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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.)
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.
Messenger RNA (mRNA) BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) COVID-19 vaccines have been shown to be effective in preventing symptomatic COVID-19 in randomized placebo-controlled Phase III trials ( 1 , 2 ); however, the benefits of these vaccines for preventing asymptomatic and symptomatic SARS-CoV-2 (the virus that causes COVID-19) infection, particularly when administered in real-world conditions, is less well understood. Using prospective cohorts of health care personnel, first responders, and other essential and frontline workers* in eight U.S. locations during December 14, 2020–March 13, 2021, CDC routinely tested for SARS-CoV-2 infections every week regardless of symptom status and at the onset of symptoms consistent with COVID-19–associated illness. Among 3,950 participants with no previous laboratory documentation of SARS-CoV-2 infection, 2,479 (62.8%) received both recommended mRNA doses and 477 (12.1%) received only one dose of mRNA vaccine. † Among unvaccinated participants, 1.38 SARS-CoV-2 infections were confirmed by reverse transcription–polymerase chain reaction (RT-PCR) per 1,000 person-days. § In contrast, among fully immunized (≥14 days after second dose) persons, 0.04 infections per 1,000 person-days were reported, and among partially immunized (≥14 days after first dose and before second dose) persons, 0.19 infections per 1,000 person-days were reported. Estimated mRNA vaccine effectiveness for prevention of infection, adjusted for study site, was 90% for full immunization and 80% for partial immunization. These findings indicate that authorized mRNA COVID-19 vaccines are effective for preventing SARS-CoV-2 infection, regardless of symptom status, among working-age adults in real-world conditions. COVID-19 vaccination is recommended for all eligible persons. HEROES-RECOVER ¶ is a network of longitudinal cohorts in eight locations (Phoenix, Tucson, and other areas in Arizona; Miami, Florida; Duluth, Minnesota; Portland, Oregon; Temple, Texas; and Salt Lake City, Utah) that share a common protocol and methods.** Enrollment in this longitudinal study started in July 2020 and included health care personnel, first responders, and other essential and frontline workers who provided written consent. The current vaccine effectiveness analytic study period began on the first day of vaccine administration at study sites (December 14–18, 2020) and ended March 13, 2021. Active surveillance for symptoms consistent with COVID-19–associated illness (defined as fever, chills, cough, shortness of breath, sore throat, diarrhea, muscle aches, or loss of smell or taste) occurred through weekly text messages, e-mails, and direct participant or medical record reports. Participants self-collected a midturbinate nasal swab weekly, regardless of COVID-19–associated illness symptom status and collected an additional nasal swab and saliva specimen at the onset of COVID-19–associated illness. Specimens shipped on cold packs were tested by RT-PCR assay at Marshfield Clinic Laboratory (Marshfield, Wisconsin) to determine SARS-CoV-2 infections (PCR-confirmed infection). Receipt of COVID-19 vaccines was documented by multiple methods: by self-report in electronic surveys, by telephone interviews, and through direct upload of vaccine card images at all sites; records were also extracted from electronic medical records at the Minnesota, Oregon, Texas, and Utah sites. Among 5,077 participants, those with laboratory documentation of SARS-CoV-2 infection before enrollment starting in July 2020 (608) or identified as part of longitudinal surveillance up until the first day of vaccine administration (240) were excluded. Another 279 were excluded because of low participation (i.e., failed to complete surveillance for ≥20% of study weeks and did not contribute COVID-19–associated illness specimens). Overall, 3,950 participants in the vaccine effectiveness analytic sample were analyzed. Hazard ratios were estimated by the Andersen-Gill extension of the Cox proportional hazards model, which accounted for time-varying vaccination status. Hazard ratios of unvaccinated person-days to partial immunization person-days (≥14 days after first dose and before second dose) and to full immunization person-days (≥14 days after second dose) were calculated separately. The 13 person-days between vaccine administration and partial or full immunization were considered excluded at-risk person-time because immunity was considered to be indeterminate. Unadjusted vaccine effectiveness was calculated as 100% × (1−hazard ratio). An adjusted vaccine effectiveness model included study site as a covariate. All analyses were conducted with SAS (version 9.4; SAS Institute). This activity was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy. †† Approximately one half of the participants (52.6%) were from the Arizona study sites (Table 1). Participants included physicians and other clinical leads (primary health care personnel) (21.1%), nurses and other allied health care personnel (33.8%), first responders (21.6%), and other essential and frontline workers (23.5%). The majority of participants were female (62.1%), aged 18–49 years (71.9%), White (86.3%), and non-Hispanic (82.9%) and had no chronic medical conditions (68.9%). Over the 13-week study period, adherence to weekly surveillance reporting and specimen collection was high (median = 100%; interquartile range = 82%–100%). TABLE 1 Characteristics of health care personnel, first responders, and other essential and frontline workers with reverse transcription–polymerase chain reaction (RT-PCR)–confirmed SARS-CoV-2 infections and percentage receiving one or more doses of a messenger RNA (mRNA) COVID-19 vaccine — eight U.S. locations, December 14, 2020–March 13, 2021 Characteristic No. (column %) of participants SARS-CoV-2 infection Unvaccinated Vaccinated with ≥1 dose* No. (row %) p-value† No. (row %) No. (row %) p-value† Total 3,950 (100) 205 (5.2) — 989 (25.0) 2,961 (75.0) — Cohort location Phoenix, Arizona 555 (14.1) 39 (7.0§) 14 days after first dose) of 60% (95% CI = 38%–74%) against PCR-confirmed infection identified by records review in Israel ( 5 ). This finding is also consistent with early descriptive findings of SARS-CoV-2 employee and clinical testing results by mRNA vaccination status in the United States ( 8 , 9 ). The findings in this report are subject to at least three limitations. First, vaccine effectiveness point estimates should be interpreted with caution given the moderately wide CIs attributable in part to the limited number of postimmunization PCR-confirmed infections observed. Second, this also precluded making product-specific vaccine effectiveness estimates and limited the ability to adjust for potential confounders; however, effects were largely unchanged when study site was included in an adjusted vaccine effectiveness model and when adjusted for sex, age, ethnicity, and occupation separately in sensitivity analyses. Finally, self-collection of specimens and delays in shipments could reduce sensitivity of virus detection by PCR ( 10 ); if this disproportionately affected those who received the vaccine (e.g., because of possible vaccine attenuation of virus shedding), vaccine effectiveness would be overestimated. The scientific rigor of these findings is enhanced by its prospective design and the participants’ very high adherence to weekly specimen collection. As the study progresses, viruses will be genetically characterized to examine the viral features of breakthrough infections. Given that there is uncertainty related to the number of days required to develop immunity postvaccination ( 3 – 5 , 7 ), future research examining vaccine effectiveness at different intervals is warranted. These interim vaccine effectiveness findings for both Pfizer-BioNTech’s and Moderna’s mRNA vaccines in real-world conditions complement and expand upon the vaccine effectiveness estimates from other recent studies ( 3 – 5 ) and demonstrate that current vaccination efforts are resulting in substantial preventive benefits among working-age adults. They reinforce CDC’s recommendation of full 2-dose immunization with mRNA vaccines. COVID-19 vaccination is recommended for all eligible persons, which currently varies by location in the United States. Summary What is already known about this topic? Messenger RNA (mRNA) COVID-19 vaccines have been shown to be effective in preventing symptomatic SARS-CoV-2 infection in randomized placebo-controlled Phase III trials. What is added by this report? Prospective cohorts of 3,950 health care personnel, first responders, and other essential and frontline workers completed weekly SARS-CoV-2 testing for 13 consecutive weeks. Under real-world conditions, mRNA vaccine effectiveness of full immunization (≥14 days after second dose) was 90% against SARS-CoV-2 infections regardless of symptom status; vaccine effectiveness of partial immunization (≥14 days after first dose but before second dose) was 80%. What are the implications for public health practice? Authorized mRNA COVID-19 vaccines are effective for preventing SARS-CoV-2 infection in real-world conditions. COVID-19 vaccination is recommended for all eligible persons.
Members of the National Study Group for COVID-19 Vaccination are listed in the
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Funding
Funded by: Biomedical Research Program and the Biostatistics, Epidemiology, and Biomathematics
Research Core, both at Weill Cornell Medicine-Qatar, the Ministry of Public Health
and Hamad Medical Corporation, FundRef http://dx.doi.org/10.13039/100007833;
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