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      COVID-19 hospital admissions and deaths after BNT162b2 and ChAdOx1 nCoV-19 vaccinations in 2·57 million people in Scotland (EAVE II): a prospective cohort study

      research-article
      , PhD a , , , Prof, PhD b , , , Prof, PhD a , , , MSci c , , , PhD a , , MSc b , , PhD a , , PhD c , , PhD d , , PhD c , , PhD c , , PhD d , , FFPH d , , PhD c , , Prof Sir, MD e , , Prof, MD f , , PhD c , , BSc g , , FRCGP g , , MSc h , , MSc h , , PhD h , , MBChB d , , PhD c , d , , PhD i , , Prof, MD i , , FMedSci i , , Prof, PhD c , , Prof, PhD c , j , , Prof, PhD d , k , , Prof, MD c , *
      The Lancet. Respiratory Medicine
      The Author(s). Published by Elsevier Ltd.
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          Abstract

          Background

          The UK COVID-19 vaccination programme has prioritised vaccination of those at the highest risk of COVID-19 mortality and hospitalisation. The programme was rolled out in Scotland during winter 2020–21, when SARS-CoV-2 infection rates were at their highest since the pandemic started, despite social distancing measures being in place. We aimed to estimate the frequency of COVID-19 hospitalisation or death in people who received at least one vaccine dose and characterise these individuals.

          Methods

          We conducted a prospective cohort study using the Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II) national surveillance platform, which contained linked vaccination, primary care, RT-PCR testing, hospitalisation, and mortality records for 5·4 million people (around 99% of the population) in Scotland. Individuals were followed up from receiving their first dose of the BNT162b2 (Pfizer–BioNTech) or ChAdOx1 nCoV-19 (Oxford–AstraZeneca) COVID-19 vaccines until admission to hospital for COVID-19, death, or the end of the study period on April 18, 2021. We used a time-dependent Poisson regression model to estimate rate ratios (RRs) for demographic and clinical factors associated with COVID-19 hospitalisation or death 14 days or more after the first vaccine dose, stratified by vaccine type.

          Findings

          Between Dec 8, 2020, and April 18, 2021, 2 572 008 individuals received their first dose of vaccine—841 090 (32·7%) received BNT162b2 and 1 730 918 (67·3%) received ChAdOx1. 1196 (<0·1%) individuals were admitted to hospital or died due to COVID-19 illness (883 hospitalised, of whom 228 died, and 313 who died due to COVID-19 without hospitalisation) 14 days or more after their first vaccine dose. These severe COVID-19 outcomes were associated with older age (≥80 years vs 18–64 years adjusted RR 4·75, 95% CI 3·85–5·87), comorbidities (five or more risk groups vs less than five risk groups 4·24, 3·34–5·39), hospitalisation in the previous 4 weeks (3·00, 2·47–3·65), high-risk occupations (ten or more previous COVID-19 tests vs less than ten previous COVID-19 tests 2·14, 1·62–2·81), care home residence (1·63, 1·32–2·02), socioeconomic deprivation (most deprived quintile vs least deprived quintile 1·57, 1·30–1·90), being male (1·27, 1·13–1·43), and being an ex-smoker (ex-smoker vs non-smoker 1·18, 1·01–1·38). A history of COVID-19 before vaccination was protective (0·40, 0·29–0·54).

          Interpretation

          COVID-19 hospitalisations and deaths were uncommon 14 days or more after the first vaccine dose in this national analysis in the context of a high background incidence of SARS-CoV-2 infection and with extensive social distancing measures in place. Sociodemographic and clinical features known to increase the risk of severe disease in unvaccinated populations were also associated with severe outcomes in people receiving their first dose of vaccine and could help inform case management and future vaccine policy formulation.

          Funding

          UK Research and Innovation (Medical Research Council), Research and Innovation Industrial Strategy Challenge Fund, Scottish Government, and Health Data Research UK.

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          Most cited references28

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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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            The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies.

            Much biomedical research is observational. The reporting of such research is often inadequate, which hampers the assessment of its strengths and weaknesses and of a study's generalisability. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) initiative developed recommendations on what should be included in an accurate and complete report of an observational study. We defined the scope of the recommendations to cover three main study designs: cohort, case-control, and cross-sectional studies. We convened a 2-day workshop in September, 2004, with methodologists, researchers, and journal editors to draft a checklist of items. This list was subsequently revised during several meetings of the coordinating group and in e-mail discussions with the larger group of STROBE contributors, taking into account empirical evidence and methodological considerations. The workshop and the subsequent iterative process of consultation and revision resulted in a checklist of 22 items (the STROBE statement) that relate to the title, abstract, introduction, methods, results, and discussion sections of articles.18 items are common to all three study designs and four are specific for cohort, case-control, or cross-sectional studies.A detailed explanation and elaboration document is published separately and is freely available on the websites of PLoS Medicine, Annals of Internal Medicine, and Epidemiology. We hope that the STROBE statement will contribute to improving the quality of reporting of observational studies
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              Is Open Access

              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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                Author and article information

                Journal
                Lancet Respir Med
                Lancet Respir Med
                The Lancet. Respiratory Medicine
                The Author(s). Published by Elsevier Ltd.
                2213-2600
                2213-2619
                29 September 2021
                29 September 2021
                Affiliations
                [a ]School of Medicine, University of St Andrews, St Andrews, UK
                [b ]MRC/CSO Social & Public Health Sciences Unit, University of Glasgow, Glasgow, UK
                [c ]Usher Institute, The University of Edinburgh, Edinburgh, UK
                [d ]Public Health Scotland, Glasgow, UK
                [e ]Academic Primary Care, University of Aberdeen School of Medicine and Dentistry, Aberdeen, UK
                [f ]School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, UK
                [g ]BREATHE—The Health Data Research Hub for Respiratory Health, Edinburgh, UK
                [h ]Population Data Science, Swansea University Medical School, Swansea, UK
                [i ]Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
                [j ]School of Health, Wellington Faculty of Health, Victoria University of Wellington, Wellington, New Zealand
                [k ]Department of Mathematics and Statistics, University of Strathclyde, Glasgow, UK
                Author notes
                [* ]Correspondence to: Professor Aziz Sheikh, Usher Institute, The University of Edinburgh, Edinburgh EH8 9DX, UK
                [†]

                Contributed equally

                Article
                S2213-2600(21)00380-5
                10.1016/S2213-2600(21)00380-5
                8480963
                34599903
                4abd2ba6-adb8-4dc7-a3e1-2c2d00aad21e
                © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

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