44 research outputs found
Genomic investigations of unexplained acute hepatitis in children
- Author
- Alrabiah DK
- Anderson G
- Andrade C
- Andreani J
- Antinao Diaz JF
- Asgarian Z
- Atkinson L
- Baillie K
- Bayzid N
- Breuer J
- Brown JR
- Brown R
- Buddle S
- Campos L
- Castellano S
- Celma C
- Chand M
- Chikowore P
- Cooray S
- Counsell JR
- Czap A
- De S
- Deheragoda M
- DIAMONDS Consortium
- Fink C
- Gallagher E
- Gissen P
- Gonzalez S
- Grammatikopoulos T
- Guerra-Assunção JA
- Gunson R
- Hadzic N
- Hanlon KS
- Hatcher J
- Holden M
- Hoschler K
- Houlihan C
- Hutchinson JC
- ISARIC 4C Investigators
- Jacques TS
- Kaufer BB
- Kelgeri C
- Lee JCD
- Lennon A
- Levin M
- Macpherson H
- Mandal S
- Martin Bernal LM
- Martin J
- McArdle A
- Montgomery K-A
- Moore C
- Moradi Marjaneh M
- Morfopoulou S
- Neill C
- Ng J
- Noursadeghi M
- Odam M
- PERFORM Consortium
- Pollara G
- Rampling T
- Reich J
- Rosenheim J
- Roy S
- Santilli G
- Semple MG
- Shah P
- Shepherd SJ
- Siam A
- Simmonds P
- Simmons R
- Steele M
- Storey N
- Talts T
- Tappouni LJ
- Templeton K
- Thalassinos K
- Thomson E
- Torres Montaguth OE
- Tutill H
- Ushiro-Lumb I
- Venturini C
- Voice M
- Waddington SN
- Watson C
- Whittaker TE
- Williams CA
- Williams R
- Zambon M
- Zennezini Chiozzi R
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 23/03/2023
- Field of study
Get PDFSince its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children
Whole-genome sequencing reveals host factors underlying critical COVID-19
- Author
- Abd Elghafar M. S.
- Abdel-Aziz M.
- Abdelrazik M.
- Abdollahi H.
- Abdullah T.
- Abecasis G. R.
- Abedalthagafi M.
- Abel L.
- Abernathy C.
- Abraheem A.
- Abul-Husn N. S.
- Acquilini D.
- Adams C.
- Adams E. L.
- Adams K.
- Adamsara A.
- Adanini O.
- Adeleye O.
- Adra D.
- Afilalo J.
- Afilalo M.
- Afolabi D.
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- Agrawal S.
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- Akhtar M. N.
- Akinkugbe O.
- Aksentijevich A.
- Al-Afghani H.
- Al-Awdah L.
- Alaamery M.
- Alahmadey Z. Z.
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- Wyllie D. H.
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- Xue X.
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- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/2022
- Field of study
Get PDFCritical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease
Genetic mechanisms of critical illness in COVID-19.
- Author
- A A Roger Thompson
- A Abraheem
- A Agasou
- A Ahmed
- A Ali
- A Allan
- A Altabaibeh
- A Alvaro
- A Aspinwall
- A Ayers
- A Bamford
- A Barron
- A Bashyal
- A Bellini
- A Bociek
- A Botello
- A Bowes
- A Brady
- A Brayne
- A Brown
- A Brown
- A Butler
- A Campbell
- A Carter
- A Collins
- A Cowley
- A Cowton
- A Cowton
- A Cox
- A Crew
- A Dance
- A Daniel
- A Daniels
- A Dela Rosa
- A Drummond
- A Durie
- A E Heron
- A Easthope
- A Easthope
- A Evans
- A Fofano
- A Gales
- A Ganesan
- A Gardner
- A Garg
- A Gherman
- A Gordon
- A Gratrix
- A Gulati
- A Gupta
- A Haigh
- A Haldeos
- A Harrison
- A Harvey
- A Hayes
- A Higham
- A Higham
- A Hilldrith
- A Holden
- A Hormis
- A Hutcheon
- A Javaid
- A Joseph
- A Kaliappan
- A Katary
- A Kay
- A Kayani
- A Kent
- A Kirkby
- A Knight
- A Kubisz-Pudelko
- A Kuravi
- A Lewis
- A Loveridge
- A Lyle
- A Mayer
- A McAlpine
- A McCarthy
- A McGregor
- A McGregor
- A Meikle
- A Mitchell
- A Mitra
- A Morris
- A Morrison
- A Naranjo
- A Nicholson
- A Nicholson
- A Nilsson
- A Noakes
- A Patel
- A Pickard
- A Poole
- A Price
- A Puxty
- A Quinn
- A Quinn
- A Raithatha
- A Rattray
- A Reddy
- A Reed
- A Reyes
- A Rose
- A Rose
- A Rostron
- A Roy
- A Roynon-Reed
- A S Raj
- A Salberg
- A Sanderson
- A Serrano-Ruiz
- A Solesbury
- A Sukha
- A Swain
- A Tariq
- A Thomas
- A Thomas
- A Todd
- A Tomas
- A Tridente
- A Tucci
- A Turnbull
- A Uriel
- A Ustianowski
- A Vochin
- A Vuylsteke
- A Waite
- A Walden
- A Whileman
- A Wilkinson
- A Williams
- A Williams
- A Wilson
- A Zak
- A Zaki
- Achille Iolascon
- Adam Auton
- Adam Brown
- Agnese Verzuri
- Agostino Ognibene
- Agostino Riva
- Ailsa Golightly
- Alan Maclean
- Alessandra
- Alessandra Stella
- Alessandra Vergori
- Alessia Giorli
- Alexander J Mentzer
- Alice Donati
- Alison M Meynert
- Alistair Nichol
- Ana da Silva Filipe
- Andrea Antinori
- Andrea Cossarizza
- Andrea Ganna
- Andrea Tommasi
- Andrew Rambaut
- Andrew Stenhouse
- Andy Law
- Anjali J Shastri
- Anna Canaccini
- Anna Maria Pinto
- Annarita Giliberti
- Annemarie B Docherty
- Antonella D'Arminio Monforte
- Antonia Ying Wai Ho
- Antonio Di Biagio
- Antony Symons
- Arianna Emiliozzi
- Arianna Gabrieli
- Audrey Coutts
- B Anwar
- B Attwood
- B Baines
- B Blackledge
- B Borislavova
- B Chandler
- B Charles
- B Creagh-Brown
- B David
- B Deacon
- B Deacon
- B Digby
- B Faulkner
- B Fuller
- B Gumbrill
- B Gurung
- B Hadebe
- B Hairsine
- B Hopkins
- B Johnston
- B Lenagh
- B Masunda
- B Ogg
- B Patel
- B Player
- B Purewal
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- B Shelley
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- Barbara Rossetti
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- Benjamin Bach
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- Caulfield Mark
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- Cinthia E Jannes
- Clare Jackson
- Clohisey Sara
- Cristina Mussini
- D Antcliffe
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- D Vedage
- D Walker
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- D Williams
- D Wood
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- Daniela Francisci
- Daniella Coker
- Danilo Tacconi
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- David Bennet
- David L Robertson
- David Stuart
- Dawn Law
- Debby Bogaert
- Derek Murphy
- Domenico A Coviello
- E Abaleke
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- E Combes
- E Davies
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- E Dooks
- E Fisher
- E Gendall
- E Goff
- E Goodwin
- E Gordon
- E Heeney
- E Horsley
- E Hughes
- E Johnson
- E Knights
- E Lee
- E London
- E Maccacari
- E Massey
- E McKenna
- E Meadows
- E Moncur
- E Morino
- E Mwaura
- E Peasgood
- E Perkins
- E Radford
- E Raith
- E Raith
- E Salciute
- E Smith
- E Smithson
- E Stoddard
- E Stones
- E Thomas
- E Tilney
- E Timlick
- E Treus Gude
- E Virgilio
- E Watson
- E Wilby
- Edoardo Conticini
- Egle Saviciute
- Elena Bargagli
- Elena Desanctis
- Elisa Benetti
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- Elisabetta Menatti
- Elisabetta Schiaroli
- Ellie Mcmaster
- Emma C Thomson
- Emmanuelle Marques
- Enrico Martinelli
- Esther Duncan
- Esther Merlini
- Ewen M Harrison
- F Anderson
- F Auld
- F Bibi
- F Davies
- F Farquhar
- F Fisher
- F Hurford
- F Kibutu
- F McNeela
- F Moore
- F Nasir
- F Trim
- F Wakinshaw
- F Williams
- Fabio Lena
- Fawkes Angie
- Federico Anedda
- Federico Franchi
- Ferdinando Giannattasio
- Filip Taneski
- Filippo Aucella
- Filippo Biscarini
- Floriana Valentino
- Fourman Max Head
- Francesca Andretta
- Francesca Fava
- Francesca Gatti
- Francesca Mari
- Francesca Montagnani
- Francesco Castelli
- Francesco Raimondi
- Furniss James
- G Andrew
- G Arbane
- G Bell
- G Bercades
- G Croston
- G Debreceni
- G Durrant
- G Hambrook
- G Hobden
- G Houston
- G Hughes
- G Jones
- G Lubimbi
- G Maloney
- G Martir
- G Millen
- G Mills
- G O'Connor
- G Padden
- G Randell
- G Sadera
- G Seddon
- G Sera Howe
- G Sloane
- G Subramanian
- G Tsinaslanidis
- G Turner
- G Watson
- G Wray
- Gabriella Coiro
- Gabriella Doddato
- Gail Carson
- Gardar Sveinbjornsson
- Gary Leeming
- Genni Spargi
- Georgios Pollakis
- Giacomo Zanelli
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- Giancarlo Bosio
- Giuseppe Fiorentino
- Giuseppe Merla
- Gountouna Elvina
- Graham S Cooke
- Griffiths Fiona
- Grimes Graeme
- H Bancroft
- H Bates
- H Belfield
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- H Blakemore
- H Brooke
- H Button
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- H Curgenven
- H Filipe
- H Fox
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- H Rehman
- H Reschreiter
- H Riley
- H Sainsbury
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- H Sturgeon
- H T-Michael
- H Tench
- H Tiveran
- H Turner
- H Whittle
- H Willis
- H Wood
- Haley Chris
- Hanning Mal
- Harrison David
- Hayley Hardwick
- Hayward Caroline
- Helen Szoor-McElhinney
- Hinds Charles
- Ho Antonia
- Horby Peter
- I Ali Mohamed Ali
- I Balagosa
- I Birkinshaw
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- I Edmond
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- I Hussain
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- I Leadbitter
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- J Finn
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- Turtle Lance
- U Poultney
- V Amin
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- V Waugh
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- Vanessa Sancho-Shimizu
- Victoria Shaw
- Vitart Veronique
- W Harrison
- W Khaliq
- W Khaliq
- W McCormick
- W Woodyatt
- Walker Susan
- Walsh Timothy
- Wang Bo
- Wei Shen Lim
- Wendy S Barclay
- William A Paxton
- William Greenhalf
- Wilson James F
- Wrobel Nicola
- Wu Yang
- X Qiu
- Y Baird
- Y Choudhury
- Y Hussain
- Y Jackson
- Y Thirlwall
- Yang Jian
- Yang Zhijian
- Z Alldis
- Z Belagodu
- Z Bradshaw
- Z Coton
- Z Daly
- Z Farzad
- Z Fernandez
- Z Garland
- Z Maqsood
- Z Omar
- Z Prime
- Z Scott
- Zechner Marie
- Zhai Ranran
- Zheng Chenqing
- Publication venue
- Nature
- Publication date
- 01/01/2020
- Field of study
Get PDFHost-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 × 10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice
Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial
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- Abdul Rasheed A.
- Abdul A.
- Abdul-Kadir R.
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- Publication venue
- Springer Science and Business Media LLC
- Publication date
- 31/01/2024
- Field of study
Get PDFDimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome
Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease
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- Zuchelkowski A
- Zulauf N
- Ågårdh A
- Öner A
- Publication venue
- 'Massachusetts Medical Society'
- Publication date
- 01/01/2017
- Field of study
Get PDFBACKGROUND:
Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes.
METHODS:
We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization.
RESULTS:
During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events.
CONCLUSIONS:
Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)
Whole-genome sequencing reveals host factors underlying critical COVID-19
- Author
- Abd Elghafar M.S.
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- Zöllner S.
- Åsvold B.O.
- Publication venue
- Springer Science and Business Media LLC
- Publication date
- 07/07/2022
- Field of study
Get PDFCritical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease
Genomic investigations of unexplained acute hepatitis in children
- Author
- Abdulla Amina
- Aebi Christoph
- Agbeko Rachel
- Aggelos Pefanis
- Agranoff Dan
- Agwuh Ken
- Agyeman Philipp
- Alba-Alejandre Irene
- Ali Ladan
- Alkema Wynand
- Allen Karen
- Alrabiah Dimah K.
- Amatya Puja
- Anderson Glenn
- Anderson Suzanne
- Andrade Catarina
- Andreani Julien
- Anpananthar Amutha
- Ansari Imran
- Antinao Diaz Juan F.
- Arif Tasnim
- Armstrong Diane
- Armstrong Jane A.
- Armstrong Lawrence
- Asgarian Zeinab
- Atkinson Laura
- Avcin Tadej
- Avramoska Tanja
- Baas Bryan
- Bahovec Natalija
- Baillie Kenneth
- Balode Anda
- Bamford Alasdair
- Barendregt A. M.
- Barral-Arca Ruth
- Barzdina Arta
- Barzdina Elza
- Basmaci Romain
- Bath David
- Bauchinger Sebastian
- Baumard Lucas
- Baumgart Hinrich
- Baxter Frances
- Bayzid Nadua
- Beer Sally
- Bell Ashley
- Bell Claire
- Bell Kathryn
- Bellini Arianna
- Bello Xabier
- Bellos Evangelos
- Benesch Martin
- Benesch Martin
- Bennet Joshua
- Berger Christoph
- Bernhard-Stirnemann Sara
- Beudeker Coco R.
- Beveridge Laura
- Bibi Sagida
- Bidlingmaier Christoph
- Biesbroek Giske
- Bijukchhe Sanjeev Man
- Billing Kyle
- Binder Alexander
- Binder Vera
- Birt Mark
- Bogovic Petra
- Bohmova Kristyna
- Bojang Kalifa
- Bont Louis J.
- Borensztajn Dorine M.
- Bories Pauline
- Branch Nicole
- Brengel-Pesce Karen
- Breuer Judith
- Broderick Claire
- Brotherton Helen
- Brown Julianne R.
- Brown Rachel
- Buddle Sarah
- Burling Sara
- Buschbeck Judith
- Cabello Laura
- Calle Irene Rivero
- Calvo-Bado Leo
- Campos Luis
- Candlish Janie
- Capozzi Lisa
- Carnota Sandra
- Caro Ivan
- Carrol Enitan D.
- Carson Gail
- Carter Michael
- Carter Michael J.
- Castellano Sergi
- Castro Maria Barreiro
- Cebey-López Miriam
- Ceesay Samba
- Celma Cristina
- Ceolotto Astrid
- Chan Adora
- Chand Meera
- Channon-Wells Samuel
- Charalambos Gogos
- Chikowore Primrose
- Chiurchiù Sara
- Chukkambotla Srikanth
- Chériaux Laura
- Clark Richard
- Clohisey Sara
- Cocklin Elizabeth
- Cohen Jonathan
- Cohen Laure
- Collings Kalvin
- Collins Emma
- Connon Maggie
- Cooray Samantha
- Cotillon Marie
- Counsell John R.
- Coutts Audrey
- Cresswell Fiona
- Crulley Stephen
- Cunnington Aubrey
- Curras-Tuala María José
- Czap Agata
- D'alessandro Umberto
- D?Souza Giselle
- Dall Anna
- Danekova Nevena
- Danhauser Katharina
- Darboe Saffiatou
- Darnell Sarah
- Daubney Esther
- Davis Francesca
- Davoust Juraté
- Dawson Joy
- de Groc Thibault
- de Groot Ronald
- de Haan L.
- de Jonge Marien I.
- de Silva Thushan
- de Tugny Alice
- de Vries Gabriella
- De Surjo
- De Tisham
- Deep Akash
- Deheragoda Maesha
- Deksne D?rta
- Devine Kirsty
- Dewez Juan Emmanuel
- Dewez Manuel
- Diaba Cynthia
- Dickinson Holly
- Dik W.
- Donelly Lorna
- Donohue Chloe
- Dorward David
- Drysdale Simon B.
- Dudley Julia
- Dunning Jake
- DuRand Ingrid
- Eber Ernst
- Eisen Sarah
- Eleftheriou Irini
- Ellis Donna
- Elorrieta Leire Estramiana
- Emonts Marieke
- Ensom Ruth
- Epalza Cristina
- Estrada-Rivadeneyra Diego
- Evans Benjamin
- Fabian Daniel
- Farmer Sarah
- Farto Cristina Balo
- Faust Saul
- Fawkes Angie
- Ferguson Susie
- Fernández Sonia Serén
- Feuchtinger Tobias
- Fidler Katy
- Fink Colin
- Finlayson Lauren
- Fish Matthew
- Fitchett Elizabeth
- Fletcher Tom
- Floyd Sharon
- Fullerton Duncan
- Galassini Rachel
- Gallagher Eileen
- Gallistl Siegfried
- Gannon Louise
- García Mirian Ben
- Gardiner Emma
- Garg Sanjeev
- Geissler J.
- Georgiou Pantelis
- Gerrits G. P. J. M.
- Giannoni Eric
- Gijón Manuel
- Gilchrist Tammy
- Gissen Paul
- Giuseppe Martina Di
- Gloerich Jolein
- Goetschalckx Ines
- Gonzalez Suam
- González Fernando Álvez
- Gores Gunther
- Gormley Stuart
- Graham Clive
- Grammatikopoulos Tassos
- Gravele Dagne
- Griese Matthias
- Grope Ilze
- Gruppen Mariken
- Guerra-Assunção José Afonso
- Gunson Rory
- Gurung Meeru
- Gutiérrez Lourdes
- Gómez-Carballa Alberto
- Haas Nikolaus
- Habgood-Coote Dominic
- Hadzic Nedim
- Hafezi Katarzyna
- Hagedoorn Nienke N.
- Haidl Harald
- Hamilton Shea
- Hamzah Lisa
- Hanlon Killian S.
- Hanson Anita
- Hardwick Hayley
- Harper Rosemary
- Hartshorn Stuart
- Hatcher James
- Hauer Almuthe
- Heidema J.
- Heightman Melissa
- Heininger Ulrich
- Henderson Paul
- Henriet Stefanie
- Herberg Jethro
- Hernández Irene
- Hibberd Martin
- Hickey Naomy
- Ho Antonia Y. W.
- Hodgson Luke
- Hoffmann Florian
- Hoggart Clive
- Holden Jennifer
- Holden Matt
- Hope Susan
- Hopton Sarah
- Hoschler Katja
- Houlihan Catherine
- Hourmat Sara
- Howman Ruth
- Hude Christa
- Huijnen Martijn
- Hutchinson J. Ciaran
- Hösele Susanne
- Iglesias Marisol Vilas
- Iglesias Pilar Leboráns
- Ijaz Samreen
- Ioanna Stergiou
- Irving Clare
- Isaacs John
- Jackson Heather
- Jacques Thomas S.
- Jansen Machiel H.
- Jarman Heather
- Jennings Aislinn
- Jennings Paul
- Jennings Rebecca
- Johnston Joanne
- Jones Amaryl
- Jongerius Ilse
- Jorgensen Rikke
- Juranek Sabrina
- Kaforou Mysini
- Kahlert Christian
- Kandasamy Rama
- Kapper Andreas
- Kappler Matthias
- Karolina Akinosoglou
- Kaufer Benedikt B.
- Kavanagh James
- Keil Julia
- Keldorfer Markus
- Kelgeri Chayarani
- Kelly Dominic F.
- Kelly Sarah
- Kenny Julia
- Khalid Nosheen
- Khanijau Aakash
- Khoo Say
- Kim Eunjung
- King Sharon
- Kishore Shyla
- Kitanovski Lidija
- Kloosterhuis Lieke
- Kohlfürst Daniela S.
- Kohlmaier Benno
- Kolberg Laura
- Kolnik Mojca
- Koshy George
- Krenn Larissa
- Kuijpers Taco
- Kuijpers Taco
- Lachaume Noémie
- Laivacuma Sniedze
- Laivacuma Sniedze
- Law Andrew
- Le Sébastien
- Lee Jack C. D.
- Leigh Simon
- Leiner Tamas
- Leitch Karen
- Leitner Manuel
- Lenihan Rebecca
- Lennon Alexander
- Lett Lauren
- Leurent Baptiste
- Levin Michael
- Lewis-Burke Nadia
- Liebeschuetz Susan
- Lim Emma
- Limb James
- Lin Naomi
- Linforth Michelle
- Little Jeff
- Liu Ching-Chuan
- Logan Sheena
- Lubinda Tim
- Luca Maia De
- Lurz Eberhard
- Löffler Sabine
- MacFarlane Susan
- MacGillivray Louise
- Machín Fátima
- Mackerness Christine
- Maclean Alan
- Maconochie Ian
- Macpherson Hannah
- Madelane Monta
- Maier Esther
- Malcolm Ivone Lancoma
- Mallet François
- Mandal Sema
- Manzanares Ángela
- Manzano Jesus-Rodriguez
- Maritsi Despoina
- Marjaneh Mahdi Moradi
- Markos Maragos
- Marmarinos Antonios
- Marmarinos Antonis
- Martin Bernal Luz Marina
- Martin Alex
- Martin Darran
- Martin Joanne
- Martin Mike
- Martinón-Torres Federico
- Martinón-Torres Nazareth
- Matovu Elijah
- Matthews Peter
- McAlinden Paul
- McArdle Andrew
- McCafferty Sarah
- McDonald Sam
- McDonald Sarah E.
- McDonnell Anne
- McGenily Laura
- McGill Fiona
- McKay Sarah
- Meiere Anija
- Meierford Anne
- Menikou Stephanie
- Merson Laura
- Michalis Voulgarelis
- Miedema C. J.
- Millar Margaret
- Miller Caroline
- Miller Danielle
- Milligan Barry
- Mills Sarah
- Miners Alec
- Mistry Ravi
- Mita Andrew
- Moll Henriëtte A.
- Mommert Marine
- Mommert-Tripon Marine
- Mondo Diana
- Montgomery Kylie-Ann
- Moore Catherine
- Moots Robert
- Moradi Marjaneh Mahdi
- Morfopoulou Sofia
- Morrice John
- Morrice Kirstie
- Morris Craig
- Moser Nicolas
- Muench Georg
- Murdoch David R.
- Murphy Lee
- Mustafa Sobia
- Márquez Sonia
- Nagelkerke Sietse
- Nahtigal Mirijam
- Nasher Magda
- Natalucci Giancarlo
- Neeleman C.
- Neill Claire
- Neshat Samira
- Newal Karen
- Newall Karen
- Ng Joanne
- Nichols Samuel
- Niederer-Loher Anita
- Niedrist Tobias
- Nijman Ruud
- Nijman Ruud
- Nokalna Ieva
- Nordberg Gudrun
- Norris Lucy
- Noursadeghi Mahdad
- Nyirenda Maggie
- O'Connor Daniel
- O?Reilly Peter
- O?Riordan Sean
- Obihara C. C.
- Obosi Lauren
- Odam Miranda
- Oliver Zoe
- Ong Kim-Thanh
- Oosthoek Wilma
- Oosthuyzen Wilna
- Openshaw Peter J. M.
- Ora Miguel Sadiki
- Osterman Veronika
- Owen Dan
- Pachot Alexandre
- Pajkrt D.
- Pajkrt Dasja
- Palmarini Massimo
- Panagiota Lourida
- Papst Lea
- Pardo-Seco Jacobo
- Patel Harsita
- Pathan Nazima
- Paulus Stéphane
- Paulus Stéphane
- Paulus Stéphane C.
- Pavare Jana
- Paz Ivonne Pena
- Pennisi Ivana
- Persand Salina
- Peters Mark
- Pfleger Andreas
- Pfurtscheller Klaus
- Philipsen Ria
- Pickering Ailsa
- Pierce Benjamin
- Pilch Heidemarie
- Pischedda Sara
- Player Jasmine
- Pokhrel Bhishma
- Pokorn Marko
- Pokorn Marko
- Pollara Gabriele
- Pollard Andrew J.
- Pollock Louisa
- Posfay-Barbe Klara M.
- Powell Natassia
- Powell Oliver
- Price Ashley
- Price David
- Price Nicholas
- Prunk Petra
- Pucuka Zanda
- Pérez Belén Mosquera
- Pölz Lena
- Rajic Glorija
- Rampling Tommy
- Ramsay Maxine
- Rashid Aqeela
- Redondo-Collazo Lorenzo
- Reich Jana
- Reid Ruth
- Reiter Karl
- Relly Christa
- Reschreiter Henrik
- Reynolds Tim
- Rhodes Mathew
- Rial Jose Gómez
- Richmond Vivien
- Riddell Anna
- Riedel Thomas
- Robbins Ceri
- Rodríguez Lidia Piñeiro
- Rodríguez-Tenreiro Carmen
- Roff Amy
- Rojo Pablo
- Romaine Sam
- Romani Lorenza
- Roome Tara
- Rosenheim Joshua
- Rowlands Emily
- Roy Sunando
- Rubick Lucy
- Rudzate Aleksandra
- Rughnani Prita
- Russell Clark D.
- Rusu Alexandra
- Rödl Siegfried
- Sagmeister Manfred G.
- Saidykhan Momodou
- Salas Antonio
- Santilli Giorgia
- Sarr Anna RocaIsatou
- Schlapbach Luregn
- Schlapbach Luregn J.
- Schlüchter Stefanie
- Schmied Patricia
- Schoen Carola
- Scholefield Barnaby J.
- Schonenberg D.
- Schonenberg Dieneke
- Schranz Rachel
- Schroepf Sebastian
- Schweintzger Nina A.
- Schöbi Nina
- Seal Matthew
- Secka Fatou
- Segal Terry
- Selecka Katrina
- Semple Malcolm Gracie
- Shackley Fiona
- Shah Priyen
- Shaji Mariya
- Shankar-Hari
- Shaw Victoria
- Shen Ching-Fen
- Shenton Geoff
- Shepherd Samantha J.
- Shrestha Shrijana
- Siam Ala?a
- Sidorova Aleksandra
- Simagan Teresa
- Simmonds Peter
- Simmons Ruth
- Skrabl-Baumgartner Andrea
- Solomon Tom
- Spencer Collette
- Sperl Matthias
- Sprenkeler Evelien
- Spyridis Nikos
- Srovin Tina Plankar
- Srpcic Anja
- Stampfer Laura
- Steele Michael
- Stevens Jake
- Stevens Molly
- Stocker Martin
- Stoiser Bianca
- Stoldere Diana
- Storey Nathaniel
- Strempfl Martina
- Strenger Volker
- Strijbosch Annelieke M.
- Strle Franc
- Suárez Carlos Durán
- Svile Dace
- Swingler Rachel
- Syggelou Kelly
- Sánchez José María Martinón
- Sée Hélène
- Tait Sarah
- Talts Tiina
- Tambouratzi Maria
- Tan Chantal
- Tappouni Luke J.
- Tauchert Maike K.
- Tavliavini Emma
- Tayler Rachel
- Tedder Richard S.
- Tempel Dennie
- Templeton Kate
- Thalassinos Konstantinos
- Thomas Daisy
- Thomson Emma
- Thomson Evelyn
- Thorson Stephen
- Tibby Shane
- Till Holger
- Tissing Wim J. E.
- Tkhayat Raja Ben
- Torres Montaguth Oscar Enrique
- Tramper-Stranders G. A.
- Trasorras Cristina Serén
- Treloar Owen
- Trobisch Andreas
- Tsolia Maria
- Turtle Lance C. W.
- Tutill Helena
- Urbane Urzula Nora
- Ushiro-Lumb Ines
- Usman Mariama
- Usuf Effua
- Valentine Lucille
- van Aerde Koen
- van de Kuip Martijn
- van den Berg J. M.
- van den Berg Merlijn
- van den Broek Bryan
- van der Flier Michiel
- van der Flier Michiel
- van der Giessen Ilona
- van der Kuip M.
- van der Velden Fabian
- van der Velden Fabian J. S.
- van der Zee Carlijn
- van Furth A. M.
- van Furth Marceline
- van Gool Alain J.
- van Hensbroek Michael Boele
- van Keulen Danielle
- van Leur M.
- van Mierlo G.
- Vastert Sebastiaan J.
- Venturini Cristina
- Vergnault Nathalie
- Verkuil Floris
- Vermont Clementien L.
- Vicente Luisa García
- Vijlbrief Daniel C.
- Villaverde Serena
- Vincek Katarina
- Vito Ortensia
- Voice Marie
- von Both Ulrich
- Vázquez Sara Rey
- Waddington Simon N.
- Wallia Diane
- Wallner Elmar
- Wang Shih-Min
- Ward Bryony
- Ward Catriona
- Watson Conall
- Weber Kathrin
- Wedderburn Catherine
- Wellings Lucy
- Wellman Paul
- Wham Murray
- White Deborah
- White Marie
- Whittaker Elizabeth
- Whittaker Paul
- Whittaker Thomas E.
- Willems Esther
- Williams Charlotte A.
- Williams Rachel
- Wilson Barbara
- Wilson Clare
- Winmill Helen
- Wolfs Tom F. W.
- Womersley Rebecca
- Wood Amanda
- Woodsford Phil
- Wright Victoria
- Wrobel Nicola
- Wyss Verena
- Wösten-van Asperen Roelie M.
- Xagorari Marietta
- Yeung Shunmay
- Zachariasse Joany
- Zaman Syed M. A.
- Zambon Maria
- Zandstra Judith
- Zavadska Dace
- Zennezini Chiozzi Riccardo
- Zenz Werner
- Zimmermann Elisa
- Zurl Christoph
- Zwerenz Manuela
- Publication venue
- Nature Research
- Publication date
- 30/03/2023
- Field of study
Get PDFSince its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children
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.
- Author
- Aban Marites
- Abayomi Fatola
- Abeyskera Kushala
- Aboagye Jeremy
- Adam Matthew
- Adams Kirsty
- Adamson James
- Adelaja Yemi A.
- Adlou Syed
- Ahmed Khatija
- Akhalwaya Saajida
- Akhalwaya Yasmeen
- Alcock Andrew
- Aley Parvinder K.
- Ali Aabidah
- Allen Elizabeth R.
- Allen Lauren
- Almeida Thamires C. D. S. C
- Alves Mariana P.S.
- Amorim Fabio
- Andritsou Foteini
- Angus Brian
- Anslow Rachel
- Appleby Matthew
- Arbe-Barnes Edward H.
- Ariaans Mark P.
- Arns Beatriz
- Arruda Laiana
- Awedetan Gbadebo
- Azi Lorena
- Azi Paula
- Babbage Gavin
- Bailey Catherine
- Baillie Vicky L.
- Baker Kenneth F.
- Baker Megan
- Baker Natalie
- Baker Philip
- Baldwin Lisa
- Baleanu Ioana
- Bandeira Danieli
- Bara Anna
- Barbosa Marcella A.S.
- Barker Debbie
- Barlow Gavin D.
- Barnabas Shaun L.
- Barnes Eleanor
- Barr Andrew S.
- Barrett Jessica
- Barrett Jordan R.
- Bates Louise
- Batten Alexander
- Beadon Kirsten
- Beales Emily
- Beckley Rebecca
- Belij-Rammerstorfer Sandra
- Bell Jonathan
- Bellamy Duncan
- Bellei Nancy
- Belton Sue
- Berg Adam
- Bermejo Laura
- Berrie Eleanor
- Berry Lisa
- Berzenyi Daniella
- Beveridge Amy
- Bewley Kevin R.
- Bexhell Helen
- Bhikha Sutika
- Bhorat Asad E.
- Bhorat Qasim E.
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- Bibi Sagida
- Bijker Else
- Birch Geeta
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- Bird Adam
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- Byard Nicholas
- Cabera Puig Ingrid
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- Castro Lucia Carratala
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- Cerbino-Neto José
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- Chester Oliver
- Chita Sunder
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- Clarke Andrea
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- Connarty Sean
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- Mazzella Andrea
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- McGregor Alastair
- McInroy Lorna
- McIntyre Zoe
- McLenaghan Daniela
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- Mpelembue Mushiya
- Msomi Sibekezelo
- Mugodi Yvonne
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- Mukhopadhyay Ekta
- Muller Jilly
- Munro Alasdair
- Munro Claire
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- Mweu Philomena
- Myasaki Celia Hatsuko
- Naik Gurudutt
- Naker Kush
- Nana Anusha
- Nastouli Eleni
- Nazir Abida
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- Njenga Cecilia
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- Zimmer Rafael
- Zizi Dalila
- Zuidewind Peter
- Publication venue
- 'Elsevier BV'
- Publication date
- 03/12/2020
- Field of study
Get PDFBACKGROUND: 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; pinteraction=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
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
- Author
- Aban Marites
- Abayomi Fatola
- Abeyskera Kushala
- Aboagye Jeremy
- Adam Matthew
- Adams Kirsty
- Adamson James
- Adelaja Yemi A.
- Adlou Syed
- Ahmed Khatija
- Akhalwaya Saajida
- Akhalwaya Yasmeen
- Alcock Andrew
- Aley Parvinder K.
- Ali Aabidah
- Allen Elizabeth R.
- Allen Lauren
- Almeida Thamires C. D. S. C
- Alves Mariana P.S.
- Amorim Fabio
- Andritsou Foteini
- Angus Brian
- Anslow Rachel
- Appleby Matthew
- Arbe-Barnes Edward H.
- Ariaans Mark P.
- Arns Beatriz
- Arruda Laiana
- Awedetan Gbadebo
- Azi Lorena
- Azi Paula
- Babbage Gavin
- Bailey Catherine
- Baillie Vicky L.
- Baker Kenneth F.
- Baker Megan
- Baker Natalie
- Baker Philip
- Baldwin Lisa
- Baleanu Ioana
- Bandeira Danieli
- Bara Anna
- Barbosa Marcella A.S.
- Barker Debbie
- Barlow Gavin D.
- Barnabas Shaun L.
- Barnes Eleanor
- Barr Andrew S.
- Barrett Jessica
- Barrett Jordan R.
- Bates Louise
- Batten Alexander
- Beadon Kirsten
- Beales Emily
- Beckley Rebecca
- Belij-Rammerstorfer Sandra
- Bell Jonathan
- Bellamy Duncan
- Bellei Nancy
- Belton Sue
- Berg Adam
- Bermejo Laura
- Berrie Eleanor
- Berry Lisa
- Berzenyi Daniella
- Beveridge Amy
- Bewley Kevin R.
- Bexhell Helen
- Bhikha Sutika
- Bhorat Asad E.
- Bhorat Qasim E.
- Bhorat Zaheda E.
- Bibi Sagida
- Bijker Else
- Birch Geeta
- Birch Sarah
- Bird Adam
- Bird Olivia
- Bisnauthsing Karen
- Bittaye Mustapha
- Blackstone Katherine
- Blackwell Luke
- Bletchly Heather
- Blundell Caitlin L.
- Blundell Susannah R.
- Bodalia Pritesh
- Boettger Bruno C.
- Bolam Emma
- Boland Elena
- Bormans Daan
- Borthwick Nicola
- Bowring Francesca
- Boyd Amy
- Bradley Penny
- Brenner Tanja
- Briner Carmen
- Brown Claire
- Brown Phillip
- Brown-O'Sullivan Charlie
- Bruce Scott
- Brunt Emily
- Buchan Ruaridh
- Budd William
- Bulbulia Yusuf A.
- Bull Melanie
- Burbage Jamie
- Burhan Hassan
- Burn Aileen
- Buttigieg Karen R.
- Byard Nicholas
- Cabera Puig Ingrid
- Calderon Gloria
- Calvert Anna
- Camara Susana
- Cao Michelangelo
- Cappuccini Federica
- Cardoso João R.
- Carr Melanie
- Carroll Miles W.
- Carson-Stevens Andrew
- Carvalho José A.M.
- Carvalho Yasmin de M.
- Casey Helen R.
- Cashen Paul
- Castro Lucia Carratala
- Castro Thais
- Cathie Katrina
- Cavey Ana
- Cerbino-Neto José
- Chadwick Jim
- Chapman David
- Charlton Sue
- Chelysheva Irina
- Chester Oliver
- Chita Sunder
- Cho Jee-Sun
- Cicconi Paola
- Cifuentes Liliana
- Clark Elizabeth
- Clark Matthew
- Clarke Andrea
- Clemens Sue Ann Costa
- Clutterbuck Elizabeth A.
- Colin-Jones Rachel
- Collins Andrea M.
- Collins Sarah L.K.
- Conlon Christopher P.
- Connarty Sean
- Coombes Naomi
- Cooper Cushla
- Cooper Rachel
- Cornelissen Lynne
- Corrah Tumena
- Cosgrove Catherine
- Cox Tony
- Crocker Wendy E.M.
- Crosbie Sarah
- Cullen Dan
- Cullen Lorraine
- Cunha Debora R.M.F.
- Cunningham Christina
- Cuthbertson Fiona C.
- Cutland Clare L.
- Da Guarda Suzete N. Farias
- da Silva Moraes Antonio Carlos
- da Silva Larissa P.
- Damratoski Brad E.
- Danos Zsofia
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- Darroch Paula
- Darton Thomas C.
- Datoo Mehreen S.
- Datta Chandrabali
- Davids Malika
- Davies Hannah
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- Davis Elizabeth
- Davis John
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- De Jager Jeanne
- De Nobrega Maristela M.D.
- De Oliveira Kalid Lis Moreno
- Dearlove David
- Demissie Tesfaye
- Desai Amisha
- Dheda Keertan
- Di Marco Stefania
- Di Maso Claudio
- Dinelli Maria I.S.
- Dinesh Tanya
- Docksey Claire
- Dold Christina
- Dong Tao
- Donnellan Francesca R.
- Dos Santos Erika Pachecho
- Dos Santos Tannyth
- dos Santos Thainá G.
- Douglas Alexander D.
- Douglas Naomi
- Downing Charlotte
- Drake Jonathan
- Drake-Brockman Rachael
- Driver Kimberley
- Drury Ruth
- Du Plessis Joan
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- Duncan Christopher J. A.
- Durham Benjamin S.
- Dutra Lidiana
- Easom Nicholas J.W.
- Edwards Mandy
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- Elias Sean C.
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- English Marcus
- Esmail Alisgair
- Essack Yakub Moosa
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- Fairlie Lee
- Farmer Eoghan
- Farooq Mutjaba
- Farrar Madi
- Farrugia Leonard
- Faulkner Beverley
- Faust Saul N.
- Fedosyuk Sofiya
- Felle Sally
- Feng Shuo
- Feng Shuo
- Ferreira Da Silva Carla
- Ferreira Daniela M.
- Field Samantha
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- Fisher Richard
- Flaxman Amy
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- Franco Marilia M.
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- Galian-Rubio Pablo
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- Greenwood Nicola
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- Grossi Leonardo
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- Howe Elizabeth
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- Humphreys Jonathan
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- Hurley Katrina
- Huson Claire
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- Hyder-Wright Angela
- Ikram Sabina
- Ishwarbhai Alka
- Ivan Monica
- Iveson Poppy
- Iyer Vidyashankara
- Izu Alane
- Jackson Frederic
- Jackson Susan
- Jaumdally Shameem
- Jeffers Helen
- Jenkin Daniel
- Jesudason Natasha
- Joe Carina C. D.
- Jones Bryony
- Jones Christopher
- Jones Elizabeth
- Jones Kathryn
- Jorge Marianna Rocha
- Jose Aylin
- Joshi Amar
- Júnior Eduardo A.M.S.
- Kadziola Joanne
- Kailath Reshma
- Kana Faeeza
- Karampatsas Konstantinos
- Kasanyinga Mwila
- Keen Jade
- Kelly Dearbhla M.
- Kelly Debbie
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- Kelly Sarah
- Kerr David
- Kerridge Simon
- Kfouri Renato de Ávila
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- Kidd Sarah
- Killen Annabel
- Kinch Jasmin
- Kinch Patrick
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- Knight Julian C.
- Knott Daniel
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- Kwatra Gaurav
- Lambe Teresa
- Lang Gail
- Lang Matilda
- Larkworthy Colin W.
- Larwood Jessica P.J.
- Law Rebecca
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- Lazarus Erica M.
- Lazarus Rajeka
- Leach Amanda
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- Lelliott Alice
- Lemm Nana-Marie
- Lessa Alvaro
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- Libri Vincenzo
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- Lipworth Samuel
- Liu Shuchang
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- Lloyd Adam
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- Loew Lisa
- Lopez Ramon Raquel
- Lora Leandro
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- Luz Kleber
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- MacGregor Gordon
- Madhavan Meera
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- Mainwaring David O.
- Makambwa Edson
- Makinson Rebecca
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- Malamatsho Ross
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- Maoko Takalani
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- Marinou Spyridoula
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- Marshall Julia L.
- Marshall Richard P.
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- Masenya Masebole
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- Masters Shauna K.
- Mathew Moncy
- Matlebjane Hosea
- Matshidiso Kedidimetse
- Mazur Olga
- Mazzella Andrea
- McCaughan Hugh
- McEwan Joanne
- McGlashan Joanna
- McGregor Alastair
- McInroy Lorna
- McIntyre Zoe
- McLenaghan Daniela
- McRobert Nicky
- McSwiggan Steve
- Megson Clare
- Mehdipour Savviz
- Meijs Wilma
- Mendes Ana V .A.
- Mendonça Renata N.Á.
- Mentzer Alexander J.
- Milan Eveline P.
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- Mirtorabi Neginsadat
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- Moran Marni
- Morey Ella
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- Morris Helen C.
- Morris Sheila
- Morris Susan
- Morrison Hazel
- Morselli Franca
- Morshead Gertraud
- Morter Richard
- Mottal Lynelle
- Moultrie Andrew
- Moya Nathifa
- Mpelembue Mushiya
- Msomi Sibekezelo
- Mugodi Yvonne
- Mujadidi Yama F.
- Mukhopadhyay Ekta
- Muller Jilly
- Munro Alasdair
- Munro Claire
- Murphy Sarah
- Mweu Philomena
- Myasaki Celia Hatsuko
- Naik Gurudutt
- Naker Kush
- Nana Anusha
- Nastouli Eleni
- Nazir Abida
- Ndlovu Bongani
- Neffa Fabio
- Njenga Cecilia
- Noal Helena
- Novaes Gabrielle
- Noé Andrés
- Nugent Fay L.
- Nunes Géssika
- O'Brien Katie
- O'Connor Daniel
- O'Reilly Paula
- O'Reilly Peter J.
- Odam Miranda
- Oelofse Suzette
- Oguti Blanche
- Olchawski Victoria
- Oldfield Neil J.
- Oliveira Catarina
- Oliveira Marianne G.
- Oosthuizen Angela
- Osborne Piper
- Owen David R.J.
- Owen Lydia
- Owens Daniel
- Owino Nelly
- Pacurar Mihaela
- Padayachee Sherman D.
- Paiva Brenda V.B.
- Palhares Edna M.F.
- Palmer Susan
- Parkinson Sivapriyai
- Parracho Helena M.R.T.
- Parsons Karen
- Patel Bhumika
- Patel Dipak
- Patel Faeezah
- Patel Kelly
- Patrick-Smith Maia
- Payne Ruth O.
- Peng Yanchun
- Penn Elizabeth J.
- Pennington Anna
- Peralta Alvarez Marco Polo
- Perring James
- Perry Nicola
- Perumal Rubeshan
- Petkar Sahir
- Philip Tricia
- Phillips Daniel J.
- Phillips Jennifer
- Phohu Mary Kgomotso
- Pickup Lorinda
- Pieterse Sonja
- Piper Jo
- Pipini Dimitra
- Pittella Ana
- Plank Mary
- Plested Emma
- Pollard Andrew J
- Pollard Samuel
- Pollock Katrina M.
- Pooley Jennifer
- Pooran Anil
- Poulton Ian
- Powers Claire
- Presa Fernando B.
- Price David A.
- Price Vivien
- Primeira Marcelo
- Proud Pamela C.
- Provstgaard-Morys Samuel
- Pueschel Sophie
- Pulido David
- Quaid Sheena
- Rabara Ria
- Radford Alexandra
- Radia Kajal
- Rajapaska Durga
- Rajeswaran Thurkka
- Ramasamy Maheshi N.
- Ramos Lopez Fernando
- Ramos Alberto San Francisco
- Rampling Tommy
- Rand Jade
- Ratcliffe Helen
- Rawlinson Tom
- Rea David
- Rees Byron
- Reiné Jesús
- Resuello-Dauti Mila
- Reyes Pabon Emilia
- Rhead Sarah
- Ribiero Carla M.
- Ricamara Marivic
- Richter Alex
- Ritchie Adam J.
- Ritchie Neil
- Robbins Alexander J.
- Roberts Hannah
- Robinson Hannah
- Robinson Ryan E.
- Rocchetti Talita T.
- Rocha Beatriz Pinho
- Roche Sophie
- Rollier Christine
- Rose Louisa
- Ross Russell Amy L.
- Rossouw Lindie
- Royal Simon
- Rudiansyah Indra
- Ruiz Sarah
- Saich Stephen
- Sala Claudia
- Sale Jessica
- Salman Ahmed M.
- Salvador Natalia
- Salvador Stephannie
- Sampaio Milla
- Samson Annette D.
- Sanchez-Gonzalez Amada
- Sanders Helen
- Sanders Katherine
- Santos Guerra Mayara F.S.
- Santos Erika
- Satti Iman
- Saunders Caroline
- Saunders Jack E.
- Sayed Aakifah
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- Schmid Annina B.
- Schofield Ella
- Schwarzbold Alexandre V.
- Screaton Gavin
- Seddiqi Samiullah
- Segireddy Rameswara R.
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- Shah Rajiv
- Shaik Imam
- Sharpe Hannah E.
- Sharrocks Katherine
- Shaw Robert
- Shea Adam
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- Shepherd James G.
- Shiham Farah
- Sidhom Emad
- Silk Sarah E.
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- Silva-Reyes Laura
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- Silveira Mariana B.V.
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- Sinha Jaisi
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- Smith Catherine C.
- Smith Daniel C.
- Smith David J.
- Smith Holly E.
- Smith Nick
- Snape Matthew D.
- Soares Airanuédida
- Soares Tiago
- Solórzano Carla
- Song Rinn
- Sorio Guilherme L.
- Sorley Kim
- Sosa-Rodriguez Tiffany
- Souza Alessandra R.
- Souza Bruno S.D.F.
- Souza Cinthia M.C.D.L.
- Spencer Alexandra J.
- Spina Fernanda
- Spoors Louise
- Sprinz Eduardo
- Stafford Lizzie
- Stamford Imogen
- Starinskij Igor
- Stein Ricardo
- Steven Jill
- Stockdale Lisa
- Stockwell Lisa V.
- Strickland Louise H.
- Stuart Arabella C.
- Sturdy Ann
- Sutherland Rebecca K.
- Sutton Natalina
- Szigeti Anna
- Tahiri-Alaoui Abdessamad
- Tanner Rachel
- Taoushanis Carol
- Tarr Alexander W.
- Tarrant Richard
- Taylor Iona Jennifer
- Taylor Justin
- Taylor Keja
- Taylor Ursula
- te Water Naude Rebecca
- Themistocleous Andreas
- Themistocleous Yrene
- Thomas Kelly
- Thomas Merin
- Thomas Tonia M.
- Thombrayil Asha
- Thompson Amber
- Thompson Ameeka
- Thompson Fawziyah
- Thompson Kevin
- Thomson Emma C.
- Thomson Julia
- Thornton-Jones Viv
- Tighe Patrick J.
- Tinoco Lygia Accioly
- Tiongson Gerlynn
- Tladinyane Bonolo
- Tomasicchio Michele
- Tomic Adriana
- Tonks Susan
- Toshner Mark
- Tran Nguyen
- Tree Julia
- Trillana Gerry
- Trinham Charlotte
- Trivett Rose
- Truby Adam
- Tsheko Betty Lebogang
- Turabi Aadil
- Turner Cheryl
- Turner David P. J.
- Turner Richard
- Török M Estée
- Ulaszewska Marta
- Underwood Benjamin R.
- van Eck Samual
- Varughese Rachel
- Vekemans Johan
- Verbart Dennis
- Verheul Marije
- Vichos Iason
- Vieira Taiane
- Villafana Tonya L.
- Voysey Merryn
- Waddington Claire S.
- Walker Laura
- Wallis Erica
- Wand Matthew
- Warbick Deborah
- Wardell Theresa
- Warimwe George
- Warren Sarah C.
- Watkins Bridget
- Watson Ekaterina
- Watson Marion E. E.
- Webb Stewart
- Webb-Bridges Alice
- Webster Angela
- Weckx Lily Y.
- Welch Jessica
- Wells Jeanette
- West Alison
- White Caroline
- White Rachel
- Williams Christopher J.
- Williams Paul
- Williams Rachel L.
- Winslow Rebecca
- Woodyer Mark
- Worth Andrew T.
- Wright Danny
- Wroblewska Marzena
- Yao Andy
- Zimmer Rafael
- Zizi Dalila
- Zuidewind Peter
- Publication venue
- 'Elsevier BV'
- Publication date
- 09/01/2021
- Field of study
Get PDFBackground
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; pinteraction=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
Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial
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- Abbas M.
- Abdul Rasheed A.
- Abdul A.
- Abdul-Kadir R.
- Abdusamad K.
- Abernethy K.
- Aboelela H.
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- Abraham M.
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- Bujazia R.
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- Buttress D.
- Byrne J.
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- Byrne-Watts V.
- Cale E.
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- Carroll A.
- Carson R.
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- Caws C.
- Central Coordinating Office (for the RECOVERY Collaborative Group)
- Century H.
- Chadwick J.
- Chakkarapani E.
- Chakraborty A.
- Chamberlain S.
- Chambers E.
- Chambers L.
- Chan E.
- Chan R.
- Chaplin J.
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- Chappell L.
- Charles B.
- Charlton D.
- Chatar K.
- Chatterton D.
- Chaudhuri N.
- Chauhan R.
- Chawla V.
- Chen F.
- Cheng F.
- Cherrie M.
- Cheung E.
- Cheyne C.
- Chilcott S.
- Chilvers A.
- Chin K.
- Chineka R.
- Chinonso E.
- Chisnall B.
- Chiswick C.
- Chivima B.
- Chmiel C.
- Chrisopoulou A.
- Christian P.
- Christides A.
- Christmas D.
- Church E.
- Cianci N.
- Cicconi P.
- Clare E.
- Clark E.
- Clark G.
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- Clark R.
- Clarke A.
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- Clayton-Smith J.
- Cleaver C.
- Clemente de la Torre C.
- Clifford S.
- Coakley M.
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- Cochrane P.
- Cocks S.
- Coe A.
- Coey D.
- Cohen D.
- Coker O.
- Cole J.
- Coleman G.
- Coles H.
- Collier D.
- Collini Paul
- Collins J.
- Collins V.
- Colton H.
- Condliffe R.
- Connell E.
- Connell L.
- Connelly K.
- Connolly G.
- Connor E.
- Conroy K.
- Conteh V.
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- Cooke G.
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- Cooper L.
- Cooper N.
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- Corbett C.
- Corbishley A.
- Cornwell J.
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- Corrigan R.
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- Cotterill D.
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- Crichton C.
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- Darbyshire Janet
- Darnell S.
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- Data Monitoring Committee of the RECOVERY Collaborative Group
- Daunt A.
- Dave V.
- Davey M.
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- de Silva T.
- De Soyza A.
- de Vos J.
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- Dear J.
- Deelchand V.
- Deery J.
- DeMets David
- Denis E.
- Dent M.
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- Desai A.
- Deshpande S.
- Dey P.
- Dhaliwal K.
- Dhani S.
- Dhasmana Devesh J.
- Dhillon R.
- Dicks P.
- Digby J.
- Dimitri P.
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- Ditchfield L.
- Dixon C.
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- Dobbie L.
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- Docherty M.
- Dockrell D.
- Dodds R.
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- Dolan D.
- Dolman M.
- Donald L.
- Donaldson D.
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- Donlon S.
- Donohoe A.
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- Dosanjh D.
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- Downey R.
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- Drewett O.
- Drogan H.
- Drummond G.
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- Du Thinh A.
- Duckles-Leech H.
- Duffield E.
- Duffy H.
- Duggan A.
- Dummer S.
- Duncan C.
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- Duncan R.
- Dunleavy J.
- Dunn A.
- Duran B.
- Durrans L.
- Durrington H.
- Duru I.
- Dymond H.
- D’Costa J.
- D’Mello A.
- Eades C.
- Early J.
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- Edgerley K.
- Edmond N.
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- Elgohary A.
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- Ellwood A.
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- Emberson Jonathan R.
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- Emonts M.
- Essa F.
- Evans B.
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- Everden C.
- Everden S.
- Evison L.
- Ezenduka C.
- Fairbairn I.
- Fairclough A.
- Falconer E.
- Faluyi D.
- Fancois V.
- Farmery T.
- Farooq H.
- Farrell B.
- Farzana S.
- Fatemi A.
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- Faust Saul N.
- Fearby S.
- Felton T.
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- Fenton C.
- Ferenando G.
- Ferguson C.
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- Ferguson V.
- Fernandez Lopez S.
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- Health records (for the RECOVERY Collaborative Group)
- Hector G.
- Heddon S.
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- Ijaz M.
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- Jackman S.
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- Jackson S.
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- Jarvis C.
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- Jeebun V.
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- Johnstone E.
- Jones A.
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- Kailey A.
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- Lo S.
- Loader D.
- Local Clinical Centre staff (for the RECOVERY Collaborative Group)
- Lock S.
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- Lodhia K.
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- Logan M.
- Logue C. A.
- Lokanathan S.
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- Majumdar Jaydip
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- Field of study
Get PDFDimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome
