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3/16/2020COVID-19-EMCritProjecthttps://emcrit.
org/ibcc/covid19/1/24Searchthesite.
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COVID-19March2,2020byJoshFarkasCONTENTSBasicbiology(#biology)InfectioncontrolTransmission(#transmission)Personalprotectiveequipment(PPE)(#personal_protective_equipment_(PPE))Screening&selectionforinvestigation(#screening_&_selection_for_investigation)DiagnosisSigns&symptoms(#signs_and_symptoms)Labs(#labs)ImagingCXR&CTscan(#CXR_&_CT_scan)Lungultrasonography(#lung_ultrasonography)Generalapproachtoimaging(#general_approach_to_imaging)Bronchoscopy(#bronchoscopy)Diagnosticapproachforadmittedpatients(#diagnostic_approach_for_admitted_patients)TreatmentOverviewKeyprinciple:supportivecareforviralpneumonia(#key_principle:_supportive_care_for_viral_pneumonia)GeneraltemplateforintubatedICUpatients(#general_template_for_intubated_ICU_patient)Potentialanti-viraltherapiesBackgroundonantiviraltherapy(#background_on_antiviral_therapy)Remdesivir(#remdesivir)Lopinavir/Ritonavir(KALETRA)(#lopinavir/ritonavir_(KALETRA))Chloroquine(#chloroquine)Oseltamavirandotherneuraminidaseinhibitors(#oseltamavir_&_other_neuraminidase_inhibitors)TOCABOUTTHEIBCCTWEETUSIBCCPODCASTAIRWAYARCHIVES3/16/2020COVID-19-EMCritProjecthttps://emcrit.
org/ibcc/covid19/2/24ImmunomodulatorytherapySteroid(#steroid)Tocilizumab(#tocilizumab)Anti-bacterialtherapy(#anti-bacterial_therapy)Cardiovascular(#cardiovascular)PulmonaryNoninvasiverespiratorysupportHighownasalcannula(HFNC)(#high_ow_nasal_cannula)BiPAP(#noninvasive_ventilation_(BiPAP))Intubationprocedure(#intubation_procedure)Invasivemechanicalventilation(#invasive_mechanical_ventilation)Disasterventilationstrategies(#disaster_ventilation_strategies)Renalfailure(#renal_failure)ECMO(#ECMO)Prognosis(#prognosis)Disposition(#disposition)Questions&discussion(#questions_&_discussion)Pitfalls(#pitfalls)PDFofthischapter(https://emcrit.
org/wp-content/uploads/2020/03/COVID-19-3-6.
pdf)(orcreatecustomizedPDF(https://emcrit.
org/ibcc/about-guide/#pdf))biology(backtocontents)(#top)basicsCOVID-19isanon-segmented,positivesenseRNAvirus.
COVID-19ispartofthefamilyofcoronaviruses.
Thiscontains:(i)Fourcoronaviruseswhicharewidelydistributedandusuallycausethecommoncold(butcancauseviralpneumoniainpatientswithcomorbidities).
(ii)SARSandMERS–thesecausedepidemicswithhighmortalitywhicharesomewhatsimilartoCOVID-19.
COVID-19ismostcloselyrelatedtoSARS.
Itbindsviatheangiotensin-convertingenzyme2(ACE2)receptorlocatedontypeIIalveolarcellsandintestinalepithelia(Hamming2004(https://www.
ncbi.
nlm.
nih.
gov/pubmed/15141377)).
ThisisthesamereceptorasusedbySARS(hencethetechnicalnamefortheCOVID-19,"SARS-CoV-2").
Whenconsideringpossibletherapies,SARS(a.
k.
a.
"SARS-CoV-1")isthemostcloselyrelatedvirustoCOVID-19.
COVID-19ismutating,whichmaycomplicatemattersevenfurther(gurebelow).
Virulenceandtransmissionwillshiftovertimes,inwayswhichwecannotpredict.
NewevidencesuggeststhatthereareroughlytwodifferentgroupsofCOVID-19.
ThisexplainswhyinitialreportsfromWuhandescribedahighermortalitythansomemorerecentcaseseries(Tangetal.
2020(https://academic.
oup.
com/nsr/advance-article/doi/10.
1093/nsr/nwaa036/5775463#.
XmA64GbsBuI.
twitter);Xuetal2020(https://www.
bmj.
com/content/368/bmj.
m606)).
ImageshowingevolutionofCOVID-19here(https://i0.
wp.
com/emcrit.
org/wp-content/uploads/2020/03/covid88evo.
jpgresize=1536%2C1218&ssl=1).
Ongoingphylogeneticmappingofnewstrainscanbefoundhere(https://nextstrain.
org/ncov).
nomenclatureusedinthischapterTechnically,thevirusissupposedtobecalled"SARS-CoV-2"andtheclinicalillnessiscalled"COVID-19.
"Thisgetsconfusing,soforthischapterthetermCOVID-19willbeusedtorefertobothentities.
Theterm"SARS"willbeusedtorefertotheoriginalSARSvirusfrom2003(whichhascurrentlybeenrenamedSARS-CoV-1).
pathophysiology(1)ARDSTheprimarypathologyisARDS,characterizedbydiffusealveolardamage(e.
g.
includinghyalinemembranes).
Pneumocyteswithviralcytopathiceffectareseen,implyingdirectvirusdamage(ratherthanapurelyhyper-inammatoryinjury;Xuetal2/17)(https://www.
thelancet.
com/action/showPdfpii=S2213-2600%2820%2930076-X).
(2)CytokinestormEmergingevidencesuggeststhatsomepatientsmayrespondtoCOVID-19withanexuberant"cytokinestorm"reaction(withfeaturesofbacterialsepsisorhemophagocyticlymphohistiocytosis(https://emcrit.
org/pulmcrit/sepsis-hlh-overlap-syndrome-shlhos/)).
ClinicalmarkersofthismayincludeelevationsofC-reactiveproteinandferritin,whichappeartotrackwithdiseaseseverityandmortality(Ruan3/3/20(https://link.
springer.
com/article/10.
1007/s00134-020-05991-x)).
3/16/2020COVID-19-EMCritProjecthttps://emcrit.
org/ibcc/covid19/3/24stagesofillnessThereseemtobedifferentstagesofillnessthatpatientsmaymovethrough.
(#1)Replicativestage–Viralreplicationoccursoveraperiodofseveraldays.
Aninnateimmuneresponseoccurs,butthisresponsefailstocontainthevirus.
Relativelymildsymptomsmayoccurduetodirectviralcytopathiceffectandinnateimmuneresponses.
(#2)Adaptiveimmunitystage–Anadaptiveimmuneresponseeventuallykicksintogear.
Thisleadstofallingtitersofvirus.
However,itmayalsoincreaselevelsofinammatorycytokinesandleadtotissuedamage–causingclinicaldeterioration.
Thereisasuggestionthatthiscouldleadtovirus-inducedhemophagocyticlymphohistiocytosis(HLH)(Mehtaetal.
(https://www.
thelancet.
com/lancet/article/S0140-6736(20)30628-0)).
Morediscussionaboutthisentityandpossibletherapyhere(https://emcrit.
org/ibcc/inuenza/#virus-associated_hemophatocytic_syndrome_(VAHS)).
ThisprogressionmayexplaintheclinicalphenomenonwhereinpatientsarerelativelyOKforseveraldays,butthensuddenlydeterioratewhentheyentertheadaptiveimmunitystage(e.
g.
Youngetal.
3/3/2020(https://jamanetwork.
com/journals/jama/fullarticle/2762688)).
Thishaspotentiallyimportantclinicalimplications:Initialclinicalsymptomsaren'tnecessarilypredictiveoffuturedeterioration.
Sophisticatedstrategiesmayberequiredtoguiderisk-straticationanddisposition(seebelowsectiononprognosis(#prognosis)).
Anti-viraltherapiesmightneedtobedeployedearlytoworkoptimally(duringthereplicativestage).
Immunosuppressivetherapy(e.
g.
low-dosesteroid)mightbebestinitiatedduringtheadaptiveimmunestage(withagoalofbluntingthisimmunopathologicresponseslightly,inthesickestpatients).
Butthisispurelyspeculative.
transmission(backtocontents)(#top)largedroplettransmissionCOVID-19transmissioncanoccurvialargedroplettransmission(witharisklimitedto~6feetfromthepatient)(CarlosdelRio2/28(https://jamanetwork.
com/journals/jama/fullarticle/2762510)).
Thisistypicalforrespiratoryvirusessuchasinuenza.
Transmissionvialargedroplettransmissioncanbepreventedbyusingastandardsurgical-stylemask.
airbornetransmissionIt'scontroversialwhetherCOVID19canbetransmittedviaanairborneroute(smallparticleswhichremainaloftintheairforlongerperiodsoftime).
AirbornetransmissionwouldimplytheneedforN95masks("FFP2"inEurope),ratherthansurgicalmasks.
ThiscontroversyisexploredfurtherinShiuetal2019(https://emcrit.
org/wp-content/uploads/2020/03/tada2019.
pdf).
AirborneprecautionsstartedbeingusedwithMERSandSARSoutofanabundanceofcaution(ratherthananyclearevidencethatcoronavirusesaretransmittedviaanairborneroute).
ThispracticehasoftenbeencarrieddowntoCOVID19.
Guidelinesdisagreeaboutwhethertouseairborneprecautions:TheCanadianGuidelines(https://www.
canada.
ca/en/public-health/services/diseases/2019-novel-coronavirus-infection/health-professionals.
html)andWorldHealthOrganizationguidelines(https://www-who-int.
ezproxy.
uvm.
edu/publications-detail/infection-prevention-and-control-during-health-care-when-novel-coronavirus-(ncov)-infection-is-suspected-20200125)bothrecommendusingonlydropletprecautionsforroutinecareofCOVID19patients.
However,bothoftheseguidelinesrecommendairborneprecautionsforprocedureswhichgenerateaerosols(e.
g.
intubation,noninvasiveventilation,CPR,bag-maskventilation,andbronchoscopy).
TheUnitedStatesCDCrecommends(https://www-cdc-gov.
ezproxy.
uvm.
edu/coronavirus/2019-ncov/infection-control/control-recommendations.
htmlCDC_AA_refVal=https%3A%2F%2Fwww.
cdc.
gov%2Fcoronavirus%2F2019-ncov%2Fhcp%2Finfection-control.
html)usingairborneprecautionsallthetimewhenmanagingCOVID19patients.
UsingairborneprecautionsforallpatientswhoaredenitelyorpotentiallyinfectedwithCOVID19willlikelyresultinrapiddepletionofN95masks.
Thiswillleavehealthcareprovidersunprotectedwhentheyactuallyneedthesemasksforaerosol-generatingprocedures.
Inthecontextofapandemic,theCanadianandWHOguidelinesmaybemoresensibleincountrieswithniteresources(i.
e.
mostlocales).
However,infectioncontrolisultimatelylocal,sobesuretofollowyourhospital'sguidanceregardingthis.
contacttransmission("fomite-to-face")Thismodeoftransmissionhasatendencytogetoverlooked,butitmaybeincrediblyimportant.
Thisishowitworks:(i)Someonewithcoronaviruscoughs,emittinglargedropletscontainingthevirus.
Dropletssettleonsurfacesintheroom,creatingathinlmofcoronavirus.
Thevirusmaybeshedinnasalsecretionsaswell,whichcouldbetransmittedtotheenvironment.
(ii)Theviruspersistsonfomitesintheenvironment.
Humancoronavirusescansurviveonsurfacesforuptoaboutaweek(Kampfetal2020(https://www.
ncbi.
nlm.
nih.
gov/pubmed/32035997)).
It'sunknownhowlongCOVID-19cansurviveintheenvironment,butitmightbeevenlonger(someanimalcoronavirusescansurviveforweeks!
).
(iii)Someoneelsetouchesthecontaminatedthesurfacehoursordayslater,transferringthevirustotheirhands.
(iv)Ifthehandstouchamucousmembrane(eyes,nose,ormouth),thismaytransmittheinfection.
Anyefforttolimitspreadofthevirusmustblockcontacttransmission.
Theabovechainofeventscanbedisruptedinavarietyofways:3/16/2020COVID-19-EMCritProjecthttps://emcrit.
org/ibcc/covid19/4/24(a)Regularcleaningofenvironmentalsurfaces(e.
g.
using70%ethanolor0.
5%sodiumhypochloritesolutions;fordetailsseeKampfetal2020(https://emcrit.
org/wp-content/uploads/2020/02/10.
1016@j.
jhin_.
2020.
01.
022-2.
pdf)andCDCguidelines(https://www-cdc-gov.
ezproxy.
uvm.
edu/coronavirus/2019-ncov/infection-control/control-recommendations.
htmlCDC_AA_refVal=https%3A%2F%2Fwww.
cdc.
gov%2Fcoronavirus%2F2019-ncov%2Fhcp%2Finfection-control.
html)).
(b)Handhygiene(highconcentrationethanolneutralizesthevirusandiseasytoperform,sothismightbepreferableifhandsaren'tvisiblysoiled)(Kampf2017(http://www.
fha.
org/les/JohnW/EM/Ethanol-hand-sanitizer-and-HAV.
pdf)).
(c)Avoidanceoftouchingyourface.
Thisisnearlyimpossible,asweunconsciouslytouchourfacesconstantly.
Themainbenetofwearingasurgicalmaskcouldbethatthemaskactsasaphysicalbarriertopreventtouchingthemouthornose.
AnymedicalequipmentcouldbecomecontaminatedwithCOVID-19andpotentiallytransfervirustoproviders(e.
g.
stethoscopeearpiecesandshoes).
ArecentstudyfoundwidespreaddepositionofCOVID-19inonepatient'sroom,butfortunatelythisseemstoberemovablebycleaningwithsodiumdichloroisocyanurate(Ongetal2020(https://jamanetwork.
com/journals/jama/fullarticle/2762692)).
whencantransmissionoccur(#1)Asymptomatictransmission(inpeoplewithnoorminimalsymptoms)appearstobepossible(CarlosdelRio2/28(https://jamanetwork.
com/journals/jama/fullarticle/2762510)).
(#2)Transmissionappearstooccuroverroughly~8daysfollowingtheinitiationofillness.
PatientsmaycontinuetohavepositivepharyngealPCRforweeksafterconvalescence(Lan2/27(https://jamanetwork.
com/journals/jama/fullarticle/2762452)).
However,virusculturemethodsareunabletorecoverviablevirusafter~8daysofclinicalillness(Wolfel2020(https://www.
medrxiv.
org/content/10.
1101/2020.
03.
05.
20030502v1.
full.
pdf)).
ThisimpliesthatprolongedPCRpositivityprobablydoesn'tcorrelatewithclinicalvirustransmission.
However,allsubjectsinWolfeletal.
(https://www.
medrxiv.
org/content/10.
1101/2020.
03.
05.
20030502v1.
full.
pdf)hadmildillness,soitremainspossiblethatprolongedtransmissioncouldoccurinmoreseverecases.
CDCguidance(https://www.
cdc.
gov/coronavirus/2019-ncov/hcp/clinical-guidance-management-patients.
html)isvagueonhowlongpatientswithknownCOVID-19shouldbeisolated.
ItmaybeadvisabletoobtaintwopairedRT-PCRtests(oneofthenasopharynxandoneofthepharynx),witheachpaircollected>24hoursapart,priortodiscontinuingprecautions.
RRistheaveragenumberofpeoplethataninfectedpersontransmitsthevirusto.
IfRis1,theepidemicwillincreaseexponentially.
CurrentestimatesputRat~2.
5-2.
9(PengPWHetal,2/28(https://bjanaesthesia.
org/article/S0007-0912(20)30098-2/pdf)).
Thisisabithigherthanseasonalinuenza.
Risareectionofboththevirusandalsohumanbehavior.
InterventionssuchassocialdistancingandimprovedhygienewilldecreaseR.
ControlofspreadofCOVID-19inChinaprovesthatRisamodiablenumberthatcanbereducedbyeffectivepublichealthinterventions.
TheRonboardtheDiamondPrincesscruiseshipwas15–illustratingthatcrampedquarterswithinadequatehygienewillincreaseR(Rocklov2/28(https://academic.
oup.
com/jtm/advance-article/doi/10.
1093/jtm/taaa030/5766334)).
personalprotectiveequipment(PPE)(backtocontents)(#top)gear(1)Contactprecautions(waterproofgownandgloves)(2)Somesortofmask(discussedaboveinthetransmission(#transmission)section)N95maskorapowered,air-purifyingrespiratory("PAPR")Surgicalmaskforpatientsnotundergoingaerosol-generatingprocedures(basedonWHO&Canadianguidelines)(3)GogglesoreyeshieldNote:Theexactgearusedisprobablylessimportantthanusingitcorrectly.
applyingandremovingPPE(donning&dong)Understandinghowtoputon(don)andremove(doff)personalprotectiveequipmentisextremelyimportant(especiallyifcontacttransmissionisadominantmodeoftransmission).
RemovingsoiledPPEisthemostcriticalanddicultaspect.
ApplyingandremovingPPEshouldideallybepracticedbeforepatientsarrive(e.
g.
usingsimulation).
ThevideobelowdescribeshowtousePPE(youmayskiptherst5minutes).
3/16/2020COVID-19-EMCritProjecthttps://emcrit.
org/ibcc/covid19/5/24somepearlsaboutpersonalprotectiveequipmentPayattentiontothejunctionbetweenglovesandgowns.
Thegownshouldbetuckedintothegloves(leavingnogapin-between).
Usinggloveswithextendedcuffsfacilitatesthis(similartosterilesurgicalgloves).
Gloveswithlongcuffsmayfacilitateremovalofthegownandglovesasasingleunit(see12:30intheabovevideoifthisdoesn'tmakesense).
WhenremovingPPE,alwaysstartbyrstapplyingalcohol-basedhandsanitizertoyourgloves.
AfterfullyremovingPPE,sanitizehandsandwristswithalcohol-basedhandsanitizeragain.
Createastep-wiseprotocolforPPEremoval.
Twoexamplesareshownbelow,butthismayverydependingonyourexactgear.
Followthestepsslowly.
Checklist(https://i2.
wp.
com/emcrit.
org/wp-content/uploads/2020/03/pperemovegood.
jpgw=1484&ssl=1)forremovingPPE,usingatear-awaygownhere(thistypeofgownispreferred)Checklist(https://i0.
wp.
com/emcrit.
org/wp-content/uploads/2020/03/pperemove2.
jpgresize=1520%2C1536&ssl=1)forremovingPPE,usingagownwithxedneckties.
Considerdongwithsomeonewatchingyou(toensuregoodtechnique).
Ifthisisn'tpossible,donginamirrormaybehelpful.
screening&selectionforinvestigation(backtocontents)(#top)keyconsiderationsinclude(1)Recenttraveltoaffectedareas.
Areaswithcommunity-basedtransmissionareincreasingrapidly.
Theincubationtimeisupto14days,sotravelwithinthatwindowisrelevant.
Theimportanceoftravelwilldecreaseovertime,ascoronavirusstartsbeingtransmittedwithinthecommunity.
(2)ContactwithanyonewithknownCOVID-19(denedasaprolongedperiodoftimespent37.
3C(Zhouetal.
3/9/20(https://www.
thelancet.
com/action/showPdfpii=S0140-6736%2820%2930566-3)).
Regardlessoftheexactnumbers–absenceofafeverdoesnotexcludeCOVID-19.
Gastrointestinalpresentations:upto10%ofpatientscanpresentinitiallywithgastrointestinalsymptoms(e.
g.
diarrhea,nausea),whichprecedethedevelopmentoffeveranddyspnea(Wangetal.
2/7/20(https://jamanetwork.
com/journals/jama/fullarticle/2761044)).
"Silenthypoxemia"–somepatientsmaydevelophypoxemiaandrespiratoryfailurewithoutdyspnea(especiallyelderly)(Xieetal.
2020(https://link.
springer.
com/content/pdf/10.
1007/s00134-020-05979-7.
pdf)).
Physicalexaminationisgenerallynonspecic.
About2%ofpatientsmayhavepharyngitisortonsilenlargement(Guanetal2/28(https://www.
nejm.
org/doi/pdf/10.
1056/NEJMoa2002032articleTools=true)).
typicaldiseasecourseIncubationisamedianof~4days(interquartilerangeof2-7days),witharangeupto14days(CarlosdelRio2/28(https://jamanetwork.
com/journals/jama/fullarticle/2762510)).
Typicalevolutionofseveredisease(basedonanalysisofmultiplestudiesbyArnoldForest(https://www.
youtube.
com/watchv=zFrghcp5pbY&feature=youtu.
be))Dyspnea~6dayspostexposure.
Admissionafter~8dayspostexposure.
ICUadmission/intubationafter~10dayspostexposure.
However,thistimingmaybevariable(somepatientsarestableforseveraldaysafteradmission,butsubsequentlydeterioraterapidly).
labs(backtocontents)(#top)Table(https://i0.
wp.
com/emcrit.
org/wp-content/uploads/2020/03/labsjpg.
jpgresize=1536%2C1115&ssl=1)ofgenerallaboratoryndingsdescribedinseveralstudies.
completebloodcountWBCcounttendstobenormal.
Lymphopeniaiscommon,seenin~80%ofpatients(Guanetal2/28(https://www.
nejm.
org/doi/pdf/10.
1056/NEJMoa2002032articleTools=true),Yangetal2/21(https://www.
thelancet.
com/action/showPdfpii=S2213-2600%2820%2930079-5)).
Mildthrombocytopeniaiscommon(butplateletsarerarely8cc/kg)ImprovementinoxygenationseenwithAPRVoftentakesseveralhoursaslungtissuegraduallyrecruits.
APRVinitiationcancausehemodynamicshifts,sopaycarefulattentiontobloodpressureduringinitiation.
TruefailuretorespondtoAPRVwithin12-24hours(e.
g.
withPaO2/FiO27.
1or>7.
15maybetolerable(hypercapniaispreferredoverlung-injuriousventilation).
SlowadministrationofIVbicarbonateisanacceptablestrategytoimprovepHwhilesimultaneouslycontinuinglung-protectiveventilation(discussedhere(https://emcrit.
org/pulmcrit/hypercapnia/)).
Targetingamildlyelevatedserumbicarbonate(e.
g.
28-30mEq/L)canfacilitatesafeventilationwithlowtidalvolumes(moreondifferentformsofIVbicarbonatehere(https://emcrit.
org/ibcc/uid/#hypertonic_&_isotonic_bicarbonate)).
proningPriortoconsiderationofproning,optimizationontheventilatorfor12-24isgenerallypreferable(discussedhere(https://emcrit.
org/pulmcrit/pseudoards/)).
Forfailuretorespondtoinitialventilatoroptimization(e.
g.
withpersistentPaO2/FiO2below150mm),proneventilationshouldbeconsidered.
ReportsfromItalydescribeproningasextremelyeffective.
Thismakessense,becauseproningisexpectedtobeeffectiveforbasilarlungrecruitmentandsecretionclearance(whichseemtobetheprimaryproblemswiththesepatients).
ThequestioniswhetherthesameeffectcouldbeachievedmoreeasilyusingAPRV.
Proningisverylabor-intensiveandwillrequireconsumptionoflotsofpersonalprotectiveequipment(sincemultipleproviderswillneedtotheturnthepatientrepeatedly).
IfthesameeffectcanbeachievedwithAPRV,thatcouldbeaneasiersolution(especiallyatcenterswhichlackextensiveexperiencewithproning).
additionalinformation:Mechanicalventilationandcoronaviruspneumonia(http://www.
ventilab.
org/2020/02/29/ventilazione-meccanica-e-polmonite-da-coronavirus/)(GiuseppeNatalini,ventilabblog,GoogletranslationfromItalian)disasterventilationstrategies(backtocontents)(#top)awakeproneventilationThisinvolvesanon-intubatedpatientonnasalcannulawhopronethemselvesbylyingontheirbelly.
Thereisrelativelylittleevidencetosupportthis.
Itisusefulonlyforhighlyselectedpatients(reviewedhere(https://emcrit.
org/pulmcrit/proning-nonintubated/)).
Awake-proneventilationcouldbeausefuloptioniftheavailabilityofmechanicalventilatorsisexhausted.
Typicallyawakeproneventilationispairedwithhigh-ownasalcannula,butitcouldalsobeusedwithastandardnasalcannula(e.
g.
runningat~6L/minorabithigheriftolerated).
Considersecuringthenasalcannulatothepatient'sfaceusingtapeortegaderm,topreventdislodgmentwhenthepatientmoves.
splittingventilatorsInadireemergency,oneventilatorcanbeusedtosupportseveralpatients.
Discussionandguidelineforthishere(https://emcrit.
org/pulmcrit/split-ventilators/).
renalfailure(backtocontents)(#top)RenalfailurerequiringdialysisisreportedinasubsetofpatientsadmittedtoICU.
Theexactmechanismisunclearatthispoint,butsomeconjecturesmaybereachedbasedonSARS(Chuetal.
2005(https://www.
kidney-international.
org/article/S0085-2538(15)50506-1/pdf)).
SARScausesrenalfailurein~7%ofpatients.
Thepathologyshowsacutetubularnecrosis,whichappearstobeareectionofgeneralizedmulti-organfailure.
Insomecasesrhabdomyolysismayhavecontributedaswell.
Renalfailurecorrelateswithapooroverallprognosis(92%mortalitywithrenalfailureversus9%without).
Inmultivariableanalysis,renalfailurewasthestrongestpredictorofmortality(more-soeventhanARDS).
ECMO3/16/2020COVID-19-EMCritProjecthttps://emcrit.
org/ibcc/covid19/22/24(backtocontents)(#top)PatientswithCOVID-19canberelativelyyoungandsufferingfromsingle-organfailureduetoareversibleetiology,somanywouldbeexcellentcandidatesforECMO.
VVECMOcouldbeusedforrespiratoryfailure(althoughit'sunclearhowcommontruerefractoryhypoxemiais).
VAECMOcouldbeusefulinpatientswithfulminantcardiomyopathyandcardiogenicshockExactindicationsandtimingareunclear.
Inanepidemic,ECMOcapabilitieswouldprobablyrapidlybecomesaturated.
Verythornyethicalissuescouldarise(e.
g.
howlongofanECMOrunisonepatientallowedtohavebeforethewithdrawaloflife-sustainingtherapy,inordertoallowthecircuittobeusedforanotherpatient).
goingfurtherInfographicsonECMOed(https://ecmoed.
blog/2020/03/11/covid-19-infographics/)byMVeliaAntoniniprognosis(backtocontents)(#top)generalprognosis(1)Itremainsunclearwhatfractionofpatientsarehospitalized.
Theremaybelotsofpatientswithmildillnesswhodon'tpresenttomedicalattentionandaren'tcounted.
Thevastmajorityofinfectedpatients(e.
g.
>80%)don'tgetsignicantlyillanddon'trequirehospitalization.
(2)Amonghospitalizedpatients(Guanetal2/28(https://www.
nejm.
org/doi/pdf/10.
1056/NEJMoa2002032articleTools=true))~10-20%ofpatientsareadmittedtoICU.
~3-10%requireintubation.
~2-5%die.
(3)Longertermoutcomes:ProlongedventilatordependencyPatientswhosurvivetheinitialphasesoftheillnessmaystillrequireprolongedventilatorsupport(possiblydevelopingsomeradiographicelementsofbrosis)(Zhang2020(https://link.
springer.
com/article/10.
1007/s00134-020-05990-y)).
Astheepidemicprogresses,anissuewhichmayariseisalargevolumeofpatientsunabletoweanfrommechanicalventilation.
(Caveat:Therearenumeroussetsofnumberspublishedandtheyvaryalot.
However,fromtheclinician'sstandpointtheprecisenumbersdon'treallymatter.
)epidemiologicalriskfactorsRiskfactors(Zhouetal.
3/9/20(https://www.
thelancet.
com/action/showPdfpii=S0140-6736%2820%2930566-3)).
OlderageCoronaryarterydiseaseHypertensionDiabetesChronicpulmonarydiseaseThelargestseriesofmortalitydatacomesfromtheChineseCDC(http://weekly.
chinacdc.
cn/en/article/id/e53946e2-c6c4-41e9-9a9b-fea8db1a8f51)(tablebelow).
Theabsolutenumbersmayvarydependingonwhethersomecasesweremissed,buttherelativeimpactofvariousriskfactorsisprobablyaccurate.
Imageofmortalityrelatedtoageandcomorbidityhere(https://i1.
wp.
com/emcrit.
org/wp-content/uploads/2020/02/mortdata.
jpgresize=768%2C1053&ssl=1).
laboratoryriskstraticationBloodcellcountabnormalitiesLymphopeniaanditstrendsovertime(prolongedorworseninglymphopeniaportendspooroutcome)(Chuetal.
2004(https://thorax.
bmj.
com/content/59/3/252.
long))Neutrophil/lymphocyteratio(NLR)(https://emcrit.
org/pulmcrit/nlr/)appearstobeasuperiorprognosticatorwhencomparedtoeitherlymphopeniaorC-reactiveprotein(Liuetal.
pre-print(https://www.
medrxiv.
org/content/10.
1101/2020.
02.
10.
20021584v1.
full.
pdf)).
Asshowninthesecondgurebelow,neutrophil/lymphocyteratios>3couldsuggestaworseprognosis.
Otherpredictorsofpooroutcomeincludemarkersofinammation(C-reactiveproteinandferritin),lactatedehydrogenase,andD-dimer.
D-dimerelevationover1ug/LwasthestrongestindependentpredictorofmortalityinZhouetal.
3/9/20(https://www.
thelancet.
com/action/showPdfpii=S0140-6736%2820%2930566-3).
Troponinisaprognosticfactor,butitmaybechallengingtocomparevaluesobtainedacrossdifferentlaboratories.
(References:Ruan3/3/20(https://link.
springer.
com/article/10.
1007/s00134-020-05991-x),Xieetal.
2020(https://link.
springer.
com/article/10.
1007/s00134-020-05979-7),Wangetal.
2/7/20.
(https://jamanetwork.
com/journals/jama/fullarticle/2761044),Zhouetal.
3/9/20(https://www.
thelancet.
com/action/showPdfpii=S0140-6736%2820%2930566-3))ImageofD-dimer,ferritin,LDH,andLymphocytetrendsovertimeinsurvivors&non-survivorshere(https://i2.
wp.
com/emcrit.
org/wp-content/uploads/2020/03/zhoupx-scaled.
jpgresize=750%2C321&ssl=1).
3/16/2020COVID-19-EMCritProjecthttps://emcrit.
org/ibcc/covid19/23/24ImageofC-reactiveprotein,troponin,andIL-6insurvivorsvs.
non-survivorshere(https://i0.
wp.
com/emcrit.
org/wp-content/uploads/2020/03/ruancovid.
jpgresize=639%2C600&ssl=1).
ImageofWBC,lymphocytes,andD-dimerovertimeinsurvivorsvs.
non-survivorshere(https://i0.
wp.
com/emcrit.
org/wp-content/uploads/2020/03/wangjamapx.
jpgresize=768%2C934&ssl=1).
disposition(backtocontents)(#top)avoidanceofunnecessaryemergencydepartmentorclinicvisitsHealthsystemsshouldideallybeputinplacetodissuadepatientsfrompresentingtotheclinicoremergencydepartmentfortestingtoseeiftheyhaveCOVID-19(e.
g.
iftheyhavemildconstitutionalsymptomsanddon'totherwiserequiremedicalattention).
Manycentershavedevelopeddrive-thrutesting,whichavoidsexposureofotherpatientsintheemergencydepartment.
Outdoortestingalsoensuresongoingcirculationoffreshair.
homedispositionThevastmajorityofpatientswithcoronaviruswillrecoverspontaneously,withoutrequiringanymedicalattention(perhaps>80%ofpatients).
Patientswithmildsymptomscangenerallybedischargedhome,withinstructionstoisolatethemselves.
Thesedecisionsshouldbemadeincoordinationwithlocalhealthdepartments,whocanassistinfollow-up.
Featuresfavoringhomedischargemayinclude:Abilitytounderstandandcomplywithself-isolation(e.
g.
separatebedroomandbathroom).
Abilitytocallforassistanceiftheyaredeteriorating.
Havinghouseholdmemberswhoaren'tatincreasedriskofcomplicationsfromCOVID-19(e.
g.
elderly,pregnantwomen,orpeoplewithsignicantmedicalcomorbidities).
Lackofhypoxemia,markedchestinltrates,orotherfeaturesthatwouldgenerallyindicateadmission.
Formore,seeCDCinterimguidancefordispositionofpatientswithCOVID-19here(https://www.
cdc.
gov/coronavirus/2019-ncov/hcp/disposition-hospitalized-patients.
html)andhere(https://www.
cdc.
gov/coronavirus/2019-ncov/hcp/guidance-home-care.
htmlCDC_AA_refVal=https%3A%2F%2Fwww.
cdc.
gov%2Fcoronavirus%2F2019-ncov%2Fguidance-home-care.
html).
podcast(backtocontents)(#top)(https://i1.
wp.
com/emcrit.
org/wp-content/uploads/2016/11/apps.
40518.
14127333176902609.
7be7b901-15fe-4c27-863c-7c0dbfc26c5c.
5c278f58-912b-4af9-88f8-a65fff2da477.
jpg)FollowusoniTunes(https://itunes.
apple.
com/ca/podcast/the-internet-book-of-critical-care-podcast/id1435679111)ThePodcastEpisodeWanttoDownloadtheEpisodeRightClickHereandChooseSave-As(http://trac.
libsyn.
com/ibccpodcast/IBCC_EP_79_-_COVID-19.
mp3)questions&discussion(backtocontents)(#top)Tokeepthispagesmallandfast,questions&discussionaboutthispostcanbefoundonanotherpagehere(https://emcrit.
org/pulmcrit/COVID19/).
00:0000:00(javascript:void(0);)3/16/2020COVID-19-EMCritProjecthttps://emcrit.
org/ibcc/covid19/24/24DelayedconsiderationofCOVID19,leadingtodelayedinitiationofprecautions(e.
g.
inapatientpresentingwithgastrointestinalillness).
TreatmentofCOVID19basedonSurvivingSepsisGuidelines(e.
g.
with30cc/kguid).
Thisiswrongonsomanylevels(https://emcrit.
org/pulmcrit/coronavirus/),forexample:Broadapplicationof30cc/kguidisoftendetrimentalinsepticshock.
COVID-19patientsdon'tactuallypresentwithsepticshockanyways.
LargevolumeuidisextremelydangerousinARDS.
Inadequateattentiontocontactprecautions(e.
g.
handhygieneandsterilizationofsurfaces).
AdmissionofpatientstohospitalforCOVID19whocouldbesafelymanagedasoutpatients.
UseoftheemergencydepartmentasaCOVID-19screeningarea.
Becarefulofmakingmajorchangestousualtreatmentapproachesforviralpneumonia,basedonlimitedevidence.
Ultimatelythekeyhereissimplyhigh-qualitysupportivecareforviralpneumonia.
Goingfurther:Journal&SocietyhomepagesonCOVID-19CDC(https://www.
cdc.
gov/coronavirus/index.
html)JAMA(https://jamanetwork.
com/journals/jama/pages/coronavirus-alert)LANCET(https://www.
thelancet.
com/coronavirus)NEJM(https://www.
nejm.
org/coronavirus)BMJ(https://www.
bmj.
com/coronavirus)ESICM(https://www.
esicm.
org/resources/coronavirus-public-health-emergency/)AMA(https://www.
ama-assn.
org/topics/coronavirus-covid-19)FOAMedonCOVID-19WHOguidelinesonuidadministrationforCOVID-19aredangerous(https://emcrit.
org/pulmcrit/coronavirus/)(PulmCrit)EMCritRACConairwaymanagement(https://emcrit.
org/emcrit/airway-covid-19/)inCOVID-19(Weingart&BrianWright)COVID-19onRebelEM(https://rebelem.
com/covid-19-the-novel-coronavirus-2019/)(SalimRezaie)COVID-19onSt.
Emlyns(https://www.
stemlynsblog.
org/2019-novel-coronavirus-wuhan-at-st-emlyns/)(AshleyLiebig)COVID-19onRadiopaedia(https://radiopaedia.
org/articles/covid-19fbclid=IwAR2G1HjFlbP1aj3Inj_-HqG27NM3lx8TXE4VpTpTHUu0PYWRTJmHvIqbVAE)(DanielBell)(Referencestosomepatientserieslistedinthetables)Yangetal(https://www.
thelancet.
com/action/showPdfpii=S2213-2600%2820%2930079-5):52criticallyillpatients,LancetChenetal(https://www.
thelancet.
com/action/showPdfpii=S0140-6736%2820%2930211-7):99infectedpatients,LancetShietal(https://www.
thelancet.
com/action/showPdfpii=S1473-3099%2820%2930086-4):81patientswithCTimaging,Lancet.
TheInternetBookofCriticalCareisanonlinetextbookwrittenbyJoshFarkas(@PulmCrit),anassociateprofessorofPulmonaryandCriticalCareMedicineattheUniversityofVermont.
EMCritisatrademarkofMetasinLLC.
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