145 research outputs found
Differences in Negative Symptom Severity Across Bipolar Disorder With and Without Psychosis
- Publication venue
- Digital Scholarship@UNLV
- Publication date
- 09/12/2022
- Field of study
There was no significant difference between BP+ and BP- groups. Significant difference were found in BP+ and SZ groups when tested for Affective Flattening and Alogia.Significant difference were found in HC and BP- when tested for Anhedonia-Asociality.https://digitalscholarship.unlv.edu/durep_posters/1129/thumbnail.jp
Communication in Individuals with Rett Syndrome: an Assessment of Forms and Functions
- Author
- Publication venue
- Springer US
- Publication date
- 01/01/2009
- Field of study
In the present study we assessed the forms and functions of prelinguistic communicative behaviors for 120 children and adults with Rett syndrome using the Inventory of Potential Communicative Acts (IPCA) (Sigafoos et al. Communication Disorders Quarterly 21:77–86, 2000a). Informants completed the IPCA and the results were analysed to provide a systematic inventory and objective description of the communicative forms and functions present in each individual’s repertoire. Results show that respondents reported a wide variety of communicative forms and functions. By far most girls used prelinguistic communicative behaviors of which eye contact/gazing was the most common form. The most often endorsed communicative functions were social convention, commenting, answering, requesting and choice-making. Problematic topographies (e.g., self-injury, screaming, non-compliance) were being used for communicative purposes in 10 to 41% of the sample. Exploratory analyses revealed that several communicative forms and functions were related to living environment, presence/absence of epilepsy, and age. That is, higher percentages of girls who showed some forms/functions were found in those who lived at home, who had no epilepsy and who were relatively young
Investigation of equilibrium and phase stability in the liquid/solid state in nickel-based wrought superalloys
- Author
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- Field of study
Whole-genome sequencing reveals host factors underlying critical COVID-19
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- Weston H.
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- White N.
- Whiteley S.
- Whiteside J.
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- Wilkinson B.
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- Wood H. -L.
- Wood S.
- Wood T.
- Woodford C.
- Woodruff M.
- Woods L.
- Woodyatt W.
- Woolley A. E.
- Worner R.
- Worsley L.
- Wray G.
- Wren L.
- Wright D.
- Wright J.
- Wright M.
- Wrobel N.
- Wu Y.
- Wulandari R.
- Wyllie D. H.
- Wynter I.
- Xavier K.
- Xue X.
- Yadav A.
- Yang J.
- Yassen A. M.
- Yates B.
- Ye C.
- Yun N.
- Zainy T.
- Zak A.
- Zaki A.
- Zamikula J.
- Zanella I.
- Zborowski A. C.
- Zeberg H.
- Zechner M.
- Zguro K.
- Zhang M.
- Zhao J. H.
- Zheng C.
- Zhou W.
- Zitter L.
- Zlatopolsky M.
- Zollner S.
- Zongo O.
- Zucchi P.
- Zyndorf M.
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/2022
- Field of study
Critical 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
- B Scholefield
- B Shelley
- B Sloan
- B Thomas
- B Wadams
- B Welsh
- B Wilkinson
- B Winter-Goodwin
- B Yates
- Baillie J Kenneth
- Barbara Rossetti
- Beale Rupert
- Beatrice Alex
- Benjamin Bach
- Bretherick Andrew D
- Bruno Frediani
- C Adams
- C Ahmed
- C Almaden-Boyle
- C Ashbrook-Raby
- C Basikolo
- C Battle
- C Beazley
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- C Brandwood
- C Brantwood
- C Burnett
- C Castro Delgado
- C Clark
- C Clulow
- C Collins
- C Cruz
- C Davis
- C Demetriou
- C Dennis
- C Dexter
- C Downes
- C Dunmore
- C Eastgate
- C Eckbad
- C Finch
- C Gibson
- C Gorman
- C Hays
- C Hewitt
- C Holl
- C Howcroft
- C Humphrey
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- C Jardine
- C Jennings
- C Jones
- C Kaye
- C Lynch
- C Lyons
- C McCulloch
- C McParland
- C McParland
- C Murphy
- C Parmar
- C Pawley
- C Phillips
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- C Pothecary
- C Pothecary
- C Prendergast
- C Price
- C Rishton
- C Sell
- C Shovelton
- C Sicat
- C Stuart
- C Summers
- C Swan
- C Thompson
- C Thorpe
- C Tibke
- C Tierney
- C Vigurs
- C Wells
- C Whitton
- C Whyte
- C Wrey Brown
- Cameron J Fairfield
- Carmelo Piscopo
- Carmen Marciano
- Caroline Abernathy
- Carrol Gamble
- Caterina Lo Rizzo
- Catherine A Shaw
- Catherine H Weldon
- Caulfield Mark
- Ceilia Boz
- Cesira Nencioni
- Chelsea Ye
- Chiara Fallerini
- Chiara Gabbi
- Chiara Spertilli
- Chloe Donohue
- Chris Ponting
- Christoper A Green
- Cinthia E Jannes
- Clare Jackson
- Clohisey Sara
- Cristina Mussini
- D Antcliffe
- D Bakthavatsalam
- D Banach
- D Baptista
- D Bell
- D Branney
- D Brealey
- D Brealey
- D Butcher
- D Butcher
- D Childs
- D Clarke
- D Collier
- D Collier
- D Cristiano
- D Dawson
- D Donaldson
- D Duffin
- D Fottrell-Gould
- D Golden
- D Griffin
- D Hamilton
- D Hawcutt
- D Hope
- D Horner
- D Kallon
- D Kaye
- D Kelly
- D Loader
- D Lomas
- D Martin
- D McGlynn
- D McLaughlanv
- D Melia
- D Menzies
- D Mullan
- D Pogson
- D Potla
- D Potoczna
- D Purohit
- D Raynard
- D Salutous
- D Salutous
- D Scaletta
- D Shaw
- D Skinner
- D Smyth
- D Strachan
- D Tetla
- D Thornton
- D Trodd
- D Vedage
- D Walker
- D Warren
- D Williams
- D Wood
- D Wright
- Daniela Francisci
- Daniella Coker
- Danilo Tacconi
- David A van Heel
- David Bennet
- David L Robertson
- David Stuart
- Dawn Law
- Debby Bogaert
- Derek Murphy
- Domenico A Coviello
- E Abaleke
- E Allan
- E Anastasescu
- E Andrews
- E Apetri
- E B Jude
- E Beech
- E Beranova
- E Bevan
- E Black
- E Brinkworth
- E Collins
- E Combes
- E Davies
- E Dobson
- 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
- Elisa Frullanti
- 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
- Gian Piero Caldarelli
- Giancarlo Bosio
- Giuseppe Fiorentino
- Giuseppe Merla
- Gountouna Elvina
- Graham S Cooke
- Griffiths Fiona
- Grimes Graeme
- H Bancroft
- H Bates
- H Belfield
- H Blackman
- H Blakemore
- H Brooke
- H Button
- H Coles
- H Curgenven
- H Filipe
- H Fox
- H Golding
- H Hill
- H Holcombe
- H Houlden
- H Jeffrey
- H Kent
- H Langton
- H McGuinness
- H Meghari
- H Millward
- H Moore
- H Parker
- H Pearson
- H Prady
- H Quinn
- H Rangarajan
- H Rehman
- H Reschreiter
- H Riley
- H Sainsbury
- H Savill
- 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
- I Burn
- I Chadbourn
- I D Clement
- I Edmond
- I Frost
- I Hass
- I Hussain
- I Lancoma-Malcolm
- I Leadbitter
- I Nagra
- I Otahal
- I Otahal
- I Turner-Bone
- I Welters
- I White
- I Wynter
- Ilaria Meloni
- Immacolata Andolfo
- Isabella Zanella
- J Allan
- J Barker
- J Bewley
- J Biddle
- J Birch
- J Birch
- J Bradley-Potts
- J Brown
- J Bryant
- J Butler
- J Camsooksai
- J Carter
- J Caterson
- J Cebrian Suarez
- J Cockerill-Taylor
- J Cole
- J Colley
- J Cooper
- J Cupitt
- J Cuttler
- J Daglish
- J Dasgin
- J Dawson
- J Dearden
- J Deery
- J Donnachie
- J Dykes
- J Easton
- J Egan
- J Fernandez Roman
- J Finn
- J Fletcher
- J Frankham
- J Gaylard
- J Gill
- J Godden
- J Goodsell
- J Gregory
- J Greig
- J Gurasashvili
- J Hardy
- J Harris
- J Hatton
- J Hawes
- J Highgate
- J Hornsby
- J Hulme
- J Hunt
- J Hutter
- J Ingham
- J Jones
- J Jones
- J K Baillie
- J Kassam
- J Kenneth Baillie
- J Kenneth Baillie
- J Keshet-Price
- J Liew
- J Little
- J Mallinson
- J Martin
- J Matthews
- J McCormick
- J Medhora
- J Melville
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- Janet T Scott
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- Keating Sean
- Kenneth A Mclean
- Kirstie Morrice
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- Knight Julian
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- L Abel
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- L Allen
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- L Barclay
- L Benham
- L Botfield
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- L Bunni
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- L Cagova
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- L Grimmer
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- L Lennon
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- L McMorrow
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- L Mew
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- L Zitter
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- Laura Marsh
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- Lia Crotti
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- Lorenzo Salerni
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- Louise Cullum
- Louise Macgillivray
- Louise Sigfrid
- Luca Cantarini
- Luca Guidelli
- Luca Masucci
- Luisa Tavecchia
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- M Williams
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- Porteous David J
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- Stephanie Roberts
- Stephen R Knight
- Summers Charlotte
- Susanna Croci
- Susanna Guerrini
- T Anderson
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- T Pogreban
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- T Samakomva
- T Smith
- T Smith
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- T Wood
- Tammy Gilchrist
- Tenesa Albert
- Teresa Filshtein-Sonmez
- Thomas M Drake
- Thushan de Silva
- Tim Walsh
- Tom Fletcher
- Tom Solomon
- Tony Wackett
- Trevor Paterson
- Tullio Trotta
- Turtle Lance
- U Poultney
- V Amin
- V Anumakonda
- V Bastion
- V Cannons
- V Crickmore
- V Gopal
- V Irvine
- V Kasipandian
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- V Linnett
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- V Page
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- V Parris
- V Pristopan
- V Ratnam
- V Rivers
- V Sarathy
- V Thomas
- V Thwaites
- V Tuckey
- V Turner
- V Wagstaff
- V Waugh
- Valentina Anemoli
- 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
Host-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
Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity
- Author
- 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. 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. Easthorpe
- 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. Noakes
- A. Patel
- A. Pickard
- 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 Brown
- Adam Krętowski
- Adriana Roży
- Agnese Verzuri
- Agnieszka Adamek
- Agnieszka Bielska
- Agostino Ognibene
- Agostino Riva
- Ailsa Golightly
- Alan Maclean
- Albert Tenesa
- Aleksandra Berkan-Kawinska
- Aleksandra Jezela-Stanek
- Aleksandra Starosz
- Alessandra Guarnaccia
- Alessandra Renieri &
- Alessandra Stella
- Alessandra Vergori
- Alessandro Pancrazzi
- Alessia Giorli
- Alice Donati
- Alison Meynert
- Alistair Nichol
- Anders Larsson
- Andrea Antinori
- Andrea Cossarizza
- Andrea Gabbuti
- Andrea Tommasi
- Andrew D. Bretherick
- Andrew Law
- Andrew Stenhouse
- Andrzej Eljaszewicz
- Andrzej Horban
- Andy Law
- Angelica Pagliazzi
- Angie Fawkes
- Anke Hinney
- Anna Canaccini
- Anna Kruk
- Anna Maria Pinto
- Anna Moniuszko-Malinowska
- Anna Parfieniuk-Kowerda
- Anna Piekarska
- Anna Szałkowska
- Annarita Giliberti
- Anne Richmond
- Antonella D. ’Arminio Monforte
- Antonella Vincenti
- Antonia Ho
- Antonio Di Biagio
- Antonio Perrella
- Arianna Emiliozzi
- Arianna Gabrieli
- Arsalin Azzadin
- Asma Al Thani &
- Athanasios Kousathanas
- Audrey Coutts
- Axel Schmidt
- Axel Schmidt
- 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
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- B. Hadebe
- B. Hairsine
- B. Hopkins
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- B. Masunda
- B. Ogg
- B. Patel
- B. Player
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- B. Shelley
- B. Sloan
- B. Thomas
- B. Wadams
- B. Welsh
- B. Wilkinson
- B. Winter-Goodwin
- B. Yates
- Barbara Rossetti
- Barbara Shih
- Barbara Sobala-Szczygiel
- Beata Puzanowska
- Benedetta Romanin
- Björn Jensen
- Bo Wang
- Brent Richards
- Bruno Frediani
- C. Adams
- C. Ahmed
- C. Almaden-Boyle
- C. Ashbrook-Raby
- C. Basikolo
- C. Battle
- C. Beazley
- C. Beith
- C. Borra
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- C. Gibson
- C. Gorman
- C. Hays
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- C. Jennings
- C. Jones
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- C. Lynch
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- C. McCulloch
- C. McParland
- C. McParland
- C. Murphy
- C. Parmar
- C. Pawley
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- C. Phillips
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- C. Pothecary
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- C. Rishton
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- C. Summers
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- C. Thompson
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- C. Tibke
- C. Tierney
- C. Vigurs
- C. Wells
- C. Whitton
- C. Whyte
- C. Wrey Brown
- Carlo Maj
- Carmelo Piscopo
- Caroline Abernathy
- Caterina Lo Rizzo
- Ce Dunmore
- Cecilia Costa
- Ceilia Boz
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- Chadi Saad
- Charles Hinds
- Charlotte Summers
- Chenqing Zheng
- Chiara Barbieri
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- Chiara Spertilli Raffaelli
- Chris P. Ponting
- Chris Ponting
- Christian Herr
- Christof Winter
- Christoph D. Spinner
- Clark D. Russell
- Claudia Suardi
- Claudio Ferri
- Clemens M. Wendtner
- Cristina Mussini
- D. Antcliffe
- D. Bakthavatsalam
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- D. Baptista
- D. Bell
- D. Branney
- D. Brealey
- D. Brealey
- D. Butcher
- D. Butcher
- D. Childs
- D. Clarke
- D. Collier
- D. Collier
- D. Cristiano
- D. Dawson
- D. Donaldson
- D. Duffin
- D. Golden
- D. Griffin
- D. Hawcutt
- D. Hope
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- D. Kallon
- D. Kaye
- D. Kelly
- D. Loader
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- D. Martin
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- D. Melia
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- D. Mullan
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- D. Purohit
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- D. Salutous
- D. Salutous
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- D. Shaw
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- D. Thornton
- D. Trodd
- D. Vedage
- D. Walker
- D. Warren
- D. Williams
- D. Wood
- D. Wright
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- Danilo Tacconi
- Danny McAuley
- David Bennett
- David Harrison
- David Maslove
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- Davide Romani
- Dawn Law
- Diana Alaverdian
- Diana Martonik
- Diego Ripamonti
- Domenico A. Coviello
- Dorota Pasko
- Dorota Zarębska-Michaluk
- E. Abaleke
- E. Allan
- E. Anastasescu
- E. Andrews
- E. Apetri
- E. Beech
- E. Beranova
- E. Bevan
- E. Black
- E. Brinkworth
- E. Collins
- E. Combes
- E. Davies
- E. Dobson
- E. Dooks
- E. Fisher
- E. Gendall
- E. Goff
- E. Goodwin
- E. Gordon
- E. Heeney
- E. Horsley
- E. Hughes
- E. Johnson
- E. Jude
- 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. Salciute L. Grauslyte
- E. Smith
- E. Smithson
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- E. Thomas
- E. Tilney
- E. Timlick
- E. Treus Gude
- E. Virgilio
- E. Watson
- E. Wilby
- E. Wraith
- Edoardo Conticini
- Elena Andreucci
- Elena Bargagli
- Elena Desanctis
- Elisa Benetti
- Elisa Frullanti
- Elisabetta Menatti
- Elisabetta Schiaroli
- Ellie Mcmaster
- Elvina Gountouna
- Emanuele Catena
- Enrico Cabri
- Enrico Martinelli
- Erika Fiorentini
- Erola Pairo-Castineira
- Erola Pairo-Castineira
- Esther Duncan
- Eugenia Quiros-Roldan
- Eva C. Schulte
- Eva C. Schulte
- 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
- Fabian Brand
- Fabio Lena
- Faisal Almalki
- Federica Gaia Miraglia
- Federico Anedda
- Federico Franchi
- Ferdinando Giannattasio
- Filip Taneski
- Filippo Aucella
- Filippo Biscarini
- Fiona Griffiths
- Floriana Valentino
- Francesca Andretta
- Francesca Ariani
- Francesca Colombo
- Francesca Fava
- Francesca Gatti
- Francesca Mari
- Francesca Minnai
- Francesca Montagnani
- Francesca Vichi
- Francesco Bianchi
- Francesco Brancati
- Francesco Castelli
- Francesco Menichetti
- Francesco Paciosi
- Francesco Raimondi
- Francesco Vladimiro Segala
- Francis P. Crawley
- Franco Maggiolo
- Franco Marinangeli
- 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. Randell
- G. Sadera
- G. Seddon
- G. Sera Howe
- G. Sloane
- G. Subramanian
- G. Tsinaslanidis
- G. Turner
- G. Watson
- G. Wray
- Gabriela Sokołowska
- Gabriella Coiro
- Gabriella Doddato
- Gabriella Maria Squeo
- GEN-COVID Multicenter Study
- Genni Spargi
- GenOMICC Consortium
- Giada Beligni
- Gian Piero Caldarelli
- Gianfranco Parati
- Giovanna Morelli
- Giulia Gori
- Giuseppe Fiorentino
- Giuseppe Merla
- Giusy Tiseo
- Graeme Grimes
- Guillaume Butler-Laporte
- Guillaume Butler-Laporte
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- H. Sturgeon
- H. T-Michael
- H. Tench
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- Miroslaw Czuczwar
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- N. Ahmad
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- Paweł Olszewski
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- S. Clamp
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- Sabrina Ravaglia
- Said I. Ismail
- Salam Massadeh
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- Sauro Luchi
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- SMelling
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- Stephan Ossowski
- Susan Walker
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- Susanna Guerrini
- Sławomir Pancewicz
- T. Anderson
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- T. Behan
- T. Bemand
- T. Cosier
- T. Coventry
- T. Duncan
- T. Felton
- T. Geary
- T. Hazleton
- T. Joefield
- T. Kannan
- T. Marsden
- T. Martin
- T. McHugh
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- T. O. Jones
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- T. Rees
- T. Samakomva
- T. Smith
- T. Smith
- T. Szakmany
- T. Varghes
- T. Williams
- T. Wood
- Tammy Gilchrist
- Thorsten Brenner
- Tim Walsh
- Tiziana Bachetti
- Tomas Luther
- Tommaso Matucci
- Tony Wackett
- Torsten Feldt
- Trevor Paterson
- Tullio Trotta
- U. Poultney
- Ulrike Protzer
- Umberto Zuccon
- Urszula Korotko
- Urszula Lechowicz
- Urszula Polowianiuk
- V. Amin
- V. Anumakonda
- V. Bastion
- V. Cannons
- V. Crickmore
- V. Gopal
- V. Irvine
- V. Kasipandian
- V. Krishnamurthy
- V. Lake
- V. Linnett
- V. Martinson
- V. Nagarajan
- V. Page
- V. Parris
- V. Parris
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- V. Sarathy
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- V. Thwaites
- V. Tuckey
- V. Turner
- V. Wagstaff
- V. Waugh
- Valentina Anemoli
- Valentina Borgo
- Valentina Perticaroli
- Verena Keitel
- Veronique Vitart
- W. Harrison
- W. Khaliq
- W. Khaliq
- W. McCormick
- W. Woodyatt
- Wadha Al-Muftah
- WES/WGS Working Group Within the HGI
- Wiktoria Izdebska
- Wilna Oosthuyzen
- X. Qiu
- Xia Shen
- Y. Baird
- Y. Choudhury
- Y. Hussain
- Y. Jackson
- Y. Thirlwall
- Yanara Marincevic-Zuniga
- Yang Wu
- Yaser Al-Sarraj
- Z. Alldis
- Z. Belagodu
- Z. Bradshaw
- Z. Coton
- Z. Daly
- Z. Farzad
- Z. Fernandez
- Z. Garland
- Z. Maqsood
- Z. Omar
- Z. Prime
- Z. Scott
- Zhijian Yang
- Publication venue
- Publication date
- 01/01/2022
- Field of study
The combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole-exome sequencing data of about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting COVID-19 severity. First, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthily, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management. © 2021, The Author(s)
Effect of niobium in the phase transformation and corrosion resistance of one austenitic-ferritic stainless steel
- Author
- Publication venue
- 'FapUNIFESP (SciELO)'
- Publication date
- Field of study
Safety, immunogenicity, and reactogenicity of BNT162b2 and mRNA-1273 COVID-19 vaccines given as fourth-dose boosters following two doses of ChAdOx1 nCoV-19 or BNT162b2 and a third dose of BNT162b2 (COV-BOOST): a multicentre, blinded, phase 2, randomised trial
- Author
- Abeywickrama Movin
- Adams Kirsty
- Ahmed Nabeela Nazir
- Aley Parvinder K
- Aley Parvinder K
- Allen Lauren
- Alves Carlota Pereira Dias
- Ambihapathy Wythehi
- Andrews Antonette
- Andrews Nick
- Andrews Nick
- Appleby Kim
- Askoolam Krishna
- Aslam Suahil
- Babbage Gavin
- Babbage Gavin
- Baker Helena
- Baker Holly
- Baker Jonathan
- Baker Natalie
- Barcella Lara
- Barker Dominique
- Barry Joshua
- Baryschpolec Sonia
- Batham Sally
- Bawa Tanveer
- Bawa Tanveer
- Baxter David
- Baxter David
- Beckett Helen
- Bell Judith
- Bennett Sara
- Bentley Ian
- Berry Lisa
- Bibi Sagida
- Bisnauthsing Karen
- Bonnaud Avril
- Borca Alessandro
- Boubriak Iryna
- Bousfield Rachel
- Brandon Jacqueline
- Branney Debbie
- Broadhead Samantha
- Brown Claire
- Brown Phillip
- Brunt Emily
- Buadi Amanda
- Bula Marcin
- Bula Marcin
- Burton Holly
- Burton Katharine
- Buttigieg Karen
- Calderwood James
- Campbell Marion
- Cathie Katrina
- Cathie Katrina
- Chalwin Olivia
- Champaneri Trishna
- Charlton Sue
- Charlton Sue
- Chatterjee Krishna
- Chatterjee Krishna
- Chiplin Emily
- Choi Bea
- Clutterbuck Elizabeth A
- Cole Christine
- Colquhoun Suzie
- Cooper Alison
- Cooper Chris
- Cornelius Victoria
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- Publication venue
- 'Elsevier BV'
- Publication date
- 01/08/2022
- Field of study
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.
- Abecasis G.R.
- Abedalthagafi M.
- Abel L.
- Abernathy C.
- Abraheem A.
- Abul-Husn N.S.
- Acquilini D.
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- Aksentijevich A.
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- Taylor M.
- Taylor M.
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- Tenesa A.
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- Thirumaran M.
- Thomas A.
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- Thomas B.
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- Thompson R.
- Thompson R.C.
- Thomson N.
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- Timmers P.R.H.J.
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- Todd L.
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- van Heel D.A.
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- Wanying Z.
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- Wilding L.
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- Wilkins J.
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- Wilkinson B.
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- Willis H.
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- Wilson J.F.
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- Woodford C.
- Woodruff M.
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- Woodyatt W.
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- Worner R.
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- Wright M.
- Wrobel N.
- Wu Y.
- Wulandari R.
- Wyllie D.H.
- Wynter I.
- Xavier K.
- Xue X.
- Yadav A.
- Yang J.
- Yassen A.M.
- Yates B.
- Ye C.
- Yun N.
- Zainy T.
- Zak A.
- Zaki A.
- Zamikula J.
- Zanella I.
- Zborowski A.C.
- Zeberg H.
- Zechner M.
- Zechner M.
- Zguro K.
- Zhang M.
- Zhao J.H.
- Zheng C.
- Zhou W.
- Zitter L.
- Zlatopolsky M.
- Zongo O.
- Zucchi P.
- Zyndorf M.
- Zöllner S.
- Åsvold B.O.
- Publication venue
- Springer Science and Business Media LLC
- Publication date
- 07/07/2022
- Field of study
Critical 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
Safety, immunogenicity, and reactogenicity of BNT162b2 and mRNA-1273 COVID-19 vaccines given as fourth-dose boosters following two doses of ChAdOx1 nCoV-19 or BNT162b2 and a third dose of BNT162b2 (COV-BOOST): a multicentre, blinded, phase 2, randomised trial
- Author
- Abeywickrama Movin
- Adams Kirsty
- Ahmed Nabeela Nazir
- Aley Parvinder K
- Aley Parvinder K
- Allen Lauren
- Alves Carlota Pereira Dias
- Ambihapathy Wythehi
- Andrews Antonette
- Andrews Nick
- Andrews Nick
- Appleby Kim
- Askoolam Krishna
- Aslam Suahil
- Babbage Gavin
- Babbage Gavin
- Baker Helena
- Baker Holly
- Baker Jonathan
- Baker Natalie
- Barcella Lara
- Barker Dominique
- Barry Joshua
- Baryschpolec Sonia
- Batham Sally
- Bawa Tanveer
- Bawa Tanveer
- Baxter David
- Baxter David
- Beckett Helen
- Bell Judith
- Bennett Sara
- Bentley Ian
- Berry Lisa
- Bibi Sagida
- Bisnauthsing Karen
- Bonnaud Avril
- Borca Alessandro
- Boubriak Iryna
- Bousfield Rachel
- Brandon Jacqueline
- Branney Debbie
- Broadhead Samantha
- Brown Claire
- Brown Phillip
- Brunt Emily
- Buadi Amanda
- Bula Marcin
- Bula Marcin
- Burton Holly
- Burton Katharine
- Buttigieg Karen
- Calderwood James
- Campbell Marion
- Cathie Katrina
- Cathie Katrina
- Chalwin Olivia
- Champaneri Trishna
- Charlton Sue
- Charlton Sue
- Chatterjee Krishna
- Chatterjee Krishna
- Chiplin Emily
- Choi Bea
- Clutterbuck Elizabeth A
- Cole Christine
- Colquhoun Suzie
- Cooper Alison
- Cooper Chris
- Cornelius Victoria
- Cornelius Victoria
- Corrah Tumena
- Coughlan Tricia
- Cox Stephen
- Cullinane James
- Cutts Rebecca
- Dare Tracey
- Davies Ceri
- Davies-Dear Sharon
- DeLosSantosDominguez Pamela
- Desai Amisha
- Dineen Emily
- Dodd Kate
- Dodd Kate
- Domingo Jason
- Drake-Brockman Rachael
- Driver Kimberley
- Edwards Christopher J
- Egbo Akamino
- Elliott Ryan Stephen
- Elliott Scott
- Ellis Kate
- Enever Yvanne
- Enever Yvanne
- Evans Julie
- Farooqi Sadaf
- Farrier Adam
- Faust Saul N
- Faust Saul N
- Feng Shuo
- Feng Shuo
- Fowler Simon
- Fox Lauren
- Frankham Jorden
- Fraser Sara
- Freedman Andrew
- Galvin Dominic
- Gardside Ben
- Garrahy Sarah
- Gavin John
- Gibney Jennifer
- Giddins Beth
- Godwin Kerry
- Gokani Karishma
- Goncalvescordeiro Lillian
- Goodman Anna L
- Goodman Anna L
- Gordon Elizabeth
- Gouriet Jade
- Gowland Andrew
- Graham Victoria
- Green Christopher A
- Green Christopher A
- Grierson Jacques
- Grundy Lynne
- Gutteridge Helen
- Habash-Bailey Haniah
- Hailstone Jessica
- Hale Colin
- Hall Fran
- Hall Jane
- Hallis Bassam
- Hallis Bassam
- Hamal Shama
- Hansen Daniel
- Hardy Anna
- Harndahl Linda
- Harndahl Linda
- Harrison Elizabeth
- Haskell Louise
- Haughney John
- Haughney John
- Haydock Helen
- Haye Anastasia de la
- Herbert Christopher
- Hicks Alexander
- Hicks Alexander
- Hladkiwskyj John
- Hogan Alison
- Holliday Kyra
- Holliday Kyra
- Honey Thomas
- Horsfall Emily
- Hughes Kerry
- Hughes Rachel
- Hurdover Steve
- Irwin Margaret
- James Rob
- Janani Leila
- Janani Leila
- John Laurence
- Jones Lona Tudor
- Justice Edwin
- Kamal Mohammed
- Kanji Nasir
- Kanji Nasir
- Kasanyinga Mwila
- Katechia Kashyap
- Keenan Samantha
- Khan Mohammed
- King Mikayala
- Klaauw Agatha A van der
- Klaauw Agatha A van der
- Knight Chanice
- Kourampa Evgenia
- Kownacka Alicia
- Kumar Dileep
- Ladikou Eleni
- Lakeman Nicki
- Lall Paminder
- Lambe Teresa
- Lambe Teresa
- Lee Kim
- Leung Stephanie
- Lewis-Taylor Jessica
- Li Grace
- Libri Vincenzo
- Libri Vincenzo
- Lingwood Aidan
- Littlewood Kelly
- Liu Xinxue
- Liu Xinxue
- Llewelyn Martin J
- Llewelyn Martin J
- Locke Emily
- Longhurst Beverley
- Lyon Rebecca
- Maallah Mina
- Maallah Mina
- Macdonald Jonathan
- Magan Javier
- Magee Alan
- Males Samantha
- Mallon Lewis
- Mansfield Becky
- Marius Phedra
- McDonnell Chloe
- McGreevy Caitlin
- McGregor Alastair C
- McGregor Alastair C
- McMillan Gillian
- Merida-Morillas Marta
- Minassian Angela M
- Minassian Angela M
- Minnis Christine
- Moon Maria
- Moorbey Chantelle
- Moore Patrick
- Moore Patrick
- Moore Sophie
- Morshead Gertraud
- Mouland Johanna
- Mpelembue Mushiya
- Mughal Mehmood
- Mughal Mehmood
- Mujadidi Yama F
- Mujadidi Yama F
- Mullan Dee
- Munro Alasdair P S
- Munro Alasdair P S
- Munusamy Malathi
- Murira Jennifer
- Nabunjo Martha
- Naker Kush
- Newman Joseph
- Nguyen-Van-Tam Jonathan S
- Nguyen-Van-Tam Jonathan S
- Nightingale Kari
- Oliver Abigail
- Osanlou Orod
- Osanlou Orod
- Osanlou Rostam
- Osanlou Rostam
- Osuji Carol
- Owens Daniel R
- Owens Daniel R
- Packham Alice
- Pacurar Mihaela
- Pacurar Mihaela
- Palfreeman Adrian
- Palfreeman Adrian
- Palmer Emily
- Pan Daniel
- Pan Daniel
- Parungao Nina
- Patel Gita
- Perkins Jonathan
- Peters Erica
- Phillips Rachael
- Pickup Lorinda
- Piper Jo
- Plested Emma
- Presland Laura
- Qureshi Ehsaan
- Qureshi Ehsaan
- Radford Helen
- Raj Sreena
- Rampling Tommy
- Rampling Tommy
- Ramsay Mary
- Ramsay Mary
- Rashid-Gardner Zalina
- Rawlins Todd
- Read Robert C
- Read Robert C
- Regan Karen
- Regan Karen
- Renals Valerie
- Ricamara Marivic
- Richmond Leah
- Riordan Andrew
- Robinson Hannah
- Roche Siobhan
- Rogers Chris
- Romani Rossana
- Ronan Nicholas
- Roy Subarna
- Russell Amy Ross
- Sabine Charlette
- Saich Stephen
- Saich Stephen
- Sakagami Yukari
- Santos Filipa Dos
- Saralaya Dinesh
- Saralaya Dinesh
- Savage Mary
- Seath Ingrid
- Seaton Andrew
- Seenan John Paul
- Serafimova Teona
- Shaik Imam
- Shamtally Djamila
- Sharma Rajni
- Sharma Sunil
- Sharma Sunil
- Shenoy Anil
- Sheridan Ray
- Sheridan Ray
- Silva Carla Ferreira Da
- Singh Michael
- Singh Stephen
- Smith Catherine
- Snape Matthew D
- Snape Matthew D
- Snashall Emma
- Soussi Najwa
- Spence Niamh
- Spencer Joanne
- Stackpoole Michael
- Starinskij Igor
- Stewart Anna
- Stokes Matthew
- Stone Megan
- Storton Kim
- Sturdy Ann
- Suggitt Debbie
- Summerton Eloise
- Tandy Bridget
- Tasker Suzanne
- Thomas Steve
- Thomson Emma C
- Thomson Emma C
- Thorp Helen
- Thorpe Jeanette
- Todd Shirley
- Todd Shirley
- Trinham Charlotte
- Tulloch Hayley
- Tunstall Simon
- Turnbull Iain
- Turner Nicola
- Twelves Chris
- Twelves Chris
- Underwood Karen
- Ustianowski Andrew
- Vail Denny
- Vamplew Luke
- Wagstaff Lynda
- Warren Sarah
- Watson Tara
- Weighell Rowena
- Welham Benjamin
- Welsenes Donald van
- Wenn Victoria
- Westwell Fran
- Whitbred Tim
- White Rachel
- Whittington Ashley
- Whittley Sarah
- Wilkins Suzanne
- Wiselka Martin
- Wixted Donna
- Woodyatt Wiesia
- Yim Yee Ting Nicole
- Publication venue
- 'Elsevier BV'
- Publication date
- 09/05/2022
- Field of study
Background Some high-income countries have deployed fourth doses of COVID-19 vaccines, but the clinical need, effectiveness, timing, and dose of a fourth dose remain uncertain. We aimed to investigate the safety, reactogenicity, and immunogenicity of fourth-dose boosters against COVID-19.Methods The COV-BOOST trial is a multicentre, blinded, phase 2, randomised controlled trial of seven COVID-19 vaccines given as third-dose boosters at 18 sites in the UK. This sub-study enrolled participants who had received BNT162b2 (Pfizer-BioNTech) as their third dose in COV-BOOST and randomly assigned them (1:1) to receive a fourth dose of either BNT162b2 (30 µg in 0·30 mL; full dose) or mRNA-1273 (Moderna; 50 µg in 0·25 mL; half dose) via intramuscular injection into the upper arm. The computer-generated randomisation list was created by the study statisticians with random block sizes of two or four. Participants and all study staff not delivering the vaccines were masked to treatment allocation. The coprimary outcomes were safety and reactogenicity, and immunogenicity (antispike protein IgG titres by ELISA and cellular immune response by ELISpot). We compared immunogenicity at 28 days after the third dose versus 14 days after the fourth dose and at day 0 versus day 14 relative to the fourth dose. Safety and reactogenicity were assessed in the per-protocol population, which comprised all participants who received a fourth-dose booster regardless of their SARS-CoV-2 serostatus. Immunogenicity was primarily analysed in a modified intention-to-treat population comprising seronegative participants who had received a fourth-dose booster and had available endpoint data. This trial is registered with ISRCTN, 73765130, and is ongoing.Findings Between Jan 11 and Jan 25, 2022, 166 participants were screened, randomly assigned, and received either full-dose BNT162b2 (n=83) or half-dose mRNA-1273 (n=83) as a fourth dose. The median age of these participants was 70·1 years (IQR 51·6–77·5) and 86 (52%) of 166 participants were female and 80 (48%) were male. The median interval between the third and fourth doses was 208·5 days (IQR 203·3–214·8). Pain was the most common local solicited adverse event and fatigue was the most common systemic solicited adverse event after BNT162b2 or mRNA-1273 booster doses. None of three serious adverse events reported after a fourth dose with BNT162b2 were related to the study vaccine. In the BNT162b2 group, geometric mean anti-spike protein IgG concentration at day 28 after the third dose was 23 325 ELISA laboratory units (ELU)/mL (95% CI 20 030–27 162), which increased to 37 460 ELU/mL (31 996–43 857) at day 14 after the fourth dose, representing a significant fold change (geometric mean 1·59, 95% CI 1·41–1·78). There was a significant increase in geometric mean anti-spike protein IgG concentration from 28 days after the third dose (25 317 ELU/mL, 95% CI 20 996–30 528) to 14 days after a fourth dose of mRNA-1273 (54 936 ELU/mL, 46 826–64 452), with a geometric mean fold change of 2·19 (1·90–2·52). The fold changes in anti-spike protein IgG titres from before (day 0) to after (day 14) the fourth dose were 12·19 (95% CI 10·37–14·32) and 15·90 (12·92–19·58) in the BNT162b2 and mRNA-1273 groups, respectively. T-cell responses were also boosted after the fourth dose (eg, the fold changes for the wild-type variant from before to after the fourth dose were 7·32 [95% CI 3·24–16·54] in the BNT162b2 group and 6·22 [3·90–9·92] in the mRNA-1273 group).Interpretation Fourth-dose COVID-19 mRNA booster vaccines are well tolerated and boost cellular and humoral immunity. Peak responses after the fourth dose were similar to, and possibly better than, peak responses after the third dose
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