 400 vaccination sites. At these sites, information about the administered vaccine was entered into the patient’s electronic health record and reported to the national database.
The analysis plan for this study was internally reviewed by senior management in the MoH Public Health Services and found to be compliant with all regulatory requirements including the MoH guidelines for human subject research. As no regulatory issues were identified, it was decided that a full ethical review was not necessary. The study followed the Strengthening the Reporting of Observational studies in Epidemiology guidelines.
Testing for SARS-CoV-2, including variant B.1.1.7
SARS-CoV-2 testing is free-of-charge and widely available in Israel. Testing is required for people returning from travel abroad, in close contact with an infected person, or with suggestive symptoms such as fever or acute respiratory illness. When seeking testing, individuals provide their identification number and a specimen is collected via nasal or nasopharyngeal swab. Specimens are tested, using national testing standards, at one of 48 clinical diagnostic laboratories with use of real-time PCR tests. B.1.1.7 prevalence was estimated on the basis of swabs tested at Leumit with the TaqPath COVID-19 test (Thermo Fisher Scientific, Pleasanton, CA, USA), which identifies spike gene target failure (SGTF) associated with gene mutations that cause deletions of amino acids 69 and 70 in the spike protein. Because these mutations are found in B.1.1.7, SGTF is used to estimate the prevalence of this variant.
Public health surveillance
MoH conducts surveillance for laboratory-confirmed SARS-CoV-2 infections, with mandatory daily reporting of PCR results by all diagnostic laboratories. An epidemiological investigation, including an interview about COVID-19 symptoms, is done for each SARS-CoV-2 infection, usually within 2 days of diagnosis. MoH also conducts surveillance of COVID-19-associated hospitalisations. Daily updates are received from all hospitals and linked to the national database using patients’ identification numbers. Hospitalisations are classified as severe (if a patient has a resting respiratory rate of >30 breaths per minute, oxygen saturation on room air of <94%, or a ratio of PaO2 to FiO2 of <300) or critical (in the event of mechanical ventilation, shock, or cardiac, hepatic, or renal failure). In accordance with national guidelines, health-care providers attributed any hospitalisations and deaths among individuals with laboratory-confirmed SARS-CoV-2 infection to COVID-19.
Vaccine effectiveness estimates were assessed against six SARS-CoV-2 outcomes, comprising asymptomatic infections and five other hierarchical laboratory-confirmed outcomes: all SARS-CoV-2 infections (symptomatic and asymptomatic), symptomatic COVID-19 cases, and COVID-19-related hospitalisations, severe or critical hospitalisations (including those who died), and deaths. Asymptomatic infection was defined as a person with laboratory-confirmed SARS-CoV-2 infection who reported no fever and no respiratory symptoms during the symptom interview portion of the epidemiological investigation, and who was not subsequently hospitalised for or did not die from COVID-19.
Individuals were defined as unvaccinated if they had not received any doses of BNT162b2, and as fully vaccinated if at least 7 days had passed since receiving the second dose of BNT162b2. Incidence rates were calculated for unvaccinated and fully vaccinated individuals aged 16 years and older for each SARS-CoV-2 outcome after excluding people with previous laboratory-confirmed SARS-CoV-2 infection. Data were stratified by age group (16–24, 25–34, 35–44, 45–54, 55–64, 65–74, 75–84, and ≥85 years, based on 2020 census data), sex, and calendar week. In the primary analysis, cases were categorised as vaccinated if the date of laboratory confirmation of infection occurred at least 7 days after the second dose of BNT162b2. Cases were excluded from the analysis if they had received only one dose, or had received two doses of BNT162b2 and fewer than 7 days had passed since the second dose. Person-days for the fully vaccinated group were ascertained each day by multiplying the proportion of people who were fully vaccinated with two doses of BNT162b2 by the census estimates for each age stratum. Person-days for the unvaccinated group were determined each day by subtracting the number of person-days contributed by those who were vaccinated from the total census population for each age stratum; this process was repeated, summed, and aggregated for each day of the study period. Individuals with previous SARS-CoV-2 infection were excluded from person-day estimates. Using STATA (version 15), a negative binomial regression model (nbreg command), which is better suited for over-dispersion of variance than the traditional Poisson regression method,
was used to derive incidence rate ratios (IRRs) with 95% CIs for each outcome adjusted for age group, sex, and calendar week. The exposure command was used to account for varying patient-days across strata.
Vaccine effectiveness estimates were calculated as (1 – IRR) × 100. In sensitivity analyses, vaccine effectiveness estimates were also calculated with the same method for people who had received two BNT162b2 doses and for whom at least 14 days had passed after the second dose, as well as for those who had received one dose and for whom 14–21 days had passed after the first dose.
Role of the funding source
The Israel MoH and Pfizer separately provided in-kind support to this study. No funding was exchanged between the Israel MoH and Pfizer. MoH and Pfizer were involved in the study design and writing of the report, and approved the decision to submit for publication.
The vaccination campaign was launched on Dec 20, 2020, around the time of a surge in SARS-CoV-2 infections in Israel that resulted in a nationwide lockdown on Dec 27, 2020 (figure 1). Additional lockdown restrictions were implemented on Jan 8, 2021. Daily SARS-CoV-2 infections increased in December, 2020, peaking at 10 213 on Jan 20, 2021. Phased reopening occurred on Feb 7 and Feb 21, 2021, and the lockdown was lifted on March 7, 2021.
Créditos: Comité científico Covid