9 research outputs found
Results from the second WHO external quality assessment for the molecular detection of respiratory syncytial virus, 2019-2020
- Author
- Abubakar Abdinasir
- Al Ariqi Lubna
- Al-Nabet Ajaeb Dakhilalla MH
- Albuaini Mona
- Aziz Ammar
- Barakat Amal
- Barr Ian
- Baumeister Elsa
- Bhiman Jinal
- Bi Shabana
- Brown Richard
- Caetano Braulia C
- Campbell Harry
- Chadha Mandeep
- Couto Paula
- Coyle Peter Valentine
- Darmaa Badarch
- Deng Yi Mo
- Dia Ndongo
- Dong Xiaomin
- Dussart Philippe
- Ellis Joanna
- Fasce Rodrigo
- Gazo Mahmoud Hamad Ibraheem
- Gerber Sue
- Govindakarnavar Arunkumar
- Guthrie Erica
- Hall Aron
- Heraud Jean-Michel
- Herring Belinda
- Hirve Siddhivinayak
- Inbanathan Francis
- Jackson Sandra
- Jha Runa
- Kadjo Herve A
- Leite Juliana
- Lindstrom Stephen
- Lindstrom Stephen
- Lumandas Mayan
- Moen Ann
- Mott Joshua A
- Naguib Amel
- Nahapetyan Karen
- Nair Harish
- Nakouné Emmanuel
- Namulondo Joyce
- Nathalie Bastien
- Nguyen Phuong Nam
- Niang Mbayame
- Oberste Steve
- Okada Pilailuk Akkapaiboon
- Oumzil Hicham
- Pebody Richard
- Peret Teresa
- Pisareva Maria
- Potdar Varsha
- Razanazatovo Norosoa
- Rughooputh Sanjiv
- Salman Muhammad
- Samuel Reuben
- Siqueira Marilda M
- Smith Peter
- Srikantiah Padmini
- Tang Patrick
- Tivane Almiro
- Venter Marietjie
- Vicari Andrea
- Viegas Mariana
- von Gottberg Anne
- Whittaker Brett
- WHO RSV Surveillance Group
- Wijesinghe Pushpa Ranjan
- Williams Thomas
- Zambon Maria
- Zhang Wenqing
- Publication venue
- 'Wiley'
- Publication date
- 18/01/2023
- Field of study
BACKGROUND: External quality assessments (EQAs) for the molecular detection of human respiratory syncytial virus (RSV) are necessary to ensure the standardisation of reliable results. The Phase II, 2019-2020 World Health Organization (WHO) RSV EQA included 28 laboratories in 26 countries. The EQA panel evaluated performance in the molecular detection and subtyping of RSV-A and RSV-B. This manuscript describes the preparation, distribution, and analysis of the 2019-2020 WHO RSV EQA. METHODS: Panel isolates underwent whole genome sequencing and in silico primer matching. The final panel included nine contemporary, one historical virus and two negative controls. The EQA panel was manufactured and distributed by the UK National External Quality Assessment Service (UK NEQAS). National laboratories used WHO reference assays developed by the United States Centers for Disease Control and Prevention, an RSV subtyping assay developed by the Victorian Infectious Diseases Reference Laboratory (Australia), or other in-house or commercial assays already in use at their laboratories. RESULTS: An in silico analysis of isolates showed a good match to assay primer/probes. The panel was distributed to 28 laboratories. Isolates were correctly identified in 98% of samples for detection and 99.6% for subtyping. CONCLUSIONS: The WHO RSV EQA 2019-2020 showed that laboratories performed at high standards. Updating the composition of RSV molecular EQAs with contemporary strains to ensure representation of circulating strains, and ensuring primer matching with EQA panel viruses, is advantageous in assessing diagnostic competencies of laboratories. Ongoing EQAs are recommended because of continued evolution of mismatches between current circulating strains and existing primer sets
Clinical Evaluation of Streptococcus pneumoniae Polymerase Chain Reaction in Children with Suspected Septicemia
- Author
- Publication venue
- 'Ovid Technologies (Wolters Kluwer Health)'
- Publication date
- 01/11/2015
- Field of study
A new One Health Framework in Qatar for future emerging and re-emerging zoonotic diseases preparedness and response
- Author
- Abdul Aziz Al-Zeyara
- Abdulla Al Marri
- Abdullatif Al Khal
- Ahmed El Idrissi
- Asmaa Ali Al Thani
- Chadia Wannous
- Devendra Bansal
- Dhouha Hamdani
- Elmoubashar Abd Farag
- Eman Radwan
- Fatima Darkhshan
- Hadi Mohamad Yassine
- Hamad Eid Al Romaihi
- Heba Marhous
- Khalid Enan
- Mahmoud Hassan
- Markos Tibbo
- Md. Mazharul Islam
- Minahil Khalid
- Mohamed Al Hajri
- Mohamed Alhosani
- Mohammed Ismail Haroun
- Mohammed Nour
- Muna A. Al-Maslamani
- Nidal M. Younus
- Noora Abdulla Al-Emadi
- Peter Valentine Coyle
- Roberto Bertollini
- Shariq Jaffrey
- Sheikh Mohammed Bin Hamad Bin J. Al Thani
- Tariq Taha
- Wasan Abdulla A. Al-Baker
- Publication venue
- 'Elsevier BV'
- Publication date
- 01/06/2023
- Field of study
One Health is increasingly recognized as an optimal approach to address the global risk of health threats originating at the human, animal, and ecosystem interface, and their impact. Qatar has successfully practiced One Health approach for investigation and surveillance of zoonotic diseases such as MERS-CoV, and other health threats. However, the current gaps at institution and policy level hinder the sustainment of One Health. In this paper, we have assessed the potential for implementation of One Health Framework to reinforce and sustain One Health capacities in Qatar for 2022–2027. To implement One Health Framework in the country, Qatar Joint External Evaluation (JEE) report, lessons learnt during One Health experiences on zoonotic, vector-borne, and food borne diseases were used to present an outline for multisectoral coordination. In addition, technical capacities of One Health and factors that are required to operationalize it in the country were also assessed in series of meetings and workshops held at Ministry of Public Health on March 2022. Present health care infrastructure and resources were found to be conducive for effective management and response to shared health threats as evident during MERS-CoV, despite being more event based. Regardless, the need for more sustainable capacity development was unanimously emphasized. The consensus between all relevant stakeholders and partners was that there is a need for better communication channels, policies and protocols for data sharing, and the need to invest more resources for better sustainability. The proposed framework is expected to strengthen and facilitate multilateral coordination, enhanced laboratory capacity and network, improve active surveillance and response, risk communication, community engagement, maximize applied research, and build One Health technical work force. This would enable advancement and sustainment of One Health activities to prevent and control health threats shared between humans-animals-ecosystem interface
EFNS guidelines on the diagnosis and management of European Lyme neuroborreliosis
- Author
- Aberer
- Agger
- Aguero-Rosenfeld
- Alban
- Arnez
- Ayaslioglu
- Barbour
- Berglund
- Blanc
- Borg
- Brainin
- Brettschneider
- Brorson
- Brouqui
- Brunner
- Burkot
- Centers for Disease Control and Prevention
- Centers for Disease Control and Prevention (CDC)
- Cerar
- Charles
- Christen
- Christen
- Coyle
- Coyle
- Dattwyler
- Dattwyler
- Dorward
- Dotevall
- Dressler
- Dumler
- Fallon
- Feder
- Goodman
- Greene
- Gruntar
- Gyllenborg
- Halperin
- Halperin
- Hammers-Berggren
- Hansen
- Hansen
- Hansen
- Hardin
- Hassler
- Huisman
- Huppertz
- Hyde
- Johnson
- Kaplan
- Karkkonen
- Karlsson
- Karlsson
- Kindstrand
- Kindstrand
- Klempner
- Klempner
- Kohlhepp
- Krause
- Krbkova
- Kruger
- Kruger
- Kruger
- Krupp
- Lebech
- Ljostad
- Ljostad
- Ljostad
- Ljostad
- Logigian
- Marcus
- Marques
- Marques
- May
- Mullegger
- Murgia
- Mygland
- Ogrinc
- Oksi
- Oksi
- Oschmann
- Panelius
- Peter
- Pfister
- Pfister
- Pfister
- Picha
- Preac
- Rauter
- Reimers
- Riesbeck
- Rupprecht
- Rupprecht
- Schmidt
- Schutzer
- Skarpaas
- Skeie
- Skogman
- Skoldenberg
- Stanek
- Steere
- Steere
- Stiernstedt
- Stricker
- Strle
- Thorstrand
- Tjernberg
- Topakian
- Treib
- Tumani
- Valentine-Thon
- Vazquez
- Vermeersch
- Volovitz
- Vrethem
- Vukelic
- Wahlberg
- Wilke
- Wilske
- Wormser
- Ylitalo
- Zelger
- Zore
- Publication venue
- 'Wiley'
- Publication date
- Field of study
Mapping the human genetic architecture of COVID-19
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- 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.
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- 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.
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- Al Thani A.
- Al-Muftah W.
- Al-Sarraj Y.
- Alarcon C.
- Alarcon-Riquelme M. E.
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- 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
Dynamic transcriptomic profiles of zebrafish gills in response to zinc supplementation
- Author
- A Krężel
- AC Li
- B Sandstrom
- BJ Ledwith
- C Andreini
- C Blanquart
- C Hiu-Mei Yan
- C Hogstrand
- C Hogstrand
- C Hogstrand
- C Hogstrand
- C Hogstrand
- C Hogstrand
- C Hogstrand
- C Taccioli
- C-D Hsiao
- CH Lee
- Christer Hogstrand
- D Beyersmann
- D Huster
- D Zheng
- DJ Mazzatti
- DL Zheng
- Dongling Zheng
- E Wingender
- G Dennis
- G Reiterer
- GA Eby
- GJ Brewer
- GJ Fosmire
- GK Andrews
- GP Feeney
- Graham P Feeney
- H Haase
- H Haase
- Ht Dieck
- IS Kwun
- JH Laity
- JM Bailey
- JY Sun
- KA Jackson
- KA Jackson
- KA Jackson
- LW Weber
- M Bunger
- M Fuccillo
- M Murakami
- M Olivares
- M Ugarte
- N Boukaiba
- N Holleville
- NA Riobo
- NR Bury
- P Coyle
- P Gonzalez
- P-P Hwang
- Peter Kille
- Phil Cunningham
- R Eisler
- R Handy
- R Kizek
- RA Valentine
- RD Palmiter
- Richard D Handy
- RJ Cousins
- RJP Williams
- RTM Baker
- S Balesaria
- S Hughes
- S Yamashita
- S-f Lin
- SDW Comber
- SL Kelleher
- T Fukada
- T Kimura
- U Wimmer
- VVT Wong
- W Maret
- X Kang
- YS Cho
- Publication venue
- BMC
- Publication date
- 01/01/2010
- Field of study
<p>Abstract</p> <p>Background</p> <p>Dietary zinc supplementation may help to promote growth, boost the immune system, protect against diabetes, and aid recovery from diarrhoea. We exploited the zebrafish (<it>Danio rerio</it>) gill as a unique vertebrate ion transporting epithelium model to study the time-dependent regulatory networks of gene-expression leading to homeostatic control during zinc supplementation. This organ forms a conduit for zinc uptake whilst exhibiting conservation of zinc trafficking components.</p> <p>Results</p> <p>Fish were maintained with either zinc supplemented water (4.0 μM) and diet (2023 mg zinc kg<sup>-1</sup>) or water and diet containing Zn<sup>2+ </sup>at 0.25 μM and 233 mg zinc kg<sup>-1</sup>, respectively. Gill tissues were harvested at five time points (8 hours to 14 days) and transcriptome changes analysed in quintuplicate using a 16 K microarray with results anchored to gill Zn<sup>2+ </sup>influx and whole body nutrient composition (protein, carbohydrate, lipid, elements). The number of regulated genes increased up to day 7 but declined as the fish acclimated. In total 525 genes were regulated (having a fold-change more than 1.8 fold change and an adjusted P-value less than 0.1 which is controlling a 10% False discovery rate, FDR) by zinc supplementation, but little overlap was observed between genes regulated at successive time-points. Many genes displayed cyclic expression, typical for homeostatic control mechanisms. Annotation enrichment analysis revealed strong overrepresentation of "transcription factors", with specific association evident with "steroid hormone receptors". A suite of genes linked to "development" were also statistically overrepresented. More specifically, early regulation of genes was linked to a few key transcription factors (e.g. Mtf1, Jun, Stat1, Ppara, Gata3) and was followed by hedgehog and bone morphogenic protein signalling.</p> <p>Conclusions</p> <p>The results suggest that zinc supplementation reactivated developmental pathways in the gill and stimulated stem cell differentiation, a response likely reflecting gill remodelling in response to its altered environment. This provides insight to the role of zinc during cell differentiation and illustrates the critical nature of maintaining zinc status. The study also highlights the importance of temporal transcriptomics analysis in order resolve the discrete elements of biological processes, such as zinc acclimation.</p
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
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- Anderson T.
- Andolfo I.
- Andretta F.
- Andreucci E.
- Andrew Angela
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- Anedda F.
- Anemoli V.
- Annis A.
- Antcliffe David
- Antinori Andrea
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- Aquino Maia
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- Arumugam Prabhu
- Ascolillo Steven
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- Atkinson E.G.
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- Åsvold Bjørn Olav
- 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
Feasibility of reporting results of large randomised controlled trials to participants:experience from the Fluoxetine or Control under supervision (FOCUS) trial
- Author
- A Abdul-Hamid
- A Ahmed
- A Ali
- A Annamalai
- A Anthony
- A Asokanathan
- A Azim
- A Bahk
- A Banaras
- A Barry
- A Barugh
- A Bell
- A Benford
- A Bhalla
- A Blight
- A Boulton
- A Bowring
- A Burns
- A Butler
- A Bwalya
- A Cape
- A Chakrabarti
- A Chamberlain
- A Cook
- A Culbert
- A Dainty
- A David
- A Deary
- A DeVeciana
- A Dunne
- A Edwards
- A Espanol
- A Fazal
- A Fields
- A Fleming
- A Frith
- A Gillian
- A Goff
- A Goulding
- A Hague
- A Hamilton
- A Hardwick
- A Hasan
- A Hashmi
- A Hassan
- A Hayes
- A Hedges
- A Hedstrom
- A Hemsley
- A Hill
- A Hogan
- A Holloway
- A House
- A Hynes
- A James
- A Johnson
- A Jones
- A Joyson
- A Keeling
- A Kent
- A Khan
- A Kundu
- A Lush
- A Lyle
- A Maatouk
- A MacRaild
- A Majid
- A Man
- A Maney
- A Manoj
- A Mate
- A Mckenna
- A McLoughlin
- A Metcalf
- A Misra
- A Mohd Nor
- A Mucha
- A Nair
- A Nallasivan
- A Nasar
- A Needle
- A Nicolson
- A OCallaghan
- A Oshodi
- A Pace
- A Parry
- A Peacocke
- A Pitt Ford
- A Porteous
- A Potter
- A Pusalkar
- A Rajapakse
- A Rana
- A Rees
- A Remegoso
- A Ritchings
- A Ropun
- A Rudd
- A Shah
- A Shakhon
- A Siddiqui
- A Sigsworth
- A Skotnicka
- A Smart
- A Smith
- A Song
- A Stanners
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- L Gordon
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- M Abdul-Saheb
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- M Goorah
- M Hackett
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- M Hancevic
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- M Haritakis
- M Harper
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- M Hassan
- M Hawkes-Blackburn
- M Holden
- M Holland
- M Hooley
- M Hough
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- M Hussain
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- M Kambafwile
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- M Keltos
- M Khan
- M Kidd
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- S Parkinson
- S Patel
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- S Prasad
- S Punekar
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- S Qamar
- S Ragab
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- S Razak
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- S Sethuraman
- S Shah
- S Shahzad
- S Shanu
- S Sharon
- S Sharpe
- S Smolen
- S Stevens
- S Stevenson
- S Sultan
- S Sundayi
- S Tauro
- S Thornthwaite
- S Tilbey
- S Tinsley
- S Todd
- S Trippier
- S Tsang
- S Tucker
- S Tysoe
- S Valentine
- S Walker
- S Weatherby
- S Whitehouse
- S Whitworth
- S Williams
- S Williamson
- S Wong
- S Young
- Steff Lewis
- T Adedoyin
- T Anjum
- T Beadling
- T Black
- T Carter
- T Cassidy
- T Chapter
- T Corbett
- T Dowling
- T Duckett
- T Edmunds
- T England
- T Fluskey
- T Garcia
- T Hammond
- T Hlaing
- T Jackson
- T James
- T Jones
- T Khan
- T Lawrence
- T Levett
- T Loganathan
- T Nishiyama
- T Sandell
- T Sargent
- T Smith
- T Soe
- T Tarkas
- T Thirugnana-Chandran
- T Trugeon-Smith
- T Webb
- T Webster
- U Ghani
- U Hamid
- U Khan
- U Pallikona
- U Sukys
- U Umasankar
- V Balasubramanian
- V Croome
- V Cvoro
- V DiMartino
- V Hankin
- V Johnson
- V Jones
- V Le
- V Lowthorpe
- V Murray
- V Nadarajan
- V Pressly
- V Sudkeo
- V Sutton
- V Taylor
- V Withers
- Veronica Murray
- W Abbott
- W Alvares
- W Gaba
- W Golding
- W Rutherford
- W Smith
- W Wareing
- X Huang
- Y Abousleiman
- Y Begum
- Y Chin
- Y Chun
- Y Davies
- Y Neves-Silva
- Y Pai
- Z Ahmed
- Z Mellor
- Publication venue
- 'BMJ'
- Publication date
- 01/11/2020
- Field of study
Objectives Informing research participants of the results of studies in which they took part is viewed as an ethical imperative. However, there is little guidance in the literature about how to do this. The Fluoxetine Or Control Under Supervision trial randomised 3127 patients with a recent acute stroke to 6 months of fluoxetine or placebo and was published in the Lancet on 5 December 2018. The trial team decided to inform the participants of the results at exactly the same time as the Lancet publication, and also whether they had been allocated fluoxetine or placebo. In this report, we describe how we informed participants of the results.Design In the 6-month and 12-month follow-up questionnaires, we invited participants to provide an email address if they wished to be informed of the results of the trial. We re-opened our trial telephone helpline between 5 December 2018 and 31 March 2019.Setting UK stroke services.Participants 3127 participants were randomised. 2847 returned 6-month follow-up forms and 2703 returned 12-month follow-up forms; the remaining participants had died (380), withdrawn consent or did not respond.Results Of those returning follow-up questionnaires, a total of 1845 email addresses were provided and a further 50 people requested results to be sent by post. Results were sent to all email and postal addresses provided; 309 emails were returned unrecognised. Seventeen people replied, of whom three called the helpline and the rest responded by email.Conclusion It is feasible to disseminate results of large trials to research participants, though only around 60% of those randomised wanted to receive the results. The system we developed was efficient and required very little resource, and could be replicated by trialists in the future.Trial registration number ISRCTN83290762; Post-results
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
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- Alldis Z
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- 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
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- Anderson M
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- Ando A
- Andolfo I
- Andrade V
- Andretta F
- Andreucci E
- Andreucci E
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- Andrikopoulos P
- Anedda F
- Aneli S
- Anemoli V
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- Antoni MD
- Anumakonda V
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- Aschard H
- Ascolillo S
- Ashish A
- Ashley E
- Ashraf S
- Ashraf S
- Ashton L
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- Asiimwe IG
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- Cosier T
- Cossarizza A
- Costantino G
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- Coton Z
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- de Gordoa LO-R
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- De la Horra C
- De Neef M
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- de Rojas I
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- De Vivo O
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- Zanelli G
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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