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10 research outputs found

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.
Afrasiabi Z.
Agasou A.
Agrawal S.
Aguero D.
Ahmad N.
Ahmadi S.
Ahmed A.
Ahmed C.
Akeroyd L.
Akhtar M. N.
Akinkugbe O.
Aksentijevich A.
Al-Afghani H.
Al-Awdah L.
Alaamery M.
Alahmadey Z. Z.
Alaverdian D.
Alavere H.
Albader A.
Albaiceta G. M.
Albakri J. K.
AlBardis H.
Albeladi M.
Albesher N.
Albrich W.
AlDhawi N.
Aldridge J.
Aleagha A. E.
Alexander P.
Alfonso J.
Alghamdi B.
Alghamdi J.
Ali A.
Ali A.
Ali I. A. M.
Ali S.
Aliannejad R.
Aljawini N.
AlJohani S.
Alkwai S.
Allan A.
Allan E.
Allan J.
Alldis Z.
Allen L.
Allen M.
Allen S.
Allibone S.
Allison K. S.
Allos R.
Ally S. M.
AlMalik A.
Almalki F.
Almohammed I.
Almutairi M.
Alotaibi S.
Alowayn A. M.
Alqahtani S.
Alqubaishi F.
Alrashed M.
Alshareef A.
Alsolm E.
Alswailm M.
Altabaibeh A.
Alvaro A.
AlZahrani D.
Amin V.
Amirsavadkouhi A.
Amitrano S.
Anastasescu E.
Anderson F.
Anderson J.
Anderson M.
Anderson P.
Anderson S.
Anderson S.
Anderson T.
Andolfo I.
Andretta F.
Andreucci E.
Andrew A.
Andrew B.
Andrew G.
Andrews E.
Andrews S. J.
Anedda F.
Anemoli V.
Annis A.
Antcliffe D.
Antinori A.
Antoni M. D.
Anumakonda V.
Apetri E.
Aquino M.
Arabi Y. M.
Aravindan L.
Arbane G.
Archer K.
Arden T.
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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

PubliCatt

Archivio istituzionale della ricerca - Università di Modena e Reggio Emilia

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.
Adams C.
Adams E.L.
Adams K.
Adamsara A.
Adanini O.
Adeleye O.
Adra D.
Afilalo J.
Afilalo M.
Afolabi D.
Afrasiabi Z.
Agasou A.
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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

White Rose Research Online

Conservative management of exomphalos major

Author: A.A. Cunningham
D. C. Merwaha
E. Drescher
M. Grob
P.G. Jones
P.P. Rickham
R. L. Gupta
R. N. Mullick
R. R. Gupta
R.E. Gross
Publication venue: 'Springer Science and Business Media LLC'
Publication date
Field of study

Crossref

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Abbasi S
Abbasi S
Abdelaziz A
Abdelfattah M
Abdul B
Abdulmumeen A
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Al-Asadi A
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Babatunde F
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Johnson A
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Webster I
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Xavier B
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Publication venue: 'Elsevier BV'
Publication date: 01/07/1994
Field of study

Controversy exists as to whether neoadjuvant chemotherapy improves survival in patients with invasive bladder cancer, despite randomised controlled trials of more than 3000 patients. We undertook a systematic review and meta-analysis to assess the effect of such treatment on survival in patients with this disease

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Mapping the human genetic architecture of COVID-19

Author: Abdelrazik M.
Abdullah T.
Abe R.
Abe S.
Abecasis G. R.
Abel L.
Abernathy C.
Abraheem A.
Abul-Husn N. S.
Acosta-Herrera M.
Acquilini D.
Adachi T.
Adachi Y.
Adams C.
Adams K.
Adanini O.
Adeleye O.
Adeniji K.
Adra D.
Afifi N.
Afilalo J.
Afilalo M.
Afolabi D.
Afrasiabi Z.
Afset J. E.
Agasou A.
Aghemo A.
Agranoff D.
Agrawal S.
Aguirre L. A.
Agwuh K.
Ahmad H. F.
Ahmad N.
Ahmed A.
Ahmed C.
Ahmed K. A.
Ai M.
Ail D.
Akeroyd L.
Akhtar M. N.
Akhtar S.
Akinkugbe O.
Aksentijevich A.
Al Thani A.
Al-Muftah W.
Al-Sarraj Y.
Alarcon C.
Alarcon-Riquelme M. E.
Alasdair F.
Alaverdian D.
Alavere H.
Albertos R.
Albillos A.
Albrecht W.
Albrich W.
Albrich W. C.
Aldera E. L.
Aldridge J.
Alegria A.
Alex B.
Alexander P.
Alfonso J.
Algera A. G.
Ali A.
Ali I. A. M.
Ali S.
Aliberti S.
Allan A.
Allan E.
Allan J.
Alldis Z.
Allen L.
Allen S.
Allibone S.
Allison K. S.
Allos R.
Ally S. M.
Almaden-Boyle C.
Altabaibeh A.
Altmuller J.
Alvaro A.
Amar D.
Amin V.
Amitrano S.
Amiya S.
Ampuero J.
Anan R.
Anania S.
Anastasescu E.
Anderson F.
Anderson J.
Anderson M.
Anderson P.
Anderson S.
Anderson S.
Anderson T.
Ando A.
Andolfo I.
Andrade V.
Andretta F.
Andreucci E.
Andrew A.
Andrew B.
Andrew G.
Andrews E.
Andrews S. J.
Andrikopoulos P.
Anedda F.
Aneli S.
Anemoli V.
Angelini C.
Angus B.
Ann Belli M.
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Zyndorf M.
Publication venue: 'Springer Science and Business Media LLC'
Publication date: 01/01/2021
Field of study

The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3–7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease

Archivio istituzionale della ricerca - Politecnico di Milano

Archivio della ricerca - Università degli studi di Napoli Federico II

Archivio della Ricerca - Università degli Studi di Siena

Archivio istituzionale della ricerca - Alma Mater Studiorum Università di Bologna

Archivio istituzionale della ricerca - Università di Genova

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Archivio istituzionale della ricerca - Università di Modena e Reggio Emilia

Archivio istituzionale della ricerca - Università di Padova

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Abedalthagafi M
Abel L
Abel L
Abellan J
Abernathy C
Abraheem A
Acklery A
Acosta-Isaac R
Adam R
Adams C
Adams K
Adams N
Adanini O
Afolabi D
Agasou A
Agravante K
Agravante K
Agrawal S
Aguado JM
Aguilar C
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Aguilera-Albesa S
Ahmad N
Ahmadhaider N
Ahmed A
Ahmed C
Aitkin E
Akeroyd L
Akhtar MN
Akinkugbe O
Al-Moasseb H
Alasdair F
Alba J
Albu S
Alcalá-Gallardo KAM
Alcoba-Florez J
Aldridge J
Alex B
Alexander P
Alfonso J
Algarin-Lara HR
Ali A
Ali HH
Ali IAM
Ali S
Allan A
Allan E
Allan J
Alldis Z
Allen L
Allen M
Allen S
Allibone S
Allison KS
Ally SM
Almadana V
Almaden-Boyle C
Almeida J
Almoguera B
Alonso MR
Altabaibeh A
Alvarez N
Alvaro A
Alves MDM
Amamio M
Amamio M
Amin V
Anastasescu E
Anderson J
Anderson M
Anderson P
Anderson S
Anderson S
Anderson T
Andreou P
Andreu-Bernabeu Á
Andrew A
Andrew B
Andrew G
Andrews J
Andrikopoulos P
Antcliffe D
Antoine P
Antonijoan MR
Antony S
Anumakonda V
Anwer M
Apetri E
Aquino M
Arana-Arri E
Aranda C
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Araque C
Araujo IMT
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Hernandez-Ortega LD
Hernández-Pérez G
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Hodgkiss T
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Huang Y-WJ
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Irvine V
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Jacob R
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Jerome E
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Jetha C
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Jimenez-Sousa MA
Jiménez P
Jiménez Á
Jiménez-Alfaro I
Jobes L
Joefield T
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Jones GAL
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Joseph A
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Joshy A
Joy R
Jude E
Kadiri S
Kajtor I
Kaliappan A
Kallon D
Kamal L
Kamangu B
Kamath P
Kamundi C
Kannan T
Kanu R
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Karthik K
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Kassam J
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Kelly C
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Kennedy-Hay S
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Kousathanas A
Krishnamurthy V
Kubisz-Pudelko A
Kumar R
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Kuravi A
Laguna-Goya R
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Lake V
Lamb T
Lamond Z
Lancaster N
Lancoma-Malcolm I
Landeg B
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Langton H
Laorden D
Lapunzina P
Lapunzina P
Larman G
Lasa-Lazaro M
Latham S
Latif M
Lattig MC
Lauder C
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Law A
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Law D
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Law S
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Leaver S
Ledgard C
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Leggett S
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Leonard B
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Lidstone-Scott R
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Linfield-Brown G
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Linnett V
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Lopez JRA
Lopez-Garcia E
Lopez-Rodriguez R
Lorah S
Lorente L
Lorusso R
Love N
Loveridge A
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Lozano JE
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Luchessi AD
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Lye A
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Lynch C
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López-Ruz MA
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Macías EM
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Maizcordoba M
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Male M
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Malinauskas T
Mallinson J
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Manley R
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Maqsood Z
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Marriott X
Marsden T
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Marshall R
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Martin-Pedraza L
Martindale T
Martinez A
Martinez ML
Martinez-Lopez I
Martinez-Nieto O
Martinez-Paz P
Martinez-Perez A
Martinez-Resendez MF
Martins L
Martinson V
Martir G
Martín BB
Martín MD
Martín MM
Martín V
Martín-López C
Martín-Oterino J-Á
Martín-Vicente M
Martínez JJ
Martínez R
Martínez S
Martínez YF
Martínez-Aquino E
Martínez-González Ó
Martínez-Ramas A
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Mathew B
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McKechnie S
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McKenna E
McKie H
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Mclean KA
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McMaster E
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Meijome XM
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Mendes I
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Mercado-Sesma AR
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Moore LSP
Moore SC
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Moraes VMS
Morano EMH
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Moreno-Docón A
Moreno-Escalante J
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Nikitas N
Nilo AC
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Oliveira SF
Olivera MR
Olufuwa O
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Openshaw PJM
Orfao A
Origlia GGS
Orlikowska I
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Ortega-Paino E
Ortiz-Flores F
Ortiz-Lopez R
Osagie A
Osbourne W
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Otahal I
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Otahal I
Otahal I
Oteo JA
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O’Brien R
O’Connell S
O’Connell S
O’Connor D
O’Connor G
O’Donohoe L
O’Hara M
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O’Neil P
O’Neill A
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Pacheco-Miranda FJ
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Page V
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Pairo-Castineira E
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Pakou G
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Panadero-Fajardo S
Panteli M
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Pickard A
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Pinsach-Abuin ML
Pinzuti I
Pinzón LA
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Pirie S
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Player B
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Pogreban T
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Polgar O
Polgarova P
Pollakis G
Pompa-Mera EN
Ponting CP
Poole A
Poole M
Pope R
Popescu M
Porras MS
Porras-Hurtado GL
Postovalova E
Pothecary C
Pothecary C
Potla D
Potoczna D
Potts K
Poulaka M
Poultney U
Prados MCS
Prady H
Prager K
Pratley A
Prendergast C
Prentice L
Preston S
Price A
Price C
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Priestley V
Prime Z
Pristopan V
Pritchard K
Pritchard L
Proudfoot N
Prout R
Pryce J
Prysyazhna O
Pugh R
Pujol A
Puras FS
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Purvis S
Puxty A
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Pye K
Pérez C
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Pérez-Matute P
Pérez-Serra A
Pérez-Tomás ME
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Quaid S
Quijada MA
Quinn A
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Quintela I
Rad L
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Radhakrishnan J
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Rodriguez-Gallego C
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Rodriguez-Nicolas A
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Sancho-Sainz C
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Silva FTC
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Solomon T
Solé-Violán J
Soria JM
Sorlí JV
Sousa RR
Souto JC
Souza KSC
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Sundaram R
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Taboada-Fraga X
Tagliavini E
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Tampsett R
Tanate A
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Taracido-Fernandez JC
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Tetla D
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Thirlwall Y
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Thwaites R
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Torrejón MCG
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Turner-Bone I
Turney S
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Villar-Garcia J
Villaverde C
Villoslada-Blanco P
Vincent R
Virgilio E
Virseda-Berdices A
Vitart V
Vizcaychipi M
Vochin A
Vuylsteke A
Vélez-Santamaría V
Víctor V
Wackett T
Wadams B
Waddell G
Waddington N
Wagstaff V
Waite AAC
Wakefield P
Wakinshaw F
Waldron J
Walker C
Walker D
Walker L
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Walker R
Walker S
Wall A
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Walther RA-S
Walton O
Ward D
Ward G
Ward K
Ward L
Ward M
Ward S
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Warren D
Warrington J
Wassall H
Wasson C
Waters A
Waters E
Watkins C
Watson E
Watson G
Watson J
Watters M
Watts S
Waugh V
Weaver J
Webb N
Webster A
Webster D
Webster K
Wei S
Weldon CH
Welford A
Wells C
Welters I
West J
Weston H
Wham M
Whileman A
Whitaker E
Whitbread J
White D
White I
White K
White M
White N
White N
Whitehead V
Whitelaw L
Whiteley S
Whiteside J
Whitton C
Whyte C
Wignall A
Wilby L
Wilcox L
Wild H
Wild L
Wilding L
Wiles M
Wiliams A
Wilkins J
Wilkinson A
Wilkinson B
Williams A
Williams A
Williams C
Williams D
Williams E
Williams E
Williams G
Williams H
Williams J
Williams K
Williams M
Williams P
Williams S
Williams T
Willis C
Willis H
Wills M
Willson J
Wilson A
Wilson J
Wilson JF
Winchester J
Winmill H
Winnard S
Winter K
Winter-Goodwin B
Wolf-Roberts R
Wong J
Wong J
Wood D
Wood H
Wood S
Wood S
Wood T
Woodford C
Woodruff M
Woods L
Woodward E
Woodward J
Woolcock M
Worner R
Worsley L
Wray G
Wren L
Wreybrown C
Wright C
Wright DJ
Wright M
Wright S
Wrobel N
Wu Y
Wulandari R
Wylie K
Wynter I
Xavier K
Yang J
Yates B
Ye C
Young M
Yun N
Yáñez Z
Zak A
Zaki A
Zambon M
Zamikula J
Zapatamartinez M
Zapatero-Gaviria A
Zarate R
Zazo S
Zborowski AC
Zechner M
Zechner M
Zhao X
Zheng C
Zitter L
Zongo O
Zorloni C
Álvarez BG
Álvarez-Benítez Y
Álvarez-Navia F
Íñiguez M
Publication venue: Springer Nature
Publication date: 17/05/2023
Field of study

Data availability: Downloadable summary data are available through the GenOMICC data site (https://genomicc.org/data). Summary statistics are available, but without the 23andMe summary statistics, except for the 10,000 most significant hits, for which full summary statistics are available. The full GWAS summary statistics for the 23andMe discovery dataset will be made available through 23andMe to qualified researchers under an agreement with 23andMe that protects the privacy of the 23andMe participants. For further information and to apply for access to the data, see the 23andMe website (https://research.23andMe.com/dataset-access/). All individual-level genotype and whole-genome sequencing data (for both academic and commercial uses) can be accessed through the UKRI/HDR UK Outbreak Data Analysis Platform (https://odap.ac.uk). A restricted dataset for a subset of GenOMICC participants is also available through the Genomics England data service. Monocyte RNA-seq data are available under the title ‘Monocyte gene expression data’ within the Oxford University Research Archives (https://doi.org/10.5287/ora-ko7q2nq66). Sequencing data will be made freely available to organizations and researchers to conduct research in accordance with the UK Policy Framework for Health and Social Care Research through a data access agreement. Sequencing data have been deposited at the European Genome–Phenome Archive (EGA), which is hosted by the EBI and the CRG, under accession number EGAS00001007111.Extended data figures and tables are available online at https://www.nature.com/articles/s41586-023-06034-3#Sec21 .Supplementary information is available online at https://www.nature.com/articles/s41586-023-06034-3#Sec22 .Code availability: Code to calculate the imputation of P values on the basis of SNPs in linkage disequilibrium is available at GitHub (https://github.com/baillielab/GenOMICC_GWAS).Acknowledgements: We thank the members of the Banco Nacional de ADN and the GRA@CE cohort group; and the research participants and employees of 23andMe for making this work possible. A full list of contributors who have provided data that were collated in the HGI project, including previous iterations, is available online (https://www.covid19hg.org/acknowledgements).Change history: 11 July 2023: A Correction to this paper has been published at: https://doi.org/10.1038/s41586-023-06383-z. -- In the version of this article initially published, the name of Ana Margarita Baldión-Elorza, of the SCOURGE Consortium, appeared incorrectly (as Ana María Baldion) and has now been amended in the HTML and PDF versions of the article.Copyright © The Author(s) 2023, Critical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown1 to be highly efficient for discovery of genetic associations2. Despite the advanced stage of illness at presentation, we have shown that host genetics in patients who are critically ill with COVID-19 can identify immunomodulatory therapies with strong beneficial effects in this group3. Here we analyse 24,202 cases of COVID-19 with critical illness comprising a combination of microarray genotype and whole-genome sequencing data from cases of critical illness in the international GenOMICC (11,440 cases) study, combined with other studies recruiting hospitalized patients with a strong focus on severe and critical disease: ISARIC4C (676 cases) and the SCOURGE consortium (5,934 cases). To put these results in the context of existing work, we conduct a meta-analysis of the new GenOMICC genome-wide association study (GWAS) results with previously published data. We find 49 genome-wide significant associations, of which 16 have not been reported previously. To investigate the therapeutic implications of these findings, we infer the structural consequences of protein-coding variants, and combine our GWAS results with gene expression data using a monocyte transcriptome-wide association study (TWAS) model, as well as gene and protein expression using Mendelian randomization. We identify potentially druggable targets in multiple systems, including inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).GenOMICC was funded by Sepsis Research (the Fiona Elizabeth Agnew Trust), the Intensive Care Society, a Wellcome Trust Senior Research Fellowship (to J.K.B., 223164/Z/21/Z), the Department of Health and Social Care (DHSC), Illumina, LifeArc, the Medical Research Council, UKRI, a BBSRC Institute Program Support Grant to the Roslin Institute (BBS/E/D/20002172, BBS/E/D/10002070 and BBS/E/D/30002275) and UKRI grants MC_PC_20004, MC_PC_19025, MC_PC_1905 and MRNO2995X/1. A.D.B. acknowledges funding from the Wellcome PhD training fellowship for clinicians (204979/Z/16/Z), the Edinburgh Clinical Academic Track (ECAT) programme. This research is supported in part by the Data and Connectivity National Core Study, led by Health Data Research UK in partnership with the Office for National Statistics and funded by UK Research and Innovation (grant MC_PC_20029). Laboratory work was funded by a Wellcome Intermediate Clinical Fellowship to B.F. (201488/Z/16/Z). We acknowledge the staff at NHS Digital, Public Health England and the Intensive Care National Audit and Research Centre who provided clinical data on the participants; and the National Institute for Healthcare Research Clinical Research Network (NIHR CRN) and the Chief Scientist’s Office (Scotland), who facilitate recruitment into research studies in NHS hospitals, and to the global ISARIC and InFACT consortia. GenOMICC genotype controls were obtained using UK Biobank Resource under project 788 funded by Roslin Institute Strategic Programme Grants from the BBSRC (BBS/E/D/10002070 and BBS/E/D/30002275) and Health Data Research UK (HDR-9004 and HDR-9003). UK Biobank data were used in the GSMR analyses presented here under project 66982. The UK Biobank was established by the Wellcome Trust medical charity, Medical Research Council, Department of Health, Scottish Government and the Northwest Regional Development Agency. It has also had funding from the Welsh Assembly Government, British Heart Foundation and Diabetes UK. The work of L.K. was supported by an RCUK Innovation Fellowship from the National Productivity Investment Fund (MR/R026408/1). J.Y. is supported by the Westlake Education Foundation. SCOURGE is funded by the Instituto de Salud Carlos III (COV20_00622 to A.C., PI20/00876 to C.F.), European Union (ERDF) ‘A way of making Europe’, Fundación Amancio Ortega, Banco de Santander (to A.C.), Cabildo Insular de Tenerife (CGIEU0000219140 ‘Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19’ to C.F.) and Fundación Canaria Instituto de Investigación Sanitaria de Canarias (PIFIISC20/57 to C.F.). We also acknowledge the contribution of the Centro National de Genotipado (CEGEN) and Centro de Supercomputación de Galicia (CESGA) for funding this project by providing supercomputing infrastructures. A.D.L. is a recipient of fellowships from the National Council for Scientific and Technological Development (CNPq)-Brazil (309173/2019-1 and 201527/2020-0)

Brunel University Research Archive

Azithromycin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

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Abbasi S
Abbasi S
Abdelaziz A
Abdelfattah M
Abdul B
Abdulmumeen A
Abdulshukkoor N
Abdusamad K
Aboaba A
Abouibrahim M
Abraham M
Abraham T
Abrams J
Abung A
Acharya D
Acharya D
Acheson J
Acosta A
Acosta A
Acton C
Adam M
Adams C
Adams K
Adamus M
Adegoke K
Adenwalla S
Adeyeye E
Adnan A
Agbo C
Aggarwal S
Agwada-Akeru J
Agyapong K Ansu
Ah-Chuen J
Ahmad M
Ahmed I
Ahmed I
Ahmed L
Ahmed L
Ahmed M
Ahmed M Cecilia
Ahmed N
Ahmed N
Ahmed R
Ahmed RA
Ahmed S
Ahmed S Haris
Ail D
Ainsley A
Ainsworth M
Aitken L
Ajibode A
Ajmi A
Ajmi A
Akhtar N
Akili S
Akindolie O
Al Balushi A
Al-Asadi A
Al-Hakim B
Al-Jibury M
Al-Rabahi A
Al-Ramadhani B
Al-Shamkhani W
Al-Sheklly B
Alam S
Aldana A
Aldouri R
Aldridge N
Alegria A
Alexander A
Alexander J
Alexander PDG
Ali F Runa
Ali M
Ali O
Ali S
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Alkhusheh M
Alkhusheh M
Allanson A
Allen L
Allen R
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Allison K
Allsop L
Alomari L
Alzetani M
Ambler S
Ambrogetti R
Ambrose C
Amezaga M
Amin A
Amosun V
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Amsha K
Anand A
Anderson J
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Aneke K
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Baird D
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Zipitis C
Zmierczak A
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Zulaikha R
Zullo C
Publication venue: 'Elsevier BV'
Publication date: 01/02/2021
Field of study

Background Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatory actions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19. Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospital with COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients were randomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once per day by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatment groups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment and were twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants and local study staff were not masked to the allocated treatment, but all others involved in the trial were masked to the outcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) were eligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was 65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomly allocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall, 561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days (rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median 10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days (rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, no significant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilation or death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24). Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or other prespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restricted to patients in whom there is a clear antimicrobial indication. Funding UK Research and Innovation (Medical Research Council) and National Institute of Health Research

University of Liverpool Repository

Spiral - Imperial College Digital Repository

A second update on mapping the human genetic architecture of COVID-19

Author: Abd Elghafar MS
Abdel-Aziz M
Abdelrazik M
Abdullah MS
Abe R
Abe S
Abel L
Abel L
Abernathy C
Abraham R
Abraheem A
Abu Alragheb BO
Abulail JA
Acklery A
Acosta-Herrera M
Adachi T
Adachi Y
Adam R
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Adanini O
Afifi N
Afilalo J
Afilalo M
Afolabi D
Afrasiabi Z
Afset JE
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Aghemo A
Agravante K
Agrawal A
Agrawal S
Aguado JM
Aguilar C
Aguilar SEV
Aguilar-Salinas CA
Aguilera-Albesa S
Agüero D
Ahmad HF
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Ahmadhaider N
Ahmed A
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Ai M
Ain Q
Aitkin E
Akeroyd L
Akhtar MN
Akinkugbe O
Al-Ani A
Al-Ja’afreh MM
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Al-Kasasbeh MM
Al-Moasseb H
Al-Muftah W
Al-Sarraj Y
Alamer LM
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Alawneh FM
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Alhousani TN
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Damås JK
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De Quirós FGB
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Dixit RD
Diz-de Almeida S
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Emblem J
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Falcone EL
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Fernandez-Cadenas I
Fernandez-Roman J
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Fernández J
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Galván-Femenia I
Galván-Femenía I
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Garcia-Fernandez A-E
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Georgiou I
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Hernández Cordero AI
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Metherell S
Metryka A
Mew L
Meyrick H
Michael A
Michaeli Y
Michalak N
Michalowska M
Mickiewicz B
Migeotte I
Mighton C
Mikami Y
Mikkelsen S
Milionis H
Milionis O
Millar J
Millen G
Miller J
Miller K
Milligan B
Mills G
Mills R
Millward H
Milne R
Milner L
Minguez P
Miozzo M
Misset B
Mitamura K
Mitchard S
Mitchell AM
Mitchelmore O
Mitra A
Miyano S
Miyawaki S
Miyazaki Y
Miyazawa N
Moakes E
Moar K
Mochimaru T
Modi B
Modi BP
Mohamed AAS
Mohammed A
Moncur E
Mondal S
Monnery S
Montano N
Montaser R
Montgomery H
Montpetit A
Monzani V
Moore F
Moore L
Moore LSP
Moore SC
Mooser V
Morales-Sosa PA
Morano EMH
Moreno V
Moreno V
Moreno-Cuesta J
Moreno-Estrada A
Moreno-Estrada A
Moreno-Macías H
Morera K
Morgan A
Morgan G
Morgan J
Mori N
Morilla R
Morino E
Morisaki H
Morita A
Morley J
Morrice K
Morris A
Morris L
Morris R
Morris S
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Morrison A
Morrison DR
Moscoso-Sánchez R
Moss S
Mostoles L
Motegi M
Motherwell N
Moultrie S
Mousas A
Moutschen M
Moutsianas L
Moya L
Msiska M
Mtuwa S
Muchenje N
Mueller NS
Muiño E
Mulcahy M
Mulla S
Mullan D
Mundy M
Munisamy M
Munt S
Mupudzi M
Murakami K
Muratov T
Murdoch E
Murdoch S
Murohashi K
Murphy A
Murphy C
Murphy L
Murphy L
Murphy S
Murphy SN
Muscatello A
Mutch R
Mutoh Y
Muñiz-Diaz E
Muñóz-Hernández LL
Mwaura E
Mwaura L
My I
Mybaya H
Myhre R
Márquez L
Müller F
Müller KE
Naffa RG
Nafria-Jimenez B
Nagai H
Nagasaki T
Nagasaki Y
Nagata K
Nagra I
Nair A
Naisbitt J
Nakachi I
Nakada T-A
Nakajima J
Nakajima Y
Nakamura A
Nakamura M
Nakamura Y
Nakanishi T
Nakano S
Nakano Y
Nakayama S
Namkoong H
Nanki K
Nannya Y
Naranjo A
Narita A
Narumoto O
Nasiou M
Nasir F
Nasir J
Nauyokas K
Navas E
Nayak M
Nazari R
Neal A
Neale BM
Neale BM
Neb H
Nebel A
Netherton K
Nevado J
Neveux I
Newell H
Newey L
Newman J
Newman T
Newton M
Ng A
Niazyan L
Nichol A
Nicholson A
Nicholson A
Nickle D
Nicol L
Nielsen KR
Nielsen SD
Niemi MEK
Nieto R
Nii T
Niitsu T
Nikitas N
Niller H-H
Nilo AC
Nilsson A
Niranjan K
Nirmalanathan K
Nishi K
Nishida N
Nishio K
Nishitsuji M
Nishiyama K
Nishiyama K
Nissen J
Niwa K
Nixon R
Nkambul L
Nkambul L
Nkambule L
Noble H
Noda J
Noda Y
Nolan C
Nolla AC
Noor A
Noor H
Norman K
Norris J
Norris M
Nortcliffe T
North J
Nova-Lamperti EA
Novis C
Nowak J
Nown A
Ntotsikas E
Ntzani E
Nune A
Nwafor L
Nyegaard M
Nyirenda M
Nöthen MM
Oakley N
Obeidat M
Obeidat NM
Oblak M
Ochoa-Guzmán A
Ochoa-Guzmán A
Odam M
Odam M
Odani T
Odhams CA
Ofori L
Ogata T
Ogawa S
Ogawa S
Ogg B
Ogorek M
Oguma T
Ogura S
Ogura T
Ohba T
Ohta S
Okada T
Okada Y
Okamori S
Okamoto M
Okasha K
Okeefe L
Olaso R
Oleary R
Oliveira M
Oliveira SF
Olivera-Ramírez A
Olufuwa O
Omae Y
Omar Z
Omodei P
Ono A
Onoi K
Ooshima N
Oosthuyzen W
Openshaw PJM
Ordoñez ML
Ordoñez-Sánchez ML
Orlikowska I
Ortega-Paino E
Ortiz AB
Osbourne W
Ostadreza M
Ostermann M
Ostrowski M
Ostrowski SR
Ostrowski SR
Otahal I
Owen S
Oxspring S
Oyamada Y
Ozaki S
Oziegb M
O’Brien L
O’Brien P
O’Brien R
O’Connell AM
O’Connell J
O’Connell S
O’Connor D
O’Connor G
O’Donohoe L
O’Hara M
O’Hare M
O’Malley L
O’Neil P
O’Neill A
O’Neill L
O’Reilly K
O’Sullivan S
Paccapelo C
Packham S
Padden G
Page V
Paine S
Pairo-Castineira E
Pajak S
Pajukanta P
Pakou G
Palmer DS
Palmieri O
Palom A
Palotie A
Pan J
Pandit RJ
Panteli M
Papathanasiou A
Papenburg J
Papiol S
Pappa C
Pappa E
Pappachan N
Paques K
Paraboschi EM
Paramsothy R
Parekh RS
Parellada M
Pargana E
Paripoorani D
Park H-Y
Park L
Parker N
Parker R
Parkin J
Parkinson N
Parmar C
Parra-Martínez A
Parris V
Parsons P
Partridge R
Pasaniuc B
Pasaniuc B
Pasko D
Passmore H
Patch C
Patel A
Patel B
Patel B
Patel K
Patel M
Patel R
Patel SK
Patel T
Patel ZZ
Paterson AD
Paterson T
Pathak GA
Pathan N
Patience D
Patil A
Patin E
Pattison N
Paul P
Pavenski K
Pawley C
Payne C
Paz-Artal E
Pearn C
Pearson H
Pearson NM
Pearson S
Peasgood E
Pedersen OB
Pedersen OB
Pellegrin I
Pelusi S
Penacerrada M
Pendergrass R
Pendlebury J
Penn R
Pereira AC
Pereira AC
Perez EF
Perez J
Perez P
Perez-Tur J
Perkins E
Perola M
Perry J
Persia P
Perucho T
Peschuck A
Pesenti A
Pestaña D
Peter W
Peterhoff D
Peterkin Z
Peters C
Peters M
Petty LE
Peyrassol X
Peyvandi F
Pezzoli G
Pheby J
Philbin J
Phillips C
Phillips P
Phipps J
Phull M-K
Pichon B
Piché A
Pickard A
Piercy C
Pigazzini S
Pink I
Pinnell J
Pinsach-Abuin ML
Pinzuti I
Pippard L
Pirie S
Pirinen M
Pita G
Pitt A
Pitts S
Place M
Planas AM
Player B
Player J
Plotnikov N
Pogreban T
Pogson D
Polgar O
Polgarova P
Polikowsky HG
Poller W
Pompa-Mera EN
Pontali E
Ponting CP
Poole A
Poole M
Pope R
Popescu M
Popov I
Porras MS
Porras-Hurtado GL
Postovalova E
Pothecary C
Potla D
Potoczna D
Potts K
Poulaka M
Poultney U
Prady H
Prager K
Praman K
Prati D
Pratley A
Preatoni P
Prendergast C
Prentice L
Preston S
Price A
Price C
Price R
Priest J
Priestley V
Prijatelj V
Prime Z
Pristopan V
Pritchard K
Pritchard L
Prokhorov A
Prokić I
Protti A
Protzer U
Proudfoot N
Prout R
Pryce J
Prysyazhna O
Pugh R
Pugh TJ
Pujol A
Pumarola T
Puopolo M
Purewal B
Purewal M
Purnell R
Purohit D
Purvis S
Puxty A
Puxty K
Pye K
Pérez-Matute P
Pérez-Tomás ME
Qiu X
Qtaish NA
Quaid S
Queiroz JGD
Quereda C
Quero JH
Quinn A
Quinn C
Quinn H
Quintana-Murci L
Quintela I
Quinto-Cortés CD
Quiñones LA
Racher H
Rad L
Radford E
Radhakrishnan J
Rafaels N
Ragoussis J
Rahmouni S
Rai S
Raith E
Raithatha A
Raj M
Rajme-López S
Rakitko A
Ralph K
Ramankulov Y
Ramirez A
Ramirez JM
Ramos H
Ramos L
Ramos-Galicia EM
Ramsay B
Ramírez-Carrillo MF
Ramírez-Jiménez ME
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Rando-Segura A
Ranga P
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Ratnakumar A
Ratnam V
Rattray A
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Raychaudhuri S
Raynard D
Readion G
Reddy A
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Reece-Anthony R
Reed A
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Rees A
Rees J
Rees S
Rees T
Rehman H
Reid K
Remesal AU
Rendon A
Renoux C
Reschreiter H
Resino S
Retamales-Ortega RM
Reverter E
Revill A
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Reyes-Grajeda JP
Reynolds J
Rhead K
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Ritzema J
Riveiro-Barciela M
Rivera JA
Rivers V
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Roberts A
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Robinson M
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Robles V
Rocha JD
Roche L
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Rodriguez-Artalejo F
Rodriguez-Frias F
Rodriguez-Garcia JA
Rodríguez M
Rodríguez-Gandía M
Rodríguez-Guillén R
Rodríguez-Ruiz E
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Rogers N
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Rojas-Martinez A
Rojo R
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Romero-Gómez M
Romero-Gómez M
Romero-Molina ÁO
Román-Montes CM
Rooney K
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Rooyackers O
Roper A
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Rosado WN
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Rose A
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Rosenberger C
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Rowan K
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Ruiz A
Ruiz V
Ruiz-Cabello F
Ruiz-Hornillos J
Ruiz-Jaén F
Runciman N
Ruolin L
Ruotsalainen S
Russell CD
Ruth J
Rutherfurd C
Ruíz-Ruíz E
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Ryan-Smith J
Rybniker J
Ryu J
Rühlemann MC
Saad C
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Sadarangani M
Sadiq F
Sado R
Saez Hidalgo JM
Sagara H
Sageshima H
Saha R
Saha R
Saha S
Sailybayeva A
Sainsbury H
Saint B
Saito F
Saito F
Saito H
Sakagami S
Sakuntabhai A
Salada S
Salberg A
Salciute E
Saleem M
Salehi S
Salmi S
Salmon K
Salutous D
Saluzzio RP
Samakomva T
Samir A
Sampson J
Sanabria GME
Sanchez - Rodriguez A
Sancho C
Sander LE
Sanders J
Sanderson A
Sandhar R
Sandhu R
Sandoval E
Sandoval E
Sangombe M
Sanhueza SA
Sano F
Santoro L
Santos NPC
Sarathy V
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Sassa C
Sathe S
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Satterstrom FK
Saunderson A
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Savage F
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Scanlon J
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Scherer SW
Scherewode J
Schiabor Barrett KM
Schmidt A
Schmidt SV
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Schulte EC
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Schurmann C
Schwinn M
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Scott RH
Scott T
Scott Z
Scriven J
Sealock JM
Seaman B
Sedaghati-khayat B
Seed C
Segura T
Segura-Kato Y
Segura-Kato Y
Sekikawa Y
Sell C
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Selvanayagam S
Semple G
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Senaratne D
Senner F
Sequeros CB
Serbanescu MA
Serna-Muñoz R
Serra-Llovich A
Serrano-Heras G
Serrano-Ruiz A
Service J
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Shah MR
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Shahin D
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Shamah-Levy T
Shankar-Hari M
Shanmugasundaram P
Sharland E
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Shiomi T
Ship L
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Shiroyama T
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Silbiger VN
Silva AX
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Sinfield E
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Stark KJ
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Taracido-Fernandez JC
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Trumper E
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Tsuchida T
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Turner-Bone I
Turney S
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Turvey SE
Tusié-Luna T
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Valdés PA
Valencia-Ramos J
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Vandernoot I
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Vasilevska-Ristovska J
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Vehreschild MJGT
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Velázquez-Cruz R
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Verdugo RA
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Vergasova E
Verlander M
Vertue M
Verula J
Vigueras-Hernández A
Vigurs C
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Villalonga JM
Vincent R
Virgilio E
Virginia M-RA
Vitart V
Vizcaychipi M
Vlasschaert C
Vochin A
Volland S
Von Hohenstaufen Puoti KA
Voza A
Vuylsteke A
Várnai R
Vázquez-Pérez JA
Wacker EM
Wackett T
Wadams B
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Waddington N
Wagner R
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Waite AAC
Wakabayashi A
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Wakefield P
Wakinshaw F
Waldron J
Walker C
Walker D
Walker L
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Walker S
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Wall A
Walsh T
Walter J
Walters RK
Walton O
Wang B
Wang QS
Wang X
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Ward D
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Warren D
Warrington J
Washington NL
Wassall H
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Waters A
Waters E
Watkins C
Watson E
Watson G
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Watters M
Watts S
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Weaver J
Webb N
Webster A
Webster D
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Wei S
Wei Z
Weiss ST
Weldon CH
Welford A
Wells C
Welters I
Wendorff M
Wendtner CM
Werge T
Wesse T
West J
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Whitaker E
Whitbread J
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Whiteside J
Whitney J
Whitton C
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Wicks SJ
Wiegrebe S
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Wignall A
Wilby L
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Wilfling S
Wiliams A
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Winkler TW
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Wolf-Roberts R
Wolford BN
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Wong J
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Wylie K
Wyllie DH
Wynter I
Xavier K
Xue X
Yagi K
Yamada M
Yamada Y
Yamagata K
Yamasaki M
Yang J
Yaspan B
Yassen AM
Yasui Y
Yates B
Yatomi M
Ye C
Yermakovich D
Yeung RSM
Yi X
Yonekawa A
Yoo S
Yoon K
Yoshida K
Yoshida S
Yoshida S
Yoshida T
Yoshihara T
Yoshiya K
Yoshiyama T
Young M
Yue F
Yun N
Yáñez CE
Yáñez Z
Zainulabid UA
Zainy T
Zak A
Zaki A
Zamikula J
Zamudio IPM
Zanella A
Zapata-Contreras D
Zapatamartinez M
Zarate R
Zarei N
Zavaleta DAF
Zawadzki P
Zawati MH
Zborowski AC
Zeberg H
Zechner M
Zhang Q
Zhao X
Zheng C
Zheng T
Zhlawi HJ
Zhlawi MWJ
Zholdybayeva E
Zhou W
Zhu W
Zitter L
Zoller H
Zongo O
Zorloni C
Zuñiga-Pacheco P
Zárate RN
Zúñiga-Ramos J
Álvarez BG
Ávila-Arcos MA
Ávila-Arcos MC
Özer O
Überla K
Þorsteinsdóttir U
Publication venue: Nature Research
Publication date: 21/06/2023
Field of study

Spiral - Imperial College Digital Repository

Mapping the human genetic architecture of COVID-19

Author: Abdelrazik M
Abdullah T
Abe R
Abe S
Abecasis GR
Abel L
Abernathy C
Abraheem A
Abul-Husn NS
Acosta-Herrera M
Acquilini D
Acquilini D
Adachi T
Adachi Y
Adams C
Adams K
Adanini O
Adeleye O
Adeniji K
Adra D
Afifi N
Afilalo J
Afilalo M
Afolabi D
Afrasiabi Z
Afset JE
Agasou A
Aghemo A
Agranoff D
Agrawal S
Aguirre LA
Agwuh K
Ahmad HF
Ahmad N
Ahmed A
Ahmed C
Ahmed KA
Ai M
Ail D
Akeroyd L
Akhtar MN
Akhtar S
Akinkugbe O
Aksentijevich A
Al Thani A
Al-Muftah W
Al-Sarraj Y
Alarcon C
Alarcon-Riquelme ME
Alasdair F
Alaverdian D
Alavere H
Albertos R
Albillos A
Albrecht W
Albrich W
Albrich WC
Aldera EL
Aldridge J
Alegria A
Alex B
Alexander P
Alfonso J
Algera AG
Ali A
Ali IMA
Ali S
Aliberti S
Allan A
Allan E
Allan J
Alldis Z
Allen L
Allen S
Allibone S
Allison KS
Allos R
Ally SM
Almaden-Boyle C
Altabaibeh A
Altmueller J
Alvaro A
Amar D
Amin V
Amitrano S
Amiya S
Ampuero J
Anan R
Anania S
Anastasescu E
Anderson F
Anderson J
Anderson M
Anderson P
Anderson S
Anderson S
Anderson T
Ando A
Andolfo I
Andrade V
Andretta F
Andreucci E
Andreucci E
Andrew A
Andrew B
Andrew G
Andrews E
Andrews SJ
Andrews SJ
Andrews SJ
Andrews SJ
Andrikopoulos P
Anedda F
Aneli S
Anemoli V
Angelini C
Angus B
Annis A
Antcliffe D
Antinori A
Antoni MD
Anumakonda V
Anwar M
Anzai T
Apetri E
Arai D
Arana E
Arbane G
Archer K
Arciero E
Arden T
Arias SS
Arif S
Arimura K
Armstrong J
Armstrong JA
Armstrong L
Armstrong R
Arning N
Arnold S
Arora J
Artuso R
Arumugam P
Asakura T
Asano K
Aschard H
Ascolillo S
Ashish A
Ashley E
Ashraf S
Ashraf S
Ashton L
Ashworth M
Asiimwe IG
Aslibekyan S
Asselta R
Atanasovska B
Atkinson D
Atkinson EG
Attwood B
Aucella F
Augustin M
Auld D
Auld F
Austin K
Austin P
Auton A
Auton A
Avendano-Ortiz J
Awano N
Ayers A
Azarzar S
Aziz F
Azuma M
Azuure C
Azzolini E
Baba R
Baba T
Bach B
Bacher P
Bachetti T
Badalamenti S
Badia JR
Badji RM
Bahmer T
Baikady RR
Baillie JK
Baillie JK
Baillie JK
Baillie JK
Baines B
Baines D
Baines K
Baird T
Baird Y
Bakshi S
Bakthavatsalam D
Balaconis MK
Baldassarri M
Baldini M
Ball CA
Bals R
Baltzell AH
Bamford A
Bamford P
Banach D
Banagan J
Banales JM
Bancroft H
Band G
Bandera A
Bandini M
Bandla N
Bano S
Baptista D
Barada O
Baras A
Baratti S
Barber R
Barbieri C
Barbieri C
Barbour A
Barclay L
Barclay WS
Barda B
Bargagli E
Bari S
Barker J
Barlow G
Barlow SL
Barnass S
Barnes KC
Baroni S
Baroni S
Barreira A
Barrett F
Barrett KMS
Barrett N
Barron A
Barry P
Bartels M
Bartley S
Baruah R
Baselli G
Bashyal A
Basikolo C
Bassetti M
Bassford C
Basso MEF
Bastion V
Basude S
Bates H
Bates M
Battle C
Bauchmuller K
Bax D
Baxter D
Baxter N
Baya N
Bayo L-A
Beadle J
Beadsworth M
Beale R
Bean S
Beaumont K
Beavis S
Beck A
Beckmann ND
Beech E
Beech V
Beekes M
Beesley K
Begg C
Beguin Y
Behan T
Beith CM
Belagodu Z
Belbin GM
Belfield H
Belhaj Y
Beligni G
Belisle A
Bell D
Bell G
Bell M
Bellamy M
Belli MA
Bellinghausen C
Bellini A
Bellwood R
Below JE
Bemand T
Benetti E
Benham L
Bennet D
Bennett S
Bentley M
Benyon S
Beppu S
Beranova E
Bercades G
Bergan J
Bergantini L
Berger MM
Bergomi M
Bergomi P
Berkowitz N
Bernardo D
Bernasconi A
Bernatoniene J
Berridge J
Bertrand A
Best N
Bettini LR
Beudel M
Bevan E
Bewley J
Bhardwaj N
Bhatia N
Bhatterjee R
Bhuie P
Bi R
Bianchi F
Bianco C
Bibert S
Bibert S
Bibi F
Biddle J
Biesecker L
Biggs H
Biondi A
Birch J
Birch J
Birch S
Birchall K
Birchall K
Bird S
Birkinshaw I
Birney E
Birt M
Biscarini F
Black E
Black K
Blackledge B
Blackledge B
Blackman H
Blakemore H
Blanco-Grau A
Blasi F
Blay N
Blay N
Blow S
Blunt M
Boada M
Board S
Bocciardi R
Bocciolone M
Bochud M
Bochud P-Y
Bochud PY
Bochud PY
Bochud PY
Bociek A
Boer C
Boezen M
Bogaard HJ
Bogaert D
Boillat N
Boillat-Blanco N
Bokhari M
Bolton M
Bolton R
Bolze A
Bombace S
Bomers M
Bonfanti P
Bonner S
Bonta PI
Booker L
Booth L
Booth S
Borislavova B
Borra C
Bos L
Bosari S
Bosio G
Bosse Y
Botello A
Bothma P
Botta G
Botta M
Boua PR
Bouab M
Bough L
Boughton AP
Boujemla B
Bouras K
Boutros P
Bouysran Y
Bowes A
Bowles R
Boyle P
Boyle R
Boz C
Bradford Y
Bradley C
Bradley P
Bradley-Potts J
Bradshaw Z
Brady A
Brady M
Brady R
Brahier T
Brandwood C
Branney D
Brantwood C
Brassard N
Braun A
Braun N
Brayne A
Brealey D
Brealey D
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Bremmer P
Brennan B
Brenner B
Brenner T
Bretherick AD
Brett M
Brett S
Brickell K
Bridgett V
Brimfield L
Brinkworth E
Briton K
Brittain-Long R
Britvan B
Bromley M
Brooke H
Brooks S
Brouwer MC
Brown A
Brown A
Brown A
Brown CW
Brown E
Brown J
Bruce M
Brunak S
Bruno R
Brunton M
Brusco A
Bruttini M
Bryant J
Bryant S
Bryant S
Buckley C
Buckley S
Bugiani M
Bujanda L
Bulik CM
Bulle E
Bullock K
Bulteel N
Bunni L
Burda D
Burden T
Burn I
Burnett C
Burns K
Burt K
Burtenshaw A
Burtenshaw A
Burton M
Busani S
Busson A
Bussotti M
Bustamante C
Butcher D
Buti M
Butler A
Butler S
Butler-Laporte G
Butler-Laporte G
Butler-Laporte G
Butler-Laporte G
Butte MJ
Butterworth AS
Butterworth-Cowin N
Button H
Buxbaum JD
Buxbaum JD
Buxbaum JD
Byun J
Caba Llero-Garralda A
Cabrelli L
Caceres M
Cadilla CL
Cagova L
Caldarelli GP
Calderon EJ
Callaghan M
Callier S
Camby S
Cameli P
Campbell A
Campbell H
Campbell R
Campbell R
Campos S
Camsooksai J
Canaccini A
Canakoglu A
Cantarini L
Cantor MN
Capasso M
Capitani K
Cappadona C
Cappelli S
Capps N
Carbral-Ortega L
Cardamone G
Carella M
Carey DJ
Carli D
Carlucci N
Carmody M
Carmody S
Carnahan M
Carnero-Montoro E
Carrabba M
Carracedo AD
Carreras Nolla A
Carreras A
Carriero ML
Carson G
Carter A
Carter E
Carter J
Carter S
Carungcong J
Caruth V
Casey M
Cass E
Castano-Vinyals G
Castelli F
Castle K
Castoldi M
Castori M
Castro P
Caswell M
Catena E
Caterson J
Cathcart S
Catlow L
Catterall BWA
Caulfield MJ
Caulfield MJ
Cavazza A
Cawley K
Cawthron K
Cazzaniga M
Cea C
Cecconi M
Ceri S
Ceri S
Ceriotti F
Cerny A
Cerrato L
Chablani M
Chadbourn I
Chadwick D
Chadwick D
Chambler D
Chan G
Chan R
Chand M
Chandler B
Chang D
Chang TS
Chang X
Chang Y
Chapman S
Charles B
Charlesworth R
Charney AW
Charnock R
Chasse M
Chassot J
Chaudhary K
Chavan S
Chechi K
Chee N
Cheema Y
Chen H-H
Cheng N
Cherian S
Chernitsov A
Cherubini A
Chetam L
Cheyne C
Chiba S
Chihara Y
Child J
Childs D
Chittoor G
Chiu A
Cho JH
Cho K
Choe K-W
Choi S
Chouchane O
Choudhury Y
Chowdhury M
Christle J
Chubachi S
Chueca N
Chukkambotla S
Chukkambotla S
Chung R
Chung W
Churchhouse C
Chwialkowska K
Chwialkowska K
Ciccarelli M
Ciesek S
Cirulli ET
Claassen S
Claire W
Clamp S
Clapham M
Claringbould A
Clarinval M
Clark A
Clark JJ
Clark M
Clark M
Clark R
Clark R
Clark S
Clark T
Clark V
Clarke D
Clarke EA
Clarke N
Clarkson M
Clayton S
Clement I
Clements S
Clerc O
Cloherty A
Clohisey S
Clohisey S
Clohisey S
Clohisey S
Coates C
Cockrell M
Coetzee S
Coghlan P
Coignet M
Coiro G
Coker D
Cole J
Cole J
Cole S
Cole S
Cole S
Coleman D
Coles H
Colley J
Collier D
Collier D
Colligan G
Collignon A
Collignon A
Collini P
Collins A
Collins BL
Collins C
Collins E
Collins E
Collins K
Collis M
Colombo F
Colombo R
Combes E
Conen A
Connolly K
Connor M
Conticini E
Convery K
Conyngham J-A
Cooke GS
Cooper J
Cooper L
Cooper L
Corcoran E
Cordero AIH
Cordioli M
Cordioli M
Cordioli M
Cordioli M
Cordioli M
Cordioli M
Cordioli M
Cornberg M
Cornell S
Cornely OA
Corral MA
Correia GDS
Corridi M
Cortes B
Cortes B
Cosgrove C
Cosgrove D
Cosier T
Cossarizza A
Costantino G
Cother N
Coton Z
Coulding M
Coutts A
Coventry T
Coviello DA
Cowley A
Cowley A
Cowley N
Cowton A
Cox A
Cox H
Cox NJ
Coyle J
Craig J
Crawley R
Creagh-Brown B
Crew A
Crickmore V
CRiPSI
Crisp N
Criste K
Cristiano D
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Croci S
Croft M
Crook DW
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Crowley M
Cruz C
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Cunningham A
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Cusack R
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Cutino-Moguel M-T
Cutler S
D'Acremont V
D'Alessandro M
D'Amato M
D'Angio M
D'Sylva S
Da Gloria EF
Dabe S
Daga S
Daglish J
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Daly M
Daly MJ
Daly Z
Dalziel J
Damas JK
Dance A
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Daniel A
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Darcis G
Dark P
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Darlington K
Darwish D
Dasgin J
Daubney E
Davey M
Davey M
David B
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Davis LK
Davison C
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de Brabander J
de Bree G
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de Cid R
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de Geus EJC
de Gordoa LO-R
de Gordoa LO-R
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de Jong H
de Jong MD
De la Horra C
De Neef M
de Pablo R
de Rojas I
de Salazar A
de Silva T
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de Vries H
Deacon B
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Death Y
Deboever C
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Della Monica M
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Demetriou C
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Dennis C
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Desanctis E
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deSouza F
Di Angelantonio E
di Bartolomeo C
Di Biagio A
Di Domenico P
Di Pietro M
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Di Valentin E
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Digby S
Dincarslan O
Ding L
Ding Y
Djeugam B
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Dobson E
Docherty AB
Doddato G
Dodds S
Domingues F
Donaldson A
Donaldson D
Donati A
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Donnachie J
Donne B
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Donnelly L
Donner K
Donnison P
Donnison P
Donohue C
Dooks E
Doonan R
Dopazo X
Dore R
Dormand N
Douglas K
Douthwaite S
Downes C
Drake TM
Dreher M
Drummond A
Drummond A
Duberly S
Dudman S
Dueker N
Duffield J
Duffin D
Duffy K
Duffy S
Duga S
Duga S
Duga S
Dumas M-E
Duncan E
Duncan T
Dunham I
Dunmore C
Dunn C
Dunning J
DuRand I
Durand M
Durga L
Durham C
Durie A
Durrans LJ
Durrant G
Dushianthan A
Duskova M
Dutta AK
Dutta AK
Dutta AK
Dyer P
Dyer T
Dykes J
Dyrhol-Riise AM
Eapen B
Earle SG
Eastgate-Jackson C
Easthope A
Easthope A
Easthope A
Easton J
Ebano P
Eckbad C
Edahiro R
Edmond I
Edwards M
Efford G
Egan J
Egger T
Eggermann T
El Kandoussi K
Elabd H
Elbers P
Elhassan M
Ellinghaus D
Elliott A
Elliott K
Ellis H
Elsaadany M
Elston K
Eltayeb A
Emiliozzi A
Emmert D
Endo A
Endo M
English K
Enomoto T
Erard V
Erard V
Erdmann J
Eriguchi Y
Esko T
Esmaeeli S
Espana PP
Esparza-Gordillo J
Evans A
Evans C
Evitts J
Ezeobu O
Eziefula C
Fabbiani M
Fadeur M
Fagan A
Fairfield CJ
Falcone M
Falcone M
Fallerini C
Farh K
Farnell-Ward S
Farquhar F
Farre X
Farre X
Farzad Z
Faucon A
Faucon AB
Faulkner B
Faulkner M
Fava F
Fave M-J
Faverio P
Fawkes A
Fazaal J
Fearby M
Febbo P
Fegan C
Feldt T
Felton T
Feng Y-CA
Ferguson S
Feri M
Fernandes K
Fernandes R
Fernandez J
Fernandez Z
Fernandez-Cadenas I
Fernandez-Cadenas I
Fernandez-Cadenas I
Fernandez-Roman J
Ferrando C
Ferreira MAR
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Ferrero GB
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Fidler K
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Filipe H
Filipovic M
Filippidis P
Filshtein-Sonmez T
Finch C
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Fine C
Finer S
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Finernan P
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Finn J
Finn S
Finney C
Finucane H
Finucane H
Fiorentino G
Fisher E
Fisher LWS
Flaherty L
Flanagan R
Fletcher T
Fleuren L
Flint N
Foco L
Fofano A
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Folkersen L
Folkes L
Folseraas T
Foote D
Force HCT
Ford A
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Forgetta V
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Foster T
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Fotiadis S
Fottrell-Gould D
Foucras S
Fourman MH
Fourman MH
Fowler S
Fowler T
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Fox J
Fracanzani AL
Francescatto M
Francescatto M
Franchi F
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Franke A
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Friaza V
Friedman P
Friolet R
Frippiat F
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Frithiof R
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Fuchimoto Y
Fuchsberger C
Fuchsberger C
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Fujiwara A
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Gamble C
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Garcia-Dorival I
Garcia-Etxebarria K
Garcia-Fernandez A-E
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Hao K
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Niemi MEK
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Page VJ
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Pairo-Castineira E
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Pancrazi A
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Pantet O
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Park WB
Parker R
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Parkinson N
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Parkinson P
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Parravicini P
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Parsons P
Partha R
Partridge R
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Pasaniuc B
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Pascual-Iglesias A
Pasko D
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Pink I
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Popov I
Porteous DJ
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Poscente M
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Pothecary C
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Russell CD
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Saito F
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Sankaran VG
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Sarathy V
Sargeant J
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Saunderson A
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Schroth GP
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Schulte EC
Schulte EC
Schultz MJ
Schulzky M
Schumacher N
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Scotton PG
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Seed C
Segala FV
Segala FV
Seilmaier MJ
Sekikawa Y
Sell C
Sellick K
Selvanayagam S
Semple G
Semple MG
Semple MG
Senaratne D
Sengupta S
Seo K
Seok W
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Serrano-Ruiz A
Shah A
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Shang N
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Shankar-Hari M
Shanmuga P
Shanmugasundaram P
Sharma A
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Shaw D
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Shaw R
Shaw V
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Shen X
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Vehreschild MJGT
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Yoshiya K
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Zechner M
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Zhang M
Zhao JH
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Zollner S
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zu Bentrup FM
Zucchi P
Zwinderman AHK
Zyndorf M
Publication venue
Publication date: 01/01/2021
Field of study

The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3,4,5,6,7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease

Whole-genome sequencing reveals host factors underlying critical COVID-19

Author: Abd Elghafar Mohamed S.
Abdel-Aziz Mahmoud
Abdelrazik Marwa
Abdollahi Hamed
Abdullah T.
Abecasis Goncalo
Abedalthagafi M.
Abel Lynn
Abernathy C.
Abraheem Azmeralde
Abul-Husn Noura S.
Acquilini D.
Adams C.
Adams Emma L.
Adams K.
Adamsara Alireza
Adanini Olurenke
Adeleye O.
Adra D.
Afilalo J.
Afilalo M.
Afolabi D.
Afrasiabi Z.
Agasou A.
Agrawal Shruti
Agüero D.
Ahmad N.
Ahmadi Saeideh
Ahmed A.
Ahmed Cecilia
Akeroyd L.
Akhtar M.N.
Akinkugbe O.
Aksentijevich Alexandra
Al-Afghani H.
Al-Awdah L.
Alaamery M.
Alahmadey Z.Z.
Alaverdian D.
Alavere H.
Albader A.
Albaiceta G.M.
Albakri J.K.
AlBardis H.
Albeladi M.
Albesher N.
Albrich W.
AlDhawi N.
Aldridge J.
Aleagha Afshar Etemadi
Alexander Peter.
Alfonso J.
Alghamdi B.
Alghamdi J.
Ali A.
Ali Altaf
Ali I.A.M.
Ali Syamlan
Aliannejad Rasoul
Aljawini N.
AlJohani S.
Alkwai S.
Allan A.
Allan E.
Allan J.
Alldis Zoe
Allen L.
Allen Meryem
Allen Schvearn
Allibone S.
Allison K.S.
Allos R.
Ally S.M.
AlMalik A.
Almalki F.
Almohammed I.
Almutairi M.
Alotaibi S.
Alowayn A.M.
Alqahtani S.
Alqubaishi F.
Alrashed M.
Alshareef A.
Alsolm E.
Alswailm M.
Altabaibeh A.
Alvaro A.
AlZahrani D.
Amin V.
Amirsavadkouhi Ali
Amitrano Sara
Anastasescu E.
Anderson F.
Anderson J.
Anderson Madeleine
Anderson Peter
Anderson S.
Anderson S.
Anderson T.
Andolfo I.
Andretta F.
Andreucci E.
Andrew Angela
Andrew B.
Andrew Gratrix
Andrews E.
Andrews Shea J.
Anedda F.
Anemoli V.
Annis A.
Antcliffe David
Antinori Andrea
Antoni M.D.
Anumakonda V.
Apetri E.
Aquino Maia
Arabi Y.M.
Aravindan Latha
Arbane Gill
Archer Katie
Arden T.
Arias Sonia Sousa
Arif S.
Armstrong Jacob
Armstrong Lisa
Armstrong Ruth
Arning N.
Arnold Sophie
Arranz María Jesús
Arribas E.
Artuso R.
Arumugam Prabhu
Ascolillo Steven
Ashraf Saima
Ashton L.
Aslibekyan S.
Astin-Chamberlain Raine
Atkinson E.G.
Attwood B.
Aucella F.
Auld D.
Auld F.
Austin Karen
Austin Pauline
Auton A.
Ayers A.
Azarzar S.
Bachetti T.
Baikady R.R.
Baillie John Kenneth
Baines Balvinder
Baines D.
Baines K.
Baird Yolanda
Bakthavatsalam Dhanalakshmi
Balaconis Mary K.
Baldassarri M.
Ball C.A.
Baltzell A.H.
Bamford A.
Bamford Peter
Banach Dorota
Bancroft Hollie
Band G.
Bandini M.
Bandla Nageswar
Bano S.
Baptista David
Barakeh D.
Baras Aris
Baratti S.
Barber R.
Barberis L.
Barbieri C.
Barclay Lucy
Bargagli E.
Barhoush E.
Barker J.
Barnes K.C.
Baroni S.
Barrett F.
Barron A.
Barry P.
Bartels M.
Bartley Shauna
Baruah R.
Bashyal Archana
Basikolo C.
Bassetti M.
Bastion V.
Bates H.
Bates Michelle
Batini Chiara
Battle Ceri
Bauchmuller K.
Baxter N.
Baya N.
Bayo L.A.
Beadle Jane
Bean S.
Beaumont K.
Beavis S.
Beck A.
Beckmann Noam D.
Bedini J. L.
Bee Catherine E.
Beech E.
Beech Valerie
Beekes M.
Beesley K.
Begg Colin
Beguin Y.
Behan T.
Beith C.M.
Belagodu Zakaula
Belbin Gillian Morven
Belfield H.
Belhaj Y.
Beligni G.
Belisle A.
Bell D.
Bell G.
Bell M.
Bell S.
Bellamy Mary
Belli M.A.
Bellini A.
Bellwood R.
Below Jennifer
Bemand T.
Benetti E.
Benham Leonie
Bennett D.
Bennett Sara
Bentley David
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Benyon S.
Beranova E.
Bercades G.
Bergantini L.
Bergomi P.
Berkowitz Nathan
Bernardo D.
Bevan E.
Bewley J.
Bhatia Nikhil
Bhatterjee Ravi
Bhuie Parminder
Bi R.
Biagio A.D.
Bianchi F.
Bibert S.
Bibi Fatima
Biddle Jack
Biggs Heather
Birch J.
Birch J.
Birch Sophie.
Birchall K.
Birchall K.
Bird S.
Birkinshaw Isobel
Birt M.
Biscarini F.
Black E.
Black K.
Blackledge B.
Blackman H.
Blakemore H.
Blay Natalia
Blow Sara
Blunt M.
Board S.
Bochud P.Y.
Bociek Aneta
Boezen M.
Boillat N.
Bokhari M.
Bolton Matthew
Bolton Rachel
Bonner Stephen
Booker L.
Borislavova B.
Borra Catherine
Botello A.
Botfield Liam
Bottà G.
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Bough L.
Boughton A.P.
Bowes A.
Bowles Ruth
Boyle P.
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Boz Ceilia
Bradford Y.
Bradley C.
Bradley P.
Bradley-Potts Joanne
Bradshaw Zena
Brady A.
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Brady R.
Brandwood C.
Branney D.
Brantwood Craig
Brassard N.
Brayne A.
Brealey D.
Bremmer P.
Brenner B.
Bretherick Andrew D.
Brett Michael
Brett Stephen
Brickell K.
Bridgett V.
Brimfield Lutece
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Publication venue
Publication date: 01/01/2022
Field of study

Altres ajuts: Department of Health and Social Care (DHSC); Illumina; LifeArc; Medical Research Council (MRC); UKRI; Sepsis Research (the Fiona Elizabeth Agnew Trust); the Intensive Care Society, Wellcome Trust Senior Research Fellowship (223164/Z/21/Z); BBSRC Institute Program Support Grant to the Roslin Institute (BBS/E/D/20002172, BBS/E/D/10002070, BBS/E/D/30002275); UKRI grants (MC_PC_20004, MC_PC_19025, MC_PC_1905, MRNO2995X/1); UK Research and Innovation (MC_PC_20029); the Wellcome PhD training fellowship for clinicians (204979/Z/16/Z); the Edinburgh Clinical Academic Track (ECAT) programme; the National Institute for Health Research, the Wellcome Trust; the MRC; Cancer Research UK; the DHSC; NHS England; the Smilow family; the National Center for Advancing Translational Sciences of the National Institutes of Health (CTSA award number UL1TR001878); the Perelman School of Medicine at the University of Pennsylvania; National Institute on Aging (NIA U01AG009740); the National Institute on Aging (RC2 AG036495, RC4 AG039029); the Common Fund of the Office of the Director of the National Institutes of Health; NCI; NHGRI; NHLBI; NIDA; NIMH; NINDS.Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care or hospitalization 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

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