Genetic mechanisms of critical illness in COVID-19 (2021)

Type of publication:
Journal article

Author(s):
Pairo-Castineira E.; Clohisey S.; Rawlik K.; Parkinson N.; Fourman M.H.; Russell C.D.; Furniss J.; Wang B.; Griffiths F.; Oosthuyzen W.; Millar J.; Shih B.; Zechner M.; Haley C.; Meikle J.; Finernan P.; Mcmaster E.; Law A.; Baillie J.K.; Paterson T.; Wackett T.; Armstrong R.; Weaver J.; Boz C.; Golightly A.; Ward M.; Mal H.; SzoorMcElhinney H.; Brown A.; Hendry R.; Stenhouse A.; Cullum L.; Law D.; Law S.; Law R.; Swets M.; Day N.; Taneski F.; Duncan E.; Kenneth Baillie J.; Lyons R.; Tenesa A.; Klaric L.; Bretherick A.D.; Richmond A.; Meynert A.; Grimes G.; Hayward C.; Ponting C.; Meynert A.M.; Wham M.; Ponting C.P.; Vitart V.; Wilson J.F.; Pasko D.; Walker S.; Kousathanas A.; Moutsianas L.; Caulfield M.; Scott R.; Bogaert D.; Gountouna E.; Porteous D.J.; Wrobel N.; Clark R.; Coutts A.; Donnelly L.; Gilchrist T.; Hafezi K.; Macgillivray L.; Maclean A.; McCafferty S.; Morrice K.; Fawkes A.; Murphy L.; Harrison D.; Rowan K.; Wu Y.; Yang Z.; Zhai R.; Zheng C.; Shen X.; Beale R.; Keating S.; Walsh T.; Docherty A.B.; Yang J.; Knight J.; Klenerman P.; Summers C.; Shankar-Hari M.; Turtle L.; Moore S.C.; Solomon T.; Turtle L.C.W.; Hardwick H.; Semple M.G.; Ho A.; Hinds C.; Horby P.; Horby P.W.; Nichol A.; Maslove D.; Ling L.; McAuley D.; Montgomery H.; Pereira A.C.; Krieger J.E.; Marques E.; Jannes C.E.; Renieri A.; Mari F.; Daga S.; Baldassarri M.; Fallerini C.; Fava F.; Valentino F.; Doddato G.; Giliberti A.; Bruttini M.; Croci S.; Meloni I.; Frullanti E.; Di Sarno L.; Tommasi A.; Palmieri M.; Tita R.; Amitrano S.; Pinto A.M.; Mencarelli M.A.; Rizzo C.L.; Dunning J.; Thwaites R.S.; Openshaw P.J.M.; Collier D.; Wood S.; Zak A.; Borra C.; Matharu M.; May P.; Alldis Z.; Mitchelmore O.; Bowles R.; Easthope A.; Bibi F.; Lancoma-Malcolm I.; Gurasashvili J.; Pheby J.; Shiel J.; Bolton M.; Patel M.; Taylor M.; Zongo O.; Ebano P.; Harding P.; Astin-Chamberlain R.; Choudhury Y.; Cox A.; Kallon D.; Burton M.; Hall R.; Blowes S.; Prime Z.; Biddle J.; Prysyazhna O.; Newman T.; Tierney C.; Kassam J.; Ostermann M.; Campos S.; Bociek A.; Lim R.; Grau N.; Jones T.O.; Whitton C.; Marotti M.; Arbane G.; Bonner S.; Hugill K.; Reid J.; Welters I.; Waugh V.; Williams K.; Shaw D.; Roman J.F.; Martinez M.L.; Johnson E.; Waite A.; Johnston B.; Hamilton D.; Mulla S.; McPhail M.; Smith J.; Barclay L.; Hope D.; McCulloch C.; McQuillan L.; Clark S.; Singleton J.; Priestley K.; Rea N.; Callaghan M.; Campbell R.; Andrew G.; Marshall L.; McKechnie S.; Hutton P.; Bashyal A.; Davidson N.; Polgarova P.; Stroud K.; Pathan N.; Elston K.; Agrawal S.; Battle C.; Newey L.; Rees T.; Harford R.; Brinkworth E.; Williams M.; Murphy C.; White I.; Croft M.; Bandla N.; Gellamucho M.; Tomlinson J.; Turner H.; Davies M.; Quinn A.; Hussain I.; Thompson C.; Parker H.; Bradley R.; Griffiths R.; Scriven J.; Nilsson A.; Bates M.; Dasgin J.; Gill J.; Puxty A.; Cathcart S.; Salutous D.; Turner L.; Duffy K.; Puxty K.; Joseph A.; Herdman-Grant R.; Simms R.; Swain A.; Naranjo A.; Crowe R.; Sollesta K.; Loveridge A.; Baptista D.; Morino E.; Davey M.; Golden D.; Jones J.; Moreno Cuesta J.; Haldeos A.; Bakthavatsalam D.; Vincent R.; Elhassan M.; Xavier K.; Ganesan A.; Purohit D.; Abdelrazik M.; Morgan J.; Akeroyd L.; Bano S.; Lawton T.; Warren D.; Bromley M.; Sellick K.; Gurr L.; Wilkinson B.; Nagarajan V.; Szedlak P.; Cupitt J.; Stoddard E.; Benham L.; Preston S.; Laha S.; Slawson N.; Bradshaw Z.; Brown J.; Caswell M.; Melling S.; Bamford P.; Faulkner M.; Cawley K.; Jeffrey H.; London E.; Sainsbury H.; Nagra I.; Nasir F.; Dunmore C.; Jones R.; Abraheem A.; Al-Moasseb M.; Girach R.; Padden G.; Egan J.; Brantwood C.; Alexander P.; Bradley-Potts J.; Allen S.; Felton T.; Manna S.; Farnell-Ward S.; Leaver S.; Queiroz J.; Maccacari E.; Dawson D.; Delgado C.C.; Saluzzio R.P.; Ezeobu O.; Ding L.; Sicat C.; Kanu R.; Durrant G.; Texeira J.; Harrison A.; Samakomva T.; Willis H.; Hopkins B.; Thrasyvoulou L.; Jackson M.; Zaki A.; Tibke C.; Bennett S.; Woodyatt W.; Kent A.; Goodwin E.; Brandwood C.; Smith L.; Rooney K.; Thomson N.; Rodden N.; Hughes E.; McGlynn D.; Clark C.; Clark P.; Abel L.; Sundaram R.; Gemmell L.; Brett M.; Hornsby J.; MacGoey P.; Price R.; Digby B.; O’Neil P.; McConnell P.; Henderson P.; Henderson S.; Sim M.; Kennedy-Hay S.; McParland C.; Rooney L.; Baxter N.; Pogson D.; Rose S.; Daly Z.; Brimfield L.; Phull M.K.; Hussain M.; Pogreban T.; Rosaroso L.; Salciute E.; Grauslyte L.; Brealey D.; Raith E.; MacCallum N.; Bercades G.; Hass I.; Smyth D.; Reyes A.; Martir G.; Clement I.D.; Webster K.; Hays C.; Gulati A.; Hodgson L.; Margarson M.; Gomez R.; Baird Y.; Thirlwall Y.; Folkes L.; Butler A.; Meadows E.; Moore S.; Raynard D.; Fox H.; Riddles L.; King K.; Kimber S.; Hobden G.; McCarthy A.; Cannons V.; Balagosa I.; Chadbourn I.; Gardner A.; Horner D.; McLaughlanv D.; Charles B.; Proudfoot N.; Marsden T.; McMorrow L.; Blackledge B.; Pendlebury J.; Harvey A.; Apetri E.; Basikolo C.; Catlow L.; Doonan R.; Knowles K.; Lee S.; Lomas D.; Lyons C.; Perez J.; Poulaka M.; Slaughter M.; Slevin K.; Thomas V.; Walker D.; Harris J.; Drummond A.; Tully R.; Dearden J.; Philbin J.; Munt S.; Rishton C.; O’Connor G.; Mulcahy M.; Dobson E.; Cuttler J.; Edward M.; Norris J.; Hanson K.; Poole A.; Rose A.; Sloan B.; Buckley S.; Brooke H.; Smithson E.; Charlesworth R.; Sandhu R.; Thirumaran M.; Wagstaff V.; Suarez J.C.; Kaliappan A.; Vertue M.; Nicholson A.; Riches J.; Solesbury A.; Kittridge L.; Forsey M.; Maloney G.; Cole J.; Davies R.; Hill H.; Thomas E.; Williams A.; Duffin D.; Player B.; Radhakrishnan J.; Gibson S.; Lyle A.; McNeela F.; Patel B.; Gummadi M.; Sloane G.; Dormand N.; Salmi S.; Farzad Z.; Cristiano D.; Liyanage K.; Thwaites V.; Varghese M.; Meredith M.; Lim W.S.; Mills G.; Willson J.; Harrington K.; Lenagh B.; Cawthron K.; Masuko S.; Raithatha A.; Bauchmuller K.; Wiles M.; Ahmad N.; Barker J.; Jackson Y.; Kibutu F.; Bird S.; Watson G.; Martin J.; Bevan E.; Brown C.W.; Trodd D.; English K.; Bell G.; Wilcox L.; Katary A.; Gopal S.; Lake V.; Harris N.; Metherell S.; Radford E.; Moore F.; Bancroft H.; Daglish J.; Sangombe M.; Carmody M.; Rhodes J.; Bellamy M.; Garg A.; Kuravi A.; Virgilio E.; Ranga P.; Butler J.; Botfield L.; Dexter C.; Fletcher J.; Shanmugasundaram P.; Hambrook G.; Burn I.; Manso K.; Thornton D.; Tebbutt J.; Penn R.; Hulme J.; Hussain S.; Maqsood Z.; Joseph S.; Colley J.; Hayes A.; Ahmed C.; Haq R.; Clamp S.; Kumar R.; Purewal M.; Baines B.; Frise M.; Jacques N.; Coles H.; Caterson J.; Rai S.G.; Brunton M.; Tilney E.; Keating L.; Walden A.; Antcliffe D.; Brett S.; Gordon A.; Templeton M.; Rojo R.; Banach D.; Arias S.S.; Fernandez Z.; Coghlan P.; Williams D.; Jardine C.; Bewley J.; Sweet K.; Grimmer L.; Johnson R.; Garland Z.; Gumbrill B.; Phillips C.; Ortiz-Ruiz de Gordoa L.; Peasgood E.; Tridente A.; Shuker K.; Greer S.; Lynch C.; Pothecary C.; Roche L.; Deacon B.; Turner K.; Singh J.; Howe G.S.; Paul P.; Gill M.; Wynter I.; Ratnam V.; Shelton S.; Naisbitt J.; Melville J.; Baruah R.; Morrison S.; McGregor A.; Parris V.; Mpelembue M.; Srikaran S.; Dennis C.; Sukha A.; Verlander M.; Holding K.; Riches K.; Downes C.; Swan C.; Rostron A.; Roy A.; Woods L.; Cornell S.; Wakinshaw F.; Creagh-Brown B.; Blackman H.; Salberg A.; Smith E.; Donlon S.; Mtuwa S.; Michalak-Glinska N.; Stone S.; Beazley C.; Pristopan V.; Nikitas N.; Lankester L.; Wells C.; Raj A.S.; Fletcher K.; Khade R.; Tsinaslanidis G.; MacMahon M.; Fowler S.; Coventry T.; Stewart R.; Wren L.; Mwaura E.; Mew L.; Scaletta D.; Williams F.; Inweregbu K.; Lancaster N.; Cunningham M.; Daniels A.; Harrison L.; Hope S.; Jones S.; Crew A.; Wray G.; Matthews J.; Crawley R.; Carter J.; Birkinshaw I.; Ingham J.; Scott Z.; Pearson H.; Howard K.; Joy R.; Roche S.; Clark M.; Purvis S.; Morrison A.; Strachan D.; Clements S.; Black K.; Parmar C.; Altabaibeh A.; Simpson K.; Mostoles L.; Gilbert K.; Ma L.; Alvaro A.; Thomas M.; Faulkner B.; Worner R.; Hayes K.; Gendall E.; Blakemore H.; Borislavova B.; Goff E.; Vuylsteke A.; Mwaura L.; Zamikula J.; Garner L.; Mitchell A.; Mepham S.; Cagova L.; Fofano A.; Holcombe H.; Praman K.; Szakmany T.; Heron A.E.; Cherian S.; Cutler S.; Roynon-Reed A.; Randell G.; Convery K.; Stammers K.; Fottrell-Gould D.; Hudig L.; Keshet-Price J.; Peters M.; O’Neill L.; Ray S.; Belfield H.; McHugh T.; Jones G.; Akinkugbe O.; Tomas A.; Abaleke E.; Beech E.; Meghari H.; Yussuf S.; Bamford A.; Hairsine B.; Dooks E.; Farquhar F.; Packham S.; Bates H.; Armstrong L.; Kaye C.; Allan A.; Medhora J.; Liew J.; Botello A.; Anderson F.; Cusack R.; Golding H.; Prager K.; Williams T.; Leggett S.; Golder K.; Male M.; Jones O.; Criste K.; Marani M.; Anumakonda V.; Amin V.; Karthik K.; Kausar R.; Anastasescu E.; Reid K.; Smith M.; Hormis A.; Walker R.; Duncan T.; Uriel A.; Ustianowski A.; T-Michael H.; Bruce M.; Connolly K.; Smith K.; Partridge R.; Griffin D.; Mupudzi M.; Muchenje N.; Martin D.; Filipe H.; Eastgate C.; Jackson C.; Gratrix A.; Foster L.; Martinson V.; Stones E.; Abernathy C.; Parkinson P.; Reed A.; Prendergast C.; Rogers P.; Woodruff M.; Shokkar R.; Kaul S.; Barron A.; Collins C.; Beavis S.; Whileman A.; Dale K.; Hawes J.; Pritchard K.; Gascoyne R.; Stevenson L.; Jha R.; Lim L.; Krishnamurthy V.; Parker R.; Turner-Bone I.; Wilding L.; Reddy A.; Whiteley S.; Wilby E.; Howcroft C.; Aspinwall A.; Charlton S.; Ogg B.; Menzies D.; Pugh R.; Allan E.; Lean R.; Davies F.; Easton J.; Qiu X.; Kumar S.; Darlington K.; Houston G.; O’Brien P.; Geary T.; Allan J.; Meikle A.; Hughes G.; Balasubramaniam M.; Latham S.; McKenna E.; Flanagan R.; Sathe S.; Davies E.; Chablani M.; Kirkby A.; Netherton K.; Archer S.; Yates B.; Ashbrook-Raby C.; Cole S.; Casey M.; Cabrelli L.; Chapman S.; Hutcheon A.; Whyte C.; Almaden-Boyle C.; Pattison N.; Cruz C.; Vochin A.; Kent H.; Thomas A.; Murdoch S.; David B.; Penacerrada M.; Lubimbi G.; Bastion V.; Wulandari R.; Lorusso R.; Valentine J.; Clarke D.; Serrano-Ruiz A.; Hierons S.; Eckbad C.; Ramos L.; Demetriou C.; Mitchard S.; White K.; White N.; Pitts S.; Branney D.; Frankham J.; Watters M.; Langton H.; Prout R.; Page V.; Varghes T.; Cowton A.; Kay A.; Potts K.; Birt M.; Kent M.; Wilkinson A.; Jude E.B.; Turner V.; Savill H.; McCormick J.; Coulding M.; Siddiqui S.; Mercer O.; Rehman H.; Potla D.; *Capps N.; *Donaldson D.; *Button H.; *Martin T.; *Hard K.; *Agasou A.; *Tonks L.; *Arden T.; *Boyle P.; *Carnahan M.; *Strickley J.; *Adams C.; *Childs D.; *Rikunenko R.; *Leigh M.; *Breekes M.; *Wilcox R.; *Bowes A.; *Tiveran H.; *Hurford F.; *Summers J.; *Carter A.; *Hussain Y.; *Ting L.; *Javaid A.; *Motherwell N.; *Moore H.; *Millward H.; *Jose S.; *Schunki N.; *Noakes A.; *Clulow C.; Sadera G.; Jacob R.; Jones C.; Blunt M.; Coton Z.; Curgenven H.; Ally S.M.; Beaumont K.; Elsaadany M.; Fernandes K.; Ali Mohamed Ali I.; Rangarajan H.; Sarathy V.; Selvanayagam S.; Vedage D.; White M.; Truman N.; Chukkambotla S.; Keith S.; Cockerill-Taylor J.; Ryan-Smith J.; Bolton R.; Springle P.; Dykes J.; Thomas J.; Khan M.; Hijazi M.T.; Massey E.; Croston G.; Reschreiter H.; Camsooksai J.; Patch S.; Jenkins S.; Humphrey C.; Wadams B.; Msiska M.; Adanini O.; Attwood B.; Parsons P.; Tatham K.; Jhanji S.; Black E.; Dela Rosa A.; Howle R.; Thomas B.; Bemand T.; Raobaikady R.; Saha R.; Staines N.; Daniel A.; Finn J.; Hutter J.; Doble P.; Shovelton C.; Pawley C.; Kannan T.; Hill M.; Combes E.; Monnery S.; Joefield T.; Popescu M.; Thankachen M.; Oblak M.; Little J.; McIvor S.; Brady A.; Whittle H.; Prady H.; Chan R.; Ahmed A.; Morris A.; Gibson C.; Gordon E.; Keenan S.; Quinn H.; Benyon S.; Marriott S.; Zitter L.; Park L.; Baines K.; Lyons M.; Holland M.; Keenan N.; Young M.; Garrioch S.; Dawson J.; Tolson M.; Scholefield B.; Bi R.; Richardson N.; Schumacher N.; Cosier T.; Millen G.; Higham A.; Turki S.; Allen L.; Crisp N.; Hazleton T.; Knight A.; Deery J.; Price C.; Turney S.; Tilbey S.; Beranova E.; Wright D.; George L.; Twiss S.; Wadd S.; Postlethwaite K.; Gondo P.; Masunda B.; Kayani A.; Hadebe B.; Whiteside J.; Clarke N.; Donnison P.; Trim F.; Leadbitter I.; Butcher D.; O’Sullivan S.; Purewal B.; Bell S.; Rivers V.; O’Leary R.; Birch J.; Collins E.; Anderson S.; Hammerton K.; Andrews E.; Burns K.; Edmond I.; Todd A.; Donnachie J.; Turner P.; Prentice L.; Symon L.; Runciman N.; Auld F.; Halkes M.; Mercer P.; Thornton L.; Debreceni G.; Wilkins J.; Crickmore V.; Subramanian G.; Marshall R.; Jennings C.; Latif M.; Bunni L.; Spivey M.; Bean S.; Burt K.; Linnett V.; Ritzema J.; Sanderson A.; McCormick W.; Bokhari M.; Kapoor R.; Loader D.; Ayers A.; Harrison W.; North J.; Belagodu Z.; Paramsothy R.; Olufuwa O.; Gherman A.; Fuller B.; Stuart C.; Kelsall O.; Davis C.; Wild L.; Wood H.; Thrush J.; Durie A.; Austin K.; Archer K.; Anderson P.; Vigurs C.; Thorpe C.; Knights E.; Boyle N.; Price A.; Kubisz-Pudelko A.; Wood D.; Lewis A.; Board S.; Pippard L.; Perry J.; Beesley K.; Rattray A.; Lee E.; Lennon L.; Douglas K.; Bell D.; Boyle R.; Glass L.; Nauman Akhtar M.; Dent K.; Potoczna D.; Pearson S.; Horsley E.; Spencer S.; Mullan D.; Skinner D.; Gaylard J.; Barber R.; Hewitt C.; Hilldrith A.; Shepardson S.; Wills M.; Jackson-Lawrence K.; Gupta A.; Timlick E.; Gorman C.; Otahal I.; Gales A.; Coetzee S.; Sell C.; Raj M.; Peiu M.; Quaid S.; Watson E.; Elliott K.; Mallinson J.; Chandler B.; Turnbull A.; Finch C.; Holl C.; Cooper J.; Evans A.; Khaliq W.; Collins A.; Gude E.T.; Love N.; van Koutrik L.; Hunt J.; Kaye D.; Fisher E.; Brayne A.; Tuckey V.; Jackson P.; Parkin J.; Tariq A.; Houlden H.; Tucci A.; Hardy J.; Moncur E.; Highgate J.; Cowley A.; Mitra A.; Stead R.; Behan T.; Burnett C.; Newton M.; Heeney E.; Pollard R.; Hatton J.; Patel A.; Kasipandian V.; Allibone S.; Genetu R.M.; O’Brien L.; Omar Z.; Perkins E.; Davies K.; Tetla D.; Shelley B.; Irvine V.; Williams S.; Williams P.; Goodsell J.; Tutton R.; Bough L.; Winter-Goodwin B.; Kitson R.; Pinnell J.; Wilson A.; Nortcliffe T.; Wood T.; Home M.; Holdroyd K.; Robinson M.; Shaw R.; Greig J.; Brady M.; Haigh A.; Matupe L.; Usher M.; Mellor S.; Dale S.; Gledhill L.; Shaw L.; Turner G.; Kelly D.; Anwar B.; Riley H.; Sturgeon H.; Ali A.; Thomis L.; Melia D.; Dance A.; Humphreys S.; Frost I.; Gopal V.; Godden J.; Holden A.; Swann S.; Smith T.; Clapham M.; Poultney U.; Harper R.; Rice P.; Reece-Anthony R.; Gurung B.; Moultrie S.; Odam M.; Mayer A.; Bellini A.; Pickard A.; Bryant J.; Roe N.; Sowter J.; Lang K.; Taylor J.; Barry P.; Hobrok M.; Tench H.; Wolf-Roberts R.; McGuinness H.; Loosley R.; Hawcutt D.; Rad L.; O’Malley L.; Saunderson P.; Seddon G.; Anderson T.; Rogers N.; Ruddy J.; Harkins M.; Beith C.; McAlpine A.; Ferguson L.; Grant P.; MacFadyen S.; McLaughlin M.; Baird T.; Rundell S.; Welsh B.; Hamill R.; Fisher F.; Gregory J.; Campbell A.; Smuts S.; Carson G.; Merson L.; Sigfrid L.; Alex B.; Bach B.; Barclay W.S.; Chand M.; Cooke G.S.; Sriskandan S.; Harrison E.M.; Norman L.; Pius R.; Drake T.M.; Fairfield C.J.; Knight S.R.; Mclean K.A.; Murphy D.; Shaw C.A.; Zambon M.; da Silva Filipe A.; Ho A.Y.W.; Palmarini M.; Robertson D.L.; Scott J.T.; Thomson E.C.; McDonald S.; Fletcher T.; Green C.A.; Hiscox J.A.; Ijaz S.; Khoo S.; Mentzer A.J.; Noursadeghi M.; Paxton W.A.; Pollakis G.; Price N.; Rambaut A.; Sancho-Shimizu V.; de Silva T.; Stuart D.; Tedder R.S.; Thompson A.A.R.; Donohue C.; Dalton J.; Girvan M.; Saviciute E.; Roberts S.; Harrison J.; Marsh L.; Connor M.; Halpin S.; Gamble C.; Leeming G.; Greenhalf W.; Shaw V.; Ganna A.; Cordioli M.; Niemi M.E.K.; Sulem P.; Sveinbjornsson G.; van Heel D.A.; Shelton J.F.; Shastri A.J.; Ye C.; Weldon C.H.; FilshteinSonmez T.; Coker D.; Symons A.; Aslibekyan S.; Auton A.; Esparza-Gordillo J.; Benetti E.; Furini S.; Montagnani F.; Emiliozzi A.; Fabbiani M.; Rossetti B.; Zanelli G.; Bargagli E.; Bergantini L.; D’Alessandro M.; Cameli P.; Bennet D.; Anedda F.; Marcantonio S.; Scolletta S.; Franchi F.; Mazzei M.A.; Guerrini S.; Conticini E.; Cantarini L.; Frediani B.; Tacconi D.; Spertilli C.; Feri M.; Donati A.; Scala R.; Guidelli L.; Spargi G.; Corridi M.; Nencioni C.; Croci L.; Caldarelli G.P.; Spagnesi M.; Piacentini P.; Bandini M.; Desanctis E.; Cappelli S.; Canaccini A.; Verzuri A.; Anemoli V.; Ognibene A.; Vaghi M.; D’Arminio Monforte A.; Merlini E.; Mondelli M.U.; Mantovani S.; Ludovisi S.; Girardis M.; Venturelli S.; Sita M.; Cossarizza A.; Antinori A.; Vergori A.; Rusconi S.; Riva A.; Siano M.; Gabrieli A.; Francisci D.; Schiaroli E.; Scotton P.G.; Andretta F.; Panese S.; Scaggiante R.; Gatti F.; Parisi S.G.; Castelli F.; Quiros-Roldan M.E.; Magro P.; Zanella I.; Della Monica M.; Piscopo C.; Capasso M.; Russo R.; Andolfo I.; Iolascon A.; Fiorentino G.; Carella M.; Castori M.; Merla G.; Aucella F.; Raggi P.; Marciano C.; Perna R.; Bassetti M.; Di Biagio A.; Sanguinetti M.; Masucci L.; Valente S.; Mandala M.; Giorli A.; Salerni L.; Zucchi P.; Parravicini P.; Menatti E.; Baratti S.; Trotta T.; Giannattasio F.; Coiro G.; Lena F.; Coviello D.A.; Mussini C.; Bosio G.; Martinelli E.; Mancarella S.; Tavecchia L.; Crotti L.; Picchiotti N.; Gori M.; Gabbi C.; Sanarico M.; Ceri S.; Pinoli P.; Raimondi F.; Biscarini F.; Stella A.

Citation:
Nature; Mar 2021; vol. 591 (no. 7848); p. 92-98

Abstract:
Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 x 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 x 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 x 10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 x 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

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Reduced vitamin D levels associated with increased COVID-19 related deaths (2021)

Type of publication:
Conference abstract

Author(s):
*Moudgil N.; *Oyegunle T.; *Makan A.; *Crawford E.; *Srinivasan K.S.; *Ahmad N.; *Dev D.; *Moudgil H

Citation:
American Journal of Respiratory and Critical Care Medicine; May 2021; vol. 203 (no. 9)

Abstract:
RATIONALE: Vitamin D supports immunity and inflammation by inhibiting proinflammatory cytokine release from macrophages and up-regulating the expression of anti-microbial peptides exhibiting anti-viral activity. Respiratory epithelial cells also convert inactive 25(OH)D (main circulating vitamin D) to 1,25(OH)2D3 enabling high local concentrations of this biologically active form to increase the expression of vitamin D-regulated genes. Studies continue to investigate the therapeutic effects and establish the optimal serum levels of 25(OH)D required to reduce the impact of respiratory tract infections whilst avoiding toxic hypercalcaemic high-dose ‘blind’ supplementation. Analysing patients admitted to hospital with COVID-19 (SARS-CoV-2 RNA) during the first phase of the pandemic, objectives and focus on reporting were to (1) document the population where measured vitamin D levels are readily available whilst quantifying those on supplements and (2) compare
outcome at discharge depending on most recent available vitamin D status. METHOD(S): Computer data including clinical outcomes were examined for the 516 patients (55% male) with mean age 67.4 (SD 18.3, range 0 to 100) years admitted from our semi-rural predominantly white European population to our District General Hospitals (Teaching) during the 4 months (March to June 2020) in the first phase of the COVID-19 illness in the UK. Outcomes (death during admission versus discharged alive) were analysed with SPSS comparing those with reduced versus adequate vitamin D levels. RESULT(S): Collectively (n=516), vitamin D levels (historical or updated) were available on 163 (31.5%) of patients; 17 (3.3%) undertaken during the admission. Data were skewed with median level 47 (interquartile range 24.1 to 66.9) nmol/L. 74 (14.3%) were already on vitamin D supplements and for an additional 10 (1.9%) this was initiated during the admission. Among the 163 patients, 86 (52.7%) had reduced vitamin D levels (deficient or insufficient) and these had worse outcomes with 29/86 (33.7%) having died during the admission compared with 13/74 (17.6%) of those with adequate levels: X2 (df 1, n=163) 6.02, p=.014. Table 1 categorises
distribution of values. CONCLUSION(S): Data highlight (1) less than a third of admitted COVID-19 patients have recorded vitamin D levels and of these more than half have reduced levels, (2) 14.3% are already taking vitamin D, (3) very few get
tested during the acute admission or get started on supplements, and (4) there is a statistical difference highlighting adverse outcome (death versus discharged alive) for those with reduced vitamin D levels.

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Appendicitis with concurrent COVID-19 infection in a patient during the third trimester of pregnancy (2021)

Type of publication:
Journal article

Author(s):
*Sanders-Davis L.J.; *Ritchie J.

Citation:
BMJ Case Reports; Jun 2021; vol. 14 (no. 6)

Abstract:
This article presents an unusual case of appendicitis in pregnancy complicated by the novel coronavirus (SARS-CoV-2). The novel coronavirus has affected the way medicine is practised across most parts of the world with over 160 000 000 global cases to date. Tackling management of these cases is more complex when other pathological processes are ongoing. Appendicitis is a common occurrence in pregnancy, with most obstetric centres seeing about one or two cases a year. Though maternal morbidity and mortality are relatively unimpacted by this event, fetal loss and preterm labour are common sequelae. This case involves a 35-year-old woman presenting in her third trimester with abdominal pain and who went on to be diagnosed with concurrent appendicitis and SARS-CoV-2 infection. Although spinal anaesthesia would be most appropriate as it avoids aerosol generation, general anaesthetic techniques were indicated due to thrombocytopenia in this case. She underwent a successful appendicectomy, although preterm delivery was indicated as a result of maternal and fetal concerns.

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Impact of COVID-19 pandemic on the 2WW breast referrals to a district general hospital (2021)

Type of publication:
Conference abstract

Author(s):
*Tokode O.; *Rastall S.; *Wilson M.

Citation:
European Journal of Surgical Oncology; May 2021; vol. 47 (no. 5)

Abstract:
Introduction: Recommendations were issued to the hospital Trusts to configure service delivery to balance cancer care with the safety of the patient and the hospital staff during the COVID-19 pandemic. The public felt the service restrictions might lead to delays in diagnosis and treatment of cancer patients. We compared the management of 2ww breast referrals in our centre between May to July 2019 and 2020. Method(s): We triaged all referrals to face-face consultation or initial telephone consultation during the pandemic. Patients with suspicious symptoms were offered face-face consultation after the telephone triage. Result(s): Overall, breast patients’ referrals fell by 28.3% during the pandemic. 10.2% reduction was noted in May (95% CI 6.73 – 13.59, p<0.001) but a non-significant increase was recorded in June and July. Waiting time reduced by 8.43 days (95% CI -8.88 to -7.98, p< 0.0001). Breast cancer suspicion increased across all age groups in 2020 (+10.4% to + 16.2%). Breast cancer diagnosis rose by 2.0% in 2020 (95% CI 0.19 – 3.92, p=0.030). No cancer was diagnosed among under 29 years. 29.1% of the 522 patients triaged to telephone consultation were discharged, and 70.9% needed face-to-face follow-up. One patient discharged after telephone consultation was later diagnosed with breast cancer. Conclusion(s): COVID-19 pandemic did not lead to a prolonged waiting time or reduced breast cancer diagnosis, but there was an overall reduction in referrals to our breast service.

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COVID-19 and the multidisciplinary care of patients with lung cancer: an evidence-based review and commentary (2021)

Type of publication:
Journal article

Author(s):
Round, Thomas; L’Esperance, Veline; Bayly, Joanne; Brain, Kate; Dallas, Lorraine; Edwards, John G; Haswell, Thomas; Hiley, Crispin; Lovell, Natasha; *McAdam, Julia; McCutchan, Grace; Nair, Arjun; Newsom-Davis, Thomas; Sage, Elizabeth K; Navani, Neal

Citation:
British Journal of Cancer; May 2021 [epub ahead of print]

Abstract:
Delivering lung cancer care during the COVID-19 pandemic has posed significant and ongoing challenges. There is a lack of published COVID-19 and lung cancer evidence-based reviews, including for the whole patient pathway. We searched for COVID-19 and lung cancer publications and brought together a multidisciplinary group of stakeholders to review and comment on the evidence and challenges. A rapid review of the literature was undertaken up to 28 October 2020, producing 144 papers, with 113 full texts screened. We focused on new primary data collection (qualitative or quantitative evidence) and excluded case reports, editorials and commentaries. Following exclusions, 15 published papers were included in the review and are summarised. They included one qualitative paper and 14 quantitative studies (surveys or cohort studies), with a total of 2295 lung cancer patients data included (mean study size 153 patients; range 7-803). Review of current evidence and commentary included awareness and help-seeking; lung cancer screening; primary care assessment and referral; diagnosis and treatment in secondary care, including oncology and surgery; patient experience and palliative care. Cross-cutting themes and challenges were identified using qualitative methods for patients, healthcare professionals and service delivery, with a clear need for continued studies to guide evidence-based decision-making.

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Anti-SARS-CoV-2 antibody responses are attenuated in patients with IBD treated with infliximab (2021)

Type of publication:
Journal article

Author(s):
Kennedy N.A.; Goodhand J.R.; Chee D.; Lin S.; Chanchlani N.; Ahmad T.; Bewshea C.; Nice R.; McDonald T.J.; *Butterworth J.; Cooney R.; Croft N.M.; Kok K.B.; Hart A.L.; Irving P.M.; Lamb C.A.; Limdi J.K.; Macdonald J.; McGovern D.P.; Mehta S.J.; Murray C.D.; Patel K.V.; Pollok R.C.; Raine T.; Russell R.K.; Selinger C.P.; Smith P.J.; Bowden J.; Lees C.W.; Sebastian S.; Powell N.

Collaborators at Shrewsbury and Telford Hospital NHS Trust: *Jeff Butterworth, *Colene Adams, *Elizabeth Buckingham, *Danielle Childs, *Alison Magness, *Jo Stickley.

Citation:
Gut; May 2021; vol. 70 (no. 5); p. 865-875

Abstract:
OBJECTIVE: Antitumour necrosis factor (anti-TNF) drugs impair protective immunity following pneumococcal, influenza and viral hepatitis vaccination and increase the risk of serious respiratory infections. We sought to determine whether infliximab-treated patients with IBD have attenuated serological responses to SARS-CoV-2 infections. DESIGN: Antibody responses in participants treated with infliximab were compared with a reference cohort treated with vedolizumab, a gut-selective anti-integrin alpha4beta7 monoclonal antibody that is not associated with impaired vaccine responses or increased susceptibility to systemic infections. 6935 patients were recruited from 92 UK hospitals between 22 September and 23 December 2020. RESULT(S): Rates of symptomatic and proven SARS-CoV-2 infection were similar between groups. Seroprevalence was lower in infliximab-treated than vedolizumab-treated patients (3.4% (161/4685) vs 6.0% (134/2250), p<0.0001). Multivariable logistic regression analyses confirmed that infliximab (vs vedolizumab; OR 0.66 (95% CI 0.51 to 0.87), p=0.0027) and immunomodulator use (OR 0.70 (95% CI 0.53 to 0.92), p=0.012) were independently associated with lower seropositivity. In patients with confirmed SARS-CoV-2 infection, seroconversion was observed in fewer infliximab-treated than vedolizumab-treated patients (48% (39/81) vs 83% (30/36), p=0.00044) and the magnitude of anti-SARS-CoV-2 reactivity was lower (median 0.8 cut-off index (0.2-5.6) vs 37.0 (15.2-76.1), p<0.0001). CONCLUSION(S): Infliximab is associated with attenuated serological responses to SARS-CoV-2 that were further blunted by immunomodulators used as concomitant therapy. Impaired serological responses to SARS-CoV-2 infection might have important implications for global public health policy and individual anti-TNF-treated patients. Serological testing and virus surveillance should be considered to detect suboptimal vaccine responses, persistent infection and viral evolution to inform public health policy. TRIAL REGISTRATION NUMBER: ISRCTN45176516.

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Continuous positive airway pressure (CPAP) as a ceiling of care treatment for hypoxemic respiratory failure due to COVID-19 (2021)

Type of publication:
Journal article

Author(s):
Patrick Bradley , *Jennifer Nixon , James Wilson , James Redfern , Tarek Saba , Emily Nuttall, Thomas Bongers

Citation:
Journal of the Intensive Care Society 2021, Vol. 0(0), 1–3 [epub ahead of print]

Abstract:
Among patients admitted to hospital with COVID-19 in the UK, 10% develop severe hypoxemic respiratory failure managed with invasive mechanical ventilation (IMV). Much interest has focused on non-invasive strategies to avert progression to IMV. UK guidelines recommend the use of continuous positive airway pressure (CPAP), including in patients for whom IMV is not appropriate. However, other nations have recommended against the use of CPAP, and within the UK, CPAP use has varied widely (personal communication). The greatest burden of COVID-19 disease is carried by older patients with comorbidities, many of whom are deemed unsuitable for IMV and critical care. However, it is unclear whether they might benefit from CPAP. The RECOVERY-RS trial is investigating the efficacy of CPAP and high-flow nasal oxygen (HFNO) in severely hypoxic patients with COVID-19, but will not complete until late 2021, and excludes patients unsuitable for IMV. Current evidence is limited to cohort studies of heterogeneous patient groups, with no published data focussing on patients for whom CPAP is the ceiling-of-care. Physicians caring for such patients, and those involved in planning the delivery of CPAP services, must balance any potential benefits of CPAP against its burden on patients, families, staff, and services. Therefore data in this patient population are urgently needed.

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Regional experiences of endotracheal intubation during the COVID-19 pandemic in The United Kingdom (2020)

Type of publication:
Conference abstract

Author(s):
Shuker B.; Smith E.; *Checketts P.; Khan Q.

Citation:
Intensive Care Medicine Experimental; 2020; vol. 8

Abstract:
Introduction: In the United Kingdom (UK), consensus guidelines for airway management were published early in the COVID-19 pandemic making recommendations to support clinicians during this potentially challenging intervention (1). Adaptions to existing guidance for airway management in critically ill adults from the Difficult Airway Society (2) included: use of personal protective equipment (PPE), preferential use of the best skilled airway manager to maximise chance of first-pass success, avoidance of aerosol-generating procedures (such as noninvasive ventilation, high flow nasal oxygenation), and use of reliable well practiced techniques (including videolaryngoscopy where appropriate). Objective(s): Areas of the West Midlands were some of the worst affected by the COVID-19 pandemic in the UK (3). We aimed to gain insight into the experiences of clinicians involved with airway management during the COVID-19 pandemic in this region. Method(s): An online survey was distributed to multiple centres within the West Midlands region of the UK. Clinicians who had experience of endotracheal intubation in patients with confirmed, suspected, or unknown COVID-19 status were asked to reflect upon their experience of one patient intubation. Result(s): 127 clinicians from 16 hospitals including 3 large university hospitals responded to the online survey, most were consultant grade (56.7%). Clinicians self-reported an average approximate number of pandemic intubations of 7.35 (range 1-30). When asked to reflect on a single intubation, clinicians reflected on intubations in ICU (42.5%), emergency departments (20.5%), wards (8.7%), and theatre (28.3%). Appropriate PPE was available in 96.1%. The most senior clinician available intubated in 65.4%. Clinicians reported first pass success in 93.7% of responses. Most intubators reported use of videolaryngoscopy (74.8%), however 26% reported not using this equipment regularly and 5.5% did not feel confident with their equipment. Despite a high success rate, difficulties were reported in 15.1%. The most common was desaturation. Other common difficulties included equipment or environment unfamiliarity, lack of skilled support. When asked what advice they would give to colleagues, frequently occurring themes included: ensuring familiarity with equipment, use of a checklist, use of videolaryngoscopy, and availability of a second intubator. Desire for simulation and equipment familiarisation was highlighted in multiple responses, and in one example a clinician attributed their success to a simulation session performed in the week prior. Conclusion(s): Experiences from clinicians in this region highlight the specific challenges encountered involved in airway management of patients with COVID-19, in particular highlighting the importance of advance preparation for intubation when faced with unfamiliar circumstances. Simulation sessions, use of checklists and standard operating procedures for emergency intubation may contribute to maintaining preparedness for intubation in this challenging patient group.

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Intensive care unit (ICU) referrals and admissions at a district general hospital (DGH) in light of the COVID-19 pandemic (2020)

Type of publication:
Conference abstract

Author(s):
*Blair J.; *Naughton E.; *Pradhan N.

Citation:
Intensive Care Medicine Experimental; 2020; vol. 8

Abstract:
Introduction: The COVID-19 pandemic has led to an increase in ICU referrals and admissions across the UK during 2020 [1]. Intensive care beds are a limited and expensive resource and decisions on patient admission are often very challenging [2]. Proformas help to standardise documentation and decision logging during patient referrals [3]. They provide easily accessible evidence in case of a future referral and allow audit of decision-making processes. A preliminary survey of doctors working in a DGH ICU was undertaken to assess the current referral and admission process in expectation of an increased volume of work.
Objective(s): As a result of the survey, three main areas for improvement were identified: 1. To maintain a record of all ICU referrals and decision-making processes 2. To reduce the time taken for documentation of referrals and admissions 3. To improve the quality and appropriateness of referrals from parent specialities Methods: A proforma was designed for dual use as a referral and admission document. All referrals were recorded on paper and staff received training on how to apply the proforma. After assessment of each referral, irrespective of admission outcome, a completed copy of the proforma was placed in both the patient’s notes and a dedicated referrals folder. After one month, a further survey was designed to assess the response postimplementation of the proforma. All referrals made over a threemonth period between April and June 2020 were audited.
Result(s): The initial survey received 12 responses. Prior to the COVID-19 pandemic, documentation of any referral or admission took on average 10-15 minutes. All survey participants felt that referring teams did not have a good understanding of the role of ICU care and estimated that up to 40% of all referrals received were inappropriate. The follow-up survey received 14 responses. Implementation of the proforma reduced the time taken to document a referral or admission on average by 5-10 minutes. Twelve participants found the proforma a useful aid, helping to provide clear documentation and ease communication between ICU team members. Less than 9% of the referrals made between April and June 2020 were admitted to ICU with over 32% of referrals deemed unsuitable for further escalation. Approximately 50% of referrals were made by registrars, with 13% discussed by consultants. The median age of patients referred was 67.5 and the most common reason was for respiratory deterioration.
Conclusion(s): This quality improvement project successfully reduced the time taken to document ICU referrals and admissions. Use of a proforma has provided many benefits, including standardisation of documentation, decision logging and improvement of intra-and inter-team communication. Only a small proportion of patients referred to ICU have been suitable for admission. A teaching session is being designed so that referral information can be fed-back to parent specialties. Referrals will be reaudited after this. Data analysis of this project has been limited by incomplete proforma documentation from participating users.

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A Tidal volume calculator to improve lung protective ventilation in COVID-19 related Acute Respiratory Distress Syndrome (ARDS) (2020)

Type of publication:
Conference abstract

Author(s):
*Blair J.; *Hester S.; Baldwin A.; Ali T.

Citation:
Intensive Care Medicine Experimental; 2020; vol. 8

Abstract:
Introduction: Routine use of lower tidal volumes (TVs) for the mechanical ventilation of patients with ARDS results in decreased mortality and increases the number of days without ventilator use [1]. Severe COVID-19 pneumonia has been associated with the development of ARDS as characterised by the Berlin definition [2]. A multi-centre preliminary audit was undertaken to identify whether ventilated COVID-19 related ARDS patients were receiving optimal TVs, as recommended by the Faculty of Intensive Care Medicine (FICM) and Intensive Care Society (ICS) ARDS management guidelines [3]. Objective(s): As a result of the audit, three main areas for improvement were identified. 1. To achieve accurate calculations for ideal body weight (IBW) and target TV 2. To improve documentation of IBW and target TV 3. To achieve TVs no greater than 6 ml/kg Methods: A ‘tidal volume calculator’ tool was developed using Microsoft Excel, which was simple, colour coded and kept on all Intensive Care Unit (ICU) computer desktops. This tool was designed to use height to calculate IBW and, if the patient’s height was unavailable, could also be utilised to calculate height from ulna length. IBW was subsequently used to calculate a target TV. Staff received training on how to apply the tool. Two snapshot audits were carried out in April and May 2020 at two ICUs. The first was conducted prior to the tool’s introduction with the second two weeks after its implementation. All patients receiving mechanical ventilation, except those spontaneously breathing, were included. Data was extracted from patient notes, charts and ventilator settings. Result(s): The initial audit included 14 patients. Six patients did not have an IBW documented. Three patients had documented IBWs that were 12 kg, 15 kg and 23 kg greater than the weight calculated using the tool, leading to increased tidal volume targets. Only three patients were achieving TVs of 4-6 ml/kg. Eleven patients were achieving a TV greater than 6 ml/kg, with two of these achieving a TV of greater than 8 ml/kg. The follow-up audit included ten patients. This revealed that all patients had an IBW clearly documented. Moreover, nine patients were achieving TVs within 4-6 ml/kg, with only one patient found to be achieving a TV greater than 6 ml/kg. Conclusion(s): This audit cycle revealed that initially adherence to lung protective ventilation and documentation of IBW was poor. In some instances, documented IBW was vastly different to the calculated IBW, suggesting that in these situations actual body weight may have been used. In a time when clinicians were being redeployed to support ICU, this simple tool was shown to support staff by clearly calculating and displaying IBW and target TV for reference. This directly led to improved adherence to lung protective ventilation and optimisation of patient care. Limitations include that no consideration was made for overall patient outcome, and only a snapshot of achieved TVs from ventilators were recorded; daily/weekly trends were not studied.

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