Laboratory-Confirmed COVID-19 Among Adults Hospitalized

These findings suggest that among hospitalized adults with COVID-19–like illness whose previous infection or vaccination occurred 90–179 days ... Skipdirectlytositecontent Skipdirectlytopageoptions SkipdirectlytoA-Zlink MorbidityandMortalityWeeklyReport(MMWR) SectionNavigation CDCHome Facebook Twitter LinkedIn Syndicate Laboratory-ConfirmedCOVID-19AmongAdultsHospitalizedwithCOVID-19–LikeIllnesswithInfection-InducedormRNAVaccine-InducedSARS-CoV-2Immunity—NineStates,January–September2021 Weekly/November5,2021/70(44);1539–1544 Minus RelatedPages OnOctober29,2021,thisreportwaspostedonlineasanMMWREarlyRelease.CatherineH.Bozio,PhD1;ShaunJ.Grannis,MD2,3;AllisonL.Naleway,PhD4;ToanC.Ong,PhD5;KristenA.Butterfield,MPH6;MaliniB.DeSilva,MD7;KarthikNatarajan,PhD8,9;Duck-HyeYang,PhD6;SuchitraRao,MBBS5;NicolaP.Klein,MD,PhD10;StephanieA.Irving,MHS4;BrianE.Dixon,PhD2,11;KristinDascomb,MD,PhD12;I-ChiaLiao,MPH13;SueReynolds,PhD1;CharleneMcEvoy,MD7;JungmiHan8;SarahE.Reese,PhD6;NedLewis,MPH10;WilliamF.Fadel,PhD2,11;NancyGrisel,MPP12;KempapuraMurthy,MBBS13;JillFerdinands,PhD1;AnupamB.Kharbanda,MD14;PatrickK.Mitchell,ScD6;KristinGoddard,MPH10;PeterJ.Embi,MD3,15;JulieArndorfer,MPH12;ChandniRaiyani,MPH13;PalakPatel,MBBS1;ElizabethA.Rowley,DrPH6;BruceFireman,MA10;NimishR.Valvi,DrPH,MBBS2;EricP.Griggs,MPH1;MatthewE.Levy,PhD6;OussenyZerbo,PhD10;RachaelM.Porter,MPH1;RebeccaJ.Birch,MPH6;LeneeBlanton,MPH1;SarahW.Ball,ScD6;AndreaSteffens,MPH1;NatalieOlson,MPH1;JeremiahWilliams,MPH1;MonicaDickerson,MPH1;MeredithMcMorrow,MD1;StephanieJ.Schrag,DPhil1;JenniferR.Verani,MD1;AliciaM.Fry,MD1;EduardoAzziz-Baumgartner,MD1;MichelleBarron,MD5;ManjushaGaglani,MBBS13;MarkG.Thompson,PhD1;EdwardStenehjem,MD12(Viewauthoraffiliations) ViewsuggestedcitationSummary Whatisalreadyknownaboutthistopic? PreviousinfectionwithSARS-CoV-2orCOVID-19vaccinationcanprovideimmunityandprotectionagainstsubsequentSARS-CoV-2infectionandillness. Whatisaddedbythisreport? AmongCOVID-19–likeillnesshospitalizationsamongadultsaged≥18yearswhosepreviousinfectionorvaccinationoccurred90–179daysearlier,theadjustedoddsoflaboratory-confirmedCOVID-19amongunvaccinatedadultswithpreviousSARS-CoV-2infectionwere5.49-foldhigherthantheoddsamongfullyvaccinatedrecipientsofanmRNACOVID-19vaccinewhohadnopreviousdocumentedinfection(95%confidenceinterval=2.75–10.99). Whataretheimplicationsforpublichealthpractice? AlleligiblepersonsshouldbevaccinatedagainstCOVID-19assoonaspossible,includingunvaccinatedpersonspreviouslyinfectedwithSARS-CoV-2. ArticleMetrics Altmetric: Citations: Views: ViewsequalspageviewsplusPDFdownloads MetricDetails TablesTable1Table2ReferencesRelatedMaterialsPDFpdficon[128K]PreviousinfectionwithSARS-CoV-2(thevirusthatcausesCOVID-19)orCOVID-19vaccinationcanprovideimmunityandprotectionfromsubsequentSARS-CoV-2infectionandillness.CDCuseddatafromtheVISIONNetwork*toexaminehospitalizationsinadultswithCOVID-19–likeillnessandcomparedtheoddsofreceivingapositiveSARS-CoV-2testresult,andthushavinglaboratory-confirmedCOVID-19,betweenunvaccinatedpatientswithapreviousSARS-CoV-2infectionoccurring90–179daysbeforeCOVID-19–likeillnesshospitalization,andpatientswhowerefullyvaccinatedwithanmRNACOVID-19vaccine90–179daysbeforehospitalizationwithnopreviousdocumentedSARS-CoV-2infection.Hospitalizedadultsaged≥18yearswithCOVID-19–likeillnesswereincludediftheyhadreceivedtestingatleasttwice:onceassociatedwithaCOVID-19–likeillnesshospitalizationduringJanuary–September2021andatleastonceearlier(sinceFebruary1,2020,and≥14daysbeforethathospitalization).AmongCOVID-19–likeillnesshospitalizationsinpersonswhosepreviousinfectionorvaccinationoccurred90–179daysearlier,theoddsoflaboratory-confirmedCOVID-19(adjustedforsociodemographicandhealthcharacteristics)amongunvaccinated,previouslyinfectedadultswerehigherthantheoddsamongfullyvaccinatedrecipientsofanmRNACOVID-19vaccinewithnopreviousdocumentedinfection(adjustedoddsratio[aOR] = 5.49;95%confidenceinterval[CI] = 2.75–10.99).ThesefindingssuggestthatamonghospitalizedadultswithCOVID-19–likeillnesswhosepreviousinfectionorvaccinationoccurred90–179daysearlier,vaccine-inducedimmunitywasmoreprotectivethaninfection-inducedimmunityagainstlaboratory-confirmedCOVID-19.AlleligiblepersonsshouldbevaccinatedagainstCOVID-19assoonaspossible,includingunvaccinatedpersonspreviouslyinfectedwithSARS-CoV-2. TocomparetheearlyprotectionagainstCOVID-19conferredbySARS-CoV-2infectionandbyreceiptofmRNACOVID-19vaccines(i.e.,90–179daysafterinfectionorvaccination),theVISIONNetworkcollecteddatafrom187hospitalsacrossninestatesduringJanuary–September2021(1).Eligiblehospitalizationsweredefinedasthoseamongadultsaged≥18yearswhohadreceivedSARS-CoV-2moleculartesting(from14daysbeforeto72hoursafteradmission)andhadaCOVID-19–likeillnessdischargediagnosis†duringJanuary–September2021.EligiblepatientshadalsobeentestedatleastoncesinceFebruary1,2020.TolimittheanalysistopatientswithaccesstoSARS-CoV-2testingbeforehospitalization,patientswhodidnotreceiveSARS-CoV-2testing≥14daysbeforehospitalizationwereexcluded. TwoexposuregroupsweredefinedbasedonCOVID-19vaccinationstatusandpreviousSARS-CoV-2infection.Vaccinationstatuswasdocumentedinelectronichealthrecordsandimmunizationregistries.PreviousinfectionwasascertainedbasedonSARS-CoV-2testingfromrapidantigentestsormolecularassays(e.g.,real-timereversetranscription–polymerasechainreaction)performedbeforemRNAvaccinationand≥14daysbeforeadmission;testingperformedafterFebruary2020wasprimarilywithinnetworkpartners’medicalfacilities.AdultswereconsideredunvaccinatedwithapreviousSARS-CoV-2infectionifnoCOVID-19vaccinedoseswerereceivedandifthemostrecentpositiveSARS-CoV-2testresultoccurred≥90daysbeforehospitalization.AdultswereconsideredfullyvaccinatedwithanmRNACOVID-19vaccinewithnopreviousdocumentedinfectioniftheseconddoseofPfizer-BioNTech(BNT162b2)orModerna(mRNA-1273)mRNAvaccinewasreceived≥14daysbeforetheindextestdate§andiftheyhadbeentestedsinceFebruary1,2020,andhadnopositivetestresults≥14daysbeforehospitalization.Patientswereexcludediftheyhadreceived1mRNAvaccinedoseonly,receivedtheseconddose<14daysbeforeindextestdate,orreceivedtheJanssen(Johnson&Johnson[Ad26.COV2])vaccine(becauseofsparsedata).ToreducethechancethatthehospitalizationwasrelatedtoanongoingSARS-CoV-2infection,patientswerealsoexcludedfromthepreviousinfectiongroupiftheirmostrecentpreviouspositivetestresultoccurred14–89daysbeforehospitalization.¶ Theoutcomeoflaboratory-confirmedCOVID-19wasdefinedasCOVID-19–likeillnessandapositiveSARS-CoV-2resultfrommoleculartesting.AmongpatientshospitalizedwithCOVID-19–likeillnesswhosepreviousinfectionorcompletionofvaccinationoccurred90–179daysearlier,theoddsoflaboratory-confirmedCOVID-19werecomparedbetweenpreviouslyinfectedpersonsandfullyvaccinatedmRNACOVID-19vaccinerecipients.aORsand95%CIswerecalculatedusingmultivariablelogisticregression,adjustedforage,geographicregion,calendartime(daysfromJanuary1tohospitalization),andlocalviruscirculation,andweightedbasedonpropensitytobeinthevaccinatedcategory(1,2).Establishedmethodswereusedtocalculateweightstoaccountfordifferencesinsociodemographicandhealthcharacteristicsbetweengroups(3).Separateweightswerecalculatedforeachmodel.aORswerestratifiedbymRNAvaccineproductandagegroup. Threesecondaryanalyseswerealsoconducted.First,theimpactofwhetherandhowthetimeintervalsincepreviousinfectionorfullvaccinationwasadjustedwasexamined.Specifically,anytimesinceeitherpreviousinfectionorcompletionofvaccinationwasconsidered.Then,previouslyinfectedpatientswerelimitedtothosewithmorerecentinfections(i.e.,90–225daysbeforehospitalization[thelowesttwotertilesofnumberofdayssinceinfection]),andfullyvaccinatedpatientswerelimitedtothosewiththelongestintervalsincecompletionofvaccination(i.e.,receiptofsecondmRNAvaccinedose45–213daysbeforehospitalization[thehighesttwotertilesofnumberofdayssincevaccination]).Then,numberofdayssincepreviousinfectionorcompletionofvaccination,ratherthancalendartime,wasadjustedinthemodel.Forthenextsecondaryanalysis,aORsforhospitalizationsthatoccurredbeforeandduringSARS-CoV-2B.1.617.2(Delta)variantpredominance(June–September2021)werecompared,beginningonthedatetheDeltavariantaccountedfor>50%ofsequencedisolatesineachmedicalfacility’sstate(2).Finally,effectmodificationwasassessedbymRNAvaccineproductorbyagegroup;p-values<0.2wereconsideredindicativeofastatisticallysignificantdifferenceinaORbyproductorage,similartopreviousmodelingstudiesofeffectmodification(4).AllanalyseswereconductedusingSAS(version9.4;SASInstitute)andR(version4.0.2;RFoundation).ThisstudywasreviewedandapprovedbyWestat,Inc.institutionalreviewboard.** DuringJanuary1–September2,2021,atotalof201,269hospitalizationsforCOVID-19–likeillnesswereidentified;139,655(69.4%)patientswerehospitalizedafterCOVID-19vaccinesweregenerallyavailabletopersonsintheiragegroupwithintheirgeographicregion.MoleculartestingforSARS-CoV-2wasperformedfor94,264(67.5%)patientswithCOVID-19–likeillnesshospitalizations.Amongthesepatients,7,348(7.8%)hadatleastoneotherSARS-CoV-2testresult≥14daysbeforehospitalizationandmetcriteriaforeitherofthetwoexposurecategories:1,020hospitalizationswereamongpreviouslyinfectedandunvaccinatedpersons,and6,328wereamongfullyvaccinatedandpreviouslyuninfectedpatients(Table1). Laboratory-confirmedSARS-CoV-2infectionwasidentifiedamong324(5.1%)of6,328fullyvaccinatedpersonsandamong89of1,020(8.7%)unvaccinated,previouslyinfectedpersons.Ahigherproportionofpreviouslyinfectedthanvaccinatedpatientswereaged18–49years(31%versus9%),Black(10%versus7%),andHispanic(19%versus12%). AmongCOVID-19–likeillnesshospitalizationsinpersonswhosepreviousinfectionorvaccinationoccurred90–179daysearlier,theoddsoflaboratory-confirmedCOVID-19werehigheramongpreviouslyinfected,unvaccinatedpatientsthanamongfullyvaccinatedpatients(aOR = 5.49;95%CI = 2.75–10.99)(Table2).Insecondaryanalyses,theaORsthatexaminedtheimpactofwhetherandhowtimesinceinfectionorvaccinationwasadjustedandthatstratifiedhospitalizationsbeforeandduringDeltavariantpredominancewereallsimilartotheprimaryaORestimate.Forproduct-andagegroup–specificestimates,sparsedatalimitedtheprecisionoftheseaORs.However,anassessmentofeffectmodificationindicatedtheaORoflaboratory-confirmedCOVID-19washigherforpreviouslyinfectedpatientscomparedwithpatientsvaccinatedwithModerna(aOR = 7.30)thancomparedwithpatientsvaccinatedwithPfizer-BioNTech(aOR = 5.11)duringJanuary–September(p=0.02).Similarly,theinteractiontermforexposuregroupbyageindicatedthattheaORwashigherforpatientsaged≥65years(aOR = 19.57)thanforthoseaged18–64years(aOR = 2.57)(interactionterm,p=0.05). Top Discussion InthismultistateanalysisofhospitalizationsforCOVID-19–likeillnessamongadultsaged≥18yearsduringJanuary–September2021whosepreviousinfectionorvaccinationoccurred90–179daysearlier,theadjustedoddsoflaboratory-confirmedCOVID-19werehigheramongunvaccinatedandpreviouslyinfectedpatientsthanamongthosewhowerefullyvaccinatedwith2dosesofanmRNACOVID-19vaccinewithoutpreviousdocumentationofaSARS-CoV-2infection.SecondaryanalysesthatdidnotadjustfortimesinceinfectionorvaccinationoradjustedtimesinceinfectionorvaccinationdifferentlyaswellasbeforeandduringDeltavariantpredominanceproducedsimilarresults.Thesefindingsareconsistentwithevidencethatneutralizingantibodytitersafterreceiptof2dosesofmRNACOVID-19vaccinearehigh(5,6);however,thesefindingsdifferfromthoseofaretrospectiverecords-basedcohortstudyinIsrael,††whichdidnotfindhigherprotectionforvaccinatedadultscomparedwiththosewithpreviousinfectionduringaperiodofDeltavariantcirculation.Thisvariationispossiblyrelatedtodifferencesintheoutcomeofinterestandrestrictionsonthetimingofvaccination.TheIsraelicohortstudyassessedanypositiveSARS-CoV-2testresult,whereasthisstudyexaminedlaboratory-confirmedCOVID-19amonghospitalizedpatients.TheIsraelicohortstudyalsoonlyexaminedvaccinationsthathadoccurred6monthsearlier,sothebenefitofmorerecentvaccinationwasnotexamined.Thisreportfocusedontheearlyprotectionfrominfection-inducedandvaccine-inducedimmunity,thoughitispossiblethatestimatescouldbeaffectedbytime.Understandinginfection-inducedandvaccine-inducedimmunityovertimeisimportant,particularlyforfuturestudiestoconsider. Inthisstudy,thebenefitofvaccinationcomparedwithinfectionwithoutvaccinationappearedtobehigherforrecipientsofModernathanPfizer-BioNTechvaccine,whichisconsistentwitharecentstudythatfoundhighervaccineeffectivenessagainstCOVID-19hospitalizationsforModernavaccinerecipientsthanforPfizer-BioNTechvaccinerecipients(7).Inthisstudy,theprotectiveeffectofvaccinationalsotrendedhigherforadultsaged≥65yearsthanforthoseaged18–64years.However,consideringthelimiteddatabybothproducttypeandage,additionalresearchisneededontherelativeprotectionofvaccinationversusinfectionwithoutvaccinationacrossdemographicgroupsandvaccineproducts,aswellasvaccinationinpreviouslyinfectedpersons. Thefindingsinthisreportaresubjecttoatleastsevenlimitations.First,althoughthisanalysiswasdesignedtocomparetwogroupswithdifferentsourcesofimmunity,patientsmighthavebeenmisclassified.IfSARS-CoV-2testingoccurredoutsideofnetworkpartners’medicalfacilitiesorifvaccinatedpersonsarelesslikelytoseektesting,somepositiveSARS-CoV-2testresultsmighthavebeenmissedandthussomepatientsclassifiedasvaccinatedandpreviouslyuninfectedmightalsohavebeeninfected.Inaddition,despitethehighspecificityofCOVID-19vaccinationstatusfromthesedatasources,misclassificationispossible.Second,theaORcouldnotbefurtherstratifiedbytimesinceinfectionorvaccinationbecauseofsparsedataandlimitedabilitytocontrolforresidualconfoundingthatcouldbemagnifiedwithinshorterintervals.TheaORthatdidnotadjustfortimemightalsobesubjecttoresidualconfounding,particularlyrelatedtowaningofbothtypesofimmunity.Third,selectionbiasmightbepossibleifvaccinationstatusinfluenceslikelihoodoftestingandifpreviousinfectioninfluencesthelikelihoodofvaccination.PreviousworkfromtheVISIONnetworkdidnotidentifysystematicbiasintestingbyvaccinationstatus,basedondatathroughMay2021(1).Fourth,residualconfoundingmightexistbecausethestudydidnotmeasureoradjustforbehavioraldifferencesbetweenthecomparisongroupsthatcouldmodifytheriskoftheoutcome.Fifth,theseresultsmightnotbegeneralizabletononhospitalizedpatientswhohavedifferentaccesstomedicalcareordifferenthealthcare–seekingbehaviors,particularlyoutsideoftheninestatescovered.Sixth,thestatisticalmodelincorporatedtheuseofaweightedpropensityscoremethodwhichissubjecttobiasesinestimatesorstandarderrorsifthepropensityscoremodelismisspecified.Numeroustechniqueswereusedtoreducepotentialsuboptimalspecificationofthemodel,includingbutnotlimitedtoincludingalargesetofcovariatesformachinelearningestimationofpropensityscores,includingcovariatesinbothregressionandpropensitymodels,ensuringlargesamplesizesandcheckingstabilityofweights,andconductingsecondaryanalysestoassessrobustnessofresults.Finally,thestudyassessedCOVID-19mRNAvaccinesonly;findingsshouldnotbegeneralizedtotheJanssenvaccine. InthisU.S.-basedepidemiologicanalysisofpatientshospitalizedwithCOVID-19–likeillnesswhosepreviousinfectionorvaccinationoccurred90–179daysearlier,vaccine-inducedimmunitywasmoreprotectivethaninfection-inducedimmunityagainstlaboratory-confirmedCOVID-19,includingduringaperiodofDeltavariantpredominance.AlleligiblepersonsshouldbevaccinatedagainstCOVID-19assoonaspossible,includingunvaccinatedpersonspreviouslyinfectedwithSARS-CoV-2. TopAcknowledgments JeffersonJones,ClaireMidgley,RuthLink-Gelles,SharonSaydah,JeromeTokars,AdiGundlapalli,NatalieThornburg,AbigailShefer,JohnKools,ErinTromble,MelissaCarter,CoryKokko,StephanieWeaver,KuzhaliMuthumalaiappan,Bao-PingZhu,RoumianaBoneva,CDC. TopCorrespondingauthor:CatherineH.Bozio,[email protected]. Top1CDCCOVID-19ResponseTeam;2CenterforBiomedicalInformatics,RegenstriefInstitute,Indianapolis,Indiana;3IndianaUniversitySchoolofMedicine,Indianapolis,Indiana;4CenterforHealthResearch,KaiserPermanenteNorthwest,Portland,Oregon;5DepartmentofMedicine,UniversityofColorado,AnschutzMedicalCampus,Aurora,Colorado;6Westat,Rockville,Maryland;7HealthPartnersInstitute,Minneapolis,Minnesota;8DepartmentofBiomedicalInformatics,ColumbiaUniversity,NewYork,NewYork;9NewYorkPresbyterianHospital,NewYorkCity,NewYork;10KaiserPermanenteVaccineStudyCenter,KaiserPermanenteNorthernCalifornia,Oakland,California;11FairbanksSchoolofPublicHealth,IndianaUniversity,Indianapolis,Indiana;12DivisionofInfectiousDiseasesandClinicalEpidemiology,IntermountainHealthcare,SaltLakeCity,Utah;13BaylorScott&WhiteHealth,TexasA&MUniversityCollegeofMedicine,Temple,Texas;14Children’sMinnesota,Minneapolis,Minnesota;15RegenstriefInstitute,Indianapolis,Indiana. Top AllauthorshavecompletedandsubmittedtheInternationalCommitteeofMedicalJournalEditorsformfordisclosureofpotentialconflictsofinterest.StephanieA.IrvingreportssupportfromWestattoKaiserPermanenteNorthwestCenterforHealthResearch.NicolaP.KleinreportssupportfromPfizertoKaiserPermanente,NorthernCaliforniaforCOVID-19vaccineclinicaltrials,andinstitutionalsupportfromMerck,GlaxoSmithKline,andSanofiPasteuroutsidethecurrentstudy.CharleneMcEvoyreportssupportfromAstraZenecatoHealthPartnersInstituteforCOVID-19vaccinetrials.AllisonL.NalewayreportsPfizerResearchfundingtoKaiserPermanenteNorthwestforunrelatedstudyofmeningococcalBvaccinesafetyduringpregnancy.SuchitraRaoreportsgrantsfromGlaxoSmithKlineandBiofireDiagnostics.Nootherpotentialconflictsofinterestweredisclosed. Top *FundedbyCDC,theVISIONNetworkincludesColumbiaUniversityIrvingMedicalCenter(NewYork),HealthPartners(MinnesotaandWisconsin),IntermountainHealthcare(Utah),KaiserPermanenteNorthernCalifornia(California),KaiserPermanenteNorthwest(OregonandWashington),RegenstriefInstitute(Indiana),andUniversityofColorado(Colorado). †MedicaleventswithadischargecodeconsistentwithCOVID-19–likeillnesswereincluded.COVID-19–likeillnessdiagnosesincludedacuterespiratoryillness(e.g.,COVID-19,respiratoryfailure,orpneumonia)orrelatedsignsorsymptoms(cough,fever,dyspnea,vomiting,ordiarrhea)usingdiagnosiscodesfromtheInternationalClassificationofDiseases,NinthRevisionandInternationalClassificationofDiseases,TenthRevision. §IndextestdatewasdefinedasthedateofrespiratoryspecimencollectionassociatedwiththemostrecentpositiveornegativeSARS-CoV-2testresultbeforethehospitalizationorthehospitalizationdateiftestingonlyoccurredafteradmission. ¶https://www.cdc.gov/coronavirus/2019-ncov/php/invest-criteria.html **45C.F.R.part46;21C.F.R.part56. ††https://www.medrxiv.org/content/10.1101/2021.08.24.21262415v1externalicon TopReferences ThompsonMG,StenehjemE,GrannisS,etal.EffectivenessofCovid-19vaccinesinambulatoryandinpatientcaresettings.NEnglJMed2021;385:1355–71.https://doi.org/10.1056/NEJMoa2110362externaliconPMID:34496194externalicon GrannisSJ,RowleyEA,OngTC,etal.;VISIONNetwork.InterimestimatesofCOVID-19vaccineeffectivenessagainstCOVID-19–associatedemergencydepartmentorurgentcareclinicalencountersandhospitalizationsamongadultsduringSARS-CoV-2B.1.617.2(Delta)variantpredominance—ninestates,June–August2021.MMWRMorbMortalWklyRep2021;70:1291–3.https://doi.org/10.15585/mmwr.mm7037e2externaliconPMID:34529642externalicon MånssonR,JoffeMM,SunW,HennessyS.Ontheestimationanduseofpropensityscoresincase-controlandcase-cohortstudies.AmJEpidemiol2007;166:332–9.https://doi.org/10.1093/aje/kwm069externaliconPMID:17504780externalicon MarshallSW.Powerfortestsofinteraction:effectofraisingtheTypeIerrorrate.EpidemiolPerspectInnov2007;4:4.https://doi.org/10.1186/1742-5573-4-4externaliconPMID:17578572externalicon EdaraVV,HudsonWH,XieX,AhmedR,SutharMS.NeutralizingantibodiesagainstSARS-CoV-2variantsafterinfectionandvaccination.JAMA2021;325:1896–8.https://doi.org/10.1001/jama.2021.4388externaliconPMID:33739374externalicon EdaraVV,PinskyBA,SutharMS,etal.Infectionandvaccine-inducedneutralizing-antibodyresponsestotheSARS-CoV-2B.1.617variants.NEnglJMed2021;385:664–6.https://doi.org/10.1056/NEJMc2107799externaliconPMID:34233096externalicon SelfWH,TenfordeMW,RhoadsJP,etal.;IVYNetwork.ComparativeeffectivenessofModerna,Pfizer-BioNTech,andJanssen(Johnson&Johnson)vaccinesinpreventingCOVID-19hospitalizationsamongadultswithoutimmunocompromisingconditions—UnitedStates,March–August2021.MMWRMorbMortalWklyRep2021;70:1337–43.https://doi.org/10.15585/mmwr.mm7038e1externaliconPMID:34555004externalicon Top TABLE1.CharacteristicsofCOVID-19–likeillnesshospitalizations*amongunvaccinatedadultswithaSARS-CoV-2infectionoccurring90–179daysbeforetheindextestdate†andamongadultswhowerefullyvaccinated§90–179daysbeforetheindextestdate†withoutapreviousdocumentedSARS-CoV-2infection—ninestates,¶January–September2021 Characteristic No.(column%) Standardizedmeanorproportiondifference** UnvaccinatedwithpreviousSARS-CoV-2infection Fullyvaccinated§withoutpreviousdocumentedinfection AllhospitalizationswithCOVID-19–likeillness 1,020(100) 6,328(100) NA SARS-CoV-2testresultassociatedwithCOVID-19–likeillnesshospitalization Positive 89(9) 324(5) 0.14 Negative 931(91) 6,004(95) Sex Male 405(40) 2,905(46) 0.13 Female 615(60) 3,423(54) Agegroup,yrs 18–49 313(31) 560(9) 0.74 50–64 243(24) 865(14) 65–74 207(20) 1,757(28) 75–84 177(17) 2,018(32) ≥85 80(8) 1,128(18) Race,irrespectiveofethnicity White 647(63) 4,356(69) 0.24 Black 100(10) 452(7) Other†† 71(7) 686(11) Unknown 202(20) 834(13) Ethnicity,irrespectiveofrace Hispanic 189(19) 756(12) 0.20 Non-Hispanic 695(68) 4,458(70) Unknown 136(13) 1,114(18) Monthofindextestdate† January 11(1) 0(—) 2.10 February 41(4) 0(—) March 114(11) 0(—) April 245(24) 6(0) May 294(29) 235(4) June 184(18) 1,300(21) July 99(10) 2,731(43) August 31(3) 2,049(32) September 1(0) 7(0) Site ColumbiaUniversity 53(5) 238(4) 0.73 HealthPartners 22(2) 94(1) IntermountainHealthcare 117(11) 454(7) KaiserPermanenteNorthernCalifornia 254(25) 3,614(57) KaiserPermanenteNorthwest 30(3) 250(4) RegenstriefInstitute 390(38) 1,145(18) UniversityofColorado 154(15) 533(8) TimesinceeitherpreviousSARS-CoV-2infectionorfullmRNAvaccinationuntilCOVID-19–likeillnessindextestdate,days 90–119 367(36) 3,325(53) 0.42 120–149 353(35) 2,101(33) 150–179 300(29) 902(14) COVID-19vaccinationstatus Unvaccinated 1,020(100) 0(—) NA Pfizer-BioNTech(BNT162b2) 0(—) 3,736(59) Moderna(mRNA-1273) 0(—) 2,592(41) Abbreviation:NA = notapplicable. *MedicaleventswithadischargecodeconsistentwithCOVID-19–likeillnesswereincluded.COVID-19–likeillnessdiagnosesincludedacuterespiratoryillness(e.g.,COVID-19,respiratoryfailure,orpneumonia)orrelatedsignsorsymptoms(cough,fever,dyspnea,vomiting,ordiarrhea)usingdiagnosiscodesfromtheInternationalClassificationofDiseases,NinthRevisionandInternationalClassificationofDiseases,TenthRevision.Clinician-orderedmolecularassays(e.g.,real-timereversetranscription–polymerasechainreaction)forSARS-CoV-2occurring≤14daysbeforeto<72hoursafterhospitaladmissionwereincluded. †IndextestdatewasdefinedasthedateofrespiratoryspecimencollectionassociatedwiththemostrecentpositiveornegativeSARS-CoV-2testresultbeforethehospitalizationorthehospitalizationdateiftestingonlyoccurredaftertheadmission. §FullvaccinationwasdefinedasreceiptoftheseconddoseofPfizer-BioNTechorModernamRNAvaccine≥14daysbeforetheindextestdate. ¶PartnerscontributinghospitalizationswereinCalifornia,Colorado,Indiana,MinnesotaandWisconsin,OregonandWashington,Utah,andNewYork. **Incomparingcharacteristicsbetweenunvaccinatedadultswithapreviousinfectionandfullyvaccinatedadultswithoutapreviousdocumentedinfection,astandardizedmeanorproportiondifference>0.2wasconsiderednoteworthy.Afterbalancingcharacteristicsthatdifferedbetweenthetwocomparisongroups,thestandardizedmeanorproportiondifferenceswere≤0.06. ††OtherraceincludesAsian,HawaiianorOtherPacificislander,AmericanIndianorAlaskanNative,Othernotlisted,andmultipleraces. Top TABLE2.Adjustedoddsratios*oflaboratory-confirmedCOVID-19amonghospitalizationsinadultswithCOVID-19–likeillnesscomparingunvaccinatedadultswithaSARS-CoV-2infectionoccurring90–179daysbeforetheindextestdateandadultswhowerefullyvaccinated90–179daysbeforetheindextestdatewithoutapreviousdocumentedSARS-CoV-2infection—ninestates,January–September2021 Outcome Totalno. No.(row%)ofSARS-CoV-2positivetestresults Adjustedoddsratio(95%CI) Alladults(aged≥18years),anyCOVID-19mRNAvaccine AnymRNAvaccine Fullyvaccinated†withoutpreviousdocumentedinfection 6,328 324(5.1) Ref UnvaccinatedwithapreviousSARS-CoV-2infection 1,020 89(8.7) 5.49(2.75–10.99) AnymRNAvaccine,norestrictionoftimesincepreviousinfectionorcompletionofvaccination Fullyvaccinated†withoutpreviousdocumentedinfection(rangeoftimesincevaccination=0–213daysbeforehospitalization) 18,397 542(3.0) Ref UnvaccinatedwithapreviousSARS-CoV-2infection(rangeoftimesincepreviousinfection=90–494daysbeforehospitalization) 2,085 130(6.2) 2.75(1.90–3.98) AnymRNAvaccine,examiningthepotentialinfluenceoftimesincepreviousinfectionorcompletionofvaccination Fullyvaccinated†withoutpreviousdocumentedinfection,limitedtothosewithlongestperiodsincevaccination(rangeoftimesincevaccination=45–213daysbeforehospitalization) 12,231 458(3.7) Ref UnvaccinatedwithapreviousSARS-CoV-2infection,limitedtothosewithmorerecentinfections(rangeoftimesincepreviousinfection=90–225daysbeforehospitalization) 1,389 107(7.7) 3.98(2.49–6.35) AnymRNAvaccine,adjustingfortimesincepreviousinfectionorcompletionofvaccinationinmodel Fullyvaccinated†withoutpreviousdocumentedinfection 6,328 324(5.1) Ref UnvaccinatedwithapreviousSARS-CoV-2infection 1,020 89(8.7) 3.22(1.68–6.20) BytimerelativetoSARS-CoV-2B.1.617.2(Delta)variantpredominance BeforeDeltapredominance(January–June2021) Fullyvaccinated†withoutpreviousdocumentedinfection 1,115 18(1.6) Ref UnvaccinatedwithapreviousSARS-CoV-2infection 831 70(8.4) 6.11(2.83–13.16) DuringDeltapredominance(June–September2021)** Fullyvaccinated†withoutpreviousdocumentedinfection 5,213 306(5.9) Ref UnvaccinatedwithapreviousSARS-CoV-2infection 189 19(10.1) 7.55(3.45–16.52) BymRNAvaccineproduct§ Pfizer-BioNTech(BNT162b2) Fullyvaccinated†withoutpreviousdocumentedinfection 3,736 215(5.8) Ref UnvaccinatedwithapreviousSARS-CoV-2infection 1,020 89(8.7) 5.11(2.53–10.29) Moderna(mRNA-1273) Fullyvaccinated†withoutpreviousdocumentedinfection 2,592 109(4.2) Ref UnvaccinatedwithapreviousSARS-CoV-2infection 1,020 89(8.7) 7.30(3.40–15.60) Byagegroup,yrs¶ 18–64 Fullyvaccinated†withoutpreviousdocumentedinfection 1,425 71(5.0) Ref UnvaccinatedwithapreviousSARS-CoV-2infection 556 49(8.8) 2.57(1.42–4.65) ≥65 Fullyvaccinated†withoutpreviousdocumentedinfection 4,903 253(5.2) Ref UnvaccinatedwithapreviousSARS-CoV-2infection 464 40(8.6) 19.57(8.34–45.91) Abbreviations:CI = confidenceinterval;ref = referentgroup. *Oddsratioswereadjustedforage,geographicregion,calendartime(dayssinceJanuary1,2021),andlocalviruscirculation(percentageofSARS-CoV-2positiveresultsfromtestingwithinthecountiessurroundingthefacilityonthedateofthehospitalization)andbalancedusinginverseweightsoncharacteristicsthatdifferedbetweenthetwogroups(calculatedseparatelyforeachoddsratiomodel)usingfacilitycharacteristics,sociodemographiccharacteristics,andunderlyingmedicalconditions.CardiovasculardiseasewasalsoadjustedinthemainmodelandinthemodelforPfizer-BioNTech.AnylikelyimmunosuppressionwasalsoincludedinthemodelforModerna.Neuromuscularandrespiratoryconditionswerealsoadjustedinthemodelforadultsaged≥65years.Numberofdayssincepreviousinfectionorcompletionofvaccination,insteadofcalendartime,wasadjustedinthemodelwithinthestatedsecondaryanalysis. †FullvaccinationwasdefinedasreceiptoftheseconddoseofPfizer-BioNTechorModernamRNAvaccine≥14daysbeforetheindextestdate. §P-valuefromassessmentofeffectmodificationbymRNAproductwas0.02. ¶P-valueforinteractiontermforexposuregroupbyagegroupwas0.05. **SARS-CoV-2B.1.617.2(Delta)variantpredominancebeganonthedatetheDeltavariantaccountedfor>50%ofsequencedisolatesineachmedicalfacility’sstate.https://doi.org/10.15585/mmwr.mm7037e2externalicon TopSuggestedcitationforthisarticle:BozioCH,GrannisSJ,NalewayAL,etal.Laboratory-ConfirmedCOVID-19AmongAdultsHospitalizedwithCOVID-19–LikeIllnesswithInfection-InducedormRNAVaccine-InducedSARS-CoV-2Immunity—NineStates,January–September2021.MMWRMorbMortalWklyRep2021;70:1539–1544.DOI:http://dx.doi.org/10.15585/mmwr.mm7044e1externalicon. 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