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      COVID-19 vaccinations are associated with reduced fatality rates: Evidence from cross-county quasi-experiments

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      Journal of Global Health
      International Society of Global Health

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          Abstract

          Background

          Scientists have demonstrated the efficacy of vaccines against severe acute respiratory syndrome coronavirus 2 in randomized controlled trials. However, the extent to which reductions in COVID-19 case fatality ratio (CFR) are attributable to mass vaccination in the real world remains unclear. This study evaluated the association of COVID-19 vaccine coverage with CFR on a global scale.

          Methods

          The sample was a longitudinal data set of 90 countries over 25 weeks, from the first week of November 2020 to the third week of April 2021. CFR was measured in deaths per 100 COVID-19 confirmed cases; vaccine coverage was defined as the number of people who received at least one vaccine dose per 10 people in the total population. Data were retrieved from open-access databases, including Our World in Data and the Oxford COVID-19 Government Response Tracker. A country-level random effects model was used; a comprehensive set of variables for country characteristics and nonpharmaceutical interventions were included.

          Results

          A 10% increase in vaccine coverage was associated with a 7.6% reduction in the CFR (95% confidence interval (CI = -12.6 to -2.7%, P = 0.002). This association was stronger in countries with more effective governments (-8.3%; 95% CI = -13.6 to -3.1%, P = 0.002) and higher transport infrastructure quality (-8.1%; 95% CI = -13.3 to -2.9%, P = 0.002). Moreover, the vaccine coverage was associated with a reduced CFR in a dose-dependent manner. When vaccine coverage achieved 0.8 to 1.6, 1.6 to 3.2 and ≥3.2 per 10 people, the CFR reduced by 12.7% (95 CI = -21.8 to -3.6%, P = 0.006), 21.2% (95 CI = -33.9 to -8.5%, P = 0.001) and 31.3% (95 CI = -51.5 to -11.0%, P = 0.002), respectively as compared with no vaccination.

          Conclusions

          Our results provide supporting evidence that vaccination is critical to preventing deaths among infected people. Vaccination programmes have yielded significant health benefits in certain countries. However, globally, a large gap remains between observed and achievable fatality reductions. Continuous improvement in vaccine coverage will be critical to transforming efficacious vaccines into desired health outcomes.

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          Most cited references23

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          Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine

          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.)
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            Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK

            Background A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. Methods This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. Findings Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; p interaction =0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. Interpretation ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. Funding UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D’Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca.
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              Estimating the effects of non-pharmaceutical interventions on COVID-19 in Europe

              Following the detection of the new coronavirus1 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its spread outside of China, Europe has experienced large epidemics of coronavirus disease 2019 (COVID-19). In response, many European countries have implemented non-pharmaceutical interventions, such as the closure of schools and national lockdowns. Here we study the effect of major interventions across 11 European countries for the period from the start of the COVID-19 epidemics in February 2020 until 4 May 2020, when lockdowns started to be lifted. Our model calculates backwards from observed deaths to estimate transmission that occurred several weeks previously, allowing for the time lag between infection and death. We use partial pooling of information between countries, with both individual and shared effects on the time-varying reproduction number (Rt). Pooling allows for more information to be used, helps to overcome idiosyncrasies in the data and enables more-timely estimates. Our model relies on fixed estimates of some epidemiological parameters (such as the infection fatality rate), does not include importation or subnational variation and assumes that changes in Rt are an immediate response to interventions rather than gradual changes in behaviour. Amidst the ongoing pandemic, we rely on death data that are incomplete, show systematic biases in reporting and are subject to future consolidation. We estimate that-for all of the countries we consider here-current interventions have been sufficient to drive Rt below 1 (probability Rt < 1.0 is greater than 99%) and achieve control of the epidemic. We estimate that across all 11 countries combined, between 12 and 15 million individuals were infected with SARS-CoV-2 up to 4 May 2020, representing between 3.2% and 4.0% of the population. Our results show that major non-pharmaceutical interventions-and lockdowns in particular-have had a large effect on reducing transmission. Continued intervention should be considered to keep transmission of SARS-CoV-2 under control.
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                Author and article information

                Journal
                J Glob Health
                J Glob Health
                JGH
                Journal of Global Health
                International Society of Global Health
                2047-2978
                2047-2986
                17 July 2021
                2021
                : 11
                : 05019
                Affiliations
                [1 ]Department of Business Management, National Sun Yat-sen University, Kaohsiung, Taiwan
                [2 ]Research Center for Epidemic Prevention, National Yang Ming Chiao Tung University, Taipei, Taiwan
                [3 ]Institute of Biomedical Informatics, National Yang Ming Chiao Tung University, Taipei, Taiwan
                [4 ]Division of Translational Research, Taipei Veterans General Hospital, Taipei, Taiwan
                [5 ]Department of Public Health, China Medical University, Taichung, Taiwan
                Author notes
                Correspondence to:
Chun-Ying Wu, M.D., MPH, Ph.D.
Institute of Biomedical Informatics
College of Medicine
National Yang Ming Chiao Tung University
No. 155, Section 2
Linong Street, Taipei 11221
Taiwan
 cywu4@ 123456ym.edu.tw
                Article
                jogh-11-05019
                10.7189/jogh.11.05019
                8285768
                34326999
                27fc1ca3-96f9-4ed1-a746-9b92b61fe57f
                Copyright © 2021 by the Journal of Global Health. All rights reserved.

                This work is licensed under a Creative Commons Attribution 4.0 International License.

                History
                Page count
                Figures: 4, Tables: 3, Equations: 1, References: 30, Pages: 9
                Categories
                Research Theme 1: COVID-19 Pandemic

                Public health
                Public health

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