Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity (2022)

Type of publication:
Journal article

Author(s):
Fallerini C.; Picchiotti N.; Baldassarri M.; Zguro K.; Daga S.; Fava F.; Benetti E.; Amitrano S.; Bruttini M.; Palmieri M.; Croci S.; Lista M.; Beligni G.; Valentino F.; Meloni I.; Tanfoni M.; Minnai F.; Colombo F.; Cabri E.; Fratelli M.; Gabbi C.; Mantovani S.; Frullanti E.; Gori M.; Crawley F.P.; Butler-Laporte G.; Richards B.; Zeberg H.; Lipcsey M.; Hultstrom M.; Ludwig K.U.; Schulte E.C.; Pairo-Castineira E.; Baillie J.K.; Schmidt A.; Frithiof R.; Mari F.; Renieri A.; Furini S.; Montagnani F.; Tumbarello M.; Rancan I.; Fabbiani M.; Rossetti B.; Bergantini L.; D'Alessandro M.; Cameli P.; Bennett D.; Anedda F.; Marcantonio S.; Scolletta S.; Franchi F.; Mazzei M.A.; Guerrini S.; Conticini E.; Cantarini L.; Frediani B.; Tacconi D.; Raffaelli C.S.; Feri M.; Donati A.; Scala R.; Guidelli L.; Spargi G.; Corridi M.; Nencioni C.; Croci L.; Caldarelli G.P.; Spagnesi M.; Romani D.; Piacentini P.; Bandini M.; Desanctis E.; Cappelli S.; Canaccini A.; Verzuri A.; Anemoli V.; Pisani M.; Ognibene A.; Pancrazzi A.; Lorubbio M.; Vaghi M.; Monforte A.D.; Miraglia F.G.; Mondelli M.U.; Girardis M.; Venturelli S.; Busani S.; Cossarizza A.; Antinori A.; Vergori A.; Emiliozzi A.; Rusconi S.; Siano M.; Gabrieli A.; Riva A.; Francisci D.; Schiaroli E.; Paciosi F.; Tommasi A.; Scotton P.G.; Andretta F.; Panese S.; Baratti S.; Scaggiante R.; Gatti F.; Parisi S.G.; Castelli F.; Quiros-Roldan E.; Antoni M.D.; Zanella I.; Monica M.D.; Piscopo C.; Capasso M.; Russo R.; Andolfo I.; Iolascon A.; Fiorentino G.; Carella M.; Castori M.; Aucella F.; Raggi P.; Perna R.; Bassetti M.; Biagio A.D.; Sanguinetti M.; Masucci L.; Guarnaccia A.; Valente S.; Vivo O.D.; Doddato G.; Tita R.; Giliberti A.; Mencarelli M.A.; Rizzo C.L.; Pinto A.M.; Perticaroli V.; Ariani F.; Carriero M.L.; Sarno L.D.; Alaverdian D.; Bargagli E.; Mandala M.; Giorli A.; Salerni L.; Zucchi P.; Parravicini P.; Menatti E.; Trotta T.; Giannattasio F.; Coiro G.; Lena F.; Lacerenza L.G.; Coviello D.A.; Mussini C.; Martinelli E.; Mancarella S.; Tavecchia L.; Belli M.A.; Crotti L.; Parati G.; Sanarico M.; Raimondi F.; Biscarini F.; Stella A.; Rizzi M.; Maggiolo F.; Ripamonti D.; Suardi C.; Bachetti T.; Rovere M.T.L.; Sarzi-Braga S.; Bussotti M.; Capitani K.; Dei S.; Ravaglia S.; Artuso R.; Andreucci E.; Gori G.; Pagliazzi A.; Fiorentini E.; Perrella A.; Bianchi F.; Bergomi P.; Catena E.; Colombo R.; Luchi S.; Morelli G.; Petrocelli P.; Iacopini S.; Modica S.; Baroni S.; Segala F.V.; Menichetti F.; Falcone M.; Tiseo G.; Barbieri C.; Matucci T.; Grassi D.; Ferri C.; Marinangeli F.; Brancati F.; Vincenti A.; Borgo V.; Stefania L.; Lenzi M.; Pietro M.A.D.; Vichi F.; Romanin B.; Attala L.; Costa C.; Gabbuti A.; Roberto M.; Zuccon U.; Vietri L.; Ceri S.; Pinoli P.; Casprini P.; Merla G.; Squeo G.M.; Maffezzoni M.; Bruno R.; Vecchia M.; Colaneri M.; Ludovisi S.; Marincevic-Zuniga Y.; Nordlund J.; Luther T.; Larsson A.; Hanslin K.; Gradin A.; Galien S.; Anderberg S.B.; Rosen J.; Rubertsson S.; Clohisey S.; Horby P.; Millar J.; Knight J.; Montgomery H.; Maslove D.; Ling L.; Nichol A.; Walsh T.; Hinds C.; Semple M.G.; Openshaw P.J.M.; Ho A.; McAuley D.; Ponting C.; Rowan K.; Griffiths F.; Oosthuyzen W.; Meikle J.; Finernan P.; Furniss J.; Mcmaster E.; Law A.; Paterson T.; Wackett T.; Armstrong R.; Murphy L.; Fawkes A.; Coutts A.; Donnelly L.; Gilchrist T.; Hafezi K.; Macgillivray L.; Maclean A.; McCafferty S.; Morrice K.; Weaver J.; Boz C.; Golightly A.; Ward M.; Mal H.; Szoor-McElhinney H.; Hendry R.; Stenhouse A.; Cullum L.; Law D.; Law S.; Law R.; Swets M.; Day N.; Taneski F.; Duncan E.; Zechner M.; Parkinson N.; Klaric L.; Bretherick A.D.; Rawlik K.; Pasko D.; Walker S.; Fourman M.H.; Russell C.D.; Richmond A.; Gountouna E.; Harrison D.; Wang B.; Wu Y.; Meynert A.; Kousathanas A.; Moutsianas L.; Yang Z.; Zhai R.; Zheng C.; Grimes G.; Shih B.; Yang J.; Shen X.; Ponting C.P.; Tenesa A.; Vitart V.; Wilson J.F.; Wood S.; Zak A.; Borra C.; Matharu M.; May P.; Alldis Z.; Mitchelmore O.; Bowles R.; Easthorpe A.; Bibi F.; Lancoma-Malcolm I.; Gurasashvili J.; Pheby J.; Shiel J.; Bolton M.; Patel 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.; Shankar-Hari M.; 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.; Fernandez Roman J.; Lopez Martinez M.; Johnson E.; Waite A.; Johnson B.; Hamilton O.; Mulla S.; McPhail M.; Smith J.; Barclay L.; Hope D.; McCulloch C.; McQuillan L.; Clark S.; Singleton J.; Priestley K.; Rea N.; Callaghan M.; Andrew G.; Marshall L.; McKechnie S.; Hutton P.; Bashyal A.; Davidson N.; Summers C.; 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.; Hussain I.; Thompson C.; Parker H.; Bradley R.; Griffiths R.; Gill J.; Puxty A.; Cathcart S.; 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.; 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.; Warren D.; Bromley M.; Sellick K.; Gurr L.; Wilkinson B.; Nagarajan V.; Szedlak P.; Cupitt J.; Stoddard E.; Benham L.; Preston 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.; Brantwood C.; Alexander P.; Bradley-Potts J.; Allen S.; Felton T.; Manna S.; Farnell-Ward S.; Leaver S.; Queiroz J.; Maccacari E.; Dawson D.; Castro Delgado C.; Pepermans Saluzzio R.; 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.; Clark R.; Smit 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.; 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.; Wraith 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.; Sloan B.; Buckley S.; Brooke H.; Smithson E.; Charlesworth R.; Sandu R.; Thirumaran M.; Wagstaff V.; Cebrian Suarez J.; Kaliappan A.; Vertue M.; Riches J.; Solesbury A.; Kittridge L.; Forsey M.; Maloney G.; Cole J.; Davies M.; Davies R.; Hill H.; Thomas E.; 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.; Mills G.; Willson J.; Harrington K.; Lenagh B.; Cawthron K.; Masuko S.; Raithatha A.; Bauchmuller K.; Ahmad N.; Barker J.; Jackson Y.; Kibutu F.; Bird S.; Watson G.; Martin J.; Bevan E.; Wrey Brown C.; Trodd D.; English K.; Bell G.; Wilcox L.; Katary A.; Gopal S.; Lake V.; Harris N.; Metherell S.; Radford E.; Scriven J.; 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.; Haque R.; Clamp S.; Kumar R.; Purewal M.; Baines B.; Frise M.; Jacques N.; Coles H.; Caterson J.; Gurung Rai S.; Brunton M.; Tilney E.; Keating L.; Walden A.; Antcliffe D.; Gordon A.; Templeton M.; Rojo R.; Banach D.; Sousa Arias S.; Fernandez Z.; Coghlan P.; Williams D.; Jardine C.; Bewley J.; Sweet K.; Grimmer L.; Johnson R.; Garland Z.; Gumbrill B.; Ortiz-Ruiz de Gordoa L.; Peasgood E.; Tridente A.; Shuker K.; Greer S.; Lynch C.; Turner K.; Singh J.; Sera Howe G.; Paul P.; Gill M.; Wynter I.; Ratnam V.; Shelton S.; Naisbitt J.; Melville J.; Baruah R.; Morrison S.; McGregor A.; Mpelembue M.; Srikaran S.; Dennis C.; Sukha A.; Williams A.; Verlande 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.; McMahon M.; Fowler S.; Coventry T.; Stewart R.; Wren L.; Mwaura E.; Mew L.; Rose A.; Scaletta D.; Williams F.; Inweregbu K.; Nicholson A.; 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.; Howard K.; Joy R.; Roche S.; Purvis S.; Morrison A.; Strachan D.; Clements S.; Black K.; Parmar C.; Altabaibeh A.; 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.; Keshetprice 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.; McParland C.; 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.; Jacqui M.; Hormis A.; Walker R.; Collier D.; Duncan T.; Uriel A.; Ustianowski A.; T-Michael H.; Bruce M.; Connolly K.; Smith K.; Partridge R.; Griffin D.; McDonald 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.; Roche L.; Chablani M.; Kirkby A.; Netherton K.; Archer S.; Yates B.; Ashbrook-Raby C.; Cole S.; Cabrelli L.; Chapman S.; Casey M.; Austin P.; Hutcheon A.; Whyte C.; Almaden-Boyle C.; Pattison N.; Cruz C.; Vochin A.; Kent H.; Murdoch S.; David B.; Penacerrada M.; Lubimbi G.; Bastion V.; Wulandari R.; Valentine J.; Clarke D.; Serrano-Ruiz A.; Hierons S.; 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.; Kay A.; Potts K.; Birt M.; Kent M.; Wilkinson A.; Jude E.; Turner V.; Savill H.; McCormick J.; Clark M.; Coulding M.; Siddiqui S.; Mercer O.; Rehman H.; Potla D.; *Capps N.; *Donaldson D.; *Jones J.; *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.; Mohamed Ally S.; Beaumont K.; Elsaadany M.; Fernandes K.; Ali Mohamed Ali I.; Rangarajan H.; Sarathy V.; Selvanayagam S.; Vedage D.; White M.; Smith 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.; Bhatia N.; 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.; Simpson K.; Turki S.; Allen L.; Crisp N.; Hazleton T.; Knight A.; Deery J.; Price C.; Turney S.; Tilbey S.; Beranova E.; Wright D.; Georg L.; Twiss S.; Cowton A.; Wadd S.; Postlethwaite K.; Gondo P.; Masunda B.; Kayani A.; Hadebe B.; Whiteside J.; Campbell R.; Clarke N.; Donnison P.; Trim F.; Leadbitter I.; O'Sullivan S.; Purewal B.; Bell S.; Rivers V.; O'Leary R.; Collins E.; Anderson S.; Hammerton K.; Andrews E.; Burns K.; Edmond I.; Salutous D.; 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.; Bokhari M.; Kapoor R.; Loader D.; Ayers A.; Harrison W.; North J.; Belagodu Z.; Parasomthy 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.; Thomas A.; 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.; Nauman Akhtar M.; Dent K.; Potoczna D.; Pearson S.; Horsley E.; Spencer S.; Phillips C.; Mullan D.; Skinner D.; Gaylard J.; Ortiz-Ruizdegordoa L.; Barber R.; Hewitt C.; Hilldrith A.; Shepardson S.; Wills M.; Jackson-Lawrence K.; Gupta A.; Easthope A.; Timlick E.; Gorman C.; Otaha I.; Gales A.; Coetzee S.; Raj M.; Peiu M.; Parris V.; Quaid S.; Watson E.; Elliott K.; Mallinson J.; Chandler B.; Turnbull A.; Quinn A.; Finch C.; Holl C.; Cooper J.; Evans A.; Collins A.; Treus Gude E.; Love N.; van Koutrik L.; Hunt J.; Kaye D.; Fisher E.; Brayne A.; Tuckey V.; Jackson P.; Parkin J.; Brealey D.; Raith E.; 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.; Otahal I.; O'Brien L.; Omar Z.; Perkins E.; Davies K.; Tetla D.; Pothecary C.; Deacon B.; Shelley B.; Irvine V.; Williams S.; Williams P.; Birch J.; 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.; Hanson K.; Humphreys S.; Frost I.; Gopal V.; Godden J.; Holden A.; Swann S.; Clapham M.; Poultney U.; Harper R.; Rice P.; Khaliq W.; Reece-Anthony R.; Gurung B.; Moultrie S.; Odam M.; Mayer A.; Bellini A.; Pickard A.; Bryant J.; Roe N.; Sowter J.; Butcher D.; 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.; Taylor M.; Beith C.; McAlpine A.; Ferguson L.; Grant P.; MacFadyen S.; McLaughlin M.; Baird T.; Rundell S.; Glass L.; Welsh B.; Hamill R.; Fisher F.; Smith T.; Gregory J.; Brown A.; Rolker S.; Nothen M.M.; Fazaal J.; Keitel V.; Jensen B.; Feldt T.; Knopp L.; Schroder J.; Maj C.; Brand F.; Berger M.M.; Brenner T.; Hinney A.; Witzke O.; Bals R.; Herr C.; Ludwig N.; Walter J.; Schneider J.; Erber J.; Spinner C.D.; Wendtner C.M.; Winter C.; Protzer U.; Casadei N.; Ossowski S.; Motameny S.; Riess O.H.; Kwasniewski M.; Korotko U.; Chwialkowska K.; Niemira M.; Jaroszewicz J.; Sobala-Szczygiel B.; Puzanowska B.; Parfieniuk-Kowerda A.; Martonik D.; Moniuszko-Malinowska A.; Pancewicz S.; Zarebska-Michaluk D.; Simon K.; Pazgan-Simon M.; Mozer-Lisewska I.; Bura M.; Adamek A.; Tomasiewicz K.; Pawlowska M.; Piekarska A.; Berkan-Kawinska A.; Horban A.; Kowalska J.; Podlasin R.; Wasilewski P.; Azzadin A.; Czuczwar M.; Czaban S.; Olszewski P.; Bogocz J.; Ochab M.; Kruk A.; Uszok S.; Bielska A.; Szalkowska A.; Raczkowska J.; Sokolowska G.; Chorostowska-Wynimko J.; Jezela-Stanek A.; Rozy A.; Lechowicz U.; Polowianiuk U.; Grubczak K.; Starosz A.; Eljaszewicz A.; Izdebska W.; Kretowski A.; Flisiak R.; Moniuszko M.; Abedalthagafi M.; Alaamery M.; Massadeh S.; Fawzy M.; AlBardis H.; Aljawini N.; Alsuwailm M.; Almalki F.; Mangul S.; Jung J.; Mbarek H.; Saad C.; Al-Sarraj Y.; Al-Muftah W.; Badji R.; Thani A.A.; Ismail S.I.;

Citation:
Human Genetics. 2022, Vol 141(1) (pp 147-173)

Abstract:
The combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole-exome sequencing data of about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting COVID-19 severity. First, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthily, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management.

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Creating and employing an admission bloods based diagnostic aide for COVID-19 to assist cohort-based isolation strategies (2022)

Type of publication:
Conference abstract

Author(s):
*Baker J.; *Day S.; *Marsh A.

Citation:
Emergency Medicine Journal. Conference: Royal College of Emergency Medicine Annual Scientific Conference, RCEM 2022. Belfast United Kingdom. 39(3) (pp 259-260), 2022. Date of Publication: March 2022.

Abstract:
Aims/Objectives/Background In the COVID-19 pandemic the Shrewsbury and Telford Hospital NHS Trust has isolated suspected cases in high and low suspicion cohort bays to reduce nosocomial infection. Before rapid PCR swabs were in routine use, we sought tools to aide identifying COVID-19 positive patients. Methods/Design We collected data from two cohorts in April and June 2020 totalling 317 patients, with positivity rates of 33% and 5% respectively. We retrospectively correlated neutrophil count, lymphocyte count, LDH and AST to positive and negative swab results. Predictive value of COVID-19 positivity was assessed via their receiver operator characteristic. Areas under the curve were as follows: Neutrophils 0.75, lymphocytes 0.64, combined neutrophil and lymphocyte count 0.82, AST 0.65 and LDH 0.7. We developed a diagnostic aide to assist in allocation of high and low suspicion based on parameters for neutrophil count, lymphocyte count and LDH, each of which was assigned red (higher probability) or green (lower probability) in a 'traffic light' system. Combined and applied retrospectively to 252 patients with suspected COVID-19, with a positivity prevalence of 5%, three green values generated a negative predictive value for COVID-19 of 100%, two greens 98% and three reds a positive predictive value for COVID-19 of 44%. Results/Conclusions This diagnostic aide was applied from August 2020 within the Trust Emergency Departments and Acute Medical Units to aide cohort decisions. A retrospective application to all 213 patients with positive swabs admitted from August to November 2020 demonstrated that 69% were highlighted as at least two 'red lights' and only 1.4% were erroneously highlighted as three 'green lights'. The aide is an example of a rapidly developed evidence based tool and, particularly if updated with data from other centres, could be widely employed in low-resource healthcare settings. (Figure Presented).

The global level of harm among surgical professionals during the COVID-19 pandemic: A multinational cross-sectional cohort study (2022)

Type of publication:Journal article

Author(s):Abouelazayem, Mohamed; Viswanath, Yirupaiahgari K S; Bangash, Ali Haider; Herrera Kok, Johnn Henry; Cheruvu, Chandra; Parmar, Chetan; Atici, Semra Demirli; Yang, Wah; Galanis, Michail; Di Maggio, Francesco; Isik, Arda; *Bandyopadhyay, Samik Kumar

Citation:Surgery; Mar 2022 [epub ahead of print]

Abstract:BACKGROUND Health care workers, including surgical professionals, experienced psychological burnout and physical harm during the coronavirus 2019 pandemic. This global survey investigated the coronavirus 2019 pandemic impact on psychological and physical health.
METHODS We conducted a global cross-sectional survey between February 18, 2021 and March 13, 2021. The primary outcome was to assess the psychological burnout, fulfillment, and self-reported physical level of harm. A validated Stanford Professional Fulfilment Index score with a self-reported physical level of harm was employed. We used a practical overall composite level ofharm score to calculate the level of harm gradient 1-4, combining psychological burnout with self-reported physical level of harm score.
RESULTS A total of 545 participants from 66 countries participated. The final analysis included 520 (95.4%) surgical professionals barring medical students. Most of the participants (81.3%)were professionally unfulfilled. The psychological burnout was evident in 57.7% and was significantly common in those <50 years (P = .002) and those working in the public sector (P = .005). Approximately 41.7% of respondents showed changes in the physical health with self-remedy and no impact on work, whereas 14.9% reported changes to their physical health with <2 weeks off work, and 10.1% reported changes in physical health requiring >2 weeks off work. Severe harm (level of harm 4) was detected in 10.6%, whereas moderate harm (level of harm 3) affected 40.2% of the participants. Low and no harm (level of harm 2 and level of harm 1) represented 27.5% and 21.7%, respectively. CONCLUSION Our study showed that high levels of psychological burnout, professional unfulfillment, work exhaustion, and severe level of harm was more frequent in younger professionals working in the public sector. The findings correlated with a high level of harm in surgical professionals impacting surgical services.

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Global Impact of COVID-19 pandemic on Gastric Cancer Treatment: findings from a global cross-sectional multicentre study (GLEOHUG-GC) (2022)

Type of publication:Conference abstract

Author(s):Herrera Kok J.H.; Viswanath Y.K.; Parmar C.; Bangash A.H.; Samaduv E.; Atici S.D.; Cheruvu C.V.; Abouelazayem M.; Yang W.; Galanis M.; Di Maggio F.; Isik A.; *Bandopyadaya S.; Mahawar K.

Citation:European Journal of Surgical Oncology; Feb 2022; vol. 48 (no. 2)

Abstract:Background: Gastric cancer (GC) is the 5th most common malignancy and remains one of the major causes of worldwide cancer-related deaths. COVID-19 pandemic has had a significant impact on the provision of cancer care. This study aims to overview the global standpoint of gastric cancer patients (GCP) during the first year of pandemic (PY1).
Material(s) and Method(s): The Upper Gastrointestinal Surgeons (TUGS), within its Global Level of Harm Project, designed an online cross-sectional survey to assess how GCP's management changed during PY1. The questionnaire included 33 questions about expertise, kind of health system, hospital organization and screening policies, personal protective equipment (PPE), change in patient's characteristics, preoperative, operative and postoperative management of GCP.Result(s): There were 209 answers from 178 centres (50 countries) around the world. Results of the survey showed: most hospitals (88,2%) had restricted areas for the management of COVID-19 patients; 53,6% of participants were redeployed; most frequent COVID-19 screening methods were PCR (78,8%) and chest CTscan (25,6%), and 55,9% thought there was a lack of PPE. Preoperative management: 43,2% decrease in the number of multidisciplinary teams (MDT) meetings; 28,4% increase in the number of cT2 or higher GCP; 34,7% increase in metastatic (M1) GCP; 26,8% increase in GCP receiving definitive palliative treatment; 23,7% increase in the number of frail patients; 50% increase in waiting list time (WLT); and 41,6% faced problems in the provision of oncological treatment. Operative management: 54,5% decrease in elective gastrectomies; 29,1% increase in the number of urgent/semi-urgent gastrectomies; 37% decrease in the number of minimally invasive gastrectomies (MIG); and 18,5% increase in the number of surgeries with palliative intent. Postoperative management: 16,5% increase in the overall complication rate (OCR); 12,6% increase in the number of Clavien-Dindo 3 or higher complications; 8% increase in the leak rate; increase in pulmonary infections (26,8%) and bowel obstruction (2,4%); 44,5% development of postoperative COVID-19 infection; 15,4% increase in 30-days mortality rate; 23,1% mortality due to COVID-19 infection; 17,6% increase in the need for adjuvant treatment. Most patients were postoperatively assessed either through a face to face consultation or a combination of face to face and remote consultation.
Conclusion(s): COVID-19 pandemic has affected GC management by decreased frequency of MDT's, higher clinical-stage migration and fuelled frailty. The pandemic increased WLT, the number of urgent and palliative surgeries, OCR, Clavien-Dindo 3 or higher complications, leak rate, and pulmonary infections. There was a noticeable high rate of postoperative COVID-19 infection and associated mortality. Further multicentric studies are warranted to affirm these findings.

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Mapping the human genetic architecture of COVID-19 (2021)

Type of publication:Journal article

Author(s):

COVID-19 Host Genetics Initiative. Includes James Moon, Nigel Capps, Sanal Jose, Colene Adams, Anita Agasou, Amy Bowes, Pauline Boyle, Mandy Carnahan, Anne Carter, Danielle Childs, Kelly Hard, Yasmin Hussain, Michael Leigh, Rachel Rikunenko, Jo Stickley, Helen Tivenan, Rebecca Wilcox, Tracie Arden, Mandy Beekes, Heather Button, Denise Donaldson, Fran Hurford, Ayesha Javaid, James Jones, Terry Martin, Helen Millward, Nichola Motherwell, Julie Summers, Louise Ting & Louise Tonks of Shrewsbury and Telford Hospital NHS Trust

Citation:Nature. 2021, Vol. 600(7889) (pp 472-477)

Abstract: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-19<sup>1,2</sup>, 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 diseases<sup>3-7</sup>. 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.

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CORONA (COre ultRasOund of covid in iNtensive care and Acute medicine) study: National service evaluation of lung and heart ultrasound in intensive care patients with suspected or proven COVID-19 (2022)

Type of publication:Journal article

Author(s):Parulekar P.; Powys-Lybbe J.; Aron J.; Knight T.; Lasserson D.; Smallwood N.; Rudge G.; *Miller A.; Peck M.

Citation:Journal of the Intensive Care Society; 2022 [epub ahead of print]

Abstract:Background: Combined Lung Ultrasound (LUS) and Focused UltraSound for Intensive Care heart (FUSIC Heart – formerly Focused Intensive Care Echocardiography, FICE) can aid diagnosis, risk stratification and management in COVID-19. However, data on its application and results are limited to small studies in varying countries and hospitals. This United Kingdom (UK) national service evaluation study assessed how combined LUS and FUSIC Heart were used in COVID-19 Intensive Care Unit (ICU) patients during the first wave of the pandemic. Method(s): Twelve trusts across the UK registered for this prospective study. LUS and FUSIC Heart data were obtained, using a standardised data set including scoring of abnormalities, between 1st February 2020 to 30th July 2020. The scans were performed by intensivists with FUSIC Lung and Heart competency as a minimum standard. Data was anonymised locally prior to transfer to a central database. Result(s): 372 studies were performed on 265 patients. There was a small but significant relationship between LUS score >8 and 30-day mortality (OR 1.8). Progression of score was associated with an increase in 30-day mortality (OR 1.2). 30-day mortality was increased in patients with right ventricular (RV) dysfunction (49.4% vs 29.2%). Severity of LUS score correlated with RV dysfunction (p < 0.05). Change in management occurred in 65% of patients following a combined scan. Conclusion(s): In COVID-19 patients, there is an association between lung ultrasound score severity, RV dysfunction and mortality identifiable by combined LUS and FUSIC Heart. The use of 12-point LUS scanning resulted in similar risk score to 6-point imaging in the majority of cases. Our findings suggest that serial combined LUS and FUSIC Heart on COVID-19 ICU patients may aid in clinical decision making and prognostication.

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Timing of surgery following SARS-CoV-2 infection: an international prospective cohort study (2021)

Type of publication:
Journal article

Author(s):
COVIDSurg Collaborative; GlobalSurg Collaborative (COVIDSurg Collaborative includes *Yen Nee Jenny Bo, *Mohammad Iqbal, *Aarti Lakhiani, *Guleed Mohamed, *William Parry-Smith, *Banchhita Sahu of Shrewsbury and Telford Hospital NHS Trust)

Citation:
Anaesthesia, June 2021, Volume 76, Issue 6, Pages 748-758

Abstract:
Peri-operative SARS-CoV-2 infection increases postoperative mortality. The aim of this study was to determine the optimal duration of planned delay before surgery in patients who have had SARS-CoV-2 infection. This international, multicentre, prospective cohort study included patients undergoing elective or emergency surgery during October 2020. Surgical patients with pre-operative SARS-CoV-2 infection were compared with those without previous SARS-CoV-2 infection. The primary outcome measure was 30-day postoperative mortality. Logistic regression models were used to calculate adjusted 30-day mortality rates stratified by time from diagnosis of SARS-CoV-2 infection to surgery. Among 140,231 patients (116 countries), 3127 patients (2.2%) had a pre-operative SARS-CoV-2 diagnosis. Adjusted 30-day mortality in patients without SARS-CoV-2 infection was 1.5% (95%CI 1.4–1.5). In patients with a pre-operative SARS-CoV-2 diagnosis, mortality was increased in patients having surgery within 0–2 weeks, 3–4 weeks and 5–6 weeks of the diagnosis (odds ratio (95%CI) 4.1 (3.3–4.8), 3.9 (2.6–5.1) and 3.6 (2.0–5.2), respectively). Surgery performed ≥ 7 weeks after SARS-CoV-2 diagnosis was associated with a similar mortality risk to baseline (odds ratio (95%CI) 1.5 (0.9–2.1)). After a ≥ 7 week delay in undertaking surgery following SARS-CoV-2 infection, patients with ongoing symptoms had a higher mortality than patients whose symptoms had resolved or who had been asymptomatic (6.0% (95%CI 3.2–8.7) vs. 2.4% (95%CI 1.4–3.4) vs. 1.3% (95%CI 0.6–2.0), respectively). Where possible, surgery should be delayed for at least 7 weeks following SARS-CoV-2 infection. Patients with ongoing symptoms ≥ 7 weeks from diagnosis may benefit from further delay.

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SARS-CoV-2 vaccination modelling for safe surgery to save lives: data from an international prospective cohort study (2021)

Type of publication:
Journal article

Author(s):
COVIDSurg Collaborative, GlobalSurg Collaborative (COVIDSurg Collaborative includes *Yen Nee Jenny Bo, *Mohammad Iqbal, *Aarti Lakhiani, *Guleed Mohamed, *William Parry-Smith, *Banchhita Sahu of Shrewsbury and Telford Hospital NHS Trust)

Citation:
British Journal of Surgery. 2021 Sep 27;108(9):1056-1063

Abstract:
Background: Preoperative SARS-CoV-2 vaccination could support safer elective surgery. Vaccine numbers are limited so this study aimed to inform their prioritization by modelling.
Methods: The primary outcome was the number needed to vaccinate (NNV) to prevent one COVID-19-related death in 1 year. NNVs were based on postoperative SARS-CoV-2 rates and mortality in an international cohort study (surgical patients), and community SARS-CoV-2 incidence and case fatality data (general population). NNV estimates were stratified by age (18–49, 50–69, 70 or more years) and type of surgery. Best- and worst-case scenarios were used to describe uncertainty.
Results: NNVs were more favourable in surgical patients than the general population. The most favourable NNVs were in patients aged 70 years or more needing cancer surgery (351; best case 196, worst case 816) or non-cancer surgery (733; best case 407, worst case 1664). Both exceeded the NNV in the general population (1840; best case 1196, worst case 3066). NNVs for surgical patients remained favourable at a range of SARS-CoV-2 incidence rates in sensitivity analysis modelling. Globally, prioritizing preoperative vaccination of patients needing elective surgery ahead of the general population could prevent an additional 58 687 (best case 115 007, worst case 20 177) COVID-19-related deaths in 1 year.
Conclusion: As global roll out of SARS-CoV-2 vaccination proceeds, patients needing elective surgery should be prioritized ahead of the general population.

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Effects of pre-operative isolation on postoperative pulmonary complications after elective surgery: an international prospective cohort study (2022)

Type of publication:
Journal article

Author(s):
COVIDSurg Collaborative; GlobalSurg Collaborative (COVIDSurg Collaborative includes *Yen Nee Jenny Bo, *Mohammad Iqbal, *Aarti Lakhiani, *Guleed Mohamed, *William Parry-Smith, *Banchhita Sahu of Shrewsbury and Telford Hospital NHS Trust)

Citation:
Anaesthesia. November 2021 Nov, Volume 76, Issue 11, Pages 1454-1464.

Abstract:
We aimed to determine the impact of pre-operative isolation on postoperative pulmonary complications after elective surgery during the global SARS-CoV-2 pandemic. We performed an international prospective cohort study including patients undergoing elective surgery in October 2020. Isolation was defined as the period before surgery during which patients did not leave their house or receive visitors from outside their household. The primary outcome was postoperative pulmonary complications, adjusted in multivariable models for measured confounders. Pre-defined sub-group analyses were performed for the primary outcome. A total of 96,454 patients from 114 countries were included and overall, 26,948 (27.9%) patients isolated before surgery. Postoperative pulmonary complications were recorded in 1947 (2.0%) patients of which 227 (11.7%) were associated with SARS-CoV-2 infection. Patients who isolated pre-operatively were older, had more respiratory comorbidities and were more commonly from areas of high SARS-CoV-2 incidence and high-income countries. Although the overall rates of postoperative pulmonary complications were similar in those that isolated and those that did not (2.1% vs 2.0%, respectively), isolation was associated with higher rates of postoperative pulmonary complications after adjustment (adjusted OR 1.20, 95%CI 1.05–1.36, p = 0.005). Sensitivity analyses revealed no further differences when patients were categorised by: pre-operative testing; use of COVID-19-free pathways; or community SARS-CoV-2 prevalence. The rate of postoperative pulmonary complications increased with periods of isolation longer than 3 days, with an OR (95%CI) at 4–7 days or ≥ 8 days of 1.25 (1.04–1.48), p = 0.015 and 1.31 (1.11–1.55), p = 0.001, respectively. Isolation before elective surgery might be associated with a small but clinically important increased risk of postoperative pulmonary complications. Longer periods of isolation showed no reduction in the risk of postoperative pulmonary complications. These findings have significant implications for global provision of elective surgical care.

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SARS-CoV-2 infection and venous thromboembolism after surgery (2022)

Type of publication:
Journal article

Author(s):
COVIDSurg Collaborative; GlobalSurg Collaborative. (COVIDSurg Collaborative involves *Yen Nee Jenny Bo, *Mohammad Iqbal, *Aarti Lakhiani, *Guleed Mohamed, *William Parry-Smith, and *Banchhita Sahu of Shrewsbury and Telford Hospitals NHS Trust)

Citation:
Anaesthesia, Jan 2022, Volume77, Issue1, Pages 28-39

Abstract:
SARS-CoV-2 has been associated with an increased rate of venous thromboembolism in critically ill patients. Since surgical patients are already at higher risk of venous thromboembolism than general populations, this study aimed to determine if patients with peri-operative or prior SARS-CoV-2 were at further increased risk of venous thromboembolism. We conducted a planned sub-study and analysis from an international, multicentre, prospective cohort study of elective and emergency patients undergoing surgery during October 2020. Patients from all surgical specialties were included. The primary outcome measure was venous thromboembolism (pulmonary embolism or deep vein thrombosis) within 30 days of surgery. SARS-CoV-2 diagnosis was defined as peri-operative (7 days before to 30 days after surgery); recent (1–6 weeks before surgery); previous (≥7 weeks before surgery); or none. Information on prophylaxis regimens or pre-operative anti-coagulation for baseline comorbidities was not available. Postoperative venous thromboembolism rate was 0.5% (666/123,591) in patients without SARS-CoV-2; 2.2% (50/2317) in patients with peri-operative SARS-CoV-2; 1.6% (15/953) in patients with recent SARS-CoV-2; and 1.0% (11/1148) in patients with previous SARS-CoV-2. After adjustment for confounding factors, patients with peri-operative (adjusted odds ratio 1.5 (95%CI 1.1–2.0)) and recent SARS-CoV-2 (1.9 (95%CI 1.2–3.3)) remained at higher risk of venous thromboembolism, with a borderline finding in previous SARS-CoV-2 (1.7 (95%CI 0.9–3.0)). Overall, venous thromboembolism was independently associated with 30-day mortality (5.4 (95%CI 4.3–6.7)). In patients with SARS-CoV-2, mortality without venous thromboembolism was 7.4% (319/4342) and with venous thromboembolism was 40.8% (31/76). Patients undergoing surgery with peri-operative or recent SARS-CoV-2 appear to be at increased risk of postoperative venous thromboembolism compared with patients with no history of SARS-CoV-2 infection. Optimal venous thromboembolism prophylaxis and treatment are unknown in this cohort of patients, and these data should be interpreted accordingly.

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