Hospital mortality and resource implications of hospitalisation with COVID-19 in London, UK: a prospective cohort study

We a imed t o de te r min e fac tor s a s s oc ia te d w ith hospi tal mor tality and d e scribe ho s p ita l and I CU strai n by c onduc t i ng a p ros pec t i ve c oho r t s tudy a t a t er tiary ac ad emi c c entre in L ondon, UK. W e inc luded a dult p ati ent s admi tted to ho s p ital with l abo rat or y -con firm ed C OV ID -19 and followe d them up un t il ho spita l disch a r g e or 30 d ay s. B a selin e fa ctor s tha t a r e a s s oc ia ted w ith h o spit al mort ality we r e iden tifi ed via s emi-p a r a me tr i c and parame tric s urviv al a nalys e s.

Our study inc luded 429 pa tie n ts; 18% o f them wer e admit ted to I CU , 52 % met c rit e r i a f o r IC U outre ac h t e am ac tivat ion a nd 61% h ad t reatm ent limita tion s pla ced d ur i ng thei r admis sion . H ospi t a l mortali ty was 26% and I CU mo rtali ty wa s 34%. H o spi tal mo r ta li ty wa s i nd epend en tly a s s oc iat ed w it h inc r e a s i ng age, mal e sex, his tory of c hron ic kidne y dis e a s e , in crea sing ba selin e C-r eac t i ve pro t e i n level an d dy spno ea a t pre s en t a t i o n. COV ID -19 re su lted in s ub st anti al I CU an d ho s pital st r a in, wi t h u p t o 9 d a i l y I C U a d m i s s i o n s a n d 4 1 d a i l y h o s p i t a l a d m i s s i o n s , t o a p e a k c e n s u s o f 8 0 i n f e c t e d p a t i e n t s admi t t ed in IC U and 250 i n t he h o spital . Ma nageme n t o f such a su rge requir ed exten sive reorgani s ation o f c ritical car e s ervic e s w ith expa ns i on o f ICU capa ci ty from 69 to 129 beds, redepl o yment o f s ta ff fr om o the r ho s pi ta l area s an d coordina ted h ospi t a l -leve l e ff ort. Conc lusions CO VI D-19 i s a ssoci a ted wi th a h igh burd en of mo rtali ty for pati en ts tr e a ted on t he wa r d a nd t h e ICU a nd req ui r e d s u bs tan tial rec on figura tion o f critica l c are s ervic e s. Thi s ha s s i gn ific ant implic a tion s for plan n ing an d re s ou rc e utili zati on. . CC-BY-NC-ND 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted July 17, 2020. ; https://doi.org/10.1101/2020.07.16.20155069doi: medRxiv preprint 3 INTR ODUC TION Coron a viru s D i se a se 2 019 ( CO VI D -19 ) , an infe cti ou s s y ndr ome ca u s e d by S ARS - Co V-2 , appe ared in Dec embe r 20 19 and evolv ed int o a pa ndemi c that c au s ed more than el eve n millio n ca se s and 530 000 death s worldw ide by July 20 20 [1 ]. T he high n umber and a cui ty of pa tien t s re s ul ted in unprec ed ent ed de mand for h os pitali s ati on a nd critic al c ar e ser vice s i n many af fe cted c ount rie s. Deve lop ed ar ea s such a s W uh an (Chin a ) , Lomba r dy (It aly), and New York (Uni ted S t a te s; USA ) repor ted a surg e i n critic ally ill pa t i e nt s, w hich quick ly l ed to signific an t st r ain on hea lt h ca re sys tem s through shor tage s in In ten sive Car e Unit (I CU) b ed s, equip m ent, a nd tra ine d pe r sonn el [2 -4 ]. Th ere wa s c oncern tha t the U ni ted Kingd om (U K) w ould f ac e simil a r c hall eng e s, p articu la rly in den sely popula ted a rea s like Lond on . Th e fi rs t inf ection wa s rep ort ed on J anu ary 30, 2020 a nd by early July th e country ha d r ecord ed a lar ge number of c a se s , w ith ove r 3 3 000 co nfirmed i n f e c tion s in the grea te r are a o f Lond on alone [5 ]. De spit e th e hi gh numbe r o f ho s pi ta l adm is sion s with CO VI D -1 9 , the ex is ti ng peer - review ed litera tur e in t he UK re main s re strict ed t o large p opula tion -level s tudie s and small re t ro sp ec t ive co hor t s with fe w det ai l s o n cli nical mana g ement and ho s p i t a l -leve l s t rain [ 6 -8 ]. M ajor repo rts f oc us ex clusive ly ei t h e r o n th e pre - ICU stag e o f ill ness [7] o r th e IC U ma nageme n t [8 ] an d foll ow- up time s are g ene rally sh ort [7 ]. E xtrap olati on fro m i nt e r na t i onal s etti ngs i s di fficul t d ue si gnific ant diff er enc e s in popula t i on cha ra cte ri s tic s [ 2 ], heal th sys tem organi s a tion [2,4,9 ] an d health sy stem s t r a in [ 1 0 ]. Det ail ed loc al p a t i e nt-l evel in forma tion o n c harac t e ri stic s and ou tcome s a s we ll a s insti tut i on- lev el info rmatio n o n s ervice pre ssu re s would guide c linic al d eci sion ma king and i nform e ffe ctive prioriti sa tion and re sou rce alloc a tion in the fu tur e , par ticula r l y in c ircums tanc e s w hen a s urg e in dema nd plac e s t he Na tion al Hea l th Servi c e a gain a t r i s k o f being overwhe lme d. Th e aim of our s t udy was t o de scribe t h e cli nica l cha r a cte ristic s and c ours e of ho spital i s e d patie n ts wi t h C O V ID -19, a s w ell a s i ts b ro ader r es ource i mplic a tion s for a t er ti a r y ac ademic ho spital in L ondon, U K. MET H O D S S t udy des i gn We c onduc te d a pro sp ective coh ort stud y at K ing’s Coll e ge Ho spi t a l (K CH), a ter ti ary a cade mic ce ntre in Lo ndon, UK. In s titu t i onal (IR AS - 256 619; April 1 5, 2020 ) and r egio nal (He alth Re sea r c h Autho rity; IR AS -25 6619; April 22, 2020 ) re view board app rov al s wai ved the ne ed f or ethic s co mmitt e e revie w and t h e nee d fo r i nfo rmed patien t c on s e n t . . CC-BY-NC-ND 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted July 17, 2020. ; https://doi.org/10.1101/2020.07.16.20155069doi: medRxiv preprint 4 All cons ecu t i ve pa tie n ts te s t e d for SA RS- CoV -2 i n f e cti on u sing r e ver se -tran scri pta se pol yme ra se ch ain reac ti on (RT -P CR ) a ss ays o f r es pira tor y tr a c t sample s be twe en F e br ua r y 25 a nd March 3 1, 2020 were c onsid er ed el igible for st udy p art i cipa tion . Inclu s ion cri teri a we r e age of 18 y ear s o r above and labo rat ory-co n f i r m e d SARS -C oV -2 i nf ection, whic h wa s de fin ed a s a t l ea s t on e po s i t i v e RT-P CR n a s op h aryngea l swab [11 ]. Pa tie nts wit h mi ssing i den tifi er s , mi ssing SARS -C oV -2 t es t r e s ul t s, and t ho s e tran s fe rr e d fr om o ther h o s pi ta ls wer e ex clude d. Inc luded p a t i e nt s w er e follow e d up un t il dea t h , ho s pi t a l disch a r g e, o r 30 da ys a ft e r hos p i t a l admi ssion . F ollow -up was con c luded on April 30 , 2020 . For pati e nts w ith mul tiple ho s pi ta l or IC U admis s i on s , only the f i rs t admis si o n wa s rec o r d ed . Trans fe r s be t w e en di ffe r e n t I CUs wi t hi n the ho spi tal w ere con sid er ed par t of t h e s a me a dmi ssio n. The pr i mary outc ome wa s mo rtali t y a t h ospi tal di s c harg e or 30 days . Se cond a r y o utcome s w er e ICU mortali ty, as well a s h ospi t a l an d I C U c ap ac ity st r a in, me a s ured i n b ed oc cupa ncy. The repor t of o ur findin g s i s b a sed on th e S treng t h e ning th e R epor t i ng of Ob s e r va tional S tudie s in E pi demiolog y (STROBE ) S t a t e men t [12 ] . Mor e det ai ls r eg arding th e institu tional se tting and pa ndemic s urg e are availab le in th e Supple m enta ry file (page 1 ) . Data c ollec t ion and manag ement Trai ned memb e rs of t he clini cal tea m ex trac ted a nony mise d dat a fr om e lect ronic health r ec ord s (EHR) [13] . We r ec or d e d th e foll ow ing fo r a ll inc luded p a tien ts: age, sex , e thnic ity , area -l evel socio e conomic depriva tion ( Index o f Mul tiple De pr i v a tion [14 ]) c linic al fr ai lt y , me dic al comorbiditi es , ag e-a djus t e d C harl son Comorbi dity Ind e x (A C C I) body ma ss ind ex (BM I) , prior r e side nc e, sel f- repor ted p re sen ting sympt oms , rea so n f or ho spital ad missio n, l abo rat ory, mic r o b iologic al and ima ging tes t s , C O V ID -19 - speci fic drug tr e atmen ts , tre atm ent limi ta t io n s such a s T reatm ent Esca la tion Pl a n s (T EP s) or Do- Not -R e s u sci t a te ( D NR ) ord er s , leng th of h o s pi tal s t a y and outc ome at hospi tal di s c harg e or at 3 0 day s. F or pati ent s who w er e initia lly a dmit t e d to the wa r d we a l s o r e co rded p ea k temp erat ure a n d Natio nal Early War ning Sc or e ver sion 2 ( NEWS2) scor e [1 5 ], maxi mum lev el of r e spir ato ry suppo rt and devel opmen t o f c omplica tion s s uc h as hypox ia, hypot en sion, tac hyc ardia , an d depre s s e d co ns c iou sn e s s . Fo r p a tien t s w ho we r e ad mitted to I CU w e addi t i o nally r e co rded r ea son f or I CU admi ssion , da ily S equen tia l O rga n Fai lu re Asse s s me n t (S O F A) s c or e [16] , organ su pport (mec hanic al ve nt i lati on, re na l repl ac emen t th erapy , c irc ulato ry suppo rt), ar t e ria l par tial pre s s ur e of oxy gen (P a O 2 ) , fr ac tion o f in spir ed ox yge n (F i O 2 ), P a O 2 /F i O 2 ra tio (PF R ), u se o f medi ca tion s such a s va s opr e s s or s, pulmon ary va s o dil at ors an d neuromu scular bl ocki ng drugs, u se of p rone p o s i tioni ng or Ex t rac orpor eal Memb ran e O x yge nation ( ECMO ), in ser t i on o f tra cheo s tomy, lengt h of I CU s tay, a nd outco me a t IC U disch a r g e or at 30 days . . CC-BY-NC-ND 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted July 17, 2020. ; https://doi.org/10.1101/2020.07.16.20155069doi: medRxiv preprint 5 We rec o rded c omorbi diti es and symp to ms ba sed on elec tronic ca s e no t e r eview and categ or i sed va r i able s ac cording to clini cal r e l evan ce a nd curren t lit era ture [4,10 ,17 ]. We u sed only va lidated lab or a t ory r e s ul t s and o ffic ia l r e po r t s o f i mag ing studi es . Ini tia l t e s t s f or newly ad mitted C OVI D-19 patie n ts re fe r to th o s e pe rfo r me d within 24 hours o f ho spi tal ad mi ssion; for p a t i e nt s al r e a dy admi t t ed, t h e y ref er t o te s ts per form ed w it h in 24 ho urs of CO VI D-19 di ag no s i s. C l inica l frail ty w as as s e ss ed on a 9-c a t e go ry scal e [18 ], u sin g i nfor ma ti on availabl e in the EH R ; pati e nts wit h a s c o r e above 4 w ere c on s ide r e d fr a il [19] . T r e a tm ent e scala t i on plan s (TEP s ) r ef er t o s t ru c t ured as s e ssme nt s o f pati ent s’ s ui t a bili ty reg ar ding spec i fic a s pe ct s o f trea tme nt suc h a s organ supp ort o r ICU admi ssion [20 ]. Ac u te Kidne y Injury ( A KI ) wa s de fine d ac co rding to Kidney -Di s ea se Impr ovi ng Global Outc ome s ( K D I GO ) crit eria [21] . More de tail s r egarding de fini tion s of c oll ec t e d da ta a r e provide d in th e Supplem e nta r y file (pa ge s 2-3 ). S t atistical methods De scrip tive anal y s e s a re pre sent ed a s median ( I Q R [ rang e ] ) or numbe r (%) a nd w e avoide d univariat e c ompari son s b e t w een g rou p s . T o identify facto rs ass oci at ed wi t h t h e ti me to dea t h at hospi tal di s c harg e or a t 3 0 day s , w e pe rf ormed mul t ivari able C ox propor tiona l -ha z a r d s an d parame t ric su r viv al analy se s. Covaria te i nc lusion follo wed a struct ured a p pr oa ch . We t e s ted t he propor tional h a z a r d s a s s u mp t i on and inves tigat ed i nte r a cti on s of the inc lud ed co v a r ia te s w ith sex and age. We al so a s s e s se d whe t he r t h e bas eline surviv al e xperi enc e di ff ered b y ca t e gori es of age , sex, f rai l t y and e t h nici ty, us i ng s t ra tifi ed Cox reg r e s sion . The e ff ect o f e ach includ e d covariat e w as quan t i fi ed by calc ulati ng adjus ted haz ard ratio s (HRs ) wi t h 95% C on fide nce In tervals (95% CI ). W e follow ed a s imi la r appro ac h fo r the p ara me t ric anal y s i s a nd plo tt ed the h a z ard fu nc tion over t i m e for s i x hy pothe tical pa tient s , in orde r to s how the e ff ect o f ea ch i nclud e d covariat e on the h azard o f dea t h . Sta ti s tic al te st s w e re 2- sid ed, w ith an α-l e vel o f 0 .05 fo r s t a t i stic al signific a nc e. We did n ot impute any mi ssing d a ta. Analy s e s w ere perf ormed u sing S ta t a / M P ver s ion 15.1 ( Sta ta Co r p) . Deta il s regardin g th e sta ti s tic al ap p r oa ch a r e provided i n the Sup pl emen tary f i l e (pag es 4 -10) . R E SU LT S Be t w e en F ebru ary 25th a nd M arch 3 1 s t, 20 20, 272 8 patient s we re te sted for S AR S -C oV - 2 infec ti on at K CH. A ft er ex cludin g 170 pati ent s ( 6 %) , 255 8 patien t s (94%) we re scre ened f or inclu sion; 2129 (83%) of t h e m did not me et th e inc l us i on cri ter ia a nd 429 (17%) w ere inc lud ed in t he s t udy . Among t he m, 353 pati ent s ( 8 2%) w er e trea te d only on the w ar d and 7 6 (18%) w e re tr eat ed in I CU . The s t udy flow di agram i s s hown in Fig ure 1. . CC-BY-NC-ND 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted July 17, 2020. ; https://doi.org/10.1101/2020.07.16.20155069doi: medRxiv preprint 6 Ba seli ne p atie n t char ac t e r i stic s ar e s h ow n in Ta ble 1. Pa tien t s had a media n age o f 65 ye ar s (I Q R 52-81 [18 -97] ) and 61% w ere o f e thnic minority b ack ground . The majority (61 %) we r e overwe igh t and 90% of t he m had a t le as t one s eriou s comorbidi t y ; th e mos t common were h y pert e n s i on (52%), dia bet e s (3 7%), a nd chronic kidn ey di sea se (CK D) (14% ). Mo st common pre sen tin g compla ints inc luded c ough ( 6 2%), fever (62%), a nd d yspnoe a (43%), bu t only 4 2% of pa t i ent s w ere ho spit ali sed for hypox aemi c re spi rat or y failu re . Initi al c hes t x-ray s were no r ma l in 2 3% of pa ti e nts a nd s howed diff us e, bil a tera l infil tra te s in mor e tha n half. On a dmi ssion, lymphope n ia w a s c ommon (T able 2 ), a s we r e eleva tion s in C -r eac t i v e p rot ein ( CR P) (m e dian 75 mg.l -1 , I Q R 2 8 -143 [0 -608 ]) a nd crea t i n ine (media n 92 mg .l -1 , I QR 68 -13 0 [25 -1000] ) . Ra i s e d La cta te Dehy drog ena se , Fe r ri tin, C r ea t i ne Kina se and D-di mers w ere al so c ommon, al b eit measu red in a mino rity o f p atie nt s . Com pared t o w ard patie n ts, th os e admi tted to I CU w ere yo u nger, le s s common ly frai l and had a low er burd en of ch r oni c c omorbiditi e s, a s de scrib ed by th e AC CI . They were, ho weve r , mor e like ly to be diab etic and to be ho s pi tal i s e d for re spira tory fai lur e, with sig ni fican t l y more d eran g ed ini t i al l ab or a t ory t e st s and abno r ma l che st ima ging. P a ti e n ts t re a t e d o n t h e w a rd Mos t pati ent s d eve lope d signi fi cant mo r bidi t y during thei r h o s pit al admi ss i on. Fi f ty-two p ercen t met c r i te r ia for cri tica l ca r e ou tre ach t ea m ac t ivation ( NEWS2 sco r e a bov e s ix ), pr edomina ntl y for re spira tor y f ailur e (Ta ble 3 ). On c he st co mputed t om og r a phy ( CT ) , mor e than 70 % of scan s showe d bila t e r a l dif fu s e infil tra te s and 2 5% reve a led p ulmonary e mboli sm ( PE) . PE wa s more f requ en t l y iden t i fi ed in I CU pa t i en t s (33% ) . La bora t or y abnormal i t i e s ( T abl e 2 ) inclu d ed wor seni ng ly mphopenia , rai s ed CR P (m edi an 159 mg.l -1 , IQR 8 1-299 [0 -686 ] ) a nd intr ace llula r e nz y me s , a s well as impa i r e d hep atic , r enal , and ha emo st atic func tio n. O verall, 21% o f pa ti ent s d e v elop ed KDI GO sta ge thr ee AK I but th e inc idenc e among ICU pa tien t s (67%) w a s much h igher th a n tha t among w ard patie n ts (11% ). We r ecord ed o nly mil d degree s o f my oca r di al inv olveme n t, evid e nced by small inc r e a s e s i n val ue s o f high- s en s i t i vity T r o pon in T a nd unrema rka ble ec hoc a r di ogr aphic finding s. Se condary in fectio n s w e re comm on in th e I CU- tre ate d group: 50% h ad a p o s it ive re s pi r a t ory trac t sampl e and 41% had a po sitive bl o od cu lt u r e . Sampl e s from th e r e spi rato ry trac t w ere f requ ently posi tive f o r Gr am ne gative o r g ani sms a n d fungi . Trea t m e nt limita tion s we re plac ed in 6 1 % of pa tie nt s o ver all, mo s t c ommonly on hospi tal admi ssion (medi an 0 da y s, I QR 0-1 [0-61 ] ). The majori ty (> 80%) o f th e se li mita tion s invol ved TE P s and D NR orde r s. Two- third s o f pati ent s with a TEP were c on s i de red frail . Amon g patien t s with trea tmen t limi t a t i on s tha t w er e not c on side r e d fr a il , ma ny had s ig ni fica n t medic al c omorbiditie s such a s a ctive malig nancy and st roke . . CC-BY-NC-ND 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted July 17, 2020. ; https://doi.org/10.1101/2020.07.16.20155069doi: medRxiv preprint 7 Pa t ie nt s t r e ated in ICU Th e cl inica l trajec tory of 76 pa tie n ts wh o were a dmit ted t o IC U is d esc ribed i n Tab l e 4. Man y patie n ts develop ed pre cipitou s r e s p ir a t o ry failur e a nd req uired ICU a d missio n di rec tly from t he emerge ncy depa rtmen t (57% ). Multi ple orga n fail ure w a s commo n with 97 % req uiring mech anica l ve nt i lati on fo r hyp oxic res pi r a tory f a il ure , 80% requiring pharmac ol ogic circ ulator y suppor t and 5 7% requiring re nal r epla ceme n t t h e r a py ( RR T) during thei r IC U stay . The s eve rity of il l ness w a s r e fl e cted in the high S O F A s c o r e s , w hic h remain ed eleva ted eve n a fte r two w eek s o f IC U s ta y. Th e media n duratio n of mech a nical ventil a tion wa s 1 2 days (I Q R 6-23 [1-37 ] ) a nd th at o f ren al r e plac emen t wa s 11 d ays (I QR 4-17 [1-37 ] ). P a t i ent s f requ ently requi red r e scue oxyg enation s tra te gies (54% ) , whic h inc luded n eur omus c ul ar bloc king drug s, i nhal ed pro stac yc lin an d pron e po siti onin g. Extrac or por ea l membran e oxy genati on (EC MO) w as u se d only i n 5% of ICU pa tien t s. A signific an t propo rt i on (38%) of pa tie n t s requir ed a t r a cheo s tomy, whic h was per form ed a t a medi a n o f 16.5 da ys (I Q R 14-20 [10 - 38]) a ft er I CU ad mi ssion . Outcomes Unadju sted mor tali ty at ho spit al di sc har ge or 30 days wa s 26 % over a ll, 23 % for w a r d pati ent s and 38% for tho se t re at ed in IC U. In u n adjus te d Cox su rviv al a nalysi s, h os pital mor tali t y was as s o ci ate d ag e, s ex, AC CI s c ore , f r a ilty c a tegory, CRP , crea t i ni ne, CKD, d ia bet e s, and dy s p no e a or feve r a s pre sen ting c omplai nts . Af te r adjus tmen t, it wa s i nde pend e nt l y a s s oc iat ed with inc r e a s i ng ag e (H R 1.07 per dec ad e a bove 4 0 yea rs ; 95% CI 1 .04-1. 09 , p<0 .001 ); mal e se x (HR 2.31; 95 %CI 1.52 -3.50 , p<0. 001) ; rai se d adm issi on CR P level (HR 1.03 pe r 1 0 mg.l -1 increme nts ab ove the up per norm al lim it of 5 m g.l -1 ; 95 %CI 1. 01 -1.04, p =0.001) ; h i s t ory of CK D (H R 1.8 7; 95% CI 1 .21-2 .8 9, p=0.0 05) a nd dyspnoe a a s a pre s enting symp t om (HR 1 .88; 95% CI 1.24 - 1 .86 , p=0 .003 ). Ethni ci t y or le vel of deprivati on we r e no t a s s oc ia ted w ith mo rt a li ty in unadjus ted or adj usted a n alys e s . Stra tif ica t i on o f the mode l by cat ego r ie s o f a ge (≤6 0, >60 years ), s e x, f railty or ethnici ty did not pr ovi de ev idenc e o f diff ering ba se line h aza r d. Th e ef fec t of e ac h inc luded c ovaria t e , ba s ed on pa ra me tr i c mode lling, i s shown i n Fig ur e 2 wi t h s ix exa mple s of h ypo t he t i c al pati ent s. In th e param e tr ic m odel , male s ex and dyspnoe a on pr es ent ation h a d th e large st impa ct on th e haz a r d func tion. M ore d e t a il s re garding t h e re sult s o f th e param etric a n alysi s ar e ava ila ble in t h e Suppl emen ta ry file ( page s 8- 10). At th e e nd o f the 30 -da y f ollo w-u p, 15 of 353 w ard patien ts (4%) rem a ined a dmi tte d in hos pital and 12 of 270 (4%) w er e re admitt ed a f te r hospi tal di s c ha rge. A m ong al l ICU p atie nts , 13 (17 %) remain ed a dmitt ed i n I CU at the en d of f ollow-up . Among the 5 0 pa tien t s disch ar ge d from I CU, thr e e (6%) were r eadmi tted t o I CU , 25 (50% ) w ere di sc harg ed fr om ho spital , t hr ee (6% ) die d on th e w ard and 22 (44% ) r e main ed ho s pi ta li s e d on t he w ard. . CC-BY-NC-ND 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted July 17, 2020. ; https://doi.org/10.1101/2020.07.16.20155069doi: medRxiv preprint 8 During t h e study peri od, th e h o s pit al expe r ie nce d a su dden surge in cri tica lly i ll pa tien ts a nd detai l s r eg arding th e n umber o f ho spi tal an d ICU admis s i on s a r e s how n in F igur e 3 . O ver a pe riod o f approx imately s ix we eks , 20-40 pa tien ts were ad mit t e d daily t o the h os pital w ith CO V I D -19 a nd betwe e n five t o ten o f th em requi r e d ad mis s i on to ICU for o rgan suppor t. At t h e peak of the pand emic, bot h the h os pital a n d IC Us e xperienc ed signi fic an t c apac ity st r ai n, wit h 2 8% of the hospi tal c apac i ty of 9 00 bed s and 70% of t he I CU surge capa ci ty of 129 be d s t ak e n up b y patien ts wi t h COVI D-19 . T his inc rea se d de mand w as s uppo rted b y ch ange s t o the s ervic e desc ribed in Ta ble 5. Ma jor chang e s incl ude d Anae s the tic cove r f o r ne wly opened I CU b ed s , r e -d e pl oymen t of t he entir e ho spit al workfo rce t o s upp ort ICU , deli very of critic al care in non -c onven tio na l area s lik e opera ting room s , and the in t roduc t i on o f team s dedi ca ted t o ta sk s lik e pron e po si tionin g, co mmunica t i on with fa milie s, an d tr a ch e os tomie s. M ore d etail s a re avai lab le i n t he Sup plemen tary file ( page 1 1) . DISC USS ION We de s c r i b e dat a fr om 4 29 patien t s ho s pitali sed w ith COVI D -19 i n an a cade mic h o s pi tal in Lo ndon UK, of w hich 7 6 (18%) wer e tre at ed in t h e I CU . We ob s erved a di sprop orti ona t e bu rden o f CO VI D -19 ho spi t a li sa tion an d IC U admis sion in patie n ts f rom an eth nic mi norit y b ac kground, co ns i st ent with repo rt s f r om s imi larly di ver s e ar ea s [9] and t he re s t o f th e UK [7, 8, 22]. The ra nge o f cl inica l pre sen tati on s was br oad, simil ar to rep orts o f Se ver e Ac ute Re spi r a to r y Synd r ome (S ARS) and M i ddle E a s t R e spira tory S yndrom e ( MERS ) [23 ,24] . Re spir ato ry in volve ment was v ery fr equen t, but not uni ve r s a lly pre se nt. H enc e, the r elia nce on t he ini t i a l pre s ence o f r e s pir at ory fa ilur e or abno r ma l che st ima ging re sult s t o make deci s i on s rega r d i ng patie nt in fecti ou sne s s and r equir emen t for i sola tion ma y be prob lema tic . Overal l ho spi tal mor tality wa s iden tic al t o tha t repo rted i n a rec en t large U K o b se rva t i onal st udy [7] bu t pa tie n t s ad mitted to the wa r d h a d hig her morbidity a nd mo rtali ty than pre viously r e p orted [4,17, 25 ]. A signi fic ant p ropor t i on ex pe ri ence d cli nical de teri ora tion w it h cardi o- r espi rat ory co mpr o mise and AKI, me eting the crit eri a for cri tic al c are o utr eac h ac t iva tion. Pa ti ent s tr ea ted o n the w ard r equir ed c on s i dera ble in pu t fro m c ritical care s ervi ce s, wi th t he ICU ou trea ch te a m s e eing alm ost fou r out o f t en a dmit ted pa tien t s. Sim ilar patie n ts may have been t re at ed in the I CU in oth er desc ribed coho rt s and thi s may expl ain t he di ffe ren ce i n una djus ted mor tality . Th e con t ribu tion o f th e critic al c ar e out r each t e am, a s evidenc ed by t h e number of pa t i en ts s een, wa s c rucia l in our c oh ort, however no c o mpariso n dat a e xis t . As pa r t o f th ei r rol e , outr e ach t e am s co mmonly b r id ge the g ap be tw een w ard and ICU by providin g ex pe rt i se , mo nito r i n g and interve n t i on s ou tside t he I CU environm e nt a nd, impor tan tly , by e ngagi ng in p hilosophy -o f-ca r e . CC-BY-NC-ND 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted July 17, 2020. ; https://doi.org/10.1101/2020.07.16.20155069doi: medRxiv preprint 9 discu s sion s with pa tie n ts and t h eir s urr o gate deci sion -mak e rs [26 ] . In a c ontext o f m any fix ed co nstrain t s s uc h a s the numb e r of ICU b e ds, the ou tre ach service i s a delivery mo del tha t grea tly ex pands the availa b ility of e xperti se and a dv anc ed tr eatm ent s on t he w ard . Dep e nding on the inst itu t i onal c on text, how eve r, o u t re a ch se rvic es req uire appr opria te e q uipmen t and tr a in ed per sonn el such a s doc tor s , nu rse s and all ied heal th pro fe s s i on al s [26 ]. Thi s ha s signi ficant impli cation s on sta f f pla nning a nd r e s ou rc e all ocatio n dur i ng a pand emic . Th e majority of ward -t rea ted p atie nts in o ur study had a deci sion to l imit e scal ati on of ther apy r e cord ed during th eir admi s sion, wh ich repre sen t s a depa r tu re f rom previ ous pra ctice . Mo s t patie n ts had trea t me n t limitati on s plac e d upo n admis s i o n. In a ddition to bei ng c li nica lly f rai l, se r i ou s co mor b iditi es s uc h a s ac tive ma ligna ncy and s tr ok e we r e more comm on in the se patie n ts. Wi thin the f ramew ork o f ge ne ric na t i o nal g uida nc e regarding t r e a tmen t e scala t i on and I CU a dmi s s ion [27 ], we belie ve tha t th e C OV ID -19 pan d emic pr o mote d more pr oac t i ve c ommunic at io n abou t goal s o f ca r e be twee n phy sici an s and t heir pa t i en ts. I n fact, the Pallia t i ve Ca r e s ervi ce i n o ur ins t i t u tion faced a d r a matic i ncr ea se in ward r ef err al s ove r the study pe r io d [28] , but c ompar ative data from ot her UK se tt i ng s ar e lac king . The re s ource implic a tion s of d elivering a compr ehe n s ive pal li ativ e care re spon s e during a pand emic are unknow n, but li ke ly t o be sub sta n t ia l [29 -31 ]. Pa t i ent s t rea ted in the I CU had high mor bidi t y and m or t al it y . Fe w o f th em h ad tri als o f C PA P or NI V and a lmo st all requir ed inva sive mec h anica l ve nt i la tion, w hich di ff ers f rom th e e xperienc e in the UK [7] and ot h e r count rie s [10] . Pulm on a ry involv eme nt was signific ant, w it h l onger pe r i o d s of mec hanic al ventila tion and mo re f requ e nt rec ou rse t o re scue oxy genati on t h e r a pies than pr ev i ou s ly desc ribed [9] . Extrapul mon ary orga n invol v ement w a s al so comm on and l ed to hi gh er utili sa tion o f pharma colog ical circu la tory suppor t and RRT tha n th at r epor t e d ac ros s t he U K [8 ] and i n r e cen t CO VI D -19 coh ort s fr om I t a ly (27 .8%) [32 ] , the U S A (31%) [9], a nd Chin a (25%) [33] . The hig h propor tion o f pati e nts n ee ding orga n s u ppor t i n t he I CU cou ld be e xplai ned by t h e fact tha t ma ny patie n ts wi t h le ss seve re or g an fail ure were t rea ted on the wa r d , with th e a id of t he ou t r eac h se rvice . Simi larly, the high i ncide nce o f si gn ifican t ext rapulmon a r y invol vement su pport s th e impre ss i on tha t critic al ly ill CO VI D-19 pa t ient s ar e more simil ar to tho se with MER S [24] , whe r e as SARS was a p r e domin antly r e s pi rat ory d i s e a se with single organ fai lu r e [34] . Hospi tal mor tality in mec hanic ally ventil ated CO VI D -19 p atie nt s wa s simila r to th at of u n sel ect ed co hor t s o f s ever e Adul t R e s pi r a tory D i s tre ss Sy ndrom e (A RDS ) pati ent s who re qui red ven t i la tion (46.1% ), a s we ll a s t hat o f mec hanic al ly ventil a ted pa tien t s wi t h SARS (45% ) and MERS (52.4% ) [24,34 ,35 ]. I n ou r surv ival an aly si s, we id enti fied a ge , ma le sex, CK D , eleva ted CR P, a nd dy spnoe a at pre sen tati on a s import ant ba seli ne p rog nos tic fa c tors a s socia t e d with 30 - d ay mo rtali ty aft er hospi tali sa tion . T he se ar e broa dl y similar to pa t i ent cha rac te ri s tic s d e s c r i b ed in re po r t s f r om oth er . CC-BY-NC-ND 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted July 17, 2020. ; https://doi.org/10.1101/2020.07.16.20155069doi: medRxiv preprint 10 co untr ie s [9,3 6,37 ] and t he UK [7 ]. We di d n ot , however id enti fy an inde p ende nt as socia tion with ethnic ity, w hich i s al s o in lin e with fin din gs fro m a rec en t large U S cohort study [3 8]. Ea r l y iden t i fi cati on o f p atie nt ch ara cte ri st i c s a ssoc ia ted w ith po or cli nica l outcom e s a n d highe r re sou rce utili sati on i s i mpo r tan t, when fa ced w ith the ne e d to p riori tise pa tien ts in the fac e of hig h dema nd for cri tic al c are se r vice s, bo th in the I CU and on the w ard . Th e CO V I D -19 p andemi c le d to a sudden surge i n the ove r a ll numbe r of cri tical ly il l patien t s ac r o ss the ho spi tal, a s w ell a s i n t he int e nsity a nd du rat ion o f tre atme nt s th ey re qui r ed . Thi s re sult ed in signi f i can t s tr a in for the I CU i n term s of ca p aci t y and servi ce d e livery. ICU be d ca pac it y wa s e f f e ctivel y doubl ed, c r itic ally ill pa tie nts o n the wa rd r e qui red frequ ent inp ut by the outr eac h team, while pa tien t s in the ICU requi red pr ol onged m echa n ical ventila t i on an d RR T , frequ ent r e s c ue oxy gena t i on the rapi es and t r ac heo s t o my. To s uppo rt thi s inc r ea sed demand f o r c r itical care se rvice s, s ev er a l op era tiona l cha nge s we re in s tit ute d, w ith suppor t from the A n a es t he t i c depa rtment . T he se wer e b a s e d o n loc al a dapta tion o f le sson s fr om pre vious in fe c t i ou s d isea s e outbr eak s a nd inf ormati on f rom c ountr i e s th a t h ad b een al ready a ff ecte d by CO VI D-19 [2,3,39 ] . The impl ementa tion o f thi s se rvic e deli very mode l requi red pr ovi s ion o f a c on s i d erab le a mount o f educ atio n a nd tra ining. Al s o , t he se c han g es wer e impl emen ted in a shor t tim e wi ndo w and r e quir ed co llabora tion acr os s the e n tire ho s p ita l. Our le sson from thi s p roce ss i s tha t cli nicia ns a n d hea l t h admi nistra tor s n e ed to c on s id er a r apidly s c ala bl e mode l, a s h eal t h s y st ems coul d ea sily become ove r w helmed, an d our e xper ienc e i s dir e ctly com parable t o tha t f rom oth er, simil arly af fec t ed, m e t r o po l i t a n ar e as [ 4 0] . Our s tudy ha s s e ver al s tr ength s . Fi rst, it i nclu des a cl early de fined c oh ort wit h nea r-c omple te 30 - day outcome s , th us mini mi s in g selec tio n bias . Se cond , i t pr ovide s a g ra nular cl inic a l de scriptio n o f patie n t t r aje cto rie s with pr evi ous l y unk n own informa tion re garding I CU out r ea ch in volve ment and pal liative car e p r a c tice . Third , the inclu si on of pa tien t s t r eat ed both on the w ar d and i n ICU o f fer s a more c omplet e pi ctur e o f the o rga n dys f unction s ex peri enc ed and the cor re s po n ding res ource impli cation s. F ina lly , we pr o vide u niqu e de t a il s re garding ho s pi tal and I C U c apac i ty st r a in and se rvic e reorgani s ation . Our s tudy re s ul ts mus t, howe ve r, be v ie we d in li ght of it s me thodol og ical limitati ons . The pro s p ective d e sign reli e d on a b s t racting data from th e E H R a nd i s su s c eptibl e to mi ssing da ta and recordin g bia s . We i de nti fied a numb er o f fac t o rs a s s oc ia ted with mo rtali ty b ut do not imply any ca us a l rela tion ship s. Fi n ally, thi s study w as pe rf or m ed in a s i ngle c en tre in the UK a nd thi s may l imit its gen eral i sa bility to o the r in s ti tution al contex ts. In conc lusi on, our s t u dy iden t i fi e d age , se x, CKD, b a sel ine CRP an d re spir ato r y invol vement a s fac t o r s a s s oc iat ed w ith ho spi tal mort alit y in COV ID-1 9 pati ent s admi tt ed to a la rge aca demic . CC-BY-NC-ND 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted July 17, 2020. ; https://doi.org/10.1101/2020.07.16.20155069doi: medRxiv preprint 11 hospi tal i n Londo n , U K . Pa tien t s tre at ed on the w ard an d in the I CU ha d s ig ni fica n t extrapulmo n ary dise a se, fre quen t tr eatm ent l imita tion s a nd a high b ur de n o f mort ality. Me dical ward s ca r i ng fo r CO VI D -19 p atie nt s expe r i e nced a sub sta ntia lly i ncrea s ed w or k load a nd requir ed f requen t I C U outre ac h input . In or d e r t o p r ovide e f fec tiv e c are und e r p and emic su r g e con ditio ns , s ig ni fica nt reorgani s ation t ook plac e w ithi n the ho s pital. As a r e s ult , w hen pla nning an e f fec t ive re spon se to suppo rt pa tien t s with C OV ID-1 9, cl inici an s and h ea lth a dmini stra tors shoul d c onsi der th e nee d for addi t i on al c r i t i cal car e re so urce s in th e IC U , as well a s t h e wide r h ospita l . . CC-BY-NC-ND 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted July 17, 2020. ; https://doi.org/10.1101/2020.07.16.20155069doi: medRxiv preprint 12 Ack nowledge ment s We tha nk Pro fe sso r Ali st a i r McGui re ( De partmen t o f Heal th Po licy , Lond on Sc ho o l of Ec onomic s) f or his va luabl e help i n th e pre para tion o f t h e manusc ript . We al s o th an k the Kin g’ s Co lleg e Ho s pi ta l Bus i n ess Int ell igenc e Uni t fo r providing us with he a t m ap ima ges o f th e pand emic evolu tion in th e area . We tha nk “Ea s y Mobile Fo rms S o ft w a re, The Dat aDyne Grou p, L LC” for pro viding 2 months o f fre e ac ces s to t h ei r dat a c ollec ti on tool M ag pi . Fi nally, the au thor s would like t o t ha nk t heir pa ti ent s a nd f ellow heal th-c a re wor ke r s for p rovidi ng out st a nding pa ti ent ca re at con sid erabl e per s on al ri sk . Competing int e r e s ts SV, AW, VM , S C, CL S, J P, KL , TP, CS , KA, B A , RB, FJ , S AH , WB a nd RM - no c ompeti n g intere st s dec lared Fundi ng No ex t e rna l fu nding Author contr i but ions SV a nd RM c onceive d the s tudy a nd it s d es i gn, h a d full ac ce ss to th e data , and t ak e re s po n s ibi li ty for the in teg r i t y o f the d a t a a nd a ccurac y of the analy s i s. S V, A W , V M , SC , CL S, J P, KL, T P, CS, KA, BA, RB , FJ, S AH , W B and RM ex t r a ct ed and en te r ed data . SV a nd RM cont ribut ed to d ata analy se s. S V , AW, VM, S C, CLS , JP, KL , WB an d RM c ont r i bu t e d to d ata i n t e rpre ta tion. S V and RM d ra fted th e manu s c r ip t. Al l auth or s critica lly r evis e d the dra f ted manu s c r ip t a nd app rove o f t he submi tt ed manu s c r ip t. . CC-BY-NC-ND 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted July 17, 2020. ; https://doi.org/10.1101/2020.07.16.20155069doi: medRxiv preprint 13 REF EREN C ES 1. World He al t h Organi z a tion . 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Mye r s L C, Pa rodi S M, E scoba r G J, L iu VX. Cha ra cte ristic s of H o spi tal ized Adul t s Wit h CO VI D-19 in a n Int egrat ed Hea l t h C are Sy s t em i n Cali f ornia . JAMA 2 020; 323 : 2195-8. 18. Roc kw ood K, S ong X, Ma cKnig ht C, et al . A globa l cl inica l mea sur e of fitn e ss and fr ailty in eld er l y pe ople . CMAJ 2 0 05; 173: 4 89-95. 19. Musce d ere J, W at ers B, Va r a mb ally A, et al . The i mpact o f f rail t y on in ten sive ca re unit outcome s: a sy st e m a t i c r e vi e w a n d m e t a - a n a l y si s. Int ens ive C a r e M ed 2017 ; 43: 110 5-22. 20. Obolen sky L, Clark T, Ma tt h e w G, Me rce r M. A pati ent an d r e la tive cent red ev alua tion of trea tmen t e sca la tion pl an s: a repl ac eme nt fo r the do - n o t-re su s c i tat e proce ss . J Med E t hi c s 2010; 36 : 518-20. 21. KDIG O. Sec t i on 2: AK I De fin i t i on. Kid ne y in t e r n a t i o n al s uppl em e nt s 2 012; 2: 1 9-36. 22. L as s al e C, G aye B, Hame r M, G ale C R, D a vid Batty G. E thnic Di s pa r i t i e s i n Ho s pi tal i s a t i on f or CO VI D-19 in E ngland : The Rol e o f Soc io e c onomic Fac tors, M ental He al th, and In fl ammatory a nd Pro -in fla mmato ry Fa ctor s i n a Commu nity -ba sed Cohor t Study . B r a i n Be hav I mm un. 2020 (In Pre s s). http s: / / doi.o rg/10.1 016 /j.bbi .202 0 .05.074 . 23. Pe iri s JS , Yuen KY, O s t erhau s A D, S tohr K. T he seve re a cut e re spi rat or y syndr ome. N Eng l J Me d 20 03; 349: 2431-41. 24. Arabi YM, Al -O m a r i A, M andour ah Y, et a l. Cri t i call y Ill Pa tien t s Wit h t h e Mid dle Ea st Re s pira tory S yndrome: A Mul tic en ter R et ro s pe ctive Cohor t Study . Crit Ca r e Me d 2017 ; 45: 16 83-95. 25. Guan WJ, Ni Z Y, Hu Y, et al . Cl inica l Char a c t e r i stic s o f Co rona viru s D i sea s e 2 019 in C hina. N En gl J Med 2020; 3 82: 1708 -20. 26. Jone s DA, De Vita M A, Be ll omo R. Ra pid- r es p on se t ea m s . N E n g l J M e d 2 011; 365 : 139-46. 27. Roy al Col leg e of Physici a ns. Ethica l dime nsion s o f C OV ID - 1 9 for fr on tli ne sta ff, 20 20. http s: //www .rcplon don. ac .uk/ new s/e t hi cal-g uidanc e -publi sh ed -f rontli ne - st a ff-d e a ling-pa nd emic (ac ce s sed Ap ril 18 , 2020). 28. L ovell N , Maddoc k s M , Etkind SN, et al . C haract eri st i c s, Sy mpt o m M anage men t, a nd O utco me s o f 10 1 Patie nt s Wi th C O V ID -19 Re fe rr ed for H ospi tal P allia t i ve Car e. Jo urna l o f P ain and S ympt om Mana gem ent 2 02 0; 60: e 77-e81 . 29. S pr u ng CL , Joyn t GM, Chri stia n M D , Truo g RD, Rel lo J, Na te s JL. Adult ICU Tri a ge D uring the Coron a viru s D i se a se 2 019 Pa nd emic: W h o W i ll L ive a nd Who Will Di e ? R ec omme ndation s t o Imp r ov e Survi val. Cr i t i cal C ar e M edic ine . 2 020 (In P re s s). . CC-BY-NC-ND 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted July 17, 2020. ; https://doi.org/10.1101/2020.07.16.20155069doi: medRxiv preprint 15 http s: //journal s .lww .com/cc mjournal /Fu l ltext/9000 /Adul t_ IC U_Triag e_ D uring _ th e_C oron avir u s_ Di sea se .9565 4.a spx . 30. May P, No rmand C, Ca ssel J B, e t al. E con omi cs of Pall ia tive C are for Ho s pi tal ized A d ult s Wi th S eriou s Illn e s s : A Me t a -an aly s i s . JAM A In tern Me d 2 018; 178 : 820-9. 31. F aus t o J, H iran o L, Lam D, e t al . Cr eati ng a Pa llia tive Ca re In p ati ent R e spon s e Plan for CO VI D-19 - Th e UW M e dicin e Expe r i ence . J P ain S ympto m Man age 20 20: S08 85-3924 (20)3 01 76-7. 32. F anelli V , Fio r e ntin o M , Can talup pi V, e t al . Acut e k idney injury in SARS- Co V-2 i n fe cted pa t i en t s . Crit Care 2020; 24 : 155. 33. Ya ng X, Yu Y, X u J, et al . Clinic al c ou rse an d outc ome s o f critica lly i ll pati e nts w it h S ARS- Co V-2 pne umonia in Wuh an, C hi na: a s ing le -ce n t e red , re t r os pec t ive , ob serv a tiona l st u d y . La ncet Re spi r Med 2020; 8: 475-81. 34. F owler RA, L apin sky SE, H a lle tt D, et al. C r i t ic all y ill pati ent s with seve re acut e re s pirato ry syndrome . JAMA 20 03; 290 : 367-73 . 35. Be llani G , L af fey JG, Ph am T, e t al. Ep id e miolog y, Pa ttern s o f C are , a nd Mor t a li ty for Pa t i e nts Wi th Ac ute R es pira tor y Di stre s s S yndrom e in I nten s i ve C a r e U ni ts in 5 0 Coun tri es . JA MA 2 016; 315 : 78 8-800. 36. L iang W , Lia ng H, Ou L, et al. Develo pme nt a nd V alida ti on o f a C linic al Ri sk S cor e t o Predi c t th e Occ urr e nc e of C r itic al Il lne s s in H o spi tali zed Pa tien t s W i t h COVI D-19 . JA MA I nter n Med. 2020 ( In Pre s s). http s: / / doi.o rg/10.1 001 /jamaint e rnmed .2020.20 33 . 37. Wu C, C hen X, C ai Y, et al . Ri sk Fac t or s A ssoci a ted Wi th Acu te R e s pi rat ory Di st r e ss Sy ndr o me and Dea th in Pa tien t s Wit h Cor onavi r u s Di s ea se 2019 Pn eumonia in Wuhan, China . J A MA In tern M e d. 20 20 (In Pr e s s ) . ht tp s ://doi .org /10.1 001/ jamainternm ed .2020.09 94 . 38. Pric e -Hayw ood EG, Burt on J, Fo rt D, Se o ane L . Ho s pi ta liz a ti on and M o rtali ty amo ng Black Patie n ts a nd Whit e Pa tien t s wi t h Covid -19. N En gl J Med 2020; 3 82: 2534 - 4 3. 39. Ka in T, F owle r R. P repa ring i nten s i ve c a r e for the nex t p andemic infl ue nz a . Crit C are 2019 ; 23: 33 7. 40. Gri ffin KM, Ka ra s MG, Ivas c u NS, L ie f L . Hos pi tal P repa redn e s s fo r C OVI D -19: A Pra c tical G ui de from a C r i t i cal Car e P er s p ec tive . Am J Re spir Crit Car e Med 2020; 201: 133 7-44 . . CC-BY-NC-ND 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted July 17, 2020. ; https://doi.org/10.1101/2020.07.16.20155069doi: medRxiv preprint 16 TABLE S Tabl e 1: Bas eline c harac teri s tics o f pat i ent s, b y a dmis s ion loc ati on. Da ta a r e r eport ed a s m edia n (I QR [r a ng e] ) or n (% ), or n / N (%) w hen s ome da t a a re mi s s i ng. Study population (n=429) Treated only on ward (n=353) Treated in ICU (n=76) A ge; years 65 (52-81 [18-97]) 68 (54-82 [18-97]) 57 (48-63 [25-79]) 18-2 9 12 (3%) 9 (2%) 3 (4%) 30-3 9 27 (6%) 21 (6 % ) 6 (8%) 40-4 9 37 (9%) 26 (7 % ) 11 (14%) 50-5 9 79 (18%) 56 (16%) 23 (30%) 60-6 9 90 (21%) 69 (19%) 21 (28%) 70-79 64 (15%) 55 (16% ) 9 (12% ) 80-8 9 82 (19%) 79 (22%) 3 (4%) ≥ 90 38 (9% ) 38 (11% ) 0 (0%) Se x Fe mal e 195 (45%) 169 (48%) 26 (34%) Male 234 (55%) 184 (52%) 50 (66%) Ethnicity * Bl a ck 187 /391 (48%) 148 (47%) 39 (53%) Asian 15 /391 (4%) 9 (3%) 6 (8%) Whi te 151 /391 (38%) 129 (40%) 22 (30%) Mix e d or ot he r 38/391 (10% ) 31 (10% ) 7 (9%) BMI † 26.6 (23.2-31.2 [14-94]) 26.2 (22. 8-31 .0 [14-49]) 27.8 (24.2-32.0 [20-40]) ≤ 2 5 115 /296 (39%) 90/222 (40 % ) 25/74 ( 34%) 26-3 0 91/296 (31%) 69/222 (31 % ) 22/74 (30%) 21-3 5 54/296 (18%) 36/222 (16 % ) 18/74 (24%) 36-4 0 18 /296 (6%) 13/222 (6%) 5/74 (7%) ≥ 40 18/296 (6% ) 14/222 (6%) 4/74 (5% ) ACCI ‡ 4 (2-6 [0-15]) 4 (2-6 [0-15]) 2 (1-4 [0-12]) 0 40/401 (10%) 33/33 (10%) 7 /70 (1 0%) 1 49/401 (12%) 34 (10%) 15 (21%) 2 51/401 (13%) 37 (11%) 14 (20%) ≥ 3 261 /401 (65%) 227 (69%) 34 (49%) IMD quinti le § 1 (Least dep rived) 9/427 (2%) 6/351 (2%) 3 (4%) 2 36 /427 (8%) 31/351 (9%) 5 (7%) 3 86/427 (20%) 72/351 (20 % ) 14 (18%) 4 204 /427 (48% ) 167/351 (48% ) 37 (49%) 5 (Most deprived) 92/427 (21% ) 75/351 (21% ) 17 (22%) Prior residence Home 382 (89%) 308 (87%) 74 (97%) Nursing home 31 (7% ) 30 (8% ) 1 (1.5% ) He alth-rel ated i nstitution 6 (1%) 6 (2%) 0 (0%) Other 10 (2% ) 9 (3%) 1 (1.5% ) Com orbid ities Hyp ertension 225 (52%) 187 (53%) 38 (50%) Diab etes mellitus 161 (37%) 122 (35%) 39 (51%) Coronary heart disease 41 (10%) 36 (10% ) 5 (7%) Chronic heart failure 28 (6% ) 28 (8% ) 0 (0%) Chroni c kidney diseas e 61 (14%) 54 (15% ) 7 (9%) End -sta ge renal di sea se 14 (3%) 12 (3 % ) 2 (3%) . CC-BY-NC-ND 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted July 17, 2020. ; https://doi.org/10.1101/2020.07.16.20155069doi: medRxiv preprint 17 Chroni c res piratory diseas e 51 (12%) 43 (12% ) 8 (10% ) Chroni c l ive r disea se 8 (2%) 6 (2%) 2 (3%) Cerebrovasc ular accident 57 (13%) 55 (16% ) 2 (3%) Imm unosuppression (incl. HIV ) 26 (6% ) 25 (7% ) 1 (1%) Sickle cell disease 7 (2% ) 5 (1%) 2 (3%) Active cancer or haem atological disease 41 (10%) 39 (11%) 2 (3%) Frailty Frai l 170 (40%) 156/351 (44 %) 14 (18%) Not frai l 259 (60%) 197/351 (56 %) 62 (82%) Chief pres enting symptoms Fe ve r 265 (62%) 212 (60%) 53 (70%) C ough 266 (62%) 212 (60%) 54 (71%) Dy spnoea 184 (43%) 143 (40%) 41 (54%) Fatigue 101 (23%) 80 (23%) 21 (28%) Lethargy 82 (19%) 67 (19% ) 15 (20%) Day s since symptom onset ¶ 3.5 (1-6 [0-37 ]) 3 (1-6 [0-37]) 4.5 (2-6 [0-14]) Reason for hospital admission Medi ca l (hypoxem ic respi ratory failure) 182 (42%) 125 (35%) 57 (75%) Med i ca l ( oth er reason) 215 (50%) 203 (57%) 12 (16%) Surgical or traum a 29 (7% ) 22 (6% ) 7 (9%) E l ective 3 (1%) 3 (1%) 0 (0%) Ini tial chest x-ray No abnormal fi ndi ngs 95/405 (23%) 88/329 (27 % ) 7 (9%) Di ffu se opa ci ties 155 /310 (50%) 105/241 (44 %) 50/69 (72%) Bi l ateral opa ci ties 178 /310 (57%) 124/241 (51 %) 54/69 (78%) Pl eural effusion 42/310 (13% ) 33/241 (14% ) 9/69 (13%) Abbrevi a tion s : I CU, Inte n s iv e Car e Unit; BMI , Bo dy Ma ss Index (ca lcula t e d a s wei ght in k ilog ram s divided by height in m eters squ are d); A C CI, Age - a dju sted Ch arl s on Com orbidi ty Inde x; IMD, I ndex o f Multiple D e p r i vation ; HI V, Human Immu nodefic i enc y Viru s . * E t hn icity was mi s s i ng in 3 8 pati ent s (9 %) † BMI wa s mis s in g in 13 3 pati ent s (31%) ‡ AC CI wa s mis s i ng for 28 pa t i en ts (6% ) § IMD w a s mi ssing in 2 pa t i en t s (< 1% ) ¶ Da ta on s ym pt o m on se t wa s mis s in g in 21 7/ 42 9 (51%) of p atie nt s . CC-BY-NC-ND 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted July 17, 2020. ; https://doi.org/10.1101/2020.07.16.20155069doi: medRxiv preprint 18 Table 2: Admis sion and mo s t a b nor ma l l ab or a t ory value s f or th e s tudy po pula tio n, by loc ation o f a dmissi on. Da ta are r ep orted as me dia n ( I Q R [ ran ge ] ) Stud y p o p ul ati o n ( n = 429 ) Tr ea t ed o nl y on w ard ( n = 353 ) Tr e at ed in I C U (n= 7 6) No rm al ran ge Ad m iss ion* M ost ab nor ma l † Ad m iss ion* M ost abn or mal † Adm issi on* M ost a b n or mal † Haemo glo bin; g .l -1 1 28 ( 11 0- 141 [4 4 - 19 3]) 1 10 ( 8 7 - 1 25 [4 4 - 17 1]) 1 27 ( 1 10- 140 [4 4-19 3]) 11 3 ( 97- 1 2 9 [44- 17 1 ]) 1 34 (114 -1 48 [56- 173]) 78 ( 68- 9 4 [52- 134]) 11 5-15 5 WB C; ×10 9 .l -1 6.7 ( 5.2- 9. 3 [0. 6 -1 0 0 ]) 9 .3 (6 .9 -13 . 3 [1. 4 -1 0 0 ]) 6 .5 (5 .0 -8 .8 [0. 6 -2 1. 6 ]) 8.6 ( 6.5- 1 1 .0 [1.4-4 8.9]) 8 . 2 ( 6 . 5- 11.2 [3 . 2-10 0]) 1 9 .5 (12 . 4 - 28 . 0 [5 . 4-1 00]) 4. 0 - 1 1. 0 Neu tro phils ; ×1 0 9 .l -1 5.2 ( 3.7- 7. 4 [0. 2 -2 0.5]) 7 .4 (5 .3 -11 . 2 [0. 8 -5 5.1]) 4 .9 (3 .6 -7 .0 [0. 2 -2 0. 5 ]) 6.8 ( 4.9- 9. 1 [0.8-3 9.6]) 6 .7 (4 .6 -9 .4 [1 . 7-19. 8]) 1 6 .8 (10 . 1 - 23 . 2 [3 . 9-5 5 . 1) 2. 2 - 6 .3 Lym phoc yt es; × 10 9 .l -1 1.0 ( 0.7- 1. 4 [0. 2 -9. 4 ] ) 0 .8 (0 .5 -1 .1 [0. 0 3- 8 5 ]) 1 .0 (0 .7 -1 .4 [0. 2 -4. 1]) 0.8 ( 0.6- 1. 1 [0.03- 85]) 1 .0 (0 .8 -1 .3 4 [0 . 5-9.4]) 0 .7 (0 .5 -0 . 8 [0 . 2-9.4]) 1. 3 - 4 .0 Pl at elets ; × 1 0 9 .l -1 2 13 ( 16 1- 278 [5- 908]) 1 87 ( 1 39- 237 [2- 790]) 2 10 ( 1 59- 279 [5- 908]) 1 89 (1 42 -2 43 [2- 790]) 2 19 (172 -2 74 [16- 511]) 1 74 (110 - 2 17 [6 - 6 52 ]) 15 0-45 0 CRP ; mg . l -1 75 (28 - 143 [0- 608]) 1 59 ( 8 1 - 2 99 [0- 686]) 61 (22 -1 19 [0. 2 -5 4 5 ) 14 3 ( 66- 2 1 8 [0- 545]) 13 4 ( 8 4- 239 [0 - 6 08 ]) 3 85 (310 - 4 87 [63- 686]) <5 Cr e a t in in e ; u mol . l -1 92 (68 - 130 [2 5 - 10 00]) 1 02 ( 7 7 - 2 07 [2 8 - 10 0 0 ]) 91 (68 -1 28 [2 5-10 0 0 ]) 97 ( 7 4 - 1 4 3 [28- 10 00]) 96 ( 69- 1 50 [29- 671]) 3 24 (108 - 5 33 [39- 100 0]) 45- 12 0 AST; IU.l -1 4 3 ( 2 9 - 6 9 [7- 172 5 ] ) 70 (44 -1 22 [1 2 - 10 0 00) 39 (27 -5 9 [7- 172 5]) 59 ( 3 9 - 9 2 [12- 65 30]) 63 ( 39- 1 02 [23- 769]) 1 96 (104 - 3 96 [37- 100 0 0 ] ) 10- 50 GGT; IU.l -1 4 7 ( 2 6 - 9 4 [6- 827]) 74 (40 -1 82 [6- 254 0]) 44 (25 -8 8 [6- 827]) 64 ( 3 5 - 1 2 6 [6- 110 6 ]) 64 ( 39- 1 13 [9 - 6 04 ]) 2 37 (106 - 4 33 [16- 254 0]) 1 -55 Biliru bi n ; u mol.l -1 8 (5 -11 [1 -13 1 ] ) 10 (7 -15 [2 -2 97 ] ) 7 (5 -11 [1 -13 1 ] ) 9 (6 -13 [2 -13 1 ] ) 9 (6 -1 3 [1 -5 1 ] ) 1 5 (1 0 -23 [4 -29 7 ]) 3 -20 Crea ti n e kina se; U . l -1 3 68 ( 89- 1 553 [0- 322 40]) 5 46 ( 1 08- 187 0 [0- 100 00 0) 3 74 ( 8 8 - 1 628 [0- 215 2 6 ]) 31 1 ( 78- 1 6 2 8 [17- 10 00 0 0 ]) 31 8 ( 9 0- 136 3 [21- 322 4 0 ]) 7 73 (168 - 2 091 [0 - 2 152 6]) < 150 LDH ; U.l -1 4 76 ( 35 5- 670 [ 12 8 - 12 21 ] ) 5 22 ( 3 53- 748 [1 42-2 5 74]) 3 65 ( 2 29- 496 [1 28-7 6 6 ]) 3 50 (2 52 -4 96 [14 2-2 57 4]) 5 64 (426 -7 57 [24 9-12 2 1 ]) 6 28 (466 - 8 05 [ 2 39 - 1 971 ]) < 240 T r op on in T ; ng . l -1 2 5 ( 1 1-5 4 [ 2 - 1 852]) 3 5 ( 1 5- 85 [ 2 - 5 33 4 ]) 2 5 ( 1 1- 60 [ 2-1 37 6 ]) 27 ( 1 1 - 6 5 [2- 4 426]) 26 ( 10- 5 1 [ 3- 1 8 5 2) 51 ( 22- 1 74 [ 3- 5 3 3 4 ] ) < 1 4 Fe rriti n; ug.l -1 9 14 ( 29 8- 159 6 [0- 284 32]) 1 039 ( 39 9-23 7 4 [0- 100 00 0) 6 66 ( 2 58- 137 4 [1 0-28 4 32]) 8 77 (3 04 -1 512 [10- 53 49 6]) 11 57 ( 4 87-1 7 77 [0 - 6 217]) 16 30 ( 6 83-3 4 23 [ 0 -10 0 000 ) 13- 15 0 D- di m ers; n g .l -1 18 5 0 ( 805 - 4 090 [0- 800 0 ] ) 1 850 ( 80 5-40 9 0 [0- 800 0]) 1 315 ( 61 0-24 7 0 [2 70-8 0 00]) 13 15 ( 6 1 0 -2 4 70 [27 0-8 00 0]) 32 40 ( 1 160- 6 95 0 [0 - 8 000]) 32 40 ( 1 160- 6 95 0 [ 0 -80 0 0 ] ) < 500 Lactate; mm ol .l -1 1.5 ( 1.1- 2. 0 [0. 4 -8. 5 ] ) 1 .7 (1 .3 -2 .5 [0. 4 -2 9]) 1 .5 (1 .1 -2 .1 [0. 4 -5. 5]) 1.5 ( 1.2- 2. 2 [0.4-9. 4 ]) 1 .5 (1 .1 -1 .9 [0 . 5-8.5]) 2 .3 (1 .8 -4 . 8 [0 . 8-2 9 ]) <2 . CC-BY-NC-ND 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted July 17, 2020. ; https://doi.org/10.1101/2020.07.16.20155069doi: medRxiv preprint 19 Abbrevi a tion s : W B C, Whit e Bl ood Cell s ; C RP, C -re activ e pro tein ; AS T , Asp arta t e Aminot ran s f e r a s e; GGT, Gam ma-glu tamy l Tran s fer as e; LDH, L acta t e Dehydrogena se . * Admi ssi on la bora to r y te s t s wer e n ot p e r form ed or avai lab le fo r th e foll owin g number of pa tien t s : H a e moglobi n 1/429 (< 1% ), Whi t e blood cell s 2/429 (<1%), Neu trophil s 1 /429 (< 1% ), L ymphoc ytes 1 / 4 29 (<1% ) , Pla tel e ts 8/429 (2% ), C- reac tiv e prot ein 2/429 (<1%), Cr ea t i ni n e 1/429 (< 1% ), AST 35/429 (8% ) , G GT 18/ 4 29 (4% ), Biliru bin 5/429 (1%) , C reati ni ne Kina se 3 45 / 4 29 (80% ) , LDH 363 /429 (85 %), Trop oni n 271/429 (63 % ), Fe rritin 3 18 / 4 29 (74% ), D-di me rs 309/429 (72 %), L acta te 8 6 / 429 (20%) . † Sub sequ ent l a bora to r y te sts w e r e n ot pe rfo rmed for the foll owi ng numb e r of p ati en ts: Haemo globin 8/ 4 29 (2%) , White blood c el l s 9/ 4 29 (2%) , N e utrophi l s 7 /429 (2%), Lymp hocyte s 9 / 42 9 (2% ), P la tel et s 8 /429 (2%), C -re activ e pr o tei n 6 /429 (1%) , Cr ea tinine 6 /4 29 (1%), AST 25 /429 (6%), G GT 14/429 (3%), Bili rubin 9/ 4 29 (2 % ), Cr ea t i nine Kina se 339 / 4 29 (7 9%), LDH 356 / 429 (83% ) , Troponi n 266 / 42 9 (62% ), F e rr itin 302/429 (70% ) , D -dime r s 309/429 (72 %), L acta te 1 15 / 4 29 (27% ) . CC-BY-NC-ND 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted July 17, 2020. ; https://doi.org/10.1101/2020.07.16.20155069doi: medRxiv preprint 20 Tabl e 3: Clinic al find i ngs a nd outcome s during th e ho spi tal a dmi s si on. Da ta a r e repor ted a s medi a n (I QR [r a ng e] ) or n (% ), or n / N (%) w hen s ome da t a a re mi s s i ng Study population (n=429) Treated only on ward (n=353) Treated in ICU (n=76) F e v e r on wa r d * † 280 /3 82 (72 % ) 25 2 / 349 (72 % ) 28 / 33 ( 82% ) Pe r sist e n t h y poxi a * ‡ 1 0 5 / 38 6 ( 2 7%) 7 4 / 35 3 ( 2 1% ) 3 1/3 3 (9 4% %) N on - i nv a s i ve r es pi r a to r y sup po r t * § 17 /3 86 (4% ) 9 /3 53 ( 2%) 8 / 33 (2 4% ) S B P 1 hou r * 40 /3 86 (1 0 %) 37 /3 53 (10 %) 3 / 33 (9 % ) H e a rt ra t e > 120 /m inu te fo r > 1 ho u r * 43 /3 86 (1 1 %) 38 /3 53 (11 %) 5 / 33 (1 5% ) A VP U sc o r e V o r b e l ow fo r > 1 h ou r * 22 /3 86 (6% ) 1 9 / 353 (5% ) 3 / 33 (9 % ) N EW S 2 s c o r e > 6 *¶ 195 /3 78 (52 % ) 16 6 / 346 (48 % ) 31 / 32 ( 91% ) I C U ou t r e a ch i nv o lv e m en t * 152 /3 86 (39 % ) 87 /3 53 (25 %) 32 / 33 ( 97% ) COVI D- 19-s pecific dru g trea tme nt * * 7 ( 2 %) 2 / 35 3 (1 % ) 5/7 6 ( 7%) S u b seq u en t ch e st x- r ay 198 (46 % ) 12 4 / 353 (35 % ) 74 / 76 ( 97% ) No a bnorm al f in din g s 2 1 / 19 8 ( 11% ) 1 9 / 12 4 ( 1 5% ) 2/7 4 ( 3%) Di f fu se o p a c i t ie s 128 /1 77 (72 % ) 64 /1 05 (61 %) 64 / 72 ( 89% ) B i la t e r a l o p a c i t ie s 141 /1 77 (80 % ) 76 /1 05 (72 %) 65 / 72 ( 90% ) P l eu r a l e f fu si on 46 /1 77 (2 6 %) 34 /1 05 (32 %) 12 / 72 ( 17% ) Pn e u m o t h o r a x 3 / 17 7 (2% ) 0( 0%) 3/7 2 ( 4%) C he st CT 59 (14 % ) 2 9 / 353 (8% ) 30 / 76 ( 39% ) D i f fu se G G O s o r c on so l id a ti on 43 /5 9 ( 7 3% ) 1 5 / 29 ( 5 2% ) 28 / 30 ( 93% ) B i la te r al G G Os o r c on so l ida ti on 47 /5 9 ( 8 0% ) 1 9 / 29 ( 6 5% ) 28 / 30 ( 93% ) Pulm o na ry em bolis m 1 5 / 59 (25 %) 5 / 29 ( 1 7 % ) 1 0/3 0 (3 3 %) O rg an i s i n g p ne u mon i a 8 /5 9 (1 4 %) 4 /2 9 (1 4%) 4 / 30 (1 3% ) F i brosi s 7 / 59 ( 12% ) 0( 0%) 7/3 0 ( 23 %) Ech ocardio gram 5 7 ( 1 3%) 2 2 ( 6% ) 3 5/7 6 (4 6 %) LV Ej ectio n Fracti o n < 5 5% 1 0 / 57 (17 %) 7 / 22 ( 3 2 % ) 3/3 5 ( 9%) R e g ion a l w a l l m o ti on abn o r ma l it i es 3 /5 7 (5 %) 1 / 22 (4 %) 2 / 35 (6 % ) Pul mo na r y h y p ertens io n † † 1 3 / 57 (23 %) 4 / 22 ( 1 8 % ) 9/3 5 ( 26 %) TA PS E< 1 7 m i l li me t r e s 2 /5 7 (3 %) 1 / 22 (4 %) 1 / 35 (3 % ) Pe r i c a r d i al e f f u s i o n 4/ 5 7 ( 7% ) 4/ 2 2 ( 18 % ) 0 ( 0 % ) V a s c ul a r sc an 23 (5 %) 6 (2% ) 17 / 76 ( 22% ) D ee p v e in th ro mb o si s 5 /2 3 (2 2 %) 2 / 6 (33 %) 3 / 17 (1 8% ) Pos itive r e s pira tor y sa mple ‡ ‡ 4 6 ( 1 1%) 8 ( 2 %) 3 8/7 6 (5 0 %) Gra m p o s it ive or ganis m 4 / 42 ( 9 % ) 1/8 ( 1 2 % ) 3/3 8 ( 8%) G r a m n e g a ti v e o r g a ni s m 32 /4 6 ( 7 0% ) 3 / 8 (37 %) 29 / 38 ( 76% ) V ir a l 1/ 4 6 ( 2% ) 1 / 8 ( 1 2% ) 0 ( 0 % ) F ung a l 19 /4 6 ( 4 1% ) 3 / 8 (37 %) 16 / 28 ( 42% ) Pos itive bl ood sa mple ‡‡ 5 7 ( 1 3%) 2 6 ( 7% ) 3 1/7 6 (4 1 %) G r a m po si ti v e o rg a n i sm 38 /5 7 ( 6 7% ) 1 9 / 26 ( 7 3% ) 19 / 31 ( 61% ) G r a m n e g a ti v e o r g a ni s m 15 /5 7 ( 2 6% ) 7 /2 6 (2 7%) 8 / 31 (2 6% ) V i r a l 13 /5 7 ( 2 9% ) 2 / 26 (8 %) 11 / 31 ( 35% ) F ung a l 5 /5 7 (9 %) 0 (0% ) 5 / 31 (1 6% ) T r e at me n t l i m i ta t io n s on wa r d * 236 /3 86 (61 % ) 23 2 / 353 (66 % ) 4 / 33 (1 2% ) T r e a tm en t e s ca la t io n p l a n 198 /2 36 (84 % ) 19 6 / 232 (84 % ) 2 / 4 (5 0 % ) Do - N ot -R e su s c i ta te o r de r 203 /2 36 (86 % ) 20 0 / 232 (86 % ) 3 / 4 (7 5 % ) T i m e t o ins t it ut io n o f TE P o r D NR , d ay s 0 (0 -1 [ 0 -6 1 ] ) 0 (0 -1 [ 0 -6 1 ] ) 4 (0 -13 .5 [0 -18 ] ) D e c e a se d a t ho sp it a l d i sch a rg e , o r 30 da y s 112 (26 % ) 83 (23 % ) 2 9 (38 %) Hos pi ta l l e n g th of s ta y , d ays § § 10 ( 4 - 2 2 [ 1 - 6 7]) 8 ( 4- 18 [ 1 - 6 7]) 2 0 ( 12- 3 5 [ 2- 55]) a mon g su r v iv o rs 8 (4 -2 0 [1 -67 ] ) 7 (4 -1 5 [1 -67 ] ) 13 (9 -16 [2 -39 ] ) am ong no n-s ur v i v o r s 10 ( 4 - 2 4 [ 0 - 6 5]) 8 ( 4- 2 0 [ 0- 65 ] ) 3 4 ( 16- 3 8 [ 6- 55]) Abbrevi a tion s : IC U , In ten s i ve Ca r e Uni t; NE WS2, Na t i o nal E arly Warning Sco re ver s i on 2; S B P , Sy s tolic Bl ood P r e s sure ; F i O 2 , F ra ct i o n of i n s p i re d O x y ge n ; AV P U, “ A l er t , Ve r b al, Pa i n , U n r es po ns i v e ” . CC-BY-NC-ND 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted July 17, 2020. ; https://doi.org/10.1101/2020.07.16.20155069doi: medRxiv preprint 21 scal e ; COVI D19, Cor ona viru s-Di se a se -19; CT, Com pute d Tomogr aphy ; G G O, G rou nd - Gl a s s O p ac itie s ; LV, Lef t V entricl e; TA PSE , Tricu spid A n nul ar Pla n e Sy stolic Ex curs i on . * Th e s e re sul t s apply to 3 86 p atien t s: all 35 3 ward pa tie n ts and 3 3/ 76 (43%) I CU patien t s who w e r e admitt ed to t he I CU a fter be ing a dmit t e d to the wa r d for 12 hou r s or longe r. † D ef ine d a s t e mpe ratu r e of 38.0 o C (100. 4 o F) o r ab o v e. T e m p e ra t ur e was mi s s in g in 4 / 38 6 p at i e n ts (1% ) ‡ D efin e d a s oxyg en r equirem ent of mo re tha n 15 litr e s pe r minut e (o r F i O 2 o f 0 . 6 or above ), for o n e hou r o r l onge r § D efi ned as ne ed for hi gh- flow n as al o x ygen, c ontinuou s p o s itiv e airway pre ss ur e (C PA P) or n on - in vasive ventil atio n (NIV ), f or on e hour o r longe r ¶ N E W S 2 s c o r e w a s m i s s i n g f o r 8 / 3 8 6 p a t i e n t s ( 2 % ) . A N E W S 2 s c o r e a b o v e 6 i s c o n s i d e r e d a t r i g g e r f o r IC U o ut r eac h t ea m a ss ess m en t ** COVI D-19 - spec i fic drug tre atmen t includ ed th e admini stra tion o f on e of t he f o llowin g me dicatio n s speci fic all y f or th e purpo s e of t r ea ting COVI D -19: huma n IL -1 r ece ptor an tago ni sts , c hloroquine , hydroxy chloroqui n e, d ex ametha son e, i n t e rfe ron -be ta, l op inav ir -ri tonav ir , remde s iv ir, t ocili z umab , and me senc hyma l stem cell th erapy †† De fined a s e s tima t e d Ri ght Ve n t ric ul ar Sys tolic P re s s ur e abo ve 35 mmHg or max imal Tric us p i d Re gurgita tion v eloci t y (TR Vmax ) abov e 2 .8 m etres p er sec ond ‡‡ N umb e rs re fe r to pa tien t s, not sampl es § § F or i n pa t i en ts a t s t u d y o ns et , l e n g t h o f st a y was c a l cu l at e d fr o m t he st a rt of t h e f ol l o w - up per io d (F ebru ary 2 5 th , 20 20). T ho se who rema ine d ad mitted to h o s pi tal at the end o f the follow - up pe r io d (Ap ril 30 th , 2 0 2 0 ) w e r e c o n s i d e r e d s u r v i v o r s a n d l e n g t h o f s t a y w a s c a l c u l a t e d u n t i l t h a t da t e . . CC-BY-NC-ND 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted July 17, 2020. ; https://doi.org/10.1101/2020.07.16.20155069doi: medRxiv preprint 22 Tabl e 4: Pa t i en t manag eme nt an d outco mes in the In ten sive Ca re U ni t. Da t a a re r eport ed a s medi a n (I QR [r a ng e] ) or n (% ) Study population (n=76) Feve r i n t h e IC U * 5 7 ( 7 8%) C P A P o r N IV 10 (13 % ) Mech a n ical v e n til a t io n 7 4 ( 9 7%) Du r a ti on ; da y s 1 2 (6 -2 3 [1 -37 ] ) R e n al re p la ce m en t the r a p y 43 (57 % ) Du r a ti on ; da y s 1 1 (4 -1 7 [1 -37 ] ) Pharmaco l o gica l circ ul a t ory s up p ort † 6 1 ( 8 0%) D ura t io n; d ays 8 ( 4- 14 [ 1- 39]) SOFA sc o r e ‡ D a y 1 ( ad m i ss io n) 14 (13 -16 [7 -20 ] ) D ay 3 15 (12 -17 [7 -20 ] ) D a y 7 1 5 ( 1 3- 1 7 [ 9- 2 0 ] ) Da y 1 0 1 5 ( 14- 1 6 [ 8 [ 7 - 2 0]- 20]) D ay 14 14 (12 -17 [8 -20 ] ) High est F i O 2 ‡ Day 1 (a dmis si on ) 0. 6 ( 0. 5 - 0. 8 [ 0. 3- 1 ]) D ay 3 0 .5 (0 .4 -0 .6 [0 .28 - 1 ]) Da y 7 0. 5 ( 0. 4- 0 . 7 [ 0 . 2 5 -1] ) D ay 10 0 .5 (0 .4 -0 .7 [0 .21 - 1 ]) D ay 14 0 .4 (0 .3 -0 .7 [0 .21 - 1 ]) Low e s t P a O 2 /F i O 2 ra ti o; kPa ‡ Day 1 (a dmis si on ) 1 7.5 ( 1 3 . 7-2 5 [ 8-60]) Da y 3 1 9 . 2 ( 14- 24.7 [ 8-42. 5 ]) Da y 7 1 9 ( 1 2. 5 - 27. 5 [ 7-45]) Da y 1 0 20. 5 ( 1 5- 2 9 [ 7-46] ) Da y 1 4 2 3.7 ( 1 4 - 30. 2 [ 9-53]) Resc ue oxygen atio n s trat egies 4 1 ( 5 4%) N e ur om u s c ula r b lo c ki ng dru g s 3 1 ( 4 1%) In ha l ed pros tacycl in 2 2 ( 2 9%) P r o n e posi ti on ing 1 9 ( 2 5%) ECMO 4 ( 5 % ) T r a che os to my 27 (38 % ) Time t o trache os to my; d ays 16. 5 ( 1 4- 20 [ 1 0 -3 8]) Tre a tm ent limit ati ons in I C U 1 8 ( 2 4%) Do - N ot -R e s u sc i ta te (D NR ) o rd e r 1 5 ( 2 0%) Ti me t o DN R or der; da y s 6. 5 ( 4- 1 3 [ 0- 22]) Tre a tm ent escal a t io n p l an ( T E P) 1 6 ( 2 1%) T im e to T E P o rd e r ; day s 7 .5 (3 .5 -12 . 5 [0 -3 6 ]) Tre a tm ent wit h draw al 8 ( 10% ) Ti me t o w it h d rawa l; da ys 1 2 ( 4 . 5- 18 [ 3- 36]) D e c e a se d a t I C U d i sc ha rg e , o r 30 d ay s 26 (34 % ) I C U l en g th o f st a y ; d ay s § 1 3 (7 -3 0 [1 -51 ] ) a mo n g s u rv iv o r s 1 9 (9 -3 2 [2 -51 ] ) a m on g n on - s u rv iv o r s 1 1 (5 -1 4 [1 -39 ] ) Abbrevi a tion s : CP AP: Con tinuou s P o sitiv e A i r w ay P res su r e ; N I V: Non- inv asive Ve nt i lati on; S O F A: Se quen tial O rgan Failur e As se ssmen t; P a O 2 : Par tial pre ssure o f oxy gen in art erial bl ood; F i O 2 : Frac tion o f In spi red Oxy gen; E C M O: Ex tra corpor eal Mem b r a ne Oxyg enation; ICU : Inten siv e Car e Unit. * De fine d as tempe ra ture o f 38. 3 o C (101 o F) or a bove . CC-BY-NC-ND 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted July 17, 2020. ; https://doi.org/10.1101/2020.07.16.20155069doi: medRxiv preprint 23 † De fine d as u se of a ny vasopr e ssor or in otropic drug ‡ Da ta ar e mis s in g f or 1 pati e nt ( 1 %) § T hose who rema in ed ad mit t e d t o ho s p i t a l at the e n d of t he f ollo w-u p period ( Ap ril 30th, 2020 ) were c on sider ed sur v ivor s and l eng th of st ay w as cal cula ted un til tha t dat e. . CC-BY-NC-ND 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted July 17, 2020. ; https://doi.org/10.1101/2020.07.16.20155069doi: medRxiv preprint 24 Tabl e 5: Ex amples of o pe r a ti onal c hange s a cro ss di ff ere nt r es ource d om ain s over the study p e r i od Resour c e domain Resour c e ex ample O perational chang es Mate rial Fa cilitie s Rec onfigu rati on of e xisti ng 4 ICUs f or in f ec t i on cont rol Opening o f 3 new ICU s i n non -conv en tio nal area s I C U c ap a c i t y e x p an s io n fr om 6 9 t o 1 29 be d s on s ho r t n ot ic e Rec onfigu rati on of a numb er o f w ard s f o r CO VI D -19 isol atio n Equip ment Real loca tio n or lo an o f 26 ve n t i lat ors Real loca tio n or lo an o f 12 RRT ma chin e s Redep loymen t o f 3 8 ana e sthet ic mac hines Rec onfigu rati on of e lect ronic heal t h r ec o rd for a dditio na l bed ca paci t y Ex pendable s a nd medic ine s Supp ly c hain foc u s on ava ilabi li ty of P PE Ration a lise d u se o f seda tive s a nd RRT fl u id s Workf orce Staf f Redep loymen t o f c ons ultan t Ana e sth eti sts Redep loymen t o f s ta ff from o ther d epar t ment s (56 nur s es, 39 doc t or s ) Formation of t eam s f or intub atio n, pron e pos i t io ning, tran s fe r, a n d t r a che os t om y Reorga ni s a t i on an d e xpan sion o f s enio r r ota w ith 24- hour c o ns u lt a nt pr es en ce Staf f w ellb ei ng and suppo rt ini t i a tive s Human re sour c e s Time and L abour Rec onfigu rati on of e ntire critica l c a r e s e rv ice delive r y model t o inc lude e xtr a ca p acity , proce s se s a nd s ta ff Devel opm ent o f new tre a tment guide lin es , prot ocol s and SO P s (22 doc ument s ) Devel opm ent o f tr aining and simula t i on materi al Provi sion o f t ra in ing an d sim ulatio n (28 trai ning s e ssion s v ia telec on f erenc e ) Or g ani sa tion Provi sion o f C PA P out s i d e the ICU by Re spi r a t o ry physici an s Provi sion o f dialy s i s (27 pa t i ent s) an d pe r itonea l dialy s i s (11 pa t i ent s) in t h e I CU Rec onfigu rati on of Gov ern ance and Ri sk ma nage ment Abbrevi a tion s : PPE, Pe rso nal P r ot ec tive E quipment; RRT , R enal R eplac eme nt The r a py; AHP , Alli ed Health Pro fe s s i on s; SOP , Sta nda r d Oper a ting Proce dure ; C P AP , Co ntinu ou s Po sit ive Ai r w ay P res su r e . . CC-BY-NC-ND 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted July 17, 2020. ; https://doi.org/10.1101/2020.07.16.20155069doi: medRxiv preprint 25 F I GUR E LEG EN D S Fi g u r e 1 : Th e st ud y flow diagram. Fi g u r e 2 : A pl ot of the prim ary o ut c ome ( hazard o f de a th a t ho spital di s c h arge or 30 days) ove r time fo r six hypoth etic al p atie nts, ba s ed o n the pa rame tric survi val analy s i s . Pa tie nt s c ha ract eri stic s we r e adju ste d to high light the a ddi tional ef fect o f ind ividua l ri s k f actor s on the ha z ard of d e a th. Pati e nt A r e pre sen t s a fem a le 40-y ear ol d pa t i en t with no r ma l C- reac tiv e pro tein le vels (CR P <5 mg.l - 1 ), no Ch roni c Kidn ey Di sea s e ( CKD ) and no dyspno ea o n pr e s e n t a t i o n. P ati ent B rep r e s ent s a ma le 40-y ear old p a t i ent with no rma l CR P, no CKD and no dy s p no ea. Pa ti ent C rep re se nts a 65-yea r old mal e pati ent w ith no rmal CR P , no CKD a nd no dyspno ea . Pati ent D rep re se nt s a 6 5-ye ar old ma l e patie n t with an abn ormal C RP o f 200 mg .l -1 , no CKD and no dy spnoe a. P ati ent E i s simila r with Pati e nt D b ut ha s a hi s tor y o f CKD . Fi nall y , Patie nt F re pre sent s a 6 5 -year ol d mal e patie nt wi t h an abno r ma l C RP o f 20 0 mg.l -1 , a hi story o f CKD a nd pr e s e n t a ti on to ho spi tal w ith dy spno ea. Fi g u r e 3 : A pl ot o f th e su r g e o f pati e nts a dmi t ted with CO VI D - 1 9 over th e study p er i od t o the wa r d and the IC U. L ef t pan el : N u mb er o f new patien t s admit ted da ily. Ri gh t pan el : O v erall num be r (ce n s u s) o f pa tien ts ho spitali s ed w ith C OVI D-19 . . CC-BY-NC-ND 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted July 17, 2020. ; https://doi.org/10.1101/2020.07.16.20155069doi: medRxiv preprint 2728 Patients tested between February 25 and March 31, 2020 2558 (94.5%) Patients screened for inclusion 429 (16.8%) Patients included in the study 2129 (83.2%) Patients excluded: 1856 (87.2%) negative SARS-CoV-2 test 273 (12.8) less than 18 years old 170 (5.5%) Patients excluded: 58 (34.1%) missing test results 112 (65.9%) missing identifiers 353 (82.3%) Patients admitted only to ward 76 (17.7%) Patients admitted to ICU . CC-BY-NC-ND 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted July 17, 2020. ; https://doi.org/10.1101/2020.07.16.20155069doi: medRxiv preprint 0 .02 .04 .06 .08Hazard function 0 10 20 30 Analysis time (days) Patient F Patient E Patient D Patient C Patient B Patient A . CC-BY-NC-ND 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted July 17, 2020. ; https://doi.org/10.1101/2020.07.16.20155069doi: medRxiv preprint 0 10 20 30 40Daily COVID-19 admissions (N) Mar 01 Apr 01 May 01 OCCUPANCY_DATE Admitted to ICU Admitted to ward 0 50 100 150 200 250Daily COVID-19 patient census (N) Mar 01 Apr 01 May 01 OCCUPANCY_DATE Admitted to ICU Admitted to ward . CC-BY-NC-ND 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted July 17, 2020. ; https://doi.org/10.1101/2020.07.16.20155069doi: medRxiv preprint