AddresscorrespondencetoGowriKaruppasamyInternalMedicineDepartmentHamadMedicalCorporationAlRayyanRoadPOBox3050DohaQatarEmailgkaruppasamyhamadqa cantinvestigationsincludedlipaseofx000012 ID: 961207
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Am.J.Trop.Med.Hyg.,103(4),2020,pp.1600doi:10.4269/ajtmh.20-0894Copyright©2020byTheAmericanSocietyofTropicalMedicineandHygieneCaseReport:ParalyticIleus:APotentialExtrapulmonaryManifestationofSevereCOVID-19YassminS.Ibrahim,GowriKaruppasamy,*JessiyaV.Parambil,HussamAlsoub,andShaikhaD.Al-ShokriInternalMedicineDepartment,HamadMedicalCorporation,Doha,Qatar;InfectiousDiseaseDepartment,HamadMedicalCorporation,Doha,Qatar *AddresscorrespondencetoGowriKaruppasamy,InternalMedicineDepartment,HamadMedicalCorporation,AlRayyanRoad,POBox3050,Doha,Qatar.E-mail:gkaruppasamy@hamad.qa cantinvestigationsincludedlipaseof�1,200U/L,am-ylase390U/L,ALT187U/L,andAST125U/L.Hewasnotedtohavederangedelectrolytes,withpotassiumof2.2mmol/Landcalcium0.96mmol/L.HisnasopharyngealRT-PCRwaspositiveforSARS-CoV-2.BilateralpneumonicpatcheswereobservedonthechestX-ray(Figure1C).Hewasintubatedandurgenthemodialysiswasinitiated,andhewasadmittedtotheintensivecareunitasacaseofsevereCOVID-19pneumonia,renalfailure,andacutepancreatitis.Ultrasoundabdomenrevealedhealthygallbladderbutnoteddilatedbowelloopsintheleftlowerabdomen.Hewasextubatedonday5ofadmission.Twodaysafterextubation,thepatientdevelopedbiliousvomitingandabdominaldiscomfort.Hedidnothavebowelmovementsforthepreceding4daysbutwasatus.Onexamination,hehadadistendedabdomenwithnoguarding,butbowelsoundsweresluggish.AbdominalX-rayshowingdiffusedilatationofthesmallandlargebowelloops(Figure1D).Computedtomographyscanoftheabdo-menshoweddiffuselydistendedlargebowel,fromtheanustothececum,lledwithuid,andairuidlevelsextendingto 1.RadiographsforpatientsdiagnosedwithCOVID-19pneumonia.()Chestradiographforcase1showingbilateralfreeairunderthediaphragmand()abdominalradiographshowingdistendedbowelloops.()Chestradiographforcase2showingbilateralpatchyinltratesand(abdominalradiographshowingdiffusedilatationofthesmallandlargebowelloops.ILEUSINCOVID-19 involvethesmallbowelproximallyuptothethirdpartoftheduodenum.Therewasnotransitionalzoneofnarrowing,mass,orbowelwallthickening.Minimalperipancreaticfatstrandingwasnotedwithnouidcollection.Bothkidneysweresmallinsize,andanincidentalndingofsofttissuelesionattherightupperpolewasnoted(Figure2B).Hewasevaluatedbythesurgeryteam,whoadvisedconservativemanagementwithanasogastrictubeinsertionandcor-rectionofelectrolytes.Thepatientwaskeptnilperoral,andtotalparenteralnutritionwasinitiated.Hereceivedproki-neticagentsandintravenouspotassiumreplacementtomaintaintargetserumpotassiumof4mmol/L.Thepatientconditionimprovedoverthenextweek,andhewasabletotolerateanoraldiet.ArepeatCTscanperformedforfurtherevaluationofrenalmassshowedimprovementinthesig-cantboweldilatationandresolutionofsmallboweldi-latation.Thepatientiscurrentlyonrenalreplacementtherapythreetimesaweekthroughapermanentsubclaviantunneledcatheter.Gastrointestinalinvolvementhasbeenincreasinglyreport-edinassociationwiththeSARS-CoV-2infection.Amulti-centercohortstudyofhospitalizedU.S.adultsfoundthattwo-thirdsofpatientswithCOVID-19hadatleastonegas-trointestinalsymptom.Areviewof29studiesnotedt
hat12%ofpatientswithSARS-CoV-2infectionhadgastrointestinalsymptoms,includingdiarrhea,nausea,andvomiting.clinicalsignicanceofthispresentationwasdemonstratedinareviewbyMaoetal.,whoreportedthatpatientswhopre-sentedwithgastrointestinalsysteminvolvementhaddelayeddiagnosisandalsotendedtohaveapoorerdiseasecourse.Ithasbeenproposedthattheangiotensin-convertingen-zyme2(ACE2)receptorplaysacentralroleinthemechanismofgastrointestinaltractinvolvementinCOVID-19.TheACE-2receptoristhefunctionalhostreceptorfortheSARS-CoV-2AlthoughACE2ishighlyexpressedinalveolarcellsinthelungs,ACE2receptorsarealsoabundantinthegastrointestinaltract,especiallyinthesmallandlarge12,13ThegastrointestinalsymptomsthatappearearlyduringCOVID-19suggestthatthesmallbowelmaybeanimportantentrysiteforthevirus.Zhangetal.thatACE2expressiononsmallintestinalenterocytesmaymediatetheinvasionofthevirusandactivationofgastroin-testinalinammation.Therefore,thiscouldbeapotentialmechanismofparalyticileusinsevereCOVID-19cases.ThereisagrowingbodyofevidencedescribinglargebowelinvolvementinCOVID-19infection.Carvalhoetal.describedacaseofSARS-CoV-2gastrointestinalinfectioncausingacutehemorrhagiccolitiswithendoscopicndingsofcoloproctopathybutnormalhistologicndings.Sattaretal.reportedthreecasesofCOVID-19withcolonicndings,in-cludingcolitisandairinthebowelwall.However,therearefewreportsofparalyticileusinpatientswithCOVID-19.Kaafaranietal.describedaseriesof141criticallyillpatientswithCOVID-19,wherehalfofthepatientsdevelopedhypomotility-relatedcomplicationsofvariablese-verity.Onlytwopatientswerediagnosedwithacolonicpar-alyticileus(Ogilviessyndrome).Similarly,thepatientincase1hadextensivelargeboweldilatationandmid-transversecolonperforation.Histopathologyoftheresectedbowelspecimenshowedfatnecrosis,acuteinammation,reactiveproliferation,andhemorrhage.However,themesentericvesselswerepatentonimaging,suggestingthattheetiologycouldbeSARS-CoV-2inducedmicro-thrombosis.IthasbeenhypothesizedthatSARS-CoV-2causesvascularendo-thelialcellinammation,leadingtoimpairedmicrocirculatoryfunctionindifferentvascularbeds.Moreover,Bhayanaetal.reportedbowelwallabnormal-itiesin31%ofabdominalCTscanimagesinCOVID-19pa-tients,includingpneumatosisandportalvenousgas.Thepatientswerefoundtohavebowelinfarctionduetoischemicenteritiswithpatchynecrosisandbrinthrombiinthearteri-oles.Oursecondcasehaddiffusedistensionofbothsmallbowelandlargebowelbutrespondedwelltoconservativemanagement.Thedevelopmentofileus,inthiscase,mayalsobeexplainedbyelectrolytederangement,asthepatienthadhypokalemiaandhypocalcemia.However,SARS-CoV-2maycauseileusinanindependentmechanism,asalludedOurcaseswerebothobservedtohaveelevatedlivertransaminases.Inasystematicreview,abnormalliverenzymelevelswerenotedin1520%ofpatients.StudiesbyMaoetal.andGuanetal.foundthatpatientswithsevereCOVID-19hadhigherratesofabnormalliverfunction.Case2developedsevereacutepancreatitisofuncleareti-ology,withelevatedlipaseandperipancreaticfatstrandingonimaging.Afewsimilarcaseshavebeenreported,butthereisuncertaintyaboutitspathogen
esis.TheoriesincludeacuteinammationassociatedwiththeexpressionofACE2inthepancreasandheightenedsystemicinammatoryre-sponsefromcytokinestormsyndromeleadingtomulti-organAreviewbyBourgonjeetal.alsopointsoutthatitistherelativeproportionofACEtoACE2receptorsthatisre-sponsiblefortheresultantpro-inammatoryandpro-symptomatology,andithasbeenreportedthatthesemaybeaffectedbygender,withmaleshavingarelativelyhigherproportionofACEtoACE2,thusfavoringinammationandcolitis.Bothourpatientsweremale,supportingthistheory.Furtherstudiesareneededtoelaborateonthecausativere-lationshipbetweenSARS-CoV-2andthegastrointestinalmanifestationsofCOVID-19. 2.Computedtomography(CT)scanoftheabdomeninpatientsdiagnosedwithCOVID-19pneumonia.()Contrast-en-hancedCTscan,anaxialplaneoftheabdomenoftherstcaseshowinglargeboweldilatationwithnostrictureorobstruction,andpatentmesentericvessels.()Contrast-enhancedCTscan,anaxialplaneoftheabdomenofthesecondcaseshowingdiffuselydistendedsmallandlargebowelwithairuidlevels.IBRAHIMANDOTHERS Inconclusion,wereportparalyticsmallandlargebowelileusasacomplicationofCOVID-19.Furthermore,weexploreapotentialmechanismofileusandexplorethemanagementstrategies.Theaddedvalueofthepresentcasereportisthedetailedhistopathologicalevidencesupportingaroleforinducedmicro-thrombosis,therebycompromis-ingmicrocirculatoryfunctionandresultantcolonicboweldi-latationandperforationintherstpatient.Recognizingparalyticileusasapossiblecomplicationnecessitatestimelydiagnosisandmanagement.ReceivedJuly22,2020.AcceptedforpublicationAugust23,2020.PublishedonlineAugust31,2020.Acknowledgments:Wethankthecriticalcare,medical,radiology,infectiousdisease,andsurgicalpersonnelinvolvedinthesepatientscare.Publicationchargesforthisarticlewerewaivedduetotheon-goingpandemicofCOVID-19.Disclosure:Allpatientsconsentedtosharetheircases.Wesoughtapprovalfromalocalcommitteeforreportingthiscaseseries.Authorsaddresses:YassminS.Ibrahim,GowriKaruppasamy,JessiyaV.Parambil,andShaikhaD.Al-Shokri,InternalMedicineDepartment,HamadMedicalCorporation,Doha,Qatar,E-mails:yibrahim4@hamad.qa,gkaruppasamy@hamad.qa,jparambil2@hamad.qa,andsalshokri@hamad.qa.HussamAlsoub,InfectiousDiseaseDepartment,HamadMedicalCorporation,Doha,Qatar,E-mail:halsoub@hamad.qa.Thisisanopen-accessarticledistributedunderthetermsoftheCreativeCommonsAttribution(CC-BY)License,whichpermitsun-restricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited.1.BikdeliBetal.,2020.COVID-19andthromboticorthromboem-bolicdisease:implicationsforprevention,antithrombotictherapy,andfollow-up:JACCstate-of-the-artreview.JAmCollCardiol75:2.OranDP,TopolEJ,2020þ.PrevalenceofasymptomaticSARS-CoV-2infection:anarrativereview.AnnInternMedM20-3012(Epubaheadofprint,2020June3].Availableat:https://www.acpjournals.org/doi/abs/10.7326/M20-3012.3.ZouLetal.,2020.SARS-CoV-2viralloadinupperrespiratoryspecimensofinfectedpatients.NEnglJMed382:4.CheungKSetal.,2020.GastrointestinalmanifestationsofSARS-CoV-2infectionandvirusloadinfecalsamplesfromaHongKongcohort:system
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