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SINGLE-DOSE ADMINISTRATION AND THE INFLUENCE OF THE TIMING OF THE BOOSTER DOSE ON IMMUNOGENICITY AND EFFICACY OF CHADOX1 NCOV-19 (AZD1222) VACCINE: A POOLED ANALYSIS OF FOUR RANDOMISED TRIALS
Assistência à Saúde
COVID-19
Infecções
Transtornos do Olfato
Organização Mundial da Saúde
Clare L Cutland, Thomas C Darton, Keertan Dheda, Christina Dold, Christopher J A Duncan, Katherine R W Emary, Katie J Ewer, Amy Flaxman, Lee Fairlie, Saul N Faust, Shuo Feng, Daniela M Ferreira, Adam Finn, Eva Galiza, Anna L Goodman, Catherine M Green, Christopher A Green, Melanie Greenland, Catherine Hill, Helen C Hill, Ian Hirsch, Alane Izu, Daniel Jenkin, Carina C D Joe, Simon Kerridge, Anthonet Koen, Gaurav Kwatra, Rajeka Lazarus, Vincenzo Libri, Patrick J Lillie, Natalie G Marchevsky, Richard P Marshall, Ana V A Mendes, Eveline P Milan, Angela M Minassian, Alastair McGregor, Yama F Mujadidi, Anusha Nana, Sherman D Padayachee, Daniel J Phillips, Ana Pittella, Emma Plested, Katrina M Pollock, Maheshi N Ramasamy, Adam J Ritchie, Hannah Robinson, Alexandre V Schwarzbold, Andrew Smith, Rinn Song, Matthew D Snape, Eduardo Sprinz, Rebecca K Sutherland, Emma C Thomson, M Estée Török, Mark Toshner, David P J Turner, Johan Vekemans, Tonya L Villafana, Thomas White, Christopher J Williams, Alexander D Douglas*, Adrian V S Hill*, Teresa Lambe*, Sarah C Gilbert*, Andrew J Pollard*, on behalf of the Oxford COVID Vaccine Trial Group†. Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK (M Voysey DPhil, P K Aley DPhil, S Bibi PhD, E A Clutterbuck PhD, C Dold PhD, K R W Emary FRCPath, S Feng PhD, M Greenland MSc, S Kerridge MSc, N G Marchevsky MSc, Y F Mujadidi MSc, D J Phillips MMath, E Plested, M N Ramasamy DPhil, H Robinson RN, M D Snape MD, R Song MD, Prof A J Pollard FMedSci); Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK (A D Douglas DPhil, A Flaxman DPhil, S C Gilbert PhD, T Lambe PhD, A V S Hill FMedSci, P M Folegatti MD, B Angus MD, P Cicconi MD, K J Ewer PhD, D Jenkin MRCP, C C D Joe PhD, A M Minassian DPhil, A J Ritchie PhD); Institute of Global Health, University of Siena, Siena, Italy (S A Costa Clemens MD); Department of Paediatrics (S A Costa Clemens) and Clinical BioManufacturing Facility (C M Green PhD), University of Oxford, Oxford, UK; South African Medical Research Council Vaccines and Infectious Diseases Analytics Research Unit, Faculty of Health Sciences (S A Madhi PhD, V L Baillie PhD, C L Cutland MD, C Hill BA, A Izu PhD, A Koen MBChB, G Kwatra PhD), Department of Science and Innovation/ National Research Foundation South African Research Chair Initiative in Vaccine Preventable Diseases Unit (S A Madhi, V L Baillie, C L Cutland, C Hill, A Izu, A Koen, G Kwatra), Wits Reproductive Health and HIV Institute, Faculty of Health Sciences (L Fairlie FCPaeds), and Perinatal HIV Research Unit, Faculty of Health Sciences (C Briner MBBCh, A Nana BPharm), University of the Witwatersrand, Johannesburg, South Africa; Department of Pediatrics, Universidade Federal de São Paulo, São Paulo, Brazil (L Y Weckx MD); AstraZeneca BioPharmaceuticals, Cambridge, UK (I Hirsch PhD, R P Marshall MD, J Vekemans MD PhD, T L Villafana PhD, T White PhD); Family Centre for Research with Ubuntu, Department of Paediatrics, University of Stellenbosch, Cape Town, South Africa (S L Barnabas PhD); Soweto Clinical Trials Centre, Soweto, South Africa (Q E Bhorat MSc); Department of Clinical Sciences, Liverpool School of Tropical Medicine and Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK (A M Collins PhD, D M Ferreira PhD, H C Hill PhD); Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK (T C Darton DPhil); Department of Infection and Tropical Medicine, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK (T C Darton); Escola Bahiana de Medicina e Saúde Pública, Salvador, Braziland Hospital São Rafael, Salvador, Brazil (A V A Mendes MD); Instituto D’Or, Salvador, Brazil (A V A Mendes); Division of Pulmonology, Groote Schuur Hospital and the University of Cape Town, Cape Town, South Africa (K Dheda FRCPCH, Faculty of Infectious and Tropical Diseases, Department of Immunology and Infection, London School of Hygiene & Tropical Medicine, London, UK (K Dheda); Department of Infection and Tropical Medicine, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK (C J A Duncan DPhil); Translational and Clinical Research Institute, Immunity and Inflammation Theme, Newcastle University, Newcastle upon Tyne, UK (C J A Duncan); NIHR Southampton Clinical Research Facility and Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust (S N Faust PhD); Faculty of Medicine and Institute for Life Sciences, University of Southampton, Southampton, UK (S N Faust); School of Population Health Sciences, University of Bristol and University Hospitals Bristol and Weston NHS Foundation Trust, UK (A Finn FRCPCH); Department of Infection, Guy’s and St Thomas’ NHS Foundation Trust, St Thomas’ Hospital, London, UK (A L Goodman FRCP); MRC Clinical Trials Unit, University College London, London, UK (A L Goodman); NIHR/Wellcome Trust Clinical Research Facility, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK (C A Green DPhil); St George’s Vaccine Institute, St George’s, University of London, London, UK (E Galiza MBBS); Severn Pathology, North Bristol NHS Trust, Bristol, UK (R Lazarus DPhil); NIHR UCLH Clinical Research Facility and NIHR UCLH Biomedical Research Centre, London, UK (V Libri FRCP); Department of Infection, Hull University Teaching Hospitals NHS Trust, Hull, UK (P J Lillie PhD); London Northwest University Healthcare, Harrow, UK (A C McGregor FRCPath); Setshaba Research Centre, Pretoria, South Africa (S D Payadachee MBChB); Universidade Federal do Rio Grande do Norte, Natal, Brazil (E P Milan PhD); Hospital Quinta D’Or, Rede D’Or, Rio De Janeiro, Brazil (A Pittella MD); NIHR Imperial Clinical Research Facility and NIHR Imperial Biomedical Research Centre, London, UK (K M Pollock PhD); College of Medical, Veterinary & Life Sciences, Glasgow Dental Hospital & School, University of Glasgow, Glasgow, UK (A Smith FRCPath); Infectious Diseases Service, Hospital de Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil (E Sprinz MD); Clinical Research Unit, Department of Clinical Medicine, Universidade Federal de Santa Maria, Santa Maria, Brazil (A V Schwarzbold PhD); Clinical Infection Research Group, Regional Infectious Diseases Unit, Western General Hospital, Edinburgh, UK (R K Sutherland FRCP); MRC-University of Glasgow Centre for Virus Research & Department of Infectious Diseases, Queen Elizabeth University Hospital, Glasgow, UK (E C Thomson FRCP PhD); Department of Medicine, University of Cambridge, UK (M E Török FRCP); Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK (M E Török); Heart Lung Research Institute, Dept of Medicine, University of Cambridge and NIHR Cambridge Clinical Research Facility, Cambridge University Hospital and Royal Papworth NHS Foundation Trusts, Cambridge, UK (M Toshner MD); University of Nottingham and Nottingham University Hospitals NHS Trust, Nottingham, UK (D P J Turner PhD); Public Health Wales, Cardiff, Wales (C J Williams FFPH); Aneurin Bevan University Health Board, Newport, Wales (C J Williams).
Author
Voysey, Merryn
Clemens, Sue Ann Costa
Madhi, Shabir A.
Weckx, Lily Yin
Folegatti, Pedro Moreira
Aley, Parvinder K.
Angus, Brian
Baillie, Vicky L.
Barnabas, Shaun L.
Bhorat, Qasim E.
Bibi, Sagida
Briner, Carmen
Cicconi, Paola
Clutterbuck, Elizabeth A.
Collins, Andrea M.
Cutland, Clare L.
Darton, Thomas C.
Dheda, Keertan
Dold, Christina
Duncan, Christopher J. A.
Emary, Katherine R. W.
Ewer, Katie J.
Flaxman, Amy
Fairlie, Lee
Faust, Saul N.
Shuo, Feng
Ferreira, Daniela M.
Finn, Adam
Galiza, Eva
Goodman, Anna L.
Green, Catherine M.
Green, Christopher A.
Greenland, Melanie
Hill, Catherine
Hill, Helen C.
Hirsch, Ian
Izu, Alane
Jenkin, Daniel
Joe, Carina C. D.
Kerridge, Simon
Koen, Anthonet
Kwatra, Gaurav
Lazarus, Rajeka
Libri, Vincenzo
Lillie, Patrick J.
Marchevsky, Natalie G.
Marshall, Richard P.
Mendes, Ana Verena Almeida
Milan, Eveline P.
Minassian, Angela M.
McGregor, Alastair
Mujadidi, Yama F.
Nana, Anusha
Padayachee, Sherman D.
Phillips, Daniel J.
Pittella, Ana
Plested, Emma
Pollock, Katrina M.
Ramasamy, Maheshi N.
Ritchie, Adam J.
Robinson, Hannah
Schwarzbold, Alexandre V.
Smith, Andrew
Song, Rinn
Snape, Matthew D.
Sprinz, Eduardo
Sutherland, Rebecca K.
Thomson, Emma C.
Török, Mili Estée
Toshner, Mark
Turner, David P. J.
Vekemans, Johan
Villafana, Tonya L.
White, Thomas
Williams, Christopher J.
Douglas, Alexander D.
Hill, Adrian V. S.
Lambe, Teresa
Gilbert, Sarah C.
Pollard, Andrew J.
Oxford COVID Vaccine Trial Group†
Clemens, Sue Ann Costa
Madhi, Shabir A.
Weckx, Lily Yin
Folegatti, Pedro Moreira
Aley, Parvinder K.
Angus, Brian
Baillie, Vicky L.
Barnabas, Shaun L.
Bhorat, Qasim E.
Bibi, Sagida
Briner, Carmen
Cicconi, Paola
Clutterbuck, Elizabeth A.
Collins, Andrea M.
Cutland, Clare L.
Darton, Thomas C.
Dheda, Keertan
Dold, Christina
Duncan, Christopher J. A.
Emary, Katherine R. W.
Ewer, Katie J.
Flaxman, Amy
Fairlie, Lee
Faust, Saul N.
Shuo, Feng
Ferreira, Daniela M.
Finn, Adam
Galiza, Eva
Goodman, Anna L.
Green, Catherine M.
Green, Christopher A.
Greenland, Melanie
Hill, Catherine
Hill, Helen C.
Hirsch, Ian
Izu, Alane
Jenkin, Daniel
Joe, Carina C. D.
Kerridge, Simon
Koen, Anthonet
Kwatra, Gaurav
Lazarus, Rajeka
Libri, Vincenzo
Lillie, Patrick J.
Marchevsky, Natalie G.
Marshall, Richard P.
Mendes, Ana Verena Almeida
Milan, Eveline P.
Minassian, Angela M.
McGregor, Alastair
Mujadidi, Yama F.
Nana, Anusha
Padayachee, Sherman D.
Phillips, Daniel J.
Pittella, Ana
Plested, Emma
Pollock, Katrina M.
Ramasamy, Maheshi N.
Ritchie, Adam J.
Robinson, Hannah
Schwarzbold, Alexandre V.
Smith, Andrew
Song, Rinn
Snape, Matthew D.
Sprinz, Eduardo
Sutherland, Rebecca K.
Thomson, Emma C.
Török, Mili Estée
Toshner, Mark
Turner, David P. J.
Vekemans, Johan
Villafana, Tonya L.
White, Thomas
Williams, Christopher J.
Douglas, Alexander D.
Hill, Adrian V. S.
Lambe, Teresa
Gilbert, Sarah C.
Pollard, Andrew J.
Oxford COVID Vaccine Trial Group†
Affilliation
Múltipla - ver em Notas.
Abstract
Background The ChAdOx1 nCoV-19 (AZD1222) vaccine has been approved for emergency use by the UK regulatory authority, Medicines and Healthcare products Regulatory Agency, with a regimen of two standard doses given with an interval of 4–12 weeks. The planned roll-out in the UK will involve vaccinating people in high-risk categories with their first dose immediately, and delivering the second dose 12 weeks later. Here, we provide both a further prespecified pooled analysis of trials of ChAdOx1 nCoV-19 and exploratory analyses of the impact on immunogenicity and efficacy of extending the interval between priming and booster doses. In addition, we show the immunogenicity and protection afforded by the first dose, before a booster dose has been offered. Methods We present data from three single-blind randomised controlled trials—one phase 1/2 study in the UK (COV001), one phase 2/3 study in the UK (COV002), and a phase 3 study in Brazil (COV003)—and one double-blind phase 1/2 study in South Africa (COV005). As previously described, individuals 18 years and older were randomly assigned 1:1 to receive two standard doses of ChAdOx1 nCoV-19 (5×10¹⁰ viral particles) or a control vaccine or saline placebo. In the UK trial, a subset of participants received a lower dose (2·2×10¹⁰ viral particles) of the ChAdOx1 nCoV-19 for the first dose. The primary outcome was virologically confirmed symptomatic COVID-19 disease, defined as a nucleic acid amplification test (NAAT)-positive swab combined with at least one qualifying symptom (fever ≥37·8°C, cough, shortness of breath, or anosmia or ageusia) more than 14 days after the second dose. Secondary efficacy analyses included cases occuring at least 22 days after the first dose. Antibody responses measured by immunoassay and by pseudovirus neutralisation were exploratory outcomes. All cases of COVID-19 with a NAATpositive swab were adjudicated for inclusion in the analysis by a masked independent endpoint review committee. The primary analysis included all participants who were SARS-CoV-2 N protein seronegative at baseline, had had at least 14 days of follow-up after the second dose, and had no evidence of previous SARS-CoV-2 infection from NAAT swabs. Safety was assessed in all participants who received at least one dose. The four trials are registered at ISRCTN89951424 (COV003) and ClinicalTrials.gov, NCT04324606 (COV001), NCT04400838 (COV002), and NCT04444674 (COV005). Findings Between April 23 and Dec 6, 2020, 24422 participants were recruited and vaccinated across the four studies, of whom 17178 were included in the primary analysis (8597 receiving ChAdOx1 nCoV-19 and 8581 receiving control vaccine). The data cutoff for these analyses was Dec 7, 2020. 332 NAAT-positive infections met the primary endpoint of symptomatic infection more than 14 days after the second dose. Overall vaccine efficacy more than 14 days after the second dose was 66·7% (95% CI 57·4–74·0), with 84 (1·0%) cases in the 8597 participants in the ChAdOx1 nCoV-19 group and 248 (2·9%) in the 8581 participants in the control group. There were no hospital admissions for COVID-19 in the ChAdOx1 nCoV-19 group after the initial 21-day exclusion period, and 15 in the control group. 108 (0·9%) of 12282 participants in the ChAdOx1 nCoV-19 group and 127 (1·1%) of 11962 participants in the control group had serious adverse events. There were seven deaths considered unrelated to vaccination (two in the ChAdOx1 nCov-19 group and five in the control group), including one COVID-19-related death in one participant in the control group. Exploratory analyses showed that vaccine efficacy after a single standard dose of vaccine from day 22 to day 90 after vaccination was 76·0% (59·3–85·9). Our modelling analysis indicated that protection did not wane during this initial 3-month period. Similarly, antibody levels were maintained during this period with minimal waning by day 90 (geometric mean ratio [GMR] 0·66 [95% CI 0·59–0·74]). In the participants who received two standard doses, after the second dose, efficacy was higher in those with a longer prime-boost interval (vaccine efficacy 81·3% [95% CI 60·3–91·2] at ≥12 weeks) than in those with a short interval (vaccine efficacy 55·1% [33·0–69·9] at <6 weeks). These observations are supported by immunogenicity data that showed binding antibody responses more than two-fold higher after an interval of 12 or more weeks compared with an interval of less than 6 weeks in those who were aged 18–55 years (GMR 2·32 [2·01–2·68]).
Keywords in Portuguese
BetacoronavirusAssistência à Saúde
COVID-19
Infecções
Transtornos do Olfato
Organização Mundial da Saúde
Publisher
Elsevier
Citation
VOYSEY, Merryn et al. Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomised trials. The Lancet, v. 397, n. 10277, p. 881-891, 19 Feb. 2021.DOI
10.1016/S0140-6736(21)00432-3ISSN
0140-6736Notes
SOUZA, Bruno Solano Freitas Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil. O autor consta da lista Oxford COVID Vaccine Trial Group.Clare L Cutland, Thomas C Darton, Keertan Dheda, Christina Dold, Christopher J A Duncan, Katherine R W Emary, Katie J Ewer, Amy Flaxman, Lee Fairlie, Saul N Faust, Shuo Feng, Daniela M Ferreira, Adam Finn, Eva Galiza, Anna L Goodman, Catherine M Green, Christopher A Green, Melanie Greenland, Catherine Hill, Helen C Hill, Ian Hirsch, Alane Izu, Daniel Jenkin, Carina C D Joe, Simon Kerridge, Anthonet Koen, Gaurav Kwatra, Rajeka Lazarus, Vincenzo Libri, Patrick J Lillie, Natalie G Marchevsky, Richard P Marshall, Ana V A Mendes, Eveline P Milan, Angela M Minassian, Alastair McGregor, Yama F Mujadidi, Anusha Nana, Sherman D Padayachee, Daniel J Phillips, Ana Pittella, Emma Plested, Katrina M Pollock, Maheshi N Ramasamy, Adam J Ritchie, Hannah Robinson, Alexandre V Schwarzbold, Andrew Smith, Rinn Song, Matthew D Snape, Eduardo Sprinz, Rebecca K Sutherland, Emma C Thomson, M Estée Török, Mark Toshner, David P J Turner, Johan Vekemans, Tonya L Villafana, Thomas White, Christopher J Williams, Alexander D Douglas*, Adrian V S Hill*, Teresa Lambe*, Sarah C Gilbert*, Andrew J Pollard*, on behalf of the Oxford COVID Vaccine Trial Group†. Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK (M Voysey DPhil, P K Aley DPhil, S Bibi PhD, E A Clutterbuck PhD, C Dold PhD, K R W Emary FRCPath, S Feng PhD, M Greenland MSc, S Kerridge MSc, N G Marchevsky MSc, Y F Mujadidi MSc, D J Phillips MMath, E Plested, M N Ramasamy DPhil, H Robinson RN, M D Snape MD, R Song MD, Prof A J Pollard FMedSci); Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK (A D Douglas DPhil, A Flaxman DPhil, S C Gilbert PhD, T Lambe PhD, A V S Hill FMedSci, P M Folegatti MD, B Angus MD, P Cicconi MD, K J Ewer PhD, D Jenkin MRCP, C C D Joe PhD, A M Minassian DPhil, A J Ritchie PhD); Institute of Global Health, University of Siena, Siena, Italy (S A Costa Clemens MD); Department of Paediatrics (S A Costa Clemens) and Clinical BioManufacturing Facility (C M Green PhD), University of Oxford, Oxford, UK; South African Medical Research Council Vaccines and Infectious Diseases Analytics Research Unit, Faculty of Health Sciences (S A Madhi PhD, V L Baillie PhD, C L Cutland MD, C Hill BA, A Izu PhD, A Koen MBChB, G Kwatra PhD), Department of Science and Innovation/ National Research Foundation South African Research Chair Initiative in Vaccine Preventable Diseases Unit (S A Madhi, V L Baillie, C L Cutland, C Hill, A Izu, A Koen, G Kwatra), Wits Reproductive Health and HIV Institute, Faculty of Health Sciences (L Fairlie FCPaeds), and Perinatal HIV Research Unit, Faculty of Health Sciences (C Briner MBBCh, A Nana BPharm), University of the Witwatersrand, Johannesburg, South Africa; Department of Pediatrics, Universidade Federal de São Paulo, São Paulo, Brazil (L Y Weckx MD); AstraZeneca BioPharmaceuticals, Cambridge, UK (I Hirsch PhD, R P Marshall MD, J Vekemans MD PhD, T L Villafana PhD, T White PhD); Family Centre for Research with Ubuntu, Department of Paediatrics, University of Stellenbosch, Cape Town, South Africa (S L Barnabas PhD); Soweto Clinical Trials Centre, Soweto, South Africa (Q E Bhorat MSc); Department of Clinical Sciences, Liverpool School of Tropical Medicine and Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK (A M Collins PhD, D M Ferreira PhD, H C Hill PhD); Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK (T C Darton DPhil); Department of Infection and Tropical Medicine, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK (T C Darton); Escola Bahiana de Medicina e Saúde Pública, Salvador, Braziland Hospital São Rafael, Salvador, Brazil (A V A Mendes MD); Instituto D’Or, Salvador, Brazil (A V A Mendes); Division of Pulmonology, Groote Schuur Hospital and the University of Cape Town, Cape Town, South Africa (K Dheda FRCPCH, Faculty of Infectious and Tropical Diseases, Department of Immunology and Infection, London School of Hygiene & Tropical Medicine, London, UK (K Dheda); Department of Infection and Tropical Medicine, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK (C J A Duncan DPhil); Translational and Clinical Research Institute, Immunity and Inflammation Theme, Newcastle University, Newcastle upon Tyne, UK (C J A Duncan); NIHR Southampton Clinical Research Facility and Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust (S N Faust PhD); Faculty of Medicine and Institute for Life Sciences, University of Southampton, Southampton, UK (S N Faust); School of Population Health Sciences, University of Bristol and University Hospitals Bristol and Weston NHS Foundation Trust, UK (A Finn FRCPCH); Department of Infection, Guy’s and St Thomas’ NHS Foundation Trust, St Thomas’ Hospital, London, UK (A L Goodman FRCP); MRC Clinical Trials Unit, University College London, London, UK (A L Goodman); NIHR/Wellcome Trust Clinical Research Facility, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK (C A Green DPhil); St George’s Vaccine Institute, St George’s, University of London, London, UK (E Galiza MBBS); Severn Pathology, North Bristol NHS Trust, Bristol, UK (R Lazarus DPhil); NIHR UCLH Clinical Research Facility and NIHR UCLH Biomedical Research Centre, London, UK (V Libri FRCP); Department of Infection, Hull University Teaching Hospitals NHS Trust, Hull, UK (P J Lillie PhD); London Northwest University Healthcare, Harrow, UK (A C McGregor FRCPath); Setshaba Research Centre, Pretoria, South Africa (S D Payadachee MBChB); Universidade Federal do Rio Grande do Norte, Natal, Brazil (E P Milan PhD); Hospital Quinta D’Or, Rede D’Or, Rio De Janeiro, Brazil (A Pittella MD); NIHR Imperial Clinical Research Facility and NIHR Imperial Biomedical Research Centre, London, UK (K M Pollock PhD); College of Medical, Veterinary & Life Sciences, Glasgow Dental Hospital & School, University of Glasgow, Glasgow, UK (A Smith FRCPath); Infectious Diseases Service, Hospital de Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil (E Sprinz MD); Clinical Research Unit, Department of Clinical Medicine, Universidade Federal de Santa Maria, Santa Maria, Brazil (A V Schwarzbold PhD); Clinical Infection Research Group, Regional Infectious Diseases Unit, Western General Hospital, Edinburgh, UK (R K Sutherland FRCP); MRC-University of Glasgow Centre for Virus Research & Department of Infectious Diseases, Queen Elizabeth University Hospital, Glasgow, UK (E C Thomson FRCP PhD); Department of Medicine, University of Cambridge, UK (M E Török FRCP); Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK (M E Török); Heart Lung Research Institute, Dept of Medicine, University of Cambridge and NIHR Cambridge Clinical Research Facility, Cambridge University Hospital and Royal Papworth NHS Foundation Trusts, Cambridge, UK (M Toshner MD); University of Nottingham and Nottingham University Hospitals NHS Trust, Nottingham, UK (D P J Turner PhD); Public Health Wales, Cardiff, Wales (C J Williams FFPH); Aneurin Bevan University Health Board, Newport, Wales (C J Williams).
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