Multi-Criteria Decision Analysis to prioritize hospital admission of patients affected by COVID-19 in low-resource settings with hospital-bed shortage

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Multi-Criteria

Decision

Analysis

to

prioritize

hospital

admission

of

patients

affected

by

COVID-19

in

low-resource

settings

with

hospital-bed

shortage

Pasquale

De

Nardo

a,

*

,1

_,

_Elisa

_Gentilotti

a,1

_,

_Fulvia

_Mazzaferri

d

_,

_Eleonora

_Cremonini

a

_,

Paul

Hansen

b

,

Herman

Goossens

c

,

Evelina

Tacconelli

a

,

the

members

of

the

COVID-19MCDA

Group

2

a

DivisionofInfectiousDiseases,DepartmentofDiagnosticsandPublicHealth,UniversityofVerona,Italy

b

DepartmentofEconomics,UniversityofOtago,Dunedin,NewZealand

c_Laboratory_of_Medical_{Microbiology,}_Vaccine_and_Infectious_Diseases_Institute,_University_of_Antwerp,_Antwerp,_Belgium d

DivisionofInfectiousDiseases,DepartmentofMedicine,VeronaUniversityHospital,Verona,Italy

ARTICLE INFO Articlehistory: Received13May2020

Receivedinrevisedform22June2020 Accepted24June2020

Keywords: SARSCoV-2 COVID-19

Multi-CriteriaDecisionAnalysis Pandemic

ABSTRACT

Objective:TouseMulti-CriteriaDecisionAnalysis(MCDA)todetermineweightsforelevencriteriain ordertoprioritizeCOVID-19non-criticalpatientsforadmissiontohospitalinhealthcaresettingswith limitedresources.

Methods:TheMCDAwasappliedintwomainsteps:speciﬁcationofcriteriaforprioritizingCOVID-19 patients(and levelswithineachcriterion);and determinationofweightsforthecriteriabasedon experts’knowledgeandexperienceinmanagingCOVID-19patients,viaanonlinesurvey.Criteriawere selectedbasedonavailable COVID-19evidencewithafocuson low-andmiddle-incomecountries (LMICs).

Results:Themostimportantcriteria(meanweights,summingto100%)are:PaO2(16.3%);peripheralO2

saturation(15.9%);chestX-ray(14.1%);ModiﬁedEarlyWarningScore-MEWS(11.4%);respiratoryrate (9.5%);comorbidities(6.5%);livingwithvulnerablepeople(6.4%);bodymassindex(5.6%);durationof symptomsbeforehospitalevaluation(5.4%);CRP(5.1%);andage(3.8%).

Conclusions:Atthebeginningofanewpandemic,whenevidencefordiseasepredictorsislimitedor unavailableandeffectivenationalcontingencyplansaredifﬁculttoestablish,theMCDAprioritization modelcouldplayapivotalroleinimprovingtheresponseofhealthsystems.

http://creativecommons.org/licenses/by-nc-nd/4.0/).

Background

Asof13thMay2020,therehavebeen4,170,424confirmedcases and287,399confirmeddeathsfromSARSCoV-2worldwide(World HealthOrganization.COVID-19diseasepandemic,2020).Sincethe firstcaseofthecoronavirusdisease2019(COVID-19)wasrecorded

inItalyon21stFebruary,2,735,628nasopharyngealswabshave been processed. The number of cases and deaths has reached 222,104 and 31,106 respectively, with Italy having one of the highest nationalratesof localtransmission.The Italian govern-mentimposedaggressivemeasurestocontainthespreadofthe disease.Nevertheless,thedailyincidenceofnewCOVID-19cases anddeathsreachedalarmingrates(MinisterodellaSalute. COVID-19SituazioneinItalia,2020).SARSCoV-2appearedinItalyinthe middleofﬂuseason,contributingtotheover-crowdingofprimary care,outpatientclinicsandemergencydepartments. Duetothe COVID-19 pandemic emergency, the Italian National Health System (NHS), which is regionally based and offers universal accesstohealthcare,hasbeenclosetocollapse(Armocidaetal., 2020).Theshortageofavailablehospitalbedsandthelackofbeds inintensivecareunits(ICUs)forcriticallyillpatientshavebeen amongthemajorchallengesfaced.

*Corresponding author at: Division of Infectious Diseases, Department of DiagnosticsandPublicHealth,UniversityofVerona,PiazzaleL.A.Scuro,37134 Verona,Italy.

E-mailaddresses:pasquale.denardo@univr.it(P.DeNardo),

elisa.gentilotti@univr.it(E.Gentilotti),fulvia.mazzaferri@univr.it(F.Mazzaferri),

eleonora.cremonini@univr.it(E.Cremonini),paul.hansen@otago.ac.nz(P.Hansen),

herman.goossens@uza.be(H.Goossens),evelina.tacconelli@univr.it(E.Tacconelli).

1

Contributedequally.

2

ThemembersoftheCOVID-19MCDAGrouparelistedinAppendixA.

https://doi.org/10.1016/j.ijid.2020.06.082

1201-9712/©2020TheAuthors.PublishedbyElsevierLtdonbehalfofInternationalSocietyforInfectiousDiseases.ThisisanopenaccessarticleundertheCCBY-NC-ND license(http://creativecommons.org/licenses/by-nc-nd/4.0/).

ContentslistsavailableatScienceDirect

International

Journal

of

Infectious

Diseases

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Becauseevencountrieswithrobusthealth caresystemsand strongeconomiescanberapidlyoverwhelmedbythisemergency, attentionstartstobefocusedonlessadvantagedareasoftheworld (Hopman et al., 2020). In low- and middle-income countries (LMICs), where over-crowdingrenders social distancing almost impossible,shortagesofhandsanitizersandcleanwaterarethe normandpreventionmeasuresaredifﬁculttoestablish,thespread ofthepandemiccouldhavecatastrophicconsequences.Healthcare facilities,alreadycongestedandlackingpersonnelandsupplies, are likely tobe rapidly overwhelmed and not able to provide potentially life-savingservices – such as caesarean sectionsor basicsurgery_–anymore(Bongetal.,2020).AnAfricantaskforce for coronavirus preparedness and response (AFTCOR) has been established, focusing on: laboratory diagnosis and subtyping, surveillance, infection prevention and control in health care facilities,clinicaltreatmentofpeoplewithsevereCOVID-19,risk communication,and supplychain management(Nkengasonget Mankoula, 2020). Nonetheless, prioritizing access to care in settings at extremely high risk of collapse appears to be unavoidable.

UnliketriageforprioritizingadmissionstoICUs– whichhas beendebated worldwide (Emanuel et al., 2020; White and Lo, 2020;TheHastingsCenter,2020)–noexplicitrecommendations have been developed to identify which COVID-19patients are prioritizedforhospitaladmissioninsettingswithanunsolvable shortageofbedsandinLMICs.Thequalityofsuchprioritization decision-making when multiple criteria need to be considered together can be improved by using structured and explicit methods. Multi-Criteria Decision Analysis (MCDA) is useful in suchacontext.FundamentaltoMCDAisspecifyingthecriteriathat arerelevantforthedecisionathandanddeterminingtheirrelative importance(usuallyrepresentedintermsofweights).Widelyused in many sectors, MCDA is increasingly employed in healthcare applications to increase the consistency, transparency, and legitimacyofdecisions(Thokalaetal.,2016;Marshetal.,2014).

TheobjectiveofthisstudywastouseMCDAtoidentify non-critical COVID-19 patientswho should be admitted tohospital becauseoftheirriskofrapidclinicaldeterioration.

Methods

MCDAandthePAPRIKAmethod

TheMCDAwasappliedintwomain steps:1.specificationof criteriaforprioritizingCOVID-19patientsforhospitalizationand thelevelswithineachcriterion,and2.determinationofweights for the criteria (and their levels), representing their relative importance,basedonexperts’knowledgeandpreferences.Atthe firststep,evidencefromthescientificliteratureonpredictorsof outcomesinpatientsaffectedbyCOVID-19was reviewedupto March15.Atthesecondstep,alargegroupofItalianexpertswere invitedtocompleteanonlinesurveytodeterminetheweightsfor the criteria. The experts were selected according to their experience in dealing with COVID-19 patients, and included physiciansbasedinemergency,infectiousdiseases,pneumology, andinternal medicinedepartmentsand workinginavarietyof institutions(i.e.universityhospitals,institutesfor researchand treatment,andcommunityhospitals).Attentionwaspaidtothe prevalenceofCOVID-19casesintheexperts’region:moreexperts based in northern Italian regions wereinvited than experts in southernregionswherethediseaseislessprevalent.

The survey was run using 1000minds MCDA software (www.1000minds.com)which implementsthePAPRIKA (Poten-tiallyAllPairwiseRanKingsofallpossibleAlternatives)method (HansenandOmbler,2008).Previousapplicationsofthesoftware andmethodincludeprioritizingpatientsforelectivesurgeryand

creatingtheWorldHealthOrganization’sprioritylistof antibiotic-resistantbacteria tosupportresearchand development ofnew drugs(Hansenetal.,2012;Tacconellietal.,2018).ThePAPRIKA methodinvolvedeachparticipantbeingshownaseriesofpairsof combinations of levels on two criteria at a time (in effect, representingapairofimaginarypatients)andaskedforeachpair: “Whichoneofthesecombinationsofcriteriaismorerelevantforthe hospitalization of aCOVID-19 patient during a health emergency, consideringashortageofhospitalbeds?”.Eachpairofcombinations involved a trade-off between thetwo criteria, suchthat when participantsansweredthequestion–bychoosingoneofthetwo combinationsor indicatingtheyareequal _–theyrevealedtheir opinion abouttherelativeimportance ofthetwo criteria.Such questions(alwaysinvolvingatrade-offbetweenthecriteria,twoat atime)wererepeatedwithdifferentcombinationsofthecriteria until enough information was collected to determine each participant’ssetofweightsfor thecriteria(usingmathematical methods based on linear programming) (Hansen and Ombler, 2008).Thecriteriawerenot disclosedtotheexperts beforethe surveyinordernottoinﬂuencetheiranswers.Twoquestionswere repeatedattheendofthesurveyasaninternalconsistencycheck. Thesoftwarerecordedthenumberofquestionsansweredandthe timetakentoanswereachquestion.Attheendofthesurvey,the expertswerealsoaskedfortheiropinionabouttheusefulnessof lung ultrasound (US) compared to chest X-ray for diagnosing COVID-19pneumonia.

Participants’weightswereaveragedtoproducemeanweights (andstandarddeviations,SD)forthegroupofexpertsasawhole. Signiﬁcant differences in the mean weights for the criteria (p<0,05)wereassessedthroughaone-wayanalysisofvariance fornormallydistributedvariables,andtheKruskal-Wallisranktest whenthenormalityassumptionwasnotmet.

Roleofthefundingsource

The fundersof thestudyhadnorole instudydesign,data collection, data analysis, data interpretation, writing of the article, or the decision to submit forpublication. All authors were responsible for the decision to submit the article for publication.

Results

A board of ﬁve Infectious Diseases (ID) physicians with experiencein treatingCOVID-19patientsselected11 criteriato prioritizehospitaladmission,basedonthecurrentevidenceand theavailabilityand feasibilityof criteriainLMICs(Zhanget al., 2020;Chenetal.,2020;Wangetal.,2020;Guanetal.,2020;Mo etal.,2020).Thecriteria(levelsinparentheses)were:1.age(18– 50,50–70,and>70);2.bodymassindex(BMI:<30,30–40,and >40); 3. Co morbidities (diabetes, pre-existing respiratory/ cardiovascular diseases, and onco-hematological diseases); 4. respiratory rate (<20 breaths/min and >20 breaths/min); 5. PaO2 (>80mmHg, 70–80mmHg,and <70mmHg); 6.peripheral

oxygen(O2)saturation(>96%,92–96%,and<92%);7.ﬁndingsat

chestX-ray(normal,consolidation,andbilateralinterstitiallung abnormalities); 8. ModiﬁedEarly WarningScore-MEWS (Subbe et al., 2001), a clinical scoring system including pulse rate, respiratory rate,systolicblood pressure,body temperature,and neurological symptoms (score: 0–2 and 3–4); 9. duration of symptomsbeforehospitalevaluation(<3days,4–7days,and>7 days);10.C-reactiveprotein(CRP:normal/highbylocalcutoff); and11.livingwithvulnerablepeople(i.e.peoplewith comorbid-ities,pregnantwomen,orimmunosuppressedpatients).CRPwas selected considering itspotential availabilityas a point-of-care (POC)testworldwide(Drainetal.,2014).

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Launchedon23rdMarch2020,theonlinesurveytodetermine thecriteria weightsranfor 15daysand wascompletedby103 experts.Ofthem,96(93%)answeredthetworepeatedquestions consistently and were therefore included in the ﬁnal analysis. These96expertswerefrom11Italianregions,withthemajority (70%)fromLombardy,PiedmontandVeneto,thethreeregionsin northernItalywiththehighestburdenofcases.Fifty-threepercent oftheexpertswereworkingatinstitutionsdealingwithmorethan

500COVID-19patientssincethebeginningofthepandemic;32% were based at university hospitals and 20% at institutes for researchandtreatment;77%wereIDphysicians;and 53%were female. The mean number of questions answered by each participantwas36(IQR12),takingmostparticipants10–15min intotal.

Fromtheexperts’answerstothesurvey,themostimportant criterion [meanweights,summing to100%]was revealedtobe

Figure1.Meanweightsforthecriteria

Theboldedvaluesrepresenttherelativeweightsofthecriteriaoverall(i.e.theboldedvaluessumto100%).

Abbreviations:MEWSmodiﬁedearlywarningscore;“comorbidities”criterionincludes:diabetespre-existingrespiratory/cardiovasculardiseases,andonco-hematological diseases;“livingwithvulnerablepeople”criterionincludes:peoplewithcomorbiditiesand/orpregnantwomen,and/orimmunosuppressedpatients.

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PaO2[16.3%],followedbyperipheralO2saturation[15.9%],chest

X-ray[14.1%],MEWS[11.4%],respiratoryrate[9.5%],comorbidities [6.5%],livingwithvulnerablepeople[6.4%],BMI[5.6%],durationof symptomsbeforehospitalevaluation[5.4%],CRP[5.1%],andage [3.8%].Thecriteriaandtheirlevelsandmeanweightsarereported inFigure1.Thevaluesforeachcriterion’shighestlevel(boldedin theﬁgure)sumacrossthecriteriatoone(100%),andthuseachof thesevaluesiseasilyinterpretableastheattribute’srelativeweight overall. The value assigned to any middle levels of a criterion representsthecombinedeffectofthelevel’srelativepositionon theparticularcriterionaswellasthecriterion’sweight;andeach criterion_’slowestlevelhasavalueofzero.Foranypairofcriteria, the ratio of their overall weights measures their relative importance; for example, MEWS (Subbe et al., 2001) was 1.2 times (e.g. 11.4%/9.5%) more important than tachypnoea alone (respiratoryrate >20breaths/min) and approximately twiceas importantasdurationofsymptoms,C-reactiveproteinandBMI respectively(Figure2).Themajorityofexperts(70%)indicatedthat theythinklung-USismorevaluablethanchestX-rayasanimaging tool for evaluating COVID-19 patients. The table presents an exampleofapplyingthemeanweights to10randomlyselected COVID-19patientsattendingtheemergencydepartmentfrom1st March2020 at the Verona University Hospital.More in detail,

patientswithatotalscore<33%werenotadmittedtoinpatient COVID-19unit.Atfollow-uptheyhadnoadverseoutcomeinterms ofneedofhospitalization,and/orneedofoxygentherapyand/or death.Patientsranked47%werealladmitted(datanotshownin the table). These patientsneeded high-ﬂow oxygen therapy or non-invasiveventilationduringinpatientstay(Table1).

Discussion

The criteria included in the MCDA prioritization model developedhereweredeliberatelyselectedinordertobeableto beapplied_‘anywhereandbyanyone_’,includingbyunskilledhealth personnel and in low-resource settings. This approach was intendedtomeettheneedsofLMICswhere,duetoverylimited resources, effective national contingency plans are difﬁcult to establish.

Atearlystage,mildhypoxemiaduetoanimpairedgasexchange canbe easilyidentiﬁedusingan arterialblood gastest (ABGT). Accordingly,PaO2wasthemostimportantcriterionidentiﬁedby

theexperts.Thesecondmostimportantcriterion,withasimilar weight,wasperipheralO2saturation–suggestingthatinsettings

whereABGTisunavailable,suchasLMICsorevenduringdomestic self-isolation,pulseoximetrymaybeausefulalternativetomore

Figure2.Relativeimportanceofthecriteria

Basedonthemeanweights,eachnumberintheﬁgureisaratiocorrespondingtotheimportanceofthecriterionontheleftrelativetothecriterionatthetop(weights reportedtoo,faded).Theratiosareobtainedbydividingtheleftweightsbythetopweights(i.e.:MEWSscoreis2timesmoreimportantthandurationofsymptoms;duration ofsymptomsis1.5timesmoreimportantthanage,etc.).Abbreviations:MEWS,modiﬁedearlywarningscore;BMI,bodymassindex;CRP,C-reactiveprotein;“comorbidities” criterionincludes:diabetes,pre-existingrespiratory/cardiovasculardiseases,andonco-hematologicaldiseases;“livingwithvulnerablepeople”criterionincludes:people withcomorbidities,and/orpregnantwomen,and/orimmunosuppressedpatients.

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invasive procedures. Chest X-ray was ranked lower than PaO2,

probablybecauseoftheloweraccuracyespeciallyatanearlyphase of the disease. Indeed, a ‘normal’ chest radiograph should not excludethepossibilitythataninterstitialdisorderispresentinthe appropriateclinicalcontext(Ryuetal.,2007).Theuseoflung-US forevaluatingCOVID-19patientshasseveraladvantages–suchas lowerriskofexposuretohealthcareworkers,repeatabilityduring follow-up and lower costsand easier application, especially in LMICs(Soldatietal.,2020a).Moreover,lung-UScanbeappliedin outpatientsettings,asatriageforsymptomaticpatientsathomeas wellasintheprehospitalphase(Soldatietal.,2020b).

MEWS isa scorethat usesreadily availableand inexpensive clinicalparametersto identifypatientsatincreasedrisk of ICU admissionordeath(Subbeetal.,2001).Withrespecttothecriteria’ ranking,MEWSscorewasconsiderablylessimportantthanPaO2

and O2 saturation. Moreover, MEWS was only 1.2 times more

importantthantachypnoeaalone,corroboratingtheimportanceof parametersrelatedtotherespiratorysystem (O2saturationand

respiratoryrate)outlinedbythisanalysis.MEWScanbeobtained quicklybyphysicalexaminationandalsobyunskilledhealthcare workers,andithastheadvantageofcombiningbothrespiratory and non-respiratory parameters to assess a possible rapid worsening of clinical conditions – making it the fourth most importantcriterion.

Although it is well known that age negatively affects the outcomeinCOVID-19patients(Lietal.,2020),agewasfoundtobe theleast-importantcriterion.Remarkably,bothBMIandCRPwere 1.5 and 1.3 times more important than age, respectively. As recentlypublishedbyZhangetal.(2020),CRPtestingcouldbeused atthepointofcareinordertodirectpatientsfurtheralongthe treatmentpath. Finally,living withvulnerable peoplewas also deemed to be a relevant criterion to consider when deciding whetherto admita COVID-19patient, even though it is not a clinicalparameter.

Accordingtoexperts’evaluationofCOVID-19patients,allages arepotentiallyatriskofrapidclinicaldeterioration.AlthoughPaO2

–oralternativelyO2saturation–areessentialparameters,both

MEWSandBMIshouldbeconsideredtopredictnegativeclinical outcomeandnotdeferrableneedofhospitalization.Finally,incase ofalargevolumeofpatientsenteringhealthcarefacilities,POCCRP

testing can be adopted as a useful criterion in the proposed prioritizationmodel.

Tothebestoftheauthors’knowledge,thisistheﬁrsttimethat MCDAhasbeenusedinapandemiceventforrankingnon-critical patients for hospitalization. Since most of the criteria can be collected also by patients themselves, a “simpliﬁed domestic model” for patients self-isolated would be easily adapted by excludingsomecriteria(e.g.chestX-rayandABGT)andincluding otherslikeperipheralO2saturation.Thisapproachrepresentsan

innovativewayofcoordinatingeffortsduringapandemiccaused byanovelvirus.Determiningcriteriaandweightsforprioritizing patientsisevenmorerelevantinconditionsofcriticalimbalance betweenneedand availableresources.Furthermore,thismodel (criteria and weights)can be adapted todifferent settingsand stagesofthepandemicinresponsetoemergingevidence.Inthe demonstrative case series shown in the table, for example, a threshold above33% maybe proposed for theidenti_ficationof patientstobehospitalized,asallthepatientsrankedbelowthis cut-offdidnot needhospitalizationand hadanoverall positive outcome. The most adequate method to validate a threshold definitionwould be that of applyingMCDA resultstoa cohort study.Atthebeginningofanewpandemic,itmaybefeasibleto prospectively gather patients’ information based on the MCDA prioritizationmodel (possibly withamulticentricapproach).In thisway,athresholdtosupportclinicaldecisionscouldbequickly available. Future research could include the validation of the patients’scoresalsothroughmachinelearning.Theresultsofthis studysuggestthat,whenevidenceislimited,usingMCDAtocodify experts’knowledgeisarapidandeffectiveapproachforcreating toolstosupportdif_ficultdecision-making.

Contributors

PDNandEGconceivedthestudyandwrotethefirstdraftofthe manuscript.FMandECreviewedtheliterature.PHworkedonthe statisticalanalysisandrevisedthemanuscript.HGandETcritically revised the manuscript. Each member of the COVID-19 MCDA Groupwasinvolvedinthesurveyandcontributedsignificantlyto thework.Allauthorshaveseenandapprovedthefinalmanuscript andcontributedsignificantlytothework.

Table1

Applicationoftheweightsto10COVID-19randomlyselectedpatientsattendingtheemergencyroomfromthe1stMarch2020atVeronaUniversityHospital,Italy.Total scoresarecalculatedbysummingtheweightsforeachpatientaccordingtothepatient’sratingonthelevelsforthecriteria.

Rank Age range Comorbidities BMIa Durationof symptoms (days) Respiratoryrate (breath/min) SpO2b (%) CRPc

ChestX-ray Livingwith vulnerablepeople MEWSd PaO2 (mmHg) Totalscore (%) 1 >70 Yes <30 >7 >20 <92 Ne interstitiallung abnormalities No 0–2 65–70 69 2 18–50 Yes >40 <3 >20 92–96 N N No 3–4 65–70 54 3 18–50 No 31– 40 >7 >20 92–96 Hf _pulmonary consolidation No 3–4 71–80 54 4 51–70 No <30 4–7 >20 92-96 H N No 3–4 71–80 50 5 51–70 No <30 4–7 <20 92–96 H N Yes 3–4 71–80 47 6 51–70 No <30 4–7 <20 >96 N interstitiallung abnormalities No 0–2 71–80 32 7 18–50 No <30 <3 >20 >96 N N Yes 3–4 >80 25 8 18–50 Yes >40 >7 <20 >96 N pulmonary consolidation No 0–2 >80 23 9 >70 No <30 4–7 <20 >96 N N No 3–4 >80 22 10 >70 Yes <30 >7 <20 >96 N N No 0–2 >80 15 a

BodyMassIndex;

b

peripheraloxygensaturation;

c

C-reactiveprotein;

d _Modiﬁed

EarlyWarningscore;

e_Normal; f

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Funding

The Value-Dx project was supported by the Innovative MedicinesInitiative 2JointUndertakingundergrant agreement No 820755. This Joint Undertaking receives support from the EuropeanUnion’sHorizon2020researchandinnovationprogram and EFPIA and bioMérieux SA, Janssen Pharmaceutica NV, Accelerate Diagnostics S.L., Abbott, Bio-Rad Laboratories, BD SwitzerlandSàrl,andTheWellcomeTrustLimited.

Ethicalapproval

Approvalwasnotrequired. Declarationofinterests

Theauthorsdeclarethattheyhavenocompetinginterests. Acknowledgments

Wewouldliketothankallthecolleagueswhoparticipatedin thesurvey. Sincerethanksalsoto1000minds LtdbasedinNew Zealandformaking1000mindssoftwareavailableforfree.

Theauthorsdedicatethisworktoallhealthcareworkerswho losttheirlivesintheﬁghtagainstCOVID-19pandemic.

AppendixA.

MembersoftheCOVID-19MCDAGroupinclude:

E.DuranteMangoni,L.L.Florio,R.Zampino,F.Mele(Internal Medicine, University of Campania “Luigi Vanvitelli” and AORN OspedalideiColli–MonaldiHospital,Naples,Italy);I.Gentile,B. Pinchera(DepartmentofClinicalMedicineandSurgery–Sectionof Infectious Diseases – University of Naples Federico II”, Naples, Italy);N.Coppola,M.Pisaturo(UniversityofCampania,Infectious Diseases Unit, AORN Sant’Anna e San Sebastiano di Caserta, Caserta, Italy); R. Luzzati (Dept. Haematology, Oncology & Infectious Diseases, University of Trieste Ospedale Maggiore, Trieste, Italy); N. Petrosillo, E. Nicastri, A. Corpolongo, M. A. Cataldo,A.D’Abramo,G.Maffongelli,L.Scorzolini,C.Palazzolo,E. Boumis(ClinicalandResearchDepartment,NationalInstitutefor Infectious Diseases “Lazzaro Spallanzani”, Rome, Italy); A. Pan (Infectious Diseases Unit, ASST Cremona, Cremona, Italy); A. D’ArminioMonforte, F.Bai (Institute of Infectious and Tropical Diseases,DepartmentofHealthSciences,ASSTSantiPaoloeCarlo, UniversityofMilan, Italy); S.Antinori(III Divisionof Infectious Diseases,LuigiSaccoHospital,ASSTFatebenefratelliSacco,Milan, Italy);F.G.DeRosa,S.Corcione,T.Lupia,S.M.Pinna,S.Scabini,F. Canta, S. Belloro (Department of Medical Sciences, Infectious DiseasesatAmedeodiSavoiaHospital,UniversityofTurin,Turin, Italy);Z.Bisof_ﬁ,A.Angheben,F.Gobbi,E.Turcato,N.Ronzoni,L. Moro,S.Calabria,P.Rodari,G.Bertoli,G.Marasca(Departmentof Infectious-TropicalDiseasesand Microbiology,IRCCSOspedale SacroCuoreDonCalabria,NegrardiValpolicella,Italy);M.Puoti (InfectiousDiseasesUnit,AOOspedaleNiguardaCa’Granda,Milan, Italy);A.Gori,A.Bandera,D.Mangioni(InfectiousDiseasesUnit, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico. CentreforMultidisciplinaryResearchinHealthScience(MACH), UniversityofMilan);M.Rizzi(InfectiousDiseasesUnit,ASSTPapa GiovanniXXIII,Bergamo,Italy);F.Castelli(UniversityDepartment ofInfectiousandTropicalDiseases,UniversityofBresciaandASST SpedalicivilidiBrescia,Brescia,Italy);A.Montineri,C.A.Coco,M. Maresca,M.Frasca(UnitofInfectious DiseasesandHepatology, Policlinico-Vittorio Emanuele, University Hospital Complex (Azienda Ospedaliero Universitaria ‘Policlinico-Vittorio Ema-nuele’),UniversityofCatania,Catania,Italy);D.Aquilini(Infectious

DiseasesUnit,NuovoOspedaleS.Stefano,Prato,Italy);M.Vincenzi (InfectiousDiseasesUnit,MaterSalutisHospital,Legnago,Italy);L. Lambertenghi,M.E.DeRui,E.Razzaboni,P.Cattaneo,A.Visentin,A. Erbogasto,I.DallaVecchia,I.Coledan,M.Vecchi,G.Be,L.Motta,A. Zaffagnini, N. Auerbach, P. Del Bravo, A. M. Azzini,E. Righi, E. Carrara,A.Savoldi,M.Sibani,E.Lattuada,G.Carolo,M.Cordioli,F. Soldani, M. D. Pezzani, S. Avallone (Infectious Diseases Unit, DepartmentofDiagnosticsandPublicHealth,VeronaUniversity Hospital,Verona,Italy);R.Bruno,A.Ricciardi(InfectiousDiseases Unit, IRCCS “San Matteo”, Pavia, Italy; Department of Medical, Surgical, Diagnostic and Paediatric Science,University of Pavia, Pavia,Italy);M.P.SaggeseEmergencyDepartment,_“SantoSpirito_” Hospital, ASLRoma 1, Rome, Italy); G.Malerba(Department of InternalMedicine,IvreaHospital,Turin,Italy).

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