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      COVID-19: Third dose booster vaccine effectiveness against breakthrough coronavirus infection, hospitalisations and death in patients with cancer: A population-based study

      research-article
      Author(s): , (DPhil) ∗ , , (MSC) 1 , , (MSci) 1 , , (MRes) 1 , , (MBChB) 1 , , (MD) 1 , , (PhD) 1 , , , , (PhD), , (PhD), , (FRCR), , (PhD), , (MBBChir), , (PhD), , (MBChB), , Hari, (MBBS), , (BSc), , (MD), , (MBChB), , (PhD), , (DPhil), , (MRCP), , NCRI Consumer Forum, , (PhD), , (MRCP), , (MRes), , , , (PhD), , (MRCP), , (FRCP), , (PhD), , (FRCR), , (MRCP), , (MMath), , , (PhD), , (BMBCh), , (FRCP), , (FRCS), , (MD), , (FRCP), , (FRCP), , (PhD), , (MD), , (PhD) 2 , , (PhD) 2 , , (MD) 2 , UK Coronavirus Cancer Programme
      Publication date (Electronic):
      Journal: European Journal of Cancer
      Publisher: The Author(s). Published by Elsevier Ltd.
      Keywords: COVID-19, cancer, vaccination, effectiveness, SARS-CoV-2, third dose, booster

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          Abstract

          Purpose

          People living with cancer and haematological malignancies are at increased risk of hospitalisation and death following infection with acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Coronavirus third dose vaccine boosters are proposed to boost waning immune responses in immunocompromised individuals and increase coronavirus protection; however, their effectiveness has not yet been systematically evaluated.

          Methods

          This study is a population-scale real-world evaluation of the United Kingdom’s third dose vaccine booster programme for cancer patients from 8 th December 2020 to 7 th December 2021. The cancer cohort comprises individuals from Public Health England’s national cancer dataset, excluding individuals less than 18 years. A test-negative case-control design was used to assess third dose booster vaccine effectiveness. Multivariable logistic regression models were fitted to compare risk in the cancer cohort relative to the general population.

          Results

          The cancer cohort comprised of 2,258,553 tests from 361,098 individuals. Third dose boosters were evaluated by reference to 87,039,743 polymerase chain reaction (PCR) coronavirus tests. Vaccine effectiveness against breakthrough infections, symptomatic infections, coronavirus hospitalisation and death in cancer patients were 59.1%, 62.8%, 80.5% and 94.5% respectively. Lower vaccine effectiveness was associated with a cancer diagnosis within 12 months, lymphoma, recent systemic anti-cancer therapy (SACT) or radiotherapy. Lymphoma patients had low levels of protection from symptomatic disease. In spite of third dose boosters, following multivariable adjustment, individuals with cancer remain at increased risk of coronavirus hospitalisation and death compared to the population control (OR 3.38, 3.01 respectively. p<0.001 for both).

          Conclusions

          Third dose boosters are effective for most individuals with cancer, increasing protection from coronavirus. However, their effectiveness is heterogenous, and lower than the general population. Many patients with cancer will remain at increased risk of coronavirus infections, even after 3 doses. In the case of patients with lymphoma, there is a particularly strong disparity of vaccine effectiveness against breakthrough infection and severe disease. Breakthrough infections will disrupt cancer care and treatment with potentially adverse consequences on survival outcomes. The data support the role of vaccine boosters in preventing severe disease, and further pharmacological intervention to prevent transmission and aid viral clearance to limit disruption of cancer care as the delivery of care continues to evolve during the coronavirus pandemic.

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          Effectiveness of Covid-19 Vaccines against the B.1.617.2 (Delta) Variant

          Jamie Lopez Bernal, Nick Andrews, Charlotte Gower … (2021)
          Background The B.1.617.2 (delta) variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (Covid-19), has contributed to a surge in cases in India and has now been detected across the globe, including a notable increase in cases in the United Kingdom. The effectiveness of the BNT162b2 and ChAdOx1 nCoV-19 vaccines against this variant has been unclear. Methods We used a test-negative case–control design to estimate the effectiveness of vaccination against symptomatic disease caused by the delta variant or the predominant strain (B.1.1.7, or alpha variant) over the period that the delta variant began circulating. Variants were identified with the use of sequencing and on the basis of the spike ( S ) gene status. Data on all symptomatic sequenced cases of Covid-19 in England were used to estimate the proportion of cases with either variant according to the patients’ vaccination status. Results Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) was notably lower among persons with the delta variant (30.7%; 95% confidence interval [CI], 25.2 to 35.7) than among those with the alpha variant (48.7%; 95% CI, 45.5 to 51.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 93.7% (95% CI, 91.6 to 95.3) among persons with the alpha variant and 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 74.5% (95% CI, 68.4 to 79.4) among persons with the alpha variant and 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant. Conclusions Only modest differences in vaccine effectiveness were noted with the delta variant as compared with the alpha variant after the receipt of two vaccine doses. Absolute differences in vaccine effectiveness were more marked after the receipt of the first dose. This finding would support efforts to maximize vaccine uptake with two doses among vulnerable populations. (Funded by Public Health England.)
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            Clinical impact of COVID-19 on patients with cancer (CCC19): a cohort study

            Nicole M Kuderer, Toni K. Choueiri, Dimpy Shah … (2020)
            Summary Background Data on patients with COVID-19 who have cancer are lacking. Here we characterise the outcomes of a cohort of patients with cancer and COVID-19 and identify potential prognostic factors for mortality and severe illness. Methods In this cohort study, we collected de-identified data on patients with active or previous malignancy, aged 18 years and older, with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection from the USA, Canada, and Spain from the COVID-19 and Cancer Consortium (CCC19) database for whom baseline data were added between March 17 and April 16, 2020. We collected data on baseline clinical conditions, medications, cancer diagnosis and treatment, and COVID-19 disease course. The primary endpoint was all-cause mortality within 30 days of diagnosis of COVID-19. We assessed the association between the outcome and potential prognostic variables using logistic regression analyses, partially adjusted for age, sex, smoking status, and obesity. This study is registered with ClinicalTrials.gov, NCT04354701, and is ongoing. Findings Of 1035 records entered into the CCC19 database during the study period, 928 patients met inclusion criteria for our analysis. Median age was 66 years (IQR 57–76), 279 (30%) were aged 75 years or older, and 468 (50%) patients were male. The most prevalent malignancies were breast (191 [21%]) and prostate (152 [16%]). 366 (39%) patients were on active anticancer treatment, and 396 (43%) had active (measurable) cancer. At analysis (May 7, 2020), 121 (13%) patients had died. In logistic regression analysis, independent factors associated with increased 30-day mortality, after partial adjustment, were: increased age (per 10 years; partially adjusted odds ratio 1·84, 95% CI 1·53–2·21), male sex (1·63, 1·07–2·48), smoking status (former smoker vs never smoked: 1·60, 1·03–2·47), number of comorbidities (two vs none: 4·50, 1·33–15·28), Eastern Cooperative Oncology Group performance status of 2 or higher (status of 2 vs 0 or 1: 3·89, 2·11–7·18), active cancer (progressing vs remission: 5·20, 2·77–9·77), and receipt of azithromycin plus hydroxychloroquine (vs treatment with neither: 2·93, 1·79–4·79; confounding by indication cannot be excluded). Compared with residence in the US-Northeast, residence in Canada (0·24, 0·07–0·84) or the US-Midwest (0·50, 0·28–0·90) were associated with decreased 30-day all-cause mortality. Race and ethnicity, obesity status, cancer type, type of anticancer therapy, and recent surgery were not associated with mortality. Interpretation Among patients with cancer and COVID-19, 30-day all-cause mortality was high and associated with general risk factors and risk factors unique to patients with cancer. Longer follow-up is needed to better understand the effect of COVID-19 on outcomes in patients with cancer, including the ability to continue specific cancer treatments. Funding American Cancer Society, National Institutes of Health, and Hope Foundation for Cancer Research.
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              Is Open Access

              Effectiveness of the Pfizer-BioNTech and Oxford-AstraZeneca vaccines on covid-19 related symptoms, hospital admissions, and mortality in older adults in England: test negative case-control study

              Jamie Lopez Bernal, Nick Andrews, Charlotte Gower … (2021)
              Objective To estimate the real world effectiveness of the Pfizer-BioNTech BNT162b2 and Oxford-AstraZeneca ChAdOx1-S vaccines against confirmed covid-19 symptoms (including the UK variant of concern B.1.1.7), admissions to hospital, and deaths. Design Test negative case-control study. Setting Community testing for covid-19 in England. Participants 156 930 adults aged 70 years and older who reported symptoms of covid-19 between 8 December 2020 and 19 February 2021 and were successfully linked to vaccination data in the National Immunisation Management System. Interventions Vaccination with BNT162b2 or ChAdOx1-S. Main outcome measures Primary outcomes were polymerase chain reaction confirmed symptomatic SARS-CoV-2 infections, admissions to hospital for covid-19, and deaths with covid-19. Results Participants aged 80 years and older vaccinated with BNT162b2 before 4 January 2021 had a higher odds of testing positive for covid-19 in the first nine days after vaccination (odds ratio up to 1.48, 95% confidence interval 1.23 to 1.77), indicating that those initially targeted had a higher underlying risk of infection. Vaccine effectiveness was therefore compared with the baseline post-vaccination period. Vaccine effects were noted 10 to 13 days after vaccination, reaching a vaccine effectiveness of 70% (95% confidence interval 59% to 78%), then plateauing. From 14 days after the second dose a vaccination effectiveness of 89% (85% to 93%) was found compared with the increased baseline risk. Participants aged 70 years and older vaccinated from 4 January (when ChAdOx1-S delivery commenced) had a similar underlying risk of covid-19 to unvaccinated individuals. With BNT162b2, vaccine effectiveness reached 61% (51% to 69%) from 28 to 34 days after vaccination, then plateaued. With ChAdOx1-S, effects were seen from 14 to 20 days after vaccination, reaching an effectiveness of 60% (41% to 73%) from 28 to 34 days, increasing to 73% (27% to 90%) from day 35 onwards. On top of the protection against symptomatic disease, a further 43% (33% to 52%) reduced risk of emergency hospital admission and 51% (37% to 62%) reduced risk of death was observed in those who had received one dose of BNT162b2. Participants who had received one dose of ChAdOx1-S had a further 37% (3% to 59%) reduced risk of emergency hospital admission. Follow-up was insufficient to assess the effect of ChAdOx1-S on mortality. Combined with the effect against symptomatic disease, a single dose of either vaccine was about 80% effective at preventing admission to hospital with covid-19 and a single dose of BNT162b2 was 85% effective at preventing death with covid-19. Conclusion Vaccination with either one dose of BNT162b2 or ChAdOx1-S was associated with a significant reduction in symptomatic covid-19 in older adults, and with further protection against severe disease. Both vaccines showed similar effects. Protection was maintained for the duration of follow-up (>6 weeks). A second dose of BNT162b2 was associated with further protection against symptomatic disease. A clear effect of the vaccines against the B.1.1.7 variant was found.
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                Author and article information

                Contributors
                Andrew Beggs: Role: Prof
                Tim Iveson: Role: Prof
                Siow Ming Lee: Role: Prof
                Gary Middleton: Role: Prof
                Mark Middleton: Role: Prof
                Andrew Protheroe: Role: Prof
                Journal
                Journal ID (nlm-ta): Eur J Cancer
                Journal ID (iso-abbrev): Eur J Cancer
                Title: European Journal of Cancer
                Publisher: The Author(s). Published by Elsevier Ltd.
                ISSN (Print): 0959-8049
                ISSN (Electronic): 1879-0852
                Publication date PMC-release: 13 July 2022
                Publication date (Electronic): 13 July 2022
                Author notes
                [∗ ] Corresponding author. Department of Oncology, University of Oxford, Oxford OX3 7DQ. . 01865 617 331, Institute of Cancer and Genomic Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK. , 0121 414 3511 . .
                [1]

                denotes equal contribution.

                [2]

                denotes joint senior authorship.

                Article
                Publisher Item ID: S0959-8049(22)00389-6
                DOI: 10.1016/j.ejca.2022.06.038
                PMC ID: 9276646
                PubMed ID: 36084618
                SO-VID: 31acb046-c896-440b-b95c-bdace0d18cc0
                Copyright © © 2022 The Author(s)
                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.

                History
                Date received : 15 June 2022
                Date accepted : 17 June 2022
                Categories
                Subject: Original Research

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: covid-19,cancer,vaccination,effectiveness,sars-cov-2,third dose,booster
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: covid-19, cancer, vaccination, effectiveness, sars-cov-2, third dose, booster

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