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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A rare case of anti-NMDA receptor encephalitis associated with an ovarian teratoma (2021)

Type of publication:
Conference abstract

Author(s):
*Korrapati S.; *Sahu B.; *Parry-Smith W.

Citation:
BJOG: An International Journal of Obstetrics and Gynaecology; May 2021; vol. 128 ; p. 135

Abstract:
Introduction Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is an auto-immune and paraneoplastic encephalitis with an incidence of 1.5 per million population per year. About 80% are women and nearly half of them have an ovarian teratoma. It is associated with antibodies against NR1 or NR2 subunits of NMDA receptor in cerebrospinal fluid (CSF) and serum. Given the rarity of occurrence, it remains an unrecognised entity among gynaecologists. Hence, we report a case of anti-NMDAR encephalitis associated with ovarian teratoma. Case report A 34-year-old woman attended under physicians with confusion, memory loss and agitation. She had a history of bilateral ovarian teratomas removed in 2018. Patient’s vitals and neurological examination were normal. She was unable to perform motor tasks. Routine laboratory examinations and CT head were normal except for mild leucocytosis (WCC 13.3). She was empirically treated for infectious encephalitis. CSF examination showed normal glucose and protein, negative for viral PCR, gram staining but positive for NMDA receptor antibodies, prompting us to explore for an underlying tumour. CT abdomen/pelvis showed 9mm focus of fat suspicious of residual/recurrent teratoma in right adnexa. PET CT showed no metabolically active pathology. She was commenced on first line immunotherapy, IV Methylprednisolone followed by IV immunoglobulins and then plasma exchange. Following gynaecology MDT decision, she underwent laparoscopic right oophorectomy. Histopathology revealed a right ovarian teratoma. Postprocedure her neurological symptoms including confusion & memory retention improved considerably. Conclusion Anti-NMDAR encephalitis is rare but potentially debilitating condition. It is important to remove any associated ovarian teratoma promptly to improve outcome.

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A case of antepartum haemorrhage at 18 weeks gestation leading to DIC (2021)

Type of publication:
Journal article

Author(s):
*Barker V.; *Biswas N.; Brett-Miller C.

Citation:
BJOG: An International Journal of Obstetrics and Gynaecology; Jun 2021; vol. 128 ; p. 77

Abstract:
Objective A rare case of vaginal bleeding before 20 weeks’ gestation with a 1.2 L blood loss leading to
Disseminated Intravascular Coagulation. Follow up of the case at 25 weeks gestation revealed an ongoing pregnancy with resolution of clotting function. Case report A 33 year old patient who had previously had six normal vaginal deliveries attended labour ward at 18 + 6 weeks gestation with pain, a sensation of pressure and a small amount of brown PV loss. She previously had a small bleed at 15 weeks’ gestation when a subchorionic bleed was demonstrated on scan. Thirty minutes after arrival she started to bleed very heavily and within forty minutes had lost more than 1 litre of fresh blood. On examination she had a closed cervix with active ongoing bleeding. A bedside ultrasound scan revealed a viable pregnancy. Tranexamic acid 1 g was given intravenously. Clotting function on admission was markedly deranged; INR 2.4, prothrombin time 23.5, activated partial thromboplastin time 56, fibrinogen < 0.3 and D-Dimer 2157. Disseminated intravascular coagulation was diagnosed. Following discussion with the haematology consultant, she received two units of cryoprecipitate. The bleeding subsequently settled with total loss of 1.2 litres. She had further blood tests which showed normalisation of clotting function within 24 h. Departmental ultrasound scan showed no evidence of bleeding on scan but placenta was noted to extend to the cervix. Follow up at 25 weeks showed an ongoing pregnancy with no further bleeding. Discussion Disseminated Intravascular Coagulation is a rare complication of pregnancy and can be associated with a number of obstetric disorders including placental abruption and praevia, amniotic fluid embolism, intrauterine fetal demise, HELLP syndrome, preeclampsia/eclampsia, septic abortion, intrauterine infection, PPH and acute fatty liver of pregnancy. It can occur at any time in pregnancy but most commonly occurs in the 3rd trimester. DIC can be diagnosed using the International Society on Thrombosis and Haemostasis DIC Diagnostic Criteria. The classic picture is a prolonged prothrombin time and activated partial thromboplastin time, low platelets, low fibrinogen and elevated D-dimer test. Management involves addressing the obstetric cause and supportive therapy. Conclusion DIC occurs secondary to a trigger which stimulates the release of procoagulant substances resulting in activation of the clotting pathway. The hypercoagulable state in pregnancy increases the vulnerability of pregnant women. This is a rare case of rapid onset DIC in the second trimester with an ongoing pregnancy.

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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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FUSIC HD. Comprehensive haemodynamic assessment with ultrasound (2021)

Type of publication:
Journal article

Author(s):
*Miller A.; Peck M.; Clark T.; Conway H.; Olusanya S.; Fletcher N.; Aron J.; Coleman N.; Parulekar P.; Kirk-Bayley J.; Wilkinson J.N.; Wong A.; Stephens J.; Rubino A.; Attwood B.; Walden A.; Breen A.; Waraich M.; Nix C.; Hayward S.

Citation:
Journal of the Intensive Care Society; 2021 [epub ahead of print]

Abstract:
FUSIC haemodynamics (HD) – the latest Focused Ultrasound in Intensive Care (FUSIC) module created by the
Intensive Care Society (ICS) – describes a complete haemodynamic assessment with ultrasound based on ten
key clinical questions: 1. Is stroke volume abnormal? 2. Is stroke volume responsive to fluid, vasopressors or
inotropes? 3. Is the aorta abnormal? 4. Is the aortic valve, mitral valve or tricuspid valve severely abnormal? 5. Is there systolic anterior motion of the mitral valve? 6. Is there a regional wall motion abnormality? 7. Are there
features of raised left atrial pressure? 8. Are there features of right ventricular impairment or raised pulmonary
artery pressure? 9. Are there features of tamponade? 10. Is there venous congestion? FUSIC HD is the first
system of its kind to interrogate major cardiac, arterial and venous structures to direct time-critical
interventions in acutely unwell patients. This article explains the rationale for this accreditation, outlines the
training pathway and summarises the ten clinical questions. Further details are included in an online
supplementary appendix.

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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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Efficacy of Reduced-Intensity Chemotherapy With Oxaliplatin and Capecitabine on Quality of Life and Cancer Control Among Older and Frail Patients With Advanced Gastroesophageal Cancer: The GO2 Phase 3 Randomized Clinical Trial (2021)

Type of publication:
Randomised controlled trial

Author(s):
Hall, Peter S; Swinson, Daniel; Cairns, David A; Waters, Justin S; Petty, Russell; Allmark, Christine; Ruddock, Sharon; Falk, Stephen; Wadsley, Jonathan; Roy, Rajarshi; Tillett, Tania; Nicoll, Jonathan; Cummins, Sebastian; Mano, Joseph; Grumett, Simon; Stokes, Zuzana; Konstantinos-Velios, Kamposioras; *Chatterjee, Anirban; Garcia, Angel; Waddell, Tom; Guptal, Kamalnayan; Maisey, Nick; Khan, Mohammed; Dent, Jo; Lord, Simon; Crossley, Ann; Katona, Eszter; Marshall, Helen; Grabsch, Heike I; Velikova, Galina; Ow, Pei Loo; Handforth, Catherine; Howard, Helen; Seymour, Matthew T; GO2 Trial Investigators

Citation:
JAMA oncology; May 2021; 7(6):869-877

Abstract:
Importance Older and/or frail patients are underrepresented in landmark cancer trials. Tailored research is needed to address this evidence gap. ObjectiveThe GO2 randomized clinical trial sought to optimize chemotherapy dosing in older and/or frail patients with advanced gastroesophageal cancer, and explored baseline geriatric assessment (GA) as a tool for treatment decision-making.Design, Setting, and Participants This multicenter, noninferiority, open-label randomized trial took place at oncology clinics in the United Kingdom with nurse-led geriatric health assessment. Patients were recruited for whom full-dose combination chemotherapy was considered unsuitable because of advanced age and/or frailty.InterventionsThere were 2 randomizations that were performed: CHEMO-INTENSITY compared oxaliplatin/capecitabine at Level A (oxaliplatin 130 mg/m2 on day 1, capecitabine 625 mg/m2 twice daily on days 1-21, on a 21-day cycle), Level B (doses 0.8 times A), or Level C (doses 0.6 times A). Alternatively, if the patient and clinician agreed the indication for chemotherapy was uncertain, the patient could instead enter CHEMO-BSC, comparing Level C vs best supportive care.Main Outcomes and MeasuresFirst, broad noninferiority of the lower doses vs reference (Level A) was assessed using a permissive boundary of 34 days reduction in progression-free survival (PFS) (hazard ratio, HR = 1.34), selected as acceptable by a forum of patients and clinicians. Then, the patient experience was compared using Overall Treatment Utility (OTU), which combines efficacy, toxic effects, quality of life, and patient value/acceptability. For CHEMO-BSC, the main outcome measure was overall survival. Results A total of 514 patients entered CHEMO-INTENSITY, of whom 385 (75%) were men and 299 (58%) were severely frail, with median age 76 years. Noninferior PFS was confirmed for Levels B vs A (HR = 1.09 [95% CI, 0.89-1.32]) and C vs A (HR = 1.10 [95% CI, 0.90-1.33]). Level C produced less toxic effects and better OTU than A or B. No subgroup benefited from higher doses: Level C produced better OTU even in younger or less frail patients. A total of 45 patients entered the CHEMO-BSC randomization: overall survival was nonsignificantly longer with chemotherapy: median 6.1 vs 3.0 months (HR = 0.69 [95% CI, 0.32-1.48], P = .34). In multivariate analysis in 522 patients with all variables available, baseline frailty, quality of life, and neutrophil to lymphocyte ratio were independently associated with OTU, and can be combined in a model to estimate the probability of different outcomes. Conclusions and Relevance This phase 3 randomized clinical trial found that reduced-intensity chemotherapy provided a better patient experience without significantly compromising cancer control and should be considered for older and/or frail patients. Baseline geriatric assessment can help predict the utility of chemotherapy but did not identify a group benefiting from higher-dose treatment. Trial Registrationisrctn.org Identifier: ISRCTN44687907.

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Randomised controlled trial of antibiotic/ hydroxychloroquine combination versus standard budesonide in active Crohn’s disease (Apricot) (2021)

Type of publication:
Conference abstract

Author(s):
Rhodes J.; Subramanian S.; Martin K.; Probert C.; Flanagan P.; Horgan G.; Mansfield J.; Parkes M.; Hart A.; Dallal H.; Iqbal T.; *Butterworth J.; Culshaw K.

Citation:
Gut; Jan 2021; vol. 70

Abstract:
Introduction Mucosal E. coli are increased in Crohn’s disease (CD). They replicate within macrophages and are then inaccessible to penicillins and gentamicin. Hydroxychloroquine is used with doxycycline to treat Whipple’s disease. It raises macrophage intra-vesicular pH and inhibits replication of bacteria that require acidic pH. Ciprofloxacin and doxycycline are also effective against E. coli within macrophages. Methods Adult patients with active CD (CDAI>220 plus CRP>=5 mg/l and/or faecal calprotectin >250 ugram/g) were randomised to receive (open label) either oral budesonide (Entocort CR 9 mg/day 8 weeks, then 6 mg/day 2 weeks and 3 mg/day 2 weeks) or antibiotics/hydroxychloroquine (AB/ HCQ) – oral ciprofloxacin 500 mg bd, doxycycline 100 mg bd, hydroxychloroquine 200 mgs tds for 4 weeks, followed by doxycycline 100 mg bd and hydroxychloroquine 200 mgs tds for 20 weeks. Use of anti-TNF in the previous 3 months was an exclusion. Primary endpoints were remission (CDAI

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