8 research outputs found
Walking with wapiti: measuring late Holocene climatic variability through Cervus elaphus abundance and stable isotope analysis in the Gulf of Georgia Region
- Publication venue
- Western CEDAR
- Publication date
- 01/01/2012
- Field of study
Native hunters of the Northwest Coast valued the local wapiti subspecies (Cervus elaphus roosevelti) greater than any other land animals as a source of both food and raw materials for tools. Wapiti population size depends on the quantity and quality of their preferred foods: easily digestible, high protein plants that occur most abundantly in meadows and thickets, particularly after spring and summer rains. Changing climate regimes affected the productivity of these foods but there is disagreement about whether climate periods with long dry summers helped or hindered wapiti populations on the Northwest Coast. Lepofsky et al. (2005) suggests wapiti abundance increased in periods with persistent summer drought due to increased fire frequency destroying forests and expanding meadows, and increasing the productivity of their preferred foods. While Broughton et al. (2008) suggests wapiti abundance decreased in periods with low spring-summer precipitation due to reductions in the duration and forage quality of the growing season. The goal of this thesis is to eliminate one of these hypotheses with a systematic analysis of wapiti remains from six sites in western Whatcom County representing 300 to 5300 cal yr BP. Stable isotope analysis of nitrogen and carbon in wapiti bone collagen from contexts closely associated with radiocarbon dates. Mammal remains from levels closely associated to these radiocarbon dates were separated and counted to determine mammal NISP, and wapiti remains were identified to determine wapiti NISP. The relative abundance of wapiti was determined by dividing wapiti NISP by mammal NISP and converting to a percentage for each radiocarbon date, and for each climate period. Relative wapiti abundance was found to be dependent on climate period, with significantly lower wapiti abundance relative to other mammals during hot, dry climate periods. The δ13C values are low compared to other regions worldwide and remain stable through time suggesting that closed canopied temperate rainforests were the dominant terrestrial environment over the last 5300 calendar years. During the Medieval Warm period δ15N values are significantly higher suggesting that the hottest driest conditions of the late Holocene occurred at that time. During the warm dry climate periods such as the Medieval Warm Period, increased seasonality would lead to reduced hunting return and plant forage rates for people
Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection: A case control study
- Author
- Aagaard B.
- Abel S.
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- Adamski A.
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- Aichelburg A.
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- Ainsworth J. G.
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- Andersen Å. Bengaard
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- Publication venue
- 'Public Library of Science (PLoS)'
- Publication date
- 01/01/2015
- Field of study
Introduction: The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods: A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results: None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR- 145 correlated with nadir CD4+ T cell count. Discussion: No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection
Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study
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- Field of study
Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe
Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19
- Author
- ?ivko Iris
- Abbass Hakam
- Abdeladim Lilia
- Abdelhady Hesham
- Abdelkharim Hussam
- Abdelrazik Marwa
- Abdi Zakee
- Abdukahil Sheryl Ann
- Abel Lynn
- Abraham Jacinta
- Abrahamson Gail
- Abusamra Yousuf
- Aceto Romina
- Adams Nick
- Adams Peter
- Adebambo Olumide
- Adhikari Neill
- Adhikari Sheetal
- Affleck Julia
- Agha Gloria
- Aghemo Alessio
- Agno Ronan
- Ahmad Norfaizan
- Ain Quratul
- Ainscough Kate
- Ainsworth James
- Aitken Lindianne
- Akamp Ceren
- Al Enezi Farhan
- Al-Bassam Wisam
- Al-Beidh Farah
- Albert Martin
- Albrett Jonathan
- Alderman Meera
- Aldo Bonizzoni Matteo
- Alegria Ana
- Alessandro Carà Gianmarco
- Alexander Brian
- Alexander Peter
- Alfonso Jordan
- Ali Maryam
- Ali Murtaza
- Allam Hayat
- Allen Barbara
- Allen Louise
- Allibone Suzanne
- Almeshhedani Hasham
- AlQahtani Samah
- Alswaidan Lolowa
- Altomy Mohammed
- Al Amri Ali
- Al Qasim Eman
- Amatya Sameena
- Ambrosino Richard
- Anderson Thomas
- Andreae Mark
- Aneman Anders
- Angus Derek C.
- Anjum Aisha
- Ankert Juliane
- Annane Djillali
- Anne-Laure Fedou
- Anstey Matthew
- Antcliffe David
- Anthony Alpha
- Antoine Marchalot
- Antoine Pierre
- Antoine Studer
- Anumakonda Vikram
- Aparicio Christelle
- Aquino Maia
- Arabi Yaseen M.
- Arachchige Malka
- Aravindan Latha
- Arbane Gill
- Archambault Patrick
- Archer Simon
- Aref Noah
- Arias Ana-Marie
- Arias Sonia
- Arishi Hatim
- Arnold Donald
- Arnold John
- Arnott Andrew
- Arora Anand
- Aryal Diptesh
- Asghar Adeeba
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- Aspinwall Angelique
- Attokaran Antony
- Attwood Ben
- Au Carly
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- Avard Bronwyn
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- Babu Suresh
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- Bart Robert
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- Brugman Curt
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- Brunkhorst Frank M.
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- Castle James
- Cathcart Susanne
- Catorze Nuno José Teodoro Amaro dos Santos
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- Cecconi Maurizio
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- Chasse Michael
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- Chen Jonathan
- Chen Lixian
- Chen Yan
- Cheng Allen C.
- Cherian Shiney
- Chhablani Manish
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- Ciccarelli Michele
- Cirstea Emanuel
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- Cook Tim
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- de la Torre Cisneros Julian
- de Man Angelique
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- Yamagishi Yoshiaki
- Yamashita Chizuru
- Yang Yang
- Yarad Elizabeth
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- Yates David
- Yealy Donald
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- Young Meredith
- Young Paul
- Youngstein Taryn
- Yu Haili
- Yusuff Hakeem
- Zaharia Mihaela
- Zaidi Abbas
- Zaki Ahmed
- Zaman Mohsin
- Zarychanski Ryan
- Zdanavidiene Ausra
- Zhao Xiao
- Zinzoni Vanessa
- Zitter Letizia
- Zouita Louisa
- Publication venue
- 'American Medical Association (AMA)'
- Publication date
- 11/04/2023
- Field of study
IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19.
Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19.
DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022).
INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days.
MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes.
RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively).
CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes.
TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570
Mapping the human genetic architecture of COVID-19
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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
Canada
- Author
- A. Appenzell
- A. Bevan
- A. Bevan
- A. Dueck
- A. Mitcham
- A. Mitcham
- A. Parkin
- A. Purdy
- A. Schroeder
- A. Schroeder
- A. Thomas
- A. Woodsworth
- A.B. Cameron
- Acorn Milton.
- Alianuk .Hrant.
- Amprimoz Alexandre.
- Anderson Patrick.
- Aquin Hubert.
- Atwood Margaret.
- Aubert de Gaspé Philippe.
- B. Amtmann.
- B. Barrie
- B. Davies
- B. Godard
- B. Godard
- B. Howell
- B. Lee.
- B. Lever.
- B. Nesbitt .
- B. Smith
- B. Stock
- B. Stock
- B. Tierney
- Bache William. B.
- Baltensperger Peter.
- Barbour Douglas.
- Barr Robert.
- Bartlett Brian.
- Bates Ronald.
- Bell John.
- Bennett Lawrence.
- Benson Eugene.
- Beresford-Howe Constance.
- Bessette Gerard.
- Biel Kent C.
- Birney Earle.
- Birney Earle.
- Bissett Bill.
- Blais Marie-Claire.
- Blaise Clark.
- Bodsworth Fred.
- Bolt Carol.
- Boston Stewart.
- Bowering George.
- Boxer Avi.
- Boyer Agnes.
- Boyle Harry J.
- Braithwaite Max.
- Brewster Elizabeth.
- Brewster Elizabeth.
- Brooke Frances.
- Brown Amy Hatchard.
- Buckaway Catherine M.
- Buckler Ernest.
- Bugnet Georges.
- Bullock Michael.
- Burrs Mick.
- C. Allen
- C. Fraser
- C. Levenson
- C. MacCulloch.
- C. Micheli
- C. Partridge
- C. Roberts-van Oordt
- C. Taylor
- C. Thomas
- C. Thomas
- C.X. Ringrose
- C.X. Ringrose
- Callaghan Morley.
- Callaghan W.N.
- Cameron Eric.
- Campbell Don.
- Campbell J. Gounod.
- Canale Raymond.
- Capson Louis.
- Carrier Jean-Guy.
- Carrier Roch.
- Chadwick W.R.
- Clark Isabel.
- Clark Joan.
- Clemence Esme.
- Cohen Leonard.
- Cohen Matt.
- Cohen Matt.
- Coleman Victor.
- Collier Diana G.
- Cone Tom.
- Connor Ralph.
- Cook Michael.
- Crerar T.H.
- Cuevas Ernesto.
- D. Arnason
- D. Arnason
- D. Arnason
- D. Aspinall
- D. Bailey
- D. Barbour
- D. Barbour
- D. Bennett
- D. Bessai
- D. Cameron
- D. Fetherling
- D. Fetherling
- D. Fetherling
- D. Fetherling
- D. Godfrey
- D. Godfrey
- D. Gutteridge
- D. Gutteridge
- D. Jewison
- D. Lee
- D. Livesay
- D. Livesay
- D. Livesay
- D. Pacey
- D. Pacey
- D. Parker
- D. Spettigue
- D.G. Jones
- D.M. Hayne
- D.O. Spettigue
- Dalrymple Andrew Angus.
- Davies Robertson.
- Day Frank Parker.
- De Felice James.
- De Lissa Richard
- del Grande Louis.
- DeMille James.
- Denham Alice.
- Denison Merrill.
- Dickinson Don.
- Dienheim Anthony.
- Dlugacz Yosek.
- Dobb Ted.
- Dorsey Candas Jane.
- Doyle Mike.
- Duncan Sara Jeannette.
- Dunham Lynne.
- E. Godfrey
- E. Mandel
- E. McNamara
- E. Mullaly
- E. Strenski
- E. Waterston
- Edwards Caterina.
- Egyedi Béla.
- Elbl Richard
- Elgaard Elin.
- Engkent Gary.
- Evans Hubert.
- Everson R.G.
- F. Davey
- F. Davey
- F. Davey
- F. Sutherland
- F. Wah.
- F. Wah.
- F. Watt
- Farro E.
- Ferron Jacques.
- Fielden Charlotte.
- Fox Gail.
- Fraser Raymond.
- Fraser Sylvia.
- Freeman David.
- French David.
- French Richard.
- Friedman Irene.
- Frye Northrop.
- G. Amabile
- G. Bowering
- G. Bowering
- G. Clever
- G. Elliott
- G. Noonan
- G. Siebrasse
- G. Stow
- G. Stow
- G. Warkentin
- G. Warkentin
- G. Warkentin
- G. Woodcock
- G. Woodcock
- G. Woodcock
- G. Woodcock
- G. Woodcock
- G. Woodcock
- Gallant Mavis.
- Galt John.
- Garner Hugh.
- Garrett Ronald.
- Gasparini Len.
- Georges Bugnet
- Gerard Lance.
- Gibbs Robert.
- Gilbert Gerry.
- Glassco John.
- Godfrey David.
- Goudie Elizabeth.
- Gray Michael.
- Green Paul.
- Grills Barry W.
- Gustafson Ralph.
- H. Bouraoui
- H. Garner
- H. Rosengarten
- H. Rosengarten
- H. Sonthoff
- Harris Christie.
- Harrison Susan Frances.
- Heath Terrence.
- Heath Terrence.
- Heavysege Charles.
- Helwig David.
- Hendry Tom.
- Hickman Tom.
- Hodder Blanche.
- Hodgins Jack.
- Hollingsworth Mike.
- Holmes Abraham S.
- Hood Hugh
- Horwood Harold.
- Howe Joseph.
- Hubert Cam.
- Hébert Anne.
- I. Bassett
- I. Montagnes
- I. Nadel
- I.B. Nadel
- Ignatow Rose Graubart.
- J. Ayre
- J. Gibbs
- J. Grifhth
- J. Harcourt
- J. Jocelyn
- J. Mays
- J. Metcalf
- J. Moss
- J. Noonan
- J. Orange
- J. Rosenblatt
- J. Sheppard
- J. Sherman
- J. Sutherland.
- J. Zilber
- J.M. Purcell
- J.W. Lennox
- Jack Donald.
- Jacques Ferron
- Jameson Anna.
- Jean Barbeau
- Johnson Linda Wilkene.
- Johnston George.
- Julian Marilyn.
- K. Dewar
- K. Mulhallen
- K. Thompson
- Kartzmark Ross.
- Keeling Nora.
- Kelly Arthur J.
- Kent Valerie.
- Kinch Martin.
- King David.
- Kirby William.
- Klein A.M.
- Klinck Carl.
- Knight David.
- Kowal Vic.
- Kroetsch Robert.
- L. Dudek
- L. Ricou
- L. Vernon
- Lachance Bertrand.
- Ladoo Harold Sonny.
- Lambert Rick.
- Lampman Archibald.
- Laurence Margaret.
- Laurentian U.
- Layton Irving.
- Lazarus John.
- Leacock Stephen.
- Leckner Carol H.
- Lee Dennis
- Lee Ronald.
- Leprohen Rosanna.
- Leslie Kenneth.
- Livesay Dorothy.
- Loby Louis.
- Lonneberg Lyle.
- Lord Peter.
- Lowry Malcolm.
- M. Atwood
- M. Atwood
- M. Atwood
- M. Brown
- M. Dawe
- M. Dixon
- M. Dorsinville
- M. Doyle
- M. Dyment
- M. Estok
- M. J. Edwards
- M. Lalonde
- M. Lane
- M. Laurence
- M. Martin
- M. Potts
- M. Primeau
- M. Wilson
- M. Wolfe
- M. Wolfe
- M. Wolfe
- M. Wolfe
- M.H. Scargill
- M.J. Ward
- M.L. Ross
- MacCormack Terry.
- MacEwen Gwendolyn.
- MacKenzie Alan.
- MacLennan Hugh.
- MacLeod Alistair.
- MacMillan Ian.
- MacSkimming Roy.
- MacSween R.J.
- Mandel Eli.
- Margoshes Dave.
- Martindale Herb.
- Mason Michael.
- McCulloch Thomas.
- McDorxald David.
- McFadden David.
- McGillivray Judy.
- McIntyre James.
- McKenna Robert Ivan.
- McKinnon Barry.
- McLachlan Richard J.
- McNamara Eugene.
- Metcalf John.
- Michel Tremblay
- Miller Lily Poritz.
- Mirolla Michael.
- Mitchell Ken.
- Mitchell Ken.
- Mitchell W.O.
- Mitchell W.O.
- Monk Douglas.
- Montgomery L.M.
- Moore Brian.
- Moore Mavor.
- Moore Peter.
- Morissey Philip.
- Mowat Farley.
- Munro Alice.
- N. Kattan
- N.B. Annual sub.
- New W.H.
- Newlove John.
- Newlove John.
- Newman C.J.
- Newman Jerry.
- Nichol B.
- Nichol B.P.
- Nowlan Alden.
- O'Brien Bill T.
- O'Brien Bill T.
- Ondaatje Michael.
- Osborne John.
- Ostenso Martha.
- P. Barclay
- P. Grosskurth
- P. Lane
- P. Page
- P. Rogers
- P. Stevens
- P. Stevens
- P. Webb
- Page P.K.
- Palmer Marian.
- Palomba Lauro.
- Park Lisa.
- Parker Gilbert.
- Payerle George.
- Perrault E.G.
- Petch Steve.
- Pifler Phil.
- Pilk Henry.
- Plourde Marc.
- Pollock Sharon.
- Potrebenko Helen.
- Powell D. Reid.
- Pratt E.J.
- Purdy Al.
- R. Adams
- R. Brandeis
- R. Brown
- R. Brown
- R. Brown
- R. Daniells
- R. Gustafson
- R. Gustafson
- R. Harrison
- R. Kalman
- R. MacSkimming
- R. Mathews
- R. Murray.
- R. Skelton
- R. Smith
- R. Sutherland
- R. Willmott
- R.T. Robertson
- Raddall Thomas.
- Rafferty Larry.
- Ravel Aviva.
- Reaney James.
- Reiter David Phillip.
- Renner Vivian.
- Rhind Pauline Elizabeth.
- Richards David.
- Richardson John.
- Richler Mordecai.
- Rikki.
- Robert Gurik
- Roberts C.G.D.
- Roberts Kevin.
- Roberts Kevin.
- Roch Carrier
- Rooke Leon.
- Rosen Sheldon.
- Rosenthal Helene.
- Rosqui Carolyn.
- Ross James.
- Ross Sinclair.
- Rosta Helen.
- Roy Gabrielle.
- S. Atherton
- S. Djwa
- S. Djwa
- S. Djwa
- S. Djwa
- S. Djwa
- S. Grace
- S. Mayne
- S. McCutcheon
- S. Repo
- S. Scobie
- S. Scobie
- Salutin Rick.
- Sangster Charles.
- Schleich David.
- Schull Joseph.
- Scobie Stephen.
- Scobie Stephen.
- Scott Munroe.
- Seton Ernest
- Shein Brian.
- Sherman Kenneth.
- Sherra Connie.
- Shovella Brock.
- Simons Beverley.
- Smith Goldwin.
- Smith Ray.
- Smith Robert.
- Smyth Donna E.
- Solokoff Steven.
- Solway David.
- Stead Robert J.
- Stegmayer Nancy.
- Stein David Lewis.
- Such Peter.
- Sutherland Ronald.
- Sutherland Barry.
- Sutherland Fraser.
- Sutherland John.
- Svoboda Terese.
- Swerdlow Robert.
- T. Hendry
- T. Marshall
- Tata Saam.
- Taylor Ron.
- Theatre Passe Muraille
- Thomas Audrey.
- Thompson Kent.
- Thomson Edward William.
- Thornton Joan.
- Thériault Yves.
- Todd Chris.
- Tomlinson Randy.
- Trent U.
- Tyhurst Rob.
- Ursell Barbara.
- V. Reid
- V. Sharman
- W. Aide
- W. Francis
- W. Gardner
- W. Tallman
- W.F.E. Morley
- W.H. New
- W.H. New
- W.J. Keith
- Waddington Miriam.
- Waddington Miriam.
- Walker George.
- Ward Norman.
- Wassermann J.F.
- Watmough David.
- Watson Sheila.
- Wayman Tom.
- Webb Phyllis.
- Weinzweig Helen.
- West Ken.
- White Derryll.
- Whyte Thomas.
- Wiebe Rudy.
- Wigle Wil.
- Wilcocke Samuel
- Willand Judith.
- Williams David.
- Wilson Ethel.
- Wiseman Adele.
- Wolczyk Alice.
- Woodcock George.
- Woods Grahame.
- Woodward Gordon.
- Wright Richard.
- Xavier U.
- Yates J. Michael.
- Zakaras Paul.
- Zilber Jacob.
- Publication venue
- 'SAGE Publications'
- Publication date
- Field of study
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
- Breen G
- 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
- Croci L
- Croci S
- Croft M
- Crook DW
- Crooks K
- Crotti L
- Crowe R
- Crowley M
- Cruz C
- Cullum L
- Cunningham A
- Cunningham M
- Cupitt J
- Cupitt J
- Curgenven H
- Curtis CJ
- Cusack R
- Cusick C
- 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
- Dale K
- Dale S
- Dalton J
- Dalton K
- Daly M
- Daly MJ
- Daly Z
- Dalziel J
- Damas JK
- Dance A
- Danesh J
- Daniel A
- Daniel P
- Daniels A
- Darcis G
- Dark P
- Dark P
- Darlington K
- Darwish D
- Dasgin J
- Daubney E
- Davey M
- Davey M
- David B
- David C
- Davidson N
- Davies C
- Davies E
- Davies F
- Davies G
- Davies K
- Davies L
- Davies M
- Davies M
- Davies R
- Davis C
- Davis C
- Davis L
- Davis LK
- Davison C
- Dawson C
- Dawson D
- Dawson J
- Day N
- Daya M
- de Brabander J
- de Bree G
- de Bruin S
- de Cid R
- de Cid R
- de Geus EJC
- de Gordoa LO-R
- de Gordoa LO-R
- De Grandi A
- 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
- De Vivo O
- De Vivo O
- de Vries H
- Deacon B
- Deacon B
- Dearden J
- Death Y
- Deboever C
- Debreceni G
- Deelen P
- Deelen P
- Deery J
- Degenhardt F
- Dei S
- Dela Rosa A
- Delaneau O
- Delgado CC
- Delgado J
- Della Monica M
- Dellot P
- Deloukas P
- Demetriou C
- Denmade C
- Dennis C
- Dent K
- Dent M
- Depante M
- Dervisevic S
- Desanctis E
- Desgranges F
- deSouza F
- Di Angelantonio E
- di Bartolomeo C
- Di Biagio A
- Di Domenico P
- Di Pietro M
- Di Sarno L
- Di Valentin E
- Digby B
- Digby S
- Dincarslan O
- Ding L
- Ding Y
- Djeugam B
- Do R
- Dobano C
- Dobson E
- Docherty AB
- Doddato G
- Dodds S
- Domingues F
- Donaldson A
- Donaldson D
- Donati A
- Dongelmans D
- Donlon S
- Donnachie J
- Donne B
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- Turner V
- Turner-Bone I
- Turney S
- Turtle LCW
- Turtle LCW
- Tutton R
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- Twiss S
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- Tyler A
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- Uddin MJ
- Uddin MM
- Ueda S
- Ueda T
- Uellendahl-Werth F
- Uffelmann E
- Umeda A
- Underwood SJ
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- Ustianowski A
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- Uwamino Y
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- Vadla MS
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- Valente S
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- Valentine J
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- Valsecchi MG
- van Agtmael M
- van Baarle F
- van Blokland I
- van de Beek D
- van den Berge M
- van der Poll T
- van der Valk M
- van Heel D
- van Heel DA
- van Heel DA
- van Koutrik L
- van Mourik N
- Van Singer M
- van Tonder L
- van Uffelen KWJ
- van Vugt M
- Vandernoot I
- Varghese M
- Vari MS
- Varnai R
- Vecchia M
- Vedage D
- Veelo D
- Veerapen K
- Veerapen K
- Veerapen K
- Vehreschild MJGT
- Velho M
- Venkatesh H
- Venturelli S
- Verdugo RA
- Vergori A
- Verlander M
- Verma A
- Verma SS
- Vertue M
- Vertue M
- Verula J
- Verzuri A
- Viala B
- Vigurs C
- Vincent R
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- Vincenti A
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- Vitart V
- Vizcaychipi MP
- Vlaar APJ
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- von Mering C
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- Vuylsteke A
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- Wagstaff V
- Waite AAC
- Wakabayashi A
- Wakahara K
- Wake R
- Wakefield P
- Wakinshaw F
- Walden A
- Waldron J
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- Walker S
- Wall A
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- Walters RK
- Walton O
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- Wang Q
- Wang X
- Wang X
- Ward G
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- Warden S
- Warmerdam R
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- Watanabe H
- Watanabe K
- Watson E
- Watson G
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- Watters M
- Waugh V
- Weaver J
- Webster A
- Webster D
- Webster K
- Wei S
- Weiss ST
- Weldon CH
- Wells C
- Welters I
- Welters ID
- Wendorff M
- Wendt FR
- Wery M
- Wesse T
- West J
- Weston H
- Wham M
- Wheeler M
- Whileman A
- Whitbread J
- White D
- White I
- White K
- White M
- White N
- White S
- Whitehouse T
- Whiteley S
- Whiteside J
- Whittaker P
- Whittington A
- Whittle H
- Whitton C
- Whyte C
- Wicks SJ
- Wienbrandt L
- Wiersinga WJ
- Wijesinghe M
- Wilby E
- Wilcock E
- Wilcox L
- Wilcox R
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- Wild L
- Wild L
- Wilding L
- Wiles M
- Wilfling S
- Wilkin F
- Wilkins J
- Wilkinson A
- Wilkinson B
- Willer CJ
- Williams A
- Williams A
- Williams A
- Williams D
- Williams F
- Williams G
- Williams H
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- Williams M
- Williams M
- Williams P
- Williams S
- Williams T
- Willis H
- Wills M
- Willson J
- Wilson A
- Wilson DJ
- Wilson J
- Wilson JF
- Wilson L
- Winchester S
- Winnard S
- Winter-Goodwin B
- Wiselka M
- Wittig M
- Witzke O
- Wolf-Roberts R
- Wolford B
- Wolford B
- Wolterman RA
- Wolverson A
- Wong J
- Wood D
- Wood H-L
- Wood S
- Wood T
- Woodford C
- Woodruff M
- Woods L
- Woodyatt W
- Woolley AE
- Wooton DG
- Working UCLAHATLASDM
- Workman A
- Worner R
- Worsley L
- Wouters D
- Wozniak H
- Wray G
- Wren L
- Wright D
- Wright J
- Wright J
- Wright M
- Wrobel N
- Wrobel N
- Wu Y
- Wulandari R
- Wyllie DH
- Wynter I
- Xavier K
- Xue X
- Yadav A
- Yagi K
- Yamada M
- Yamada Y
- Yamagata K
- Yamasaki M
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- Yang Z
- Yaspan B
- Yasui Y
- Yates B
- Yates B
- Yatomi M
- Ye C
- Yengo L
- Yermakovich D
- Yi X
- Yonekawa A
- Yoon H
- Yoon KJ
- Yoshida K
- Yoshida S
- Yoshida S
- Yoshida T
- Yoshihara T
- Yoshiya K
- Yoshiyama T
- Youlton N
- Younes SE
- Young P
- Yun N
- Zak A
- Zaki A
- Zambon M
- Zamikula J
- Zanella A
- Zanella I
- Zanelli G
- Zara F
- Zara F
- Zarate R
- Zarate R
- Zborowski AC
- Zeberg H
- Zechner M
- Zechner M
- Zguro K
- Zhai R
- Zhang JE
- Zhang M
- Zhao JH
- Zhen J
- Zheng C
- Zheng T
- Zhou W
- Zhou W
- Zhu W
- Zitter L
- Zlatopolsky M
- Zoller H
- Zollner S
- Zongo O
- 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
Association between administration of IL-6 antagonists and mortality among patients hospitalized for COVID-19 : a meta-analysis
- Author
- Abad-Santos Francisco
- Adegunsoye Ayodeji
- Al-Beidh Farah
- Aleman Soo
- ALMEIDA THIAGO M.L.
- Almuedo Alex
- Alonso Pérez Tamara
- Altice Frederick
- ANDRADE LUIS E.C.
- Angus Derek
- Annane Djillali
- Arabi Yaseen
- Arip Masita
- Asensi Victor
- Asgeirsson Hilmir
- Avendaño Solá Cristina
- AVEZUM ALVARO
- Axelrod Matthew
- AZEVEDO LUCIANO C.P.
- Azoulay Elie
- Baillie J Kenneth
- Baillie Kenneth J
- Baron Gabriel
- Barrios Ana
- Basri Sazali
- Bautista-Hernández Azucena
- Beane Abigail
- Beasley Richard
- Benbenishty Julie S.
- Bensaci Ana Maria
- Berry Lindsay
- Berry Lindsay R.
- Berry Scott
- BERWANGER OTÁVIO
- Bhimani Zahra
- Bidin Farah Nadiah
- Blennow Ola
- Bonten Marc
- Bosteels Cedric
- Bradbury Charlotte
- Broman Niklas
- Brunkhorst Frank
- Buch Maya H
- Bureau Serge
- Buxton Meredith
- Cadranel Jacques
- Campos Esteban José
- Carbonell Cristina
- CARCEL SHEILA
- CARVALHO JULIO CESAR
- CASTRO CLAUDIO G.
- Castro Pedro
- Castán Clara
- CAVALCANTI ALEXANDRE B.
- Cavalcanti Alexandre Biasi
- Chappell Lucy C
- Chatzidionysiou Katerina
- Cheng Allen
- Chidambaram Suresh
- Chong Meng Li
- Chun Geok Ying
- COELHO JULIANA C.
- Colman Roos
- CONCEIÇÃO FABIO G.
- Cooper Nichola
- Corbacho Noemí
- COSTA ANDRÉ N.
- Cove Matt
- Dalmau David
- DAMIANI LUCAS P.
- Day Jeremy N
- de Benito Natividad
- De Buyser Stefanie
- De Jong Menno
- De Leeuw Elisabeth
- DE SOUZA DENISE
- Declercq Jozefien
- Derde Lennie
- Derde Lennie P. G.
- Diaz Janet V.
- Domingo Pere
- Domingo Pere
- Dougados Maxime
- DOURADO LETICIA K.
- Emmerich Joseph
- Espinosa Gerard
- Estcourt Lise
- Estrada Vicente
- FARIAS DANIELLE L.C.
- Fartoukh Muriel
- Faust Saul N
- Fernandes Ana
- Fernandez-Cruz Ana
- Feuth Thijs
- Fisher David
- Fleisher Jorge
- Fortun Jesús
- Foulkes Andrea S
- Fowler Robert
- FREITAS FLAVIO G.R.
- Frigault Matthew J
- Galea James
- Galun Eitan
- Garcia Felipe
- Garcia-Vicuna Rosario
- García-Fraile Lucio
- GARRIDO JOSE CARLOS
- GEBARA OTAVIO C.E.
- Godolphin Peter J.
- Gonzalez-Alvaro Isidoro
- Goossens Herman
- Gordon Anthony
- Gordon Anthony C.
- Green Cameron
- Guidet Bertrand
- Gutierrez Felix
- Gutierrez Maria del Mar
- Gutiérrez Liarte Ángela
- Halid Luqman Alhakim
- Haniffa Rashan
- Harvey Liam
- Hasan Mohd Shahnaz
- Haynes Richard
- Haynes Richard
- Healy Brian C
- Henter Jan-Inge
- Hermine Olivier
- Hermine Olivier
- Herrera Silvia
- Higgins Alisa
- Higgins Julian P. T.
- Hills Thomas
- Hohenthal Ulla
- Horby Peter W
- Horby Peter W.
- Horcajada Juan Pablo
- Horick Nora K.
- Horne Anna Carin
- Huckins David S.
- Humbert Marc
- Ibrahim Nur Munirah
- Ichihara Nao
- ISHIHARA LUCIANA M.
- Jaki Thomas
- Janols Helena
- Jeffery Katie
- Juszczak Edmund
- Kamarulzaman Adeeba
- Karrison Theodore
- King Andrew
- Koh Hui Moon
- Kukreja Anjanna
- Kumar Kuldeep
- Lacombe Karine
- Lambrecht Bart
- Lamontagne Francois
- Lampa Jon
- Landray Martin J
- Landray Martin J.
- Lawler Patrick
- Leal Lorna
- Lederer David J.
- Lee Cheng Siang
- LEITE RODRIGO T.
- Leon Rafael
- LEON RAFAEL
- Lim Wei Shen
- Lin Nina
- LISBOA THIAGO C.
- Litton Ed
- LOPES RENATO D.
- Lorenzi Elizabeth
- Lorenzi Elizabeth
- MACHADO DAVID J.B.
- MACHADO FLAVIA R.
- Maes Bastiaan
- Mafham Marion
- Mahevas Matthieu
- Malinis Maricar
- Malouf Jorge
- Mansour Michael K
- Mariette Xavier
- Mariette Xavier
- Marshall John
- Marshall John C.
- MARTIN JOSIANE
- Marttila Harri
- Martínez José Antonio
- Mateo Gracia María
- McArthur Colin
- McAuley Daniel
- McGuinness Shay
- McVerry Bryan
- Megat Johari Bushra
- Mejía-Abril Gina
- MERCHANTE NICOLAS
- Merchante Nicolas
- Millan Lucia
- Misnan Nor Arisah
- Misnan Nor Arisah
- Mohamed Gani Yasmin
- Mohan Shalini V.
- Mohd Abd Rahim Mohd Abd Hafiz
- Mohd Thabit Alif Adlan
- Molas Maria Ema
- Montgomery Alan
- Montgommery Stephanie
- Morpeth Susan
- Mouncey Paul
- Mukri Mohd Noor Azreet
- Mumford Andrew
- Mur Isabel
- Murthy Srinivas
- Murthy Srinivas
- Muñez Rubio Elena
- Muñoz Jessica
- Muñóz José
- Neelamegam Malinee
- Netea Mihai
- Ng Rong Xiang
- Nichol Alistair
- Nikiforow Sarah
- Nivens Michael C.
- Niward Katarina F
- Nordberg Marika
- Nowak Piotr
- Ogungbenro Kayode
- Oksi Jarmo
- Omar Sharifah Faridah
- Ong Hang Cheng
- PACHECO EDUARDO S.
- Pacheco Iván
- Paredes Roger
- Parke Rachael
- Parke Åsa
- Parker Jane
- Patel Naomi J
- Pene Frédéric
- Perez-Molina Jose A
- Perez-Molina Jose A.
- Pettila Ville
- Pincus Michael D
- PINTÃO MARIA CAROLINA T.
- Pisano Jennifer
- Pizov Reuven
- Pizov Reuven
- Pomar Virginia
- Ponnampalavanar Sasheela
- Porcher Raphael
- Porcher Raphael
- Postma Simone
- Pourchet-Martinez Valérie
- PRATS JOÃO G.
- Price Christina
- Prieto Jose Carlos
- Prieto Sergio
- Raja Azwa Raja Iskandar Syah
- Raja Sureja Letchumi
- Rajasuriar Reena
- Rajasuriar Reena
- Ramanan Athimalaipet V.
- Ramos Martínez Antonio
- Rasmuson Johan
- Ratain Mark
- Ravaud Philippe
- Ravaud Philippe
- Reid Pankti D.
- Resche Rigon Matthieu
- Reyes Felipe
- Rodríguez-García Sebastian C
- ROJAS SALOMÓN S.O.
- ROSA REGIS G.
- Rosas Ivan O.
- Rowan Kathryn
- Ruiz-Antorán Belén
- Rutgers Abraham
- Sagar Manish
- Saito Hiroki
- Salama Carlos
- Sancho-Lopez Aranzazu
- SANDES ALEX R.
- Santos Marlene
- SANTOS SUELI V.
- Sanz Sanz Jesus
- Saravanamuttu Sujana
- Savovic Jelena
- SCHEINBERG PHILLIP
- Schlemmer Frédéric
- SCHNEIDER DANIEL
- Seto Todd B.
- Seymour Chris
- Shah Ruta
- Shankar-Hari Manu
- Shankar-Hari Manu
- Shrager Harry
- Sim Benedict
- SIQUEIRA SUELLEN R.R.
- Sivapalasingam Sumathi
- Skorup Paul
- Soin Arvinder Singh
- Soriano Alex
- Spiga Francesca
- Staplin Natalie
- Sterne Jonathan A. C.
- Stone John H.
- Strek Mary
- Strohbehn Garth W.
- Sulaiman Helmi
- Sunden-Cullberg Jonas
- Svensson Anna-Karin
- Syed Badaruddin Syarifah Nurul Ain
- Syed Mansor Syed Mukhtar
- Syed Omar Sharifah Faridah
- Sönnerborg Anders
- Tan Kok Tong
- Tay Kim Heng
- Thangavelu Suvintheran
- Tharaux Pierre Louis
- The WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group [missing]
- Thwaites Guy
- Tibi Annick
- Tierney Jayne
- Tong Steve
- TORRE-CISNEROS JULIAN
- Torre-Cisneros Julian
- Torres Ferran
- Tsai Larry W.
- Tuang Wei Xuan
- Turgeon Alexis
- Turner Anne
- Uyeki Tim
- Vale Claire L.
- Valtonen Mika
- van Bentum-Puijk Wilma
- Van Damme Karel
- van de Veerdonk Frank
- van Hoogstraten Hubert
- van Meerten Tom
- VEIGA VIVIANE C.
- Veiga Viviane Cordeiro
- Vesterbacka Jan C.
- Villar Luisa M
- Vuorinen Tytti
- Webb Steve
- Westerweel Peter E.
- Wong Chee Kuan
- Wong Pui Li
- Woolley Ann E.
- Yazdanpanah Yazdan
- Youngstein Taryn
- ZAMPIERI FERNANDO G.
- Zarychanski Ryan
- Zulhaimi Nurul Syuhada
- Publication venue
- 'American Medical Association (AMA)'
- Publication date
- 01/01/2021
- Field of study
IMPORTANCE Clinical trials assessing the efficacy of IL-6 antagonists in patients hospitalized for COVID-19 have variously reported benefit, no effect, and harm.
OBJECTIVE To estimate the association between administration of IL-6 antagonists compared with usual care or placebo and 28-day all-cause mortality and other outcomes.
DATA SOURCES Trials were identified through systematic searches of electronic databases between October 2020 and January 2021. Searches were not restricted by trial status or language. Additional trials were identified through contact with experts.
STUDY SELECTION Eligible trials randomly assigned patients hospitalized for COVID-19 to a group in whom IL-6 antagonists were administered and to a group in whom neither IL-6 antagonists nor any other immunomodulators except corticosteroids were administered. Among 72 potentially eligible trials, 27 (37.5%) met study selection criteria.
DATA EXTRACTION AND SYNTHESIS In this prospectivemeta-analysis, risk of biaswas assessed using the Cochrane Risk of Bias Assessment Tool. Inconsistency among trial results was assessed using the I-2 statistic. The primary analysis was an inverse variance-weighted fixed-effects meta-analysis of odds ratios (ORs) for 28-day all-cause mortality.
MAIN OUTCOMES AND MEASURES The primary outcome measurewas all-cause mortality at 28 days after randomization. There were 9 secondary outcomes including progression to invasive mechanical ventilation or death and risk of secondary infection by 28 days.
RESULTS A total of 10 930 patients (median age, 61 years [range of medians, 52-68 years]; 3560 [33%] were women) participating in 27 trials were included. By 28 days, there were 1407 deaths among 6449 patients randomized to IL-6 antagonists and 1158 deaths among 4481 patients randomized to usual care or placebo (summary OR, 0.86 [95% CI, 0.79-0.95]; P =.003 based on a fixed-effects meta-analysis). This corresponds to an absolute mortality risk of 22% for IL-6 antagonists compared with an assumed mortality risk of 25% for usual care or placebo. The corresponding summary ORs were 0.83 (95% CI, 0.74-0.92; P <.001) for tocilizumab and 1.08 (95% CI, 0.86-1.36; P =.52) for sarilumab. The summary ORs for the association with mortality compared with usual care or placebo in those receiving corticosteroids were 0.77 (95% CI, 0.68-0.87) for tocilizumab and 0.92 (95% CI, 0.61-1.38) for sarilumab. The ORs for the association with progression to invasive mechanical ventilation or death, compared with usual care or placebo, were 0.77 (95% CI, 0.70-0.85) for all IL-6 antagonists, 0.74 (95% CI, 0.66-0.82) for tocilizumab, and 1.00 (95% CI, 0.74-1.34) for sarilumab. Secondary infections by 28 days occurred in 21.9% of patients treated with IL-6 antagonists vs 17.6% of patients treated with usual care or placebo (OR accounting for trial sample sizes, 0.99; 95% CI, 0.85-1.16).
CONCLUSIONS AND RELEVANCE In this prospectivemeta-analysis of clinical trials of patients hospitalized for COVID-19, administration of IL-6 antagonists, compared with usual care or placebo, was associated with lower 28-day all-cause mortality