51 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.
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- Wakefield P.
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- Waldron J.
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- Woodford C.
- Woodruff M.
- Woods L.
- Woodyatt W.
- Woolley A. E.
- Worner R.
- Worsley L.
- Wray G.
- Wren L.
- Wright D.
- Wright J.
- Wright M.
- Wrobel N.
- Wu Y.
- Wulandari R.
- Wyllie D. H.
- Wynter I.
- Xavier K.
- Xue X.
- Yadav A.
- Yang J.
- Yassen A. M.
- Yates B.
- Ye C.
- Yun N.
- Zainy T.
- Zak A.
- Zaki A.
- Zamikula J.
- Zanella I.
- Zborowski A. C.
- Zeberg H.
- Zechner M.
- Zguro K.
- Zhang M.
- Zhao J. H.
- Zheng C.
- Zhou W.
- Zitter L.
- Zlatopolsky M.
- Zollner S.
- Zongo O.
- Zucchi P.
- Zyndorf M.
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/2022
- Field of study
Get PDFCritical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease
Genetic mechanisms of critical illness in COVID-19.
- Author
- A A Roger Thompson
- A Abraheem
- A Agasou
- A Ahmed
- A Ali
- A Allan
- A Altabaibeh
- A Alvaro
- A Aspinwall
- A Ayers
- A Bamford
- A Barron
- A Bashyal
- A Bellini
- A Bociek
- A Botello
- A Bowes
- A Brady
- A Brayne
- A Brown
- A Brown
- A Butler
- A Campbell
- A Carter
- A Collins
- A Cowley
- A Cowton
- A Cowton
- A Cox
- A Crew
- A Dance
- A Daniel
- A Daniels
- A Dela Rosa
- A Drummond
- A Durie
- A E Heron
- A Easthope
- A Easthope
- A Evans
- A Fofano
- A Gales
- A Ganesan
- A Gardner
- A Garg
- A Gherman
- A Gordon
- A Gratrix
- A Gulati
- A Gupta
- A Haigh
- A Haldeos
- A Harrison
- A Harvey
- A Hayes
- A Higham
- A Higham
- A Hilldrith
- A Holden
- A Hormis
- A Hutcheon
- A Javaid
- A Joseph
- A Kaliappan
- A Katary
- A Kay
- A Kayani
- A Kent
- A Kirkby
- A Knight
- A Kubisz-Pudelko
- A Kuravi
- A Lewis
- A Loveridge
- A Lyle
- A Mayer
- A McAlpine
- A McCarthy
- A McGregor
- A McGregor
- A Meikle
- A Mitchell
- A Mitra
- A Morris
- A Morrison
- A Naranjo
- A Nicholson
- A Nicholson
- A Nilsson
- A Noakes
- A Patel
- A Pickard
- A Poole
- A Price
- A Puxty
- A Quinn
- A Quinn
- A Raithatha
- A Rattray
- A Reddy
- A Reed
- A Reyes
- A Rose
- A Rose
- A Rostron
- A Roy
- A Roynon-Reed
- A S Raj
- A Salberg
- A Sanderson
- A Serrano-Ruiz
- A Solesbury
- A Sukha
- A Swain
- A Tariq
- A Thomas
- A Thomas
- A Todd
- A Tomas
- A Tridente
- A Tucci
- A Turnbull
- A Uriel
- A Ustianowski
- A Vochin
- A Vuylsteke
- A Waite
- A Walden
- A Whileman
- A Wilkinson
- A Williams
- A Williams
- A Wilson
- A Zak
- A Zaki
- Achille Iolascon
- Adam Auton
- Adam Brown
- Agnese Verzuri
- Agostino Ognibene
- Agostino Riva
- Ailsa Golightly
- Alan Maclean
- Alessandra
- Alessandra Stella
- Alessandra Vergori
- Alessia Giorli
- Alexander J Mentzer
- Alice Donati
- Alison M Meynert
- Alistair Nichol
- Ana da Silva Filipe
- Andrea Antinori
- Andrea Cossarizza
- Andrea Ganna
- Andrea Tommasi
- Andrew Rambaut
- Andrew Stenhouse
- Andy Law
- Anjali J Shastri
- Anna Canaccini
- Anna Maria Pinto
- Annarita Giliberti
- Annemarie B Docherty
- Antonella D'Arminio Monforte
- Antonia Ying Wai Ho
- Antonio Di Biagio
- Antony Symons
- Arianna Emiliozzi
- Arianna Gabrieli
- Audrey Coutts
- B Anwar
- B Attwood
- B Baines
- B Blackledge
- B Borislavova
- B Chandler
- B Charles
- B Creagh-Brown
- B David
- B Deacon
- B Deacon
- B Digby
- B Faulkner
- B Fuller
- B Gumbrill
- B Gurung
- B Hadebe
- B Hairsine
- B Hopkins
- B Johnston
- B Lenagh
- B Masunda
- B Ogg
- B Patel
- B Player
- B Purewal
- B Scholefield
- B Shelley
- B Sloan
- B Thomas
- B Wadams
- B Welsh
- B Wilkinson
- B Winter-Goodwin
- B Yates
- Baillie J Kenneth
- Barbara Rossetti
- Beale Rupert
- Beatrice Alex
- Benjamin Bach
- Bretherick Andrew D
- Bruno Frediani
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- C Dennis
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- C Stuart
- C Summers
- C Swan
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- C Wrey Brown
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- Carmen Marciano
- Caroline Abernathy
- Carrol Gamble
- Caterina Lo Rizzo
- Catherine A Shaw
- Catherine H Weldon
- Caulfield Mark
- Ceilia Boz
- Cesira Nencioni
- Chelsea Ye
- Chiara Fallerini
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- Chiara Spertilli
- Chloe Donohue
- Chris Ponting
- Christoper A Green
- Cinthia E Jannes
- Clare Jackson
- Clohisey Sara
- Cristina Mussini
- D Antcliffe
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- D Martin
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- D Tetla
- D Thornton
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- D Vedage
- D Walker
- D Warren
- D Williams
- D Wood
- D Wright
- Daniela Francisci
- Daniella Coker
- Danilo Tacconi
- David A van Heel
- David Bennet
- David L Robertson
- David Stuart
- Dawn Law
- Debby Bogaert
- Derek Murphy
- Domenico A Coviello
- E Abaleke
- E Allan
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- E Andrews
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- E B Jude
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- E Beranova
- E Bevan
- E Black
- E Brinkworth
- E Collins
- E Combes
- E Davies
- E Dobson
- E Dooks
- E Fisher
- E Gendall
- E Goff
- E Goodwin
- E Gordon
- E Heeney
- E Horsley
- E Hughes
- E Johnson
- E Knights
- E Lee
- E London
- E Maccacari
- E Massey
- E McKenna
- E Meadows
- E Moncur
- E Morino
- E Mwaura
- E Peasgood
- E Perkins
- E Radford
- E Raith
- E Raith
- E Salciute
- E Smith
- E Smithson
- E Stoddard
- E Stones
- E Thomas
- E Tilney
- E Timlick
- E Treus Gude
- E Virgilio
- E Watson
- E Wilby
- Edoardo Conticini
- Egle Saviciute
- Elena Bargagli
- Elena Desanctis
- Elisa Benetti
- Elisa Frullanti
- Elisabetta Menatti
- Elisabetta Schiaroli
- Ellie Mcmaster
- Emma C Thomson
- Emmanuelle Marques
- Enrico Martinelli
- Esther Duncan
- Esther Merlini
- Ewen M Harrison
- F Anderson
- F Auld
- F Bibi
- F Davies
- F Farquhar
- F Fisher
- F Hurford
- F Kibutu
- F McNeela
- F Moore
- F Nasir
- F Trim
- F Wakinshaw
- F Williams
- Fabio Lena
- Fawkes Angie
- Federico Anedda
- Federico Franchi
- Ferdinando Giannattasio
- Filip Taneski
- Filippo Aucella
- Filippo Biscarini
- Floriana Valentino
- Fourman Max Head
- Francesca Andretta
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- Furniss James
- G Andrew
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- G Bell
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- G Sera Howe
- G Sloane
- G Subramanian
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- G Turner
- G Watson
- G Wray
- Gabriella Coiro
- Gabriella Doddato
- Gail Carson
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- Gary Leeming
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- Giancarlo Bosio
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- Graham S Cooke
- Griffiths Fiona
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- H Reschreiter
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- H Sainsbury
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- H Tench
- H Tiveran
- H Turner
- H Whittle
- H Willis
- H Wood
- Haley Chris
- Hanning Mal
- Harrison David
- Hayley Hardwick
- Hayward Caroline
- Helen Szoor-McElhinney
- Hinds Charles
- Ho Antonia
- Horby Peter
- I Ali Mohamed Ali
- I Balagosa
- I Birkinshaw
- I Burn
- I Chadbourn
- I D Clement
- I Edmond
- I Frost
- I Hass
- I Hussain
- I Lancoma-Malcolm
- I Leadbitter
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- I Otahal
- I Turner-Bone
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- I White
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- Ilaria Meloni
- Immacolata Andolfo
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- J Allan
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- J Biddle
- J Birch
- J Birch
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- J Brown
- J Bryant
- J Butler
- J Camsooksai
- J Carter
- J Caterson
- J Cebrian Suarez
- J Cockerill-Taylor
- J Cole
- J Colley
- J Cooper
- J Cupitt
- J Cuttler
- J Daglish
- J Dasgin
- J Dawson
- J Dearden
- J Deery
- J Donnachie
- J Dykes
- J Easton
- J Egan
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- J Finn
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- J Gregory
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- J Jones
- J Jones
- J K Baillie
- J Kassam
- J Kenneth Baillie
- J Kenneth Baillie
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- McAuley Danny
- Meera Chand
- Meynert Alison
- Michelle Girvan
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- Turtle Lance
- U Poultney
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- V Waugh
- Valentina Anemoli
- Vanessa Sancho-Shimizu
- Victoria Shaw
- Vitart Veronique
- W Harrison
- W Khaliq
- W Khaliq
- W McCormick
- W Woodyatt
- Walker Susan
- Walsh Timothy
- Wang Bo
- Wei Shen Lim
- Wendy S Barclay
- William A Paxton
- William Greenhalf
- Wilson James F
- Wrobel Nicola
- Wu Yang
- X Qiu
- Y Baird
- Y Choudhury
- Y Hussain
- Y Jackson
- Y Thirlwall
- Yang Jian
- Yang Zhijian
- Z Alldis
- Z Belagodu
- Z Bradshaw
- Z Coton
- Z Daly
- Z Farzad
- Z Fernandez
- Z Garland
- Z Maqsood
- Z Omar
- Z Prime
- Z Scott
- Zechner Marie
- Zhai Ranran
- Zheng Chenqing
- Publication venue
- Nature
- Publication date
- 01/01/2020
- Field of study
Get PDFHost-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 × 10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice
Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.
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- Ab Majid MA
- Ab Rahman AS
- Ab Rahman R
- Abayasinghe C
- Abbott T
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- Abdur-Rahman L
- Abeloos J
- Abernethy C
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- Aimoniotou-Georgiou E
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- Zsisku L
- Publication venue
- 'Oxford University Press (OUP)'
- Publication date
- 01/01/2016
- Field of study
Get PDFBACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700
Intraperitoneal drain placement and outcomes after elective colorectal surgery: international matched, prospective, cohort study
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- Aba M
- Abdellatif M
- Abdelmahmoud S
- Abu Hassan F
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- Aktas MK
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- Zafer F
- Zafer F
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- Zagibová D
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- Zaheer M
- Zahid A
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- Zanframundo C
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- Zazza S
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- Ziolkowska K
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- Zografos G
- Zonta S
- Çetin B
- Ölmez M
- Özbalcı GS
- Özen D
- Özen D
- Öztürk OU
- Čustović S
- Štefanová H
- Ευσταθίου Η
- Publication venue
- 'Oxford University Press (OUP)'
- Publication date
- 01/01/2022
- Field of study
Get PDFDespite current guidelines, intraperitoneal drain placement after elective colorectal surgery remains widespread. Drains were not associated with earlier detection of intraperitoneal collections, but were associated with prolonged hospital stay and increased risk of surgical-site infections.Background Many surgeons routinely place intraperitoneal drains after elective colorectal surgery. However, enhanced recovery after surgery guidelines recommend against their routine use owing to a lack of clear clinical benefit. This study aimed to describe international variation in intraperitoneal drain placement and the safety of this practice. Methods COMPASS (COMPlicAted intra-abdominal collectionS after colorectal Surgery) was a prospective, international, cohort study which enrolled consecutive adults undergoing elective colorectal surgery (February to March 2020). The primary outcome was the rate of intraperitoneal drain placement. Secondary outcomes included: rate and time to diagnosis of postoperative intraperitoneal collections; rate of surgical site infections (SSIs); time to discharge; and 30-day major postoperative complications (Clavien-Dindo grade at least III). After propensity score matching, multivariable logistic regression and Cox proportional hazards regression were used to estimate the independent association of the secondary outcomes with drain placement. Results Overall, 1805 patients from 22 countries were included (798 women, 44.2 per cent; median age 67.0 years). The drain insertion rate was 51.9 per cent (937 patients). After matching, drains were not associated with reduced rates (odds ratio (OR) 1.33, 95 per cent c.i. 0.79 to 2.23; P = 0.287) or earlier detection (hazard ratio (HR) 0.87, 0.33 to 2.31; P = 0.780) of collections. Although not associated with worse major postoperative complications (OR 1.09, 0.68 to 1.75; P = 0.709), drains were associated with delayed hospital discharge (HR 0.58, 0.52 to 0.66; P < 0.001) and an increased risk of SSIs (OR 2.47, 1.50 to 4.05; P < 0.001). Conclusion Intraperitoneal drain placement after elective colorectal surgery is not associated with earlier detection of postoperative collections, but prolongs hospital stay and increases SSI risk
Comparative Treatment Outcomes for Patients With Idiopathic Subglottic Stenosis.
- Author
- Amin Milan R
- Anderson Catherine
- Benninger Michael S
- Berry Lynne D
- Blumin Joel H
- Bock Jonathan M
- Bryson Paul C
- Castellanos Paul F
- Chen Sheau-Chiann
- Clary Matthew S
- Cohen Seth M
- Crawley Brianna K
- Dailey Seth H
- Daniero James J
- de Alarcon Alessandro
- Donovan Donald T
- Edell Eric S
- Ekbom Dale C
- Fernandes-Taylor Sara
- Fink Daniel S
- Francis David O
- Franco Ramon A
- Garrett C Gaelyn
- Gelbard Alexander
- Guardiani Elizabeth A
- Hillel Alexander T
- Hoffman Henry T
- Hogikyan Norman D
- Howell Rebecca J
- Huang Li-Ching
- Hussain Lena K
- Johns Michael M
- Kasperbauer Jan L
- Khosla Sid M
- Kinnard Cheryl
- Kupfer Robbi A
- Langerman Alexander J
- Lentz Robert J
- Lorenz Robert R
- Lott David G
- Lowery Anne S
- Makani Samir S
- Maldonado Fabien
- Mannion Kyle
- Matrka Laura
- McWhorter Andrew J
- Merati Albert L
- Mori Matthew C
- Netterville James L
- O'Dell Karla
- Ongkasuwan Julina
- Postma Gregory N
- Reder Lindsay S
- Richardson Brent E
- Rickman Otis B
- Rohde Sarah L
- Rosen Clark A
- Rutter Michael J
- Sandhu Guri S
- Schindler Joshua S
- Schneider G Todd
- Shah Rupali N
- Shyr Yu
- Sikora Andrew G
- Sinard Robert J
- Smith Libby J
- Smith Marshall E
- Soliman Ahmed M S
- Sveinsdóttir Sigríður
- Van Daele Douglas J
- Veivers David
- Verma Sunil P
- Weinberger Paul M
- Weissbrod Philip A
- Wootten Christopher T
- Publication venue
- 'American Medical Association (AMA)'
- Publication date
- 01/03/2020
- Field of study
Get PDFTo access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadImportance: Surgical treatment comparisons in rare diseases are difficult secondary to the geographic distribution of patients. Fortunately, emerging technologies offer promise to reduce these barriers for research.
Objective: To prospectively compare the outcomes of the 3 most common surgical approaches for idiopathic subglottic stenosis (iSGS), a rare airway disease.
Design, setting, and participants: In this international, prospective, 3-year multicenter cohort study, 810 patients with untreated, newly diagnosed, or previously treated iSGS were enrolled after undergoing a surgical procedure (endoscopic dilation [ED], endoscopic resection with adjuvant medical therapy [ERMT], or cricotracheal resection [CTR]). Patients were recruited from clinician practices in the North American Airway Collaborative and an online iSGS community on Facebook.
Main outcomes and measures: The primary end point was days from initial surgical procedure to recurrent surgical procedure. Secondary end points included quality of life using the Clinical COPD (chronic obstructive pulmonary disease) Questionnaire (CCQ), Voice Handicap Index-10 (VHI-10), Eating Assessment Test-10 (EAT-10), the 12-Item Short-Form Version 2 (SF-12v2), and postoperative complications.
Results: Of 810 patients in this cohort, 798 (98.5%) were female and 787 (97.2%) were white, with a median age of 50 years (interquartile range, 43-58 years). Index surgical procedures were ED (n = 603; 74.4%), ERMT (n = 121; 14.9%), and CTR (n = 86; 10.6%). Overall, 185 patients (22.8%) had a recurrent surgical procedure during the 3-year study, but recurrence differed by modality (CTR, 1 patient [1.2%]; ERMT, 15 [12.4%]; and ED, 169 [28.0%]). Weighted, propensity score-matched, Cox proportional hazards regression models showed ED was inferior to ERMT (hazard ratio [HR], 3.16; 95% CI, 1.8-5.5). Among successfully treated patients without recurrence, those treated with CTR had the best CCQ (0.75 points) and SF-12v2 (54 points) scores and worst VHI-10 score (13 points) 360 days after enrollment as well as the greatest perioperative risk.
Conclusions and relevance: In this cohort study of 810 patients with iSGS, endoscopic dilation, the most popular surgical approach for iSGS, was associated with a higher recurrence rate compared with other procedures. Cricotracheal resection offered the most durable results but showed the greatest perioperative risk and the worst long-term voice outcomes. Endoscopic resection with medical therapy was associated with better disease control compared with ED and had minimal association with vocal function. These results may be used to inform individual patient treatment decision-making.Patient-Centered Outcomes Research Institute - PCOR
A randomized longitudinal dietary intervention study during pregnancy: effects on fish intake, phospholipids, and body composition
- Author
- A Baylin
- A Baylin
- A Katz
- Agneta Holmäng
- AK Duttaroy
- AK Lindroos
- AL Brantsaeter
- AM Stuebe
- Ann-Sofie Sandberg
- Aysha Hussain
- BT Wu
- Cecilia Svelander
- CJ Suitor
- CM Lee
- E Amcoff
- E Forsum
- E Herrera
- E Herrera
- E Oken
- EA McCarthy
- F Fidanza
- G Desoye
- G Lepage
- H Gerster
- I Cetin
- I Thorsdottir
- I Thorsdottir
- Ingrid Larsson
- Institute of Medicine
- JD Buckley
- JE Cade
- JM Hopkinson
- JR Hebert
- K Ghebremeskel
- L Arab
- L Rode
- Lars Ellegård
- LE Kopp-Hoolihan
- Lena Hulthén
- Louise Andersson
- M Cedergren
- M Lof
- M Saadatian-Elahi
- MA Kaluzny
- MA Klebanoff
- Marja Bosaeus
- MD Al
- ME Cogswell
- MP Bonham
- NF Butte
- NF Butte
- Nordiska ministerrådet
- P Henriksson
- P Lagiou
- PC Calder
- PM Catalano
- PM Dietz
- R Matorras
- RW Friesen
- S Johansson
- S Johansson
- SA Lederman
- SF Olsen
- SJ Herring
- SJ Otto
- Swedish National Food Administration
- T Dovydaitis
- T Piirainen
- The Norwegian Directorate of Health
- The Swedish National Food Agency
- Therese Karlsson
- TO Scholl
- U Uusitalo
- WE Siri
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- Field of study
Full text linkWhole-genome sequencing reveals host factors underlying critical COVID-19
- Author
- Abd Elghafar M.S.
- Abdel-Aziz M.
- Abdelrazik M.
- Abdollahi H.
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- Zhou W.
- Zitter L.
- Zlatopolsky M.
- Zongo O.
- Zucchi P.
- Zyndorf M.
- Zöllner S.
- Åsvold B.O.
- Publication venue
- Springer Science and Business Media LLC
- Publication date
- 07/07/2022
- Field of study
Get PDFCritical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease
A first update on mapping the human genetic architecture of COVID-19
- Author
- Abd Elghafar Mohamed S.
- Abdel-Aziz Mahmoud
- Abdollahi Hamed
- Abdullah Tala
- Abecasis Goncalo R.
- Abedalthagafi Malak
- Abul-Husn Noura S.
- Acquilini Donatella
- Adams Emma L.
- Adamsara Alireza
- Adeleye Olumide
- Adra Darin
- Afilalo Jonathan
- Afilalo Marc
- Afrasiabi Zaman
- Agüero Daiana
- Ahmadi Saeideh
- Akhtar Shaheen
- Aksentijevich Alexandra
- Al-Afghani Hani
- Al-Awdah Laila
- Alaamery Manal
- Alahmadey Ziab Z.
- Alaverdian Diana
- Alavere Helene
- Albader Anoud
- Albaiceta Guillermo M.
- Albakri Jehad K.
- AlBardis Hadeel
- Albeladi Maha
- Albesher Nour
- Albrich W. C.
- Albrich Werner
- AlDhawi Nouf
- Aleagha Afshar Etemadi
- Alghamdi Bader
- Alghamdi Jahad
- Ali Altaf
- Aliannejad Rasoul
- Aljawini Nora
- AlJohani Sameera
- Alkwai Sarah
- Allos Raili
- AlMalik Abdulaziz
- Almalki Faisal
- Almohammed Iman
- Almutairi Mansour
- Alotaibi Sara
- Alowayn Albandary M.
- Alqahtani Saleh
- Alqubaishi Fatimah
- Alrashed May
- Alshareef Abdulraheem
- Alsolm Ebtehal
- Alswailm Moneera
- AlZahrani Deema
- Amirsavadkouhi Ali
- Amitrano Sara
- Andolfo Immacolata
- Andretta Francesca
- Andreucci Elena
- Andrews Shea J.
- Anedda Federico
- Anemoli Valentina
- Angelantonio Emanuele Di
- Annis Aubrey
- Antinori Andrea
- Antoni Melania Degli
- Anwar Mohammad
- Arabi Yaseen M.
- Arciero Elena
- Armstrong Jacob
- Arning Nicolas
- Arranz Maria J.
- Arribas Elisa
- Artuso Rosangela
- Arumugam Prabhu
- Ascolillo Steven
- Ashraf Samina
- Atkinson Elizabeth G.
- Aucella Filippo
- Auld Daniel
- AZARZAR Samira
- Bachetti Tiziana
- Baillie J. Kenneth
- Balaconis Mary K.
- Baldassarri Margherita
- Ball Catherine A.
- Baltzell Asher Haug
- Band Gavin
- Bandini Maria
- Baraka Dona
- Baras Aris
- Baratti Stefano
- Barbieri Chiara
- Barda B.
- Bargagli Elena
- Barhoush Eman
- Barnes Kathleen C.
- Baroni Silvia
- Bartels Meike
- Bassetti Matteo
- Batini Chiara
- Baya Nikolas
- Beck Andrew
- Beckmann Noam D.
- Bedini Josep L.
- Bee Catherine E.
- Beguin Yves
- Belbin Gillian M.
- Belhaj Yasmine
- Beligni Giada
- Belisle Alexandre
- Belli Mary Ann
- Below Jennifer
- Benetti Elisa
- Bennett David
- Bergantini Laura
- Bergomi Paola
- Berkowitz Nathan
- Bernardo David
- Biagio Antonio Di
- Bianchi Francesco
- Bibert Stéphanie
- Bibert Stéphanie
- Biesecker Les
- Biscarini Filippo
- Blay Natalia
- Bochud M.
- Bochud P. Y.
- Bochud P. Y.
- Bochud Pierre-Yves
- Bochud Pierre-Yves
- Boezen Marike
- Boillat Noémie
- Boillat-Blanco N.
- Bottà Giordano
- Bouab Meriem
- Boughton Andrew P.
- Bouras K.
- Bradford Yuki
- Brahier T.
- Brassard Nathalie
- Breen Gerome
- Brenner Bluma
- Britvan Bari
- Brumpton Ben M.
- Bruno Raffaele
- Bruttini Mirella
- Bryant Sam
- Bryant Sam
- Buring Julie E.
- Busani Stefano
- Bussotti Maurizio
- Butler-Laporte Guillaume
- Butterworth Adam S.
- Buxbaum Joseph D.
- Caldarelli Gian Piero
- Callier Shawneequa
- Cameli Paolo
- Campbell Archie
- Campbell Archie
- Canaccini Anna
- Cantarini Luca
- Cantor Michael N.
- Capasso Mario
- Capitani Katia
- Cappelli Silvia
- Carella Massimo
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- Carreras Anna
- Carriero Miriam Lucia
- Castaño-Vinyals Gemma
- Castelli Francesco
- Castori Marco
- Catena Emanuele
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- Cerny A.
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- Chan Georgia
- Chang Xiao
- Chang Xiao
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- Chavan Sameer
- Chen Hung-Hsin
- Cheng Nathan
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- Chittoor Geetha
- Cho Judy H.
- Cho Kelly
- Choi Sam
- Chowdhury Maharun
- Chung Raymond
- Churchhouse Claire
- Chwialkowska Karolina
- Claassen Sabine
- Claringbould Annique
- Clerc O.
- Coignet Marie
- Coiro Gabriella
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- Colobrán Roger
- Colombo Riccardo
- Conen A.
- Conticini Edoardo
- Cordioli Mattia
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- Cortés Beatriz
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- Domínguez-Mayoral Anna
- Donati Alice
- Donner Kati
- Durand Madeleine
- Durham Ceri
- D’Acremont V.
- D’Alessandro Miriana
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- Emma Duncan
- Erard Véronique
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- Fabbiani Massimiliano
- Falcone Marco
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- Fava Francesca
- Fawns-Ritchie Chloe
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- Feng Yen-Chen Anne
- Feri Marco
- Fernandez-Cadenas Israel
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- Finer Sarah
- Finer Sarah
- Finucane Hilary
- Fiorentino Giuseppe
- Fiz-López Aida
- Forgetta Vincenzo
- Foucras S.
- Fowler Tom
- Franchi Federico
- Francisci Daniela
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- Franke Lude
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- Free Robert C.
- Frenckell Christian Von
- Friolet R.
- Frippiat Frédéric
- Frischknecht M.
- Frithiof Robert
- Frullanti Elisa
- Furini Simone
- Gabbi Chiara
- Gabrieli Arianna
- Gaddis Michael
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- García-Clemente Marta
- García-Madrona Sebastian
- Gass Matthew C.
- Gatti Francesca
- Gaziano J. Michael
- Georges Michel
- Gettler Kyle
- Ghosh Biswarup
- Giannattasio Ferdinando
- Gignoux Christopher R.
- Giliberti Annarita
- Giorli Alessia
- Giot Jean-Baptiste
- Girardis Massimo
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- Glessner Joseph R.
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- Goldstein Jacqueline I.
- Gomez Juan
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- González-Villa Esther
- Gori Marco
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- Gupta Rahul
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- Hegazy Mohamed A. F.
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- Huang Qin Qin
- Huckins Laura M.
- Huffman Jennifer E.
- Hultström Michael
- Hunt Karen A.
- Hunt Karen A.
- Hurles Matt
- Hussain Shapna
- Huynen Pascale
- Hveem Kristian
- Hügli O.
- Iglesias Lara Lloret
- Ikram M. Arfan
- Iolascon Achille
- Islam Kamrul
- Itan Yuval
- Jacques Jessica
- Jantarabenjakul Watsamon
- Jaquet M.
- Jiménez-Xarrié Elena
- John Catherine
- Jordan Daniel M.
- Josyula Navya Shilpa
- Jung Junghyun
- Justice Anne E.
- Kahlert C. R.
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- Kamdar Dhryata
- Kamdar Dhryata
- Kampouri E. E.
- Kanai Masahiro
- Kanai Masahiro
- Karczewski Konrad J.
- Karjalainen Juha
- Karlson Elizabeth W.
- Karp Avromie
- Kaufmann Daniel E.
- Kaunisto Mari
- Keller Katherine
- Kenny Eimear E.
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- Kerr Shona M.
- Khafaga Walid T.
- Khan Ahsan
- Khan Amara
- Khattab Amin K.
- Kimchi Nofar
- King Daniel
- Kisand Kai
- Kivinen Katja
- Kleger G-R.
- Knapp C.
- Knight Spencer
- Koelling Nils
- Kogevinas Manolis
- Koskelainen Sami
- Kosmicki Jack A.
- Kousathanas Athanasios
- Kristiansson Kati
- Laane Edward
- Labkowsky Alexander
- Laisk Triin
- Lambermont Bernard
- Lannepoudenx Y.
- Lanting Pauline
- Lathrop G. Mark
- Lauren Petty E.
- Laurent Laetitia
- Lavery Cath
- Leader Joseph B.
- Lee Paul H.
- Lee Sang Hyuck
- Lee Sulggi
- Lee Yunsung
- LeFaive Jonathon
- Lena Fabio
- Lepage Pierre
- Lepamets Maarja
- Lerner Robin
- Levy Tess
- Li Binglan
- Li Kevin W.
- Li Rui
- Liao Rachel G.
- Lin Shang-Kuan
- Lipcsey Miklos
- Lista Mirjam
- Llucià-Carol Laia
- Loos Ruth J. F.
- Lopera Esteban
- Lorubbio Maria
- Lozano Francisco
- Lu Wenhan
- Lucas Anastasia
- Luchi Sauro
- Ludovisi Serena
- Läll Kristi
- Léonard Philippe
- MacArthur Daniel
- MacLaughlin Bev
- Maggiolo Franco
- Magnus Per
- Mahmoud Ebrahim S.
- Malaise Olivier
- Mamlouk Noor
- Mancarella Sandro
- Mandalà Marco
- Mangino Massimo
- Mangul Serghei
- Manson JoAnn E.
- Mantovani Stefania
- Manuel O.
- Marcantonio Simona
- MARCHETTI Oreste
- Marciano Carmen
- Mari Francesca
- Maricic Tomislav
- Martin Alicia R.
- Martin Hilary
- Martin Hilary C.
- Martinelli Enrico
- Martí-Fàbregas Joan
- Martín-Nalda Andrea
- Martínez Alba Parra
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- Mason Dan
- Mason Dan
- Massadeh Salam
- Masucci Luca
- Mazzei Maria Antonietta
- McCormick Joseph B.
- McCurdy Shannon
- Medina-Gomez Carolina
- Meigs James B.
- Meloni Ilaria
- Menatti Elisabetta
- Mencarelli Maria Antonietta
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- Mercader Josep
- Mercader Josep Maria
- Merla Giuseppe
- Metsalu Kristjan
- Metspalu Andres
- Meuris Christelle
- Meuwly J. Y.
- Miah Shefa
- Milani Lili
- Miraglia Federica Gaia
- Mirshahi Tooraj
- Misset Benoît
- Moahmed Hanteera S.
- Moghaddam Seyed Behrooz Mohseni
- Mohamed Attia A. S.
- Mondelli Mario Umberto
- Monica Matteo Della
- Montagnani Francesca
- Montillier P.
- Mooser Vincent
- Moreno Victor
- Morris Marcela
- Morrison David R.
- Moutschen Michel
- Moutsianas Loukas
- Muiño Elena
- Munting A.
- Murphy Shawn N.
- Mussini Cristina
- Mutairi Amal Al
- Márquez Leonardo
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- Naaber Paul
- Naderpour Zeinab
- Nadkarni Girish N.
- Nakanishi Tomoko
- Neale Benjamin M.
- Neale Benjamin M.
- Negro T. Rochat
- Nencioni Cesira
- Neofytos Dionysios
- Neofytos Dionysios
- Newman Bill
- Nguyen Huy
- Niavarani Ahmadreza
- Niblo Kristi
- Niemi Mari E. K.
- Nilaratanakul Voraphoj
- Nivard Michel M. G.
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- Nkambul Lindokuhle
- Nkambule Lindokuhle
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- Parati Gianfranco
- Parisi Saverio Giuseppe
- Park Danny
- Parravicini Pierpaolo
- Partha Raghavendran
- Pasko Dorota
- Pathak Gita A.
- Pavlovic Milos
- Peloso Gina
- Perez Emma F.
- Perez-Tur Jordi
- Perna Rita
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- Perrella Antonio
- Perret A.
- Peruggia Michael
- Pessina Gloria
- Pesukova Jaana
- Peterson Pärt
- Petitjean Louis
- Petrocelli Paola
- Phokaew Chureerat
- Piacentini Paolo
- Picchiotti Nicola
- Pietro Massimo Di
- Pigazzini Sara
- Pinoli Pietro
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- Pirinen Matti
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- Polikowski Hannah
- Polimanti Renato
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- Puthanakit Thanyawee
- Puusepp Mairo
- Quinodoz Mathieu
- Quinodoz Mathieu
- Quiros-Roldan Eugenia
- Rader Daniel
- Rafaels Nicholas
- Raggi Pamela
- Ragoussis Jiannis
- Rahmouni Souad
- Raimondi Francesco
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- Regina J.
- Reimann Ene
- Rendon Augusto
- Renieri Alessandra
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- Ritchie Marylyn D.
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- Rivolta Carlo
- Rivolta Carlo
- Rizzi Marco
- Rizzo Caterina Lo
- Roberts Genevieve
- Robles Veronica
- Rochat-Stettler L.
- Rogne Tormod
- Rojo Silvia
- Romani Davide
- Rooyackers Olav
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- Ruiz-Jaén Francisca
- Ruotsalainen Sanni
- Rusconi Stefano
- Russo Roberta
- Sabrina Ravaglia
- Saeedi Morteza
- Safa Nishat
- Safieh Leen Abu
- Salerni Lorenzo
- Salib Irene
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- Scaggiante Renzo
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- Wilson James F.
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- Zhou Wei
- Zlatopolsky Menachem
- zu Bentrup F. Meyer
- Zucchi Patrizia
- Zyndorf Marissa
- Zöllner Sebastian
- Åsvold Bjørn Olav
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/2022
- Field of study
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Results from a prospective, international, epidemiologic study of invasive candidiasis in children and neonates
- Author
- Abzug Mark J
- Arrieta Antonio
- Benjamin Daniel K
- Berger Christoph
- Berman David
- Bin-Hussain Ibrahim
- Castagnola Elio
- Charkabarti Arunaloke
- Danziger-Isakov Lara
- Dvorak Christopher C
- Groll Andreas H
- Halasa Natasha
- Hoffman Jill A
- Klingspor Lena
- Knapp Katherine
- Lachenauer Catherine
- Leckerman Kateri
- Lehrnbecher Thomas
- Martling Teresa
- Palazzi Debra L
- Roilides Emmanuel
- Steinbach William J
- Sung Lillian
- Velegraki Aristea
- Walsh Thomas J
- Warris Adilia
- Zaoutis Theoklis E
- Ziebold Christine
- Publication venue
- 'Ovid Technologies (Wolters Kluwer Health)'
- Publication date
- 01/01/2012
- Field of study
Full text linkBACKGROUND: Candida species are the third most common cause of pediatric health care-associated bloodstream infection in the United States and Europe. To our knowledge, this report from the International Pediatric Fungal Network is the largest prospective, multicenter observational study dedicated to pediatric and neonatal invasive candidiasis.
METHODS: From 2007 to 2011, we enrolled 196 pediatric and 25 neonatal patients with invasive candidiasis.
RESULTS: Non-albicans Candida species predominated in pediatric (56%) and neonatal (52%) age groups, yet Candida albicans was the most common species in both groups. Successful treatment responses were observed in pediatric (76%) and neonatal patients (92%). Infection with Candida parapsilosis led to successful responses in pediatric (92%) and neonatal (100%) patients, whereas infection with Candida glabrata was associated with a lower successful outcome in pediatric patients (55%). The most commonly used primary antifungal therapies for pediatric invasive candidiasis were fluconazole (21%), liposomal amphotericin B (20%) and micafungin (18%). Outcome of pediatric invasive candidiasis was similar in response to polyenes (73%), triazoles (67%) and echinocandins (73%). The most commonly used primary antifungal therapies for neonatal invasive candidiasis were fluconazole (32%), caspofungin (24%) and liposomal amphotericin B (16%) and micafungin (8%). Outcomes of neonatal candidiasis by antifungal class again revealed similar response rates among the classes.
CONCLUSIONS: We found a predominance of non-albicans Candida infection in children and similar outcomes based on antifungal class used. This international collaborative study sets the foundation for large epidemiologic studies focusing on the unique features of neonatal and pediatric candidiasis and comparative studies of therapeutic interventions in these populations
Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity
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- Publication venue
- country:DEU
- Publication date
- 01/01/2021
- Field of study
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