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      Effectiveness of COVID-19 mRNA vaccine in preventing infection against Omicron strain: Findings from the Hiroshima Prefecture COVID-19 version J-SPEED for PCR center

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          Abstract

          Background and purpose

          Despite the widespread adoption of various preventive measures since the spread of COVID-19, there remains a lack of consensus on universally acknowledged best practices. However, the significance of vaccination has risen to prominence as a paramount preventive strategy. Numerous investigations have demonstrated vaccine effectiveness against the omicron strain in severe disease and symptomatic disease, however, the scope of research pertaining to vaccine effectiveness in preventing infection is presently limited. Therefore, the current study aimed to evaluate COVID-19 mRNA (Pfizer-BioNTech BNT162b2 or Moderna mRNA-1273) vaccine effectiveness in preventing infection.

          Methods

          We conducted a test-negative case-control study using a dataset of 117,335 individuals. These data were collected through the COVID-19 J-SPEED form in the PCR center at Hiroshima Prefecture, Japan from 1 February to 17 March 2022. We estimated propensity score matching for vaccine status based on participants’ demographic characteristics. Subsequently, odds ratio was calculated from logistic regression to determine the association between vaccination status and test positivity rate adjusting for symptoms, exposure to close contact, and previous infection history. Vaccine effectiveness was defined as (1 –aORs) ×100%.

          Results

          The PCR test positivity rates were 7.9%, 4.5%, and 2.8% for the non-vaccinated (non-vaccinated, vaccinated with a single dose, and vaccinated with two doses less than 14 days ago), vaccinated with two doses (vaccinated over 14 days ago), and three doses, respectively. In unadjusted and adjusted analyses, vaccine effectiveness of two doses against infection were 38.5% (95% confidence interval [CI]: 32.8%–43.8%) and 34.7% (95%CI: 28.4%–40.4%), respectively, compared to non-vaccinated group. Vaccine effectiveness of three doses were 33.8% (95%CI: 25.0%–41.5%) and 26.4% (95%CI: 16.4%–35.2%), respectively, compared to those vaccinated with two doses.

          Conclusions

          These results illustrate the protective effect of mRNA vaccines against Omicron strain infections and emphasize the significance of completing the suggested vaccination schedule.

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          Most cited references24

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

          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.
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            Optimal caliper widths for propensity-score matching when estimating differences in means and differences in proportions in observational studies

            In a study comparing the effects of two treatments, the propensity score is the probability of assignment to one treatment conditional on a subject's measured baseline covariates. Propensity-score matching is increasingly being used to estimate the effects of exposures using observational data. In the most common implementation of propensity-score matching, pairs of treated and untreated subjects are formed whose propensity scores differ by at most a pre-specified amount (the caliper width). There has been a little research into the optimal caliper width. We conducted an extensive series of Monte Carlo simulations to determine the optimal caliper width for estimating differences in means (for continuous outcomes) and risk differences (for binary outcomes). When estimating differences in means or risk differences, we recommend that researchers match on the logit of the propensity score using calipers of width equal to 0.2 of the standard deviation of the logit of the propensity score. When at least some of the covariates were continuous, then either this value, or one close to it, minimized the mean square error of the resultant estimated treatment effect. It also eliminated at least 98% of the bias in the crude estimator, and it resulted in confidence intervals with approximately the correct coverage rates. Furthermore, the empirical type I error rate was approximately correct. When all of the covariates were binary, then the choice of caliper width had a much smaller impact on the performance of estimation of risk differences and differences in means. Copyright © 2010 John Wiley & Sons, Ltd.
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              Effectiveness of mRNA BNT162b2 COVID-19 vaccine up to 6 months in a large integrated health system in the USA: a retrospective cohort study

              Background Vaccine effectiveness studies have not differentiated the effect of the delta (B.1.617.2) variant and potential waning immunity in observed reductions in effectiveness against SARS-CoV-2 infections. We aimed to evaluate overall and variant-specific effectiveness of BNT162b2 (tozinameran, Pfizer–BioNTech) against SARS-CoV-2 infections and COVID-19-related hospital admissions by time since vaccination among members of a large US health-care system. Methods In this retrospective cohort study, we analysed electronic health records of individuals (≥12 years) who were members of the health-care organisation Kaiser Permanente Southern California (CA, USA), to assess BNT162b2 vaccine effectiveness against SARS-CoV-2 infections and COVID-19-related hospital admissions for up to 6 months. Participants were required to have 1 year or more previous membership of the organisation. Outcomes comprised SARS-CoV-2 PCR-positive tests and COVID-19-related hospital admissions. Effectiveness calculations were based on hazard ratios from adjusted Cox models. This study was registered with ClinicalTrials.gov , NCT04848584. Findings Between Dec 14, 2020, and Aug 8, 2021, of 4 920 549 individuals assessed for eligibility, we included 3 436 957 (median age 45 years [IQR 29–61]; 1 799 395 [52·4%] female and 1 637 394 [47·6%] male). For fully vaccinated individuals, effectiveness against SARS-CoV-2 infections was 73% (95% CI 72–74) and against COVID-19-related hospital admissions was 90% (89–92). Effectiveness against infections declined from 88% (95% CI 86–89) during the first month after full vaccination to 47% (43–51) after 5 months. Among sequenced infections, vaccine effectiveness against infections of the delta variant was high during the first month after full vaccination (93% [95% CI 85–97]) but declined to 53% [39–65] after 4 months. Effectiveness against other (non-delta) variants the first month after full vaccination was also high at 97% (95% CI 95–99), but waned to 67% (45–80) at 4–5 months. Vaccine effectiveness against hospital admissions for infections with the delta variant for all ages was high overall (93% [95% CI 84–96]) up to 6 months. Interpretation Our results provide support for high effectiveness of BNT162b2 against hospital admissions up until around 6 months after being fully vaccinated, even in the face of widespread dissemination of the delta variant. Reduction in vaccine effectiveness against SARS-CoV-2 infections over time is probably primarily due to waning immunity with time rather than the delta variant escaping vaccine protection. Funding Pfizer.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: MethodologyRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: MethodologyRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: MethodologyRole: Writing – review & editing
                Role: Writing – review & editing
                Role: Writing – review & editing
                Role: Funding acquisitionRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Funding acquisitionRole: MethodologyRole: SupervisionRole: Writing – review & editing
                Role: Editor
                Journal
                PLOS Glob Public Health
                PLOS Glob Public Health
                plos
                PLOS Global Public Health
                Public Library of Science (San Francisco, CA USA )
                2767-3375
                17 April 2024
                2024
                : 4
                : 4
                : e0003071
                Affiliations
                [1 ] Department of Public Health and Health Policy, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
                [2 ] Medical Economics Division, Health Insurance Bureau, Ministry of Health, Labour and Welfare, Tokyo, Japan
                [3 ] Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan
                [4 ] Medical Policy Office, Hiroshima University, Hiroshima, Japan
                Yale School of Medicine: Yale University School of Medicine, UNITED STATES
                Author notes

                The authors have declared that no competing interests exist.

                Author information
                https://orcid.org/0000-0003-3198-835X
                https://orcid.org/0000-0002-5669-4051
                Article
                PGPH-D-22-01418
                10.1371/journal.pgph.0003071
                11023596
                38630696
                282b9840-b83e-41c5-a8bf-e634d65e1b05
                © 2024 Yumiya et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 1 September 2022
                : 7 March 2024
                Page count
                Figures: 1, Tables: 2, Pages: 10
                Funding
                Funded by: AMED
                Award ID: JP20fk0108453h0001&21fk0108550h0001
                Award Recipient :
                Funded by: AMED
                Award ID: JP20fk0108453h0001&21fk0108550h0001
                Award Recipient :
                This research was supported by the AMED (grant no. JP20fk0108453h0001, JP21fk0108550h0001) to JT & TK. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
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                Custom metadata
                The data used in the study were collected during the public health response to novel coronavirus infection in Hiroshima Prefecture, and the data are jointly managed by Hiroshima Prefecture and Hiroshima University. Researchers need to apply for and receive approval from the Hiroshima Prefecture in order to access the data. Please contact covid-19bunseki@ 123456pref.hiroshima.jp .
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