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MASKREFERENCES

NaturalDisastersandSevereWeather|WildfireSmokeandCOVID-19

https://www.cdc.gov/disasters/covid-19/wildfire_smoke_covid-19.html

Wildfiresmokecanirritateyourlungs,causeinflammation,affectyourimmunesystem,andmakeyoumorepronetolunginfections,includingSARS-CoV-2,thevirusthatcauseCOVID-19.BecauseoftheCOVID-19pandemic,preparingforwildfiresmightbealittledifferentthisyear.KnowhowwildfiresmokecanaffectyouandyourlovedonesduringtheCOVID-19pandemicandwhatyoucandotoprotectyourselves.

Prepareforwildfires.

Prepareforthewildfiresmokeseason[PDF-205KB]asyouwouldinanyothersummer.

Giveyourselfmoretimethanusualtoprepareforwildfireevents.Homedeliveryisthesafestchoiceforbuyingdisastersupplies;however,thatmaynotbeanoptionforeveryone.Ifin-personshoppingisyouronlyoption,takestepstoprotectyourandothers’healthwhenrunningessentialerrands.

Talkwithahealthcareprovider.Planhowyouwillprotectyourselfagainstwildfiresmoke.

Stockuponmedicinesroutinelytaken.Storea7to10-daysupplyofprescriptionmedicinesinawaterproof,childproofcontainertotakewithyouifyouevacuate.

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Aspartofyourplanningforapotentialevacuation,considerdevelopingafamilydisasterplan.

Clothmaskswillnotprotectyoufromwildfiresmoke.

ClothmasksthatareusedtoslowthespreadofCOVID-19byblockingrespiratorydropletsofferlittleprotectionagainstwildfiresmoke.Theydonotcatchsmall,harmfulparticlesinsmokethatcanharmyourhealth.

AlthoughN95respiratorsdoprovideprotectionfromwildfiresmoke,theymightbeinshortsupplyasfrontlinehealthcareworkersusethemduringthepandemic.

TakeactionstoprotectyourselffromwildfiresmokeduringtheCOVID-19pandemic.

Thebestwaytoprotectagainstthepotentiallyharmfuleffectsofwildfiresmokeistoreduceyourexposuretowildfiresmoke,forexample,byseekingcleanerairsheltersandcleanerairspaces.

Limityouroutdoorexercisewhenitissmokyoutsideorchooselower-intensityactivitiestoreduceyoursmokeexposure.

Keepinmindthatwhilesocialdistancingguidelinesareinplace,findingcleanerairmightbeharderifpublicfacilitiessuchaslibraries,communitycenters,andshoppingmallsareclosedorhavelimitedtheircapacity.

CreateacleanerairspaceathometoprotectyourselffromwildfiresmokeduringtheCOVID-19pandemic.

Useaportableaircleanerinoneormorerooms.Portableaircleanersworkbestwhenruncontinuouslywithdoorsandwindowsclosed.

Ifyouuseado-it-yourselfboxfanfiltrationunit,neverleaveitunattended.

Duringperiodsofextremeheat,payattentiontotemperatureforecastsandknowhowtostaysafeintheheat.

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Wheneveryoucan,useairconditioners,heatpumps,fans,andwindowshadestokeepyourcleanerairspacecomfortablycoolonhotdays.

Ifyouhaveaforcedairsysteminyourhome,youmayneedtospeakwithaqualifiedheating,ventilation,andairconditioning(HVAC)professionalaboutdifferentfilters(HEPAorMERV-13orhigher)andsettings(“Recirculate”and“On”ratherthan“Auto”)youcanusetoreduceindoorsmoke.

Avoidactivitiesthatcreatemoreindoorandoutdoorairpollution,suchasfryingfoods,sweeping,vacuuming,and"usinggas-poweredappliances.

KnowthedifferencebetweensymptomsfromsmokeexposureandCOVID-19.

Somesymptoms,likedrycough,sorethroat,anddifficultybreathingcanbecausedbybothwildfiresmokeexposureandCOVID-19.

LearnaboutsymptomsofCOVID-19.Symptomslikefeverorchills,muscleorbodyaches,anddiarrheaarenotrelatedtosmokeexposure.

Ifyouhaveanyofthesesymptoms,theCDCCOVID-19Self-CheckercanhelpyoudeterminewhetheryouneedfurtherassessmentortestingforCOVID-19.IfyouhavequestionsafterusingtheCDCCOVID-19Self-Checker,contactahealthcareprovider.

Ifyouhaveseveresymptoms,likedifficultybreathingorchestpain,immediatelycall911orthenearestemergencyfacility.

PeoplewithCOVID-19areatincreasedriskfromwildfiresmokeduringthepandemic.

PeoplewhocurrentlyhaveorwhoarerecoveringfromCOVID-19maybeatincreasedriskofhealtheffectsfromexposuretowildfiresmokeduetocompromisedheartand/orlungfunctionrelatedtoCOVID-19.

KnowwhetheryouareatriskfromwildfiresmokeduringtheCOVID-19pandemic.

Somepeoplearemoreatriskofharmfulhealtheffectsfromwildfiresmokethanothers.

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Thosemostatriskinclude:

Childrenlessthan18yearsold

Adultsaged65yearsorolder

Pregnantwomen

Peoplewithchronichealthconditionssuchasheartorlungdisease,asthma,anddiabetes

OutdoorworkersPeoplewhohavelowersocioeconomicstatus,includingindividualsexperiencinghomelessnessorthosewhohavelimitedaccesstomedicalcare

Peoplewhoareimmunocompromisedortakingdrugsthatsuppresstheimmunesystem

Knowwhattodoifyoumustevacuate.

• Payattentiontolocalguidanceaboutupdatedplansforevacuationsandshelters,includingpotentialsheltersforyourpets.

• Whetheryoudecidetoevacuateorareaskedtoevacuatebystateorlocalauthorities,evacuatesafely.

• Whenyoucheckonneighborsandfriendsbeforeevacuating,besuretofollowsocialdistancingrecommendations(stayingatleast6feetfromothers)andotherCDCrecommendationstoprotectyourselfandothers.

• Ifyouneedtogotoadisastershelter,followCDCrecommendationsforstayingsafeandhealthyinapublicdisastershelterduringtheCOVID-19pandemic.

Stayinformed.KnowwheretofindinformationaboutairqualityandCOVID-19inyourarea.

• UsetheAirQualityIndexexternalicon(AQI)tochecktheairqualityinyourarea.

• Visitairnow.govexternalicontofindreliableinformationaboutwildfiresmokeandairquality.

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• Ifthereisalargewildfireinyourarea,thenthereislikelyanAirResourceAdvisorexternaliconassignedtoprovidewildfiresmokeoutlooksexternalicon.

• Forfurtherinformationaboutwildfiresmokeandyourhealth,visit,https://www.cdc.gov/air/wildfire-smoke/default.htm.

• VisittheCDCCOVIDDataTrackerformoreinformationaboutCOVID-19.

• Checkresourcesfromstate,local,tribal,andterritorialhealthdepartmentsformoreinformationonCOVID-19casesanddeathsinagivenarea.

FormoreinformationaboutCOVID-19,gotohttps://www.cdc.gov/coronavirus/2019-ncov/index.html

Formoreinformationaboutthehealtheffectsofwildfiresmokeandreducingexposuretoit:

• CreateaCleanRoomtoProtectIndoorAirQualityDuringaWildfireexternalicon

• DIYBoxFanFilterexternalicon

• NaturalDisastersandSevereWeather:Wildfires

• ProtectYourselffromWildfireSmoke

• WildfireGuideFactsheet:IndoorAirFiltrationpdficon[PDF-122KB]externalicon

• WildfiresandIndoorAirQualityexternalicon

Formoreinformationonairquality,wildfireinformation,smokeforecasts,andvulnerablepopulations:

• airnow.govexternalicon

• https://airquality.weather.gov/externalicon

• https://inciweb.nwcg.gov/externalicon

• https://www.cdc.gov/disasters/wildfires/links.html

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UseofsurgicalfacemaskstoreducetheincidenceofthecommoncoldamonghealthcareworkersinJapan:Arandomizedcontrolled

trial

https://www.ajicjournal.org/article/S0196-6553(08)00909-7/fulltext

Published:February13,2009

JoshuaL.Jacobs,MDSachikoOhde,EdMOsamuTakahashi,MD,MPHYasuharuTokuda,MD,MPHFumioOmata,MD,MPHTsuguyaFukui,MD,MPH

Background

HealthcareworkersoutsidesurgicalsuitesinAsiausesurgical-typefacemaskscommonly.Preventionofupperrespiratoryinfectionisonereasongiven,althoughevidenceofeffectivenessislacking.

Methods

HealthcareworkersinatertiarycarehospitalinJapanwererandomizedinto2groups:1thatworefacemasksand1thatdidnot.Theyprovidedinformationaboutdemographics,healthhabits,andqualityoflife.Participantsrecordedsymptomsdailyfor77consecutivedays,startinginJanuary2008.Presenceofacoldwasdeterminedbasedonapreviouslyvalidatedmeasureofself-reportedsymptoms.Thenumberofcoldsbetweengroupswascompared,aswereriskfactorsforexperiencingcoldsymptoms.

Results

Thirty-twohealthcareworkerscompletedthestudy,resultingin2464subjectdays.Therewere2coldsduringthistimeperiod,1ineachgroup.Ofthe8symptomsrecordeddaily,subjectsinthemaskgroupweresignificantlymorelikelytoexperienceheadacheduringthestudyperiod(P<.05).Subjectslivingwithchildrenweremorelikelytohavehighcoldseverityscoresoverthecourseofthestudy.

Conclusion

Facemaskuseinhealthcareworkershasnotbeendemonstratedtoprovidebenefitintermsofcoldsymptomsorgettingcolds.Alargerstudyisneededtodefinitivelyestablishnoninferiorityofnomaskuse.

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Facemaskstopreventtransmissionofinfluenzavirus:asystematicreview

B.J.COWLING(a1),Y.ZHOU(a1),D.K.M.IP(a1),G.M.LEUNG(a1)...

PublishedonlinebyCambridgeUniversityPress:22January2010

https://www.cambridge.org/core/journals/epidemiology-and-infection/article/face-masks-to-prevent-transmission-of-influenza-virus-a-systematic-review/64D368496EBDE0AFCC6639CCC9D8BC05

SUMMARY

Influenzavirusescirculatearoundtheworldeveryyear.Fromtimetotimenewstrainsemergeandcauseglobalpandemics.Manynationalandinternationalhealthagenciesrecommendedtheuseoffacemasksduringthe2009influenzaA(H1N1)pandemic.WereviewedtheEnglish-languageliteratureonthissubjecttoinformpublichealthpreparedness.Thereissomeevidencetosupportthewearingofmasksorrespiratorsduringillnesstoprotectothers,andpublichealthemphasisonmaskwearingduringillnessmayhelptoreduceinfluenzavirustransmission.Therearefewerdatatosupporttheuseofmasksorrespiratorstopreventbecominginfected.Furtherstudiesincontrolledsettingsandstudiesofnaturalinfectionsinhealthcareandcommunitysettingsarerequiredtobetterdefinetheeffectivenessoffacemasksandrespiratorsinpreventinginfluenzavirustransmission.

INTRODUCTION

PandemicinfluenzaA(H1N1)virusemergedinMexicoinearly2009andrapidlyspreadworldwide.Severityofillnessnowappearstobemoremoderatethaninitiallyfeared[1,2],althoughhighpopulationattackrateswouldbeassociatedwithsignificantnumbersofsevereinfections,hospitalizationsanddeaths.Whilesomegovernments,particularlyinthedevelopedworld,havelargeantiviralstockpilesonhandandcontractsforvaccinesthatarenowinproduction,theprimaryinterventionscurrentlyavailableinbothdevelopedandless-developedsettingsarenonpharmaceutical[3,4].Atthepopulationlevel,thesecanincludebordercontrolstodelaycross-bordertransmission,andsocialdistancing

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measuressuchasschoolorworkplaceclosures.Attheindividuallevel,interventionstoreducetransmissionincludeimprovedhygieneandtheuseoffacemasks,respirators,andotherphysicalbarriers[5].Weconductedasystematicreview[6]toinvestigatetheevidencesupportingtheeffectivenessoffacemasksinreducinginfluenzavirusinfectionundercontrolledandnaturalconditions.

METHODS

Searchstrategy

On18August2009wesearchedthefollowingdatabasesforarticlespublishedinEnglishfromJanuary1960toAugust2009:PubMed(1960–2009),ScienceCitationIndex(WebofScience)(1970–2009),andtheCochraneLibrary(1988–2009).Wesearchedforarticlesusingthefollowingsearchstrategy:#1:‘facemask’OR‘facemasks’OR‘mask’OR‘masks’OR‘respirator’OR‘respirators’OR‘N100’OR‘N99’OR‘N95’OR‘P2’OR‘FFP2’#2:‘influenza’OR‘flu’OR‘respiratoryvirus’OR‘respiratoryinfection’OR‘respiratorytractinfection’#3:#1AND#2.Thesearchresultsweresurveyedformethodologicalarticles.Reviewarticleswereexcluded,butthereferencelistsinallretrievedreviewpapersweresearchedforadditionalrelatedarticles.Inaddition,amanualsearchwasperformedwiththecorrespondingauthors’referencedatabase.

Selection

Twoauthors(B.J.C.andY.Z.)independentlyevaluatedthetitlesandabstractsofallstudiesforpotentialinclusioninthisreview.Thesameauthorsthenreviewedfull-lengthversionsofselectedarticlestodetermineinclusion.Whenconsensuswasnotreached,discussionandfurtherstudyevaluationwithotherauthorswasusedtoresolvedataextractiondiscrepancies.Articleswereincludedinthereviewifthey(1)describedcontrolledvolunteerstudiesofinfluenzavirusfiltrationoffacemasksorrespirators,(2)describedobservationalorinterventionstudiesoffacemasksorrespiratorstopreventinfluenzaorinfluenza-likeillness(ILI)inhealthcaresettings,(3)describedobservationalorinterventionstudiesoffacemasksorrespiratorstopreventinfluenzaorILIincommunitysettings.Studiesfocusedonspecificnon-influenzarespiratoryinfections,suchasSARS,wereexcluded.Theinitialsearchresultedin279citations.Fifty-sixarticleswere

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acceptedattheabstractstageandfinally12articleswereconsideredrelevantforinclusioninthisreview(Fig.1).

RESULTS

Experimentalvolunteerstudies

Weidentifiedonestudythatexaminedtheefficacyoffacemasksinfilteringinfluenzavirusinvolunteersubjects.JohnsonandcolleaguestestedtheperformanceofsurgicalandN95maskstofiltervirusinninevolunteerswithconfirmedinfluenzaAorBvirusinfection[7].ParticipantscoughedfivetimesontoaPetridishcontainingviraltransportmediumheld20cminfrontoftheirmouth.Theexperimentwasrepeatedwithsubjectswearingasurgicalmask,andwearinganN95respirator.WhileinfluenzaviruscouldbedetectedbyRT–PCRinallninevolunteerswithoutamask,noinfluenzaviruscouldbedetectedonthePetridishspecimenswhenparticipantsworeeithertypeoffacemask.Alimitationwasthatthestudydidnotconsidertheroleofleakagearoundthesidesofthemask.

StudiesinhealthcaresettingsWeidentifiedsixstudiesoffacemaskuseinhealthcaresettings(Table1)[8–13].Becausethestudydesigns,participants,interventionsandreportedoutcomemeasuresvariedmarkedly,wefocusedondescribingthestudies,theirresults,theirapplicabilityandtheirlimitationsandonqualitativesynthesisratherthanmeta-analysis.ArandomizedcontrolledtrialinCanadafoundnosignificantdifferencesinprotectionagainstlaboratoryconfirmedinfluenzainfectionassociatedwiththeuseofsurgicalmasksorN95masksamongnurses[absoluteriskdifferencex0.73%,95%confidenceinterval(CI)x8.8to7.3]with24%ofnursesinthesurgicalmaskarmhavinglaboratory-confirmedinfectionduringaninfluenzaseason[8].ArandomizedcontrolledtrialinJapanallocated32healthcarepersonneltowearingsurgicalfacemasksornot,butwasunderpoweredtodetectsignificantdifferencesbetweenarmswithoneobservedacuterespiratoryillnessineacharmofthestudyduringthefollow-upperiod[9].

Asurveyof133nursesinHongKongfoundthatsuboptimaladherencetowearingafaceshieldduringhigh-riskprocedures[adjustedoddsratio(OR)3.56,95%CI1.18–10.69]wasassociatedwithhigherriskofILI,whilesuboptimaladherencetouseofglovesandgownswerealsoassociatedwithhigheradjustedriskofILI

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althoughnotstatisticallysignificant[10].Twoothercross-sectionalstudiesfoundnoevidenceforaprotectiveeffectoffacemasksagainstinfection[11,12].Finally,Hobday&Cason[13]speculatedthatnaturalventilation,handhygieneandgauzefacemaskswereassociatedwithfewerobserveddeathsinopen-airhospitalsinBostonduringthe1918–1919influenzaA(H1N1)‘Spanishflu’pandemic,althoughthereweremanypotentialconfounders.StudiesincommunitysettingsWeidentifiedfourrandomizedcontrolledtrialsthatexaminedtheeffectivenessoffacemaskstopreventrespiratoryvirustransmissionincommunitysettings[14–16](Table2).Inahousehold-basedstudyinHongKong,indexcasesandhouseholdmemberswererandomizedtothreearms,includingcontrol,handhygieneandhandhygieneplussurgicalmasks(tobewornbytheindexcaseandhouseholdmembers)[14].Intheprimaryintention-to-treatanalysistherewasnostatisticallysignificantdifferenceinlaboratory-confirmedinfluenzainhouseholdcontactsacrossinterventiongroups.Howeverwhenaprespecifiedanalysisrestrictedattentionto154householdsinwhichtheinterventionwasappliedwithin36hoursofsymptomonsetintheindexcase,statisticallysignificantreductionsinlaboratory-confirmedinfluenzavirusinfectionsinhouseholdcontactswereobservedinthefacemaskandhandhygienearm(adjustedOR0.33,95%CI0.13–0.87).Adherencetothefacemaskinterventioninindexcaseswasmoderate,butpoorerinhouseholdcontacts.Thepilotstudywithasimilardesignwasunderpoweredtoidentifysignificantdifferencesbetweenstudyarms[15].Anotherrecentstudyrandomized145symptomaticindexcasesaged0–15yearsfromoutpatientclinicsandtheirhouseholdmemberstothreearms:control,surgicalmasks(wornbyhouseholdcontactsonly),orN95-typerespirators(wornbyhouseholdcontactsonly)withoutfit-testing[16].TherewerenodifferencesinILIinhouseholdcontactsacrossinterventionarms.Asecondaryper-protocolanalysisfoundthatTable2.adherentuseofN95orsurgicalmaskssignificantlyreducedtheriskforILIinhouseholdcontacts(hazardratio0.26,95%CI0.09–0.77)comparedtononadherentmaskuseorallocationtothecontrolarm.Aielloandcolleaguesdescribedastudyinwhich1437universitystudentswererandomizedbydormitorytothreearms:control,surgicalmasksalone,andsurgicalmasksplushandhygiene[17].Studentswerefollowedfor6weeksduringtheinfluenzaseasonandassessedforclinicallydiagnosedorsurvey-reportedILI.Comparedwiththecontrolgroup,significantreductionsinILIwereobservedduringweeks4–6inthemaskandhandhygienegrouprangingfrom35%(95%CI

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9–53)to51%(95%CI13–73),afteradjustingforvaccinationandothercovariates;similarreductions,althoughnotstatisticallysignificant,wereobservedinthemask-onlygroupcomparedtothecontrolgroup.NeithermaskuseandhandhygienenormaskusealonewasassociatedwithsignificantreductioninILIratecumulatively;continuedsubjectrecruitment(largersamplesize)afterstudystart,increasedparticipationintheinterventionlaterinthestudy,alate,mildinfluenzaseason,and/orinterruptionoftheinterventionfor1weekbyspringbreakmayexplainthisfinding.Thestudywasunderpoweredtodeterminetherelativecontributionoftheprotectiveeffectsofmaskscomparedtohandhygiene.Finally,Loandcolleagues[18]investigatedrespiratoryvirusisolationsinspecimenscollectedprimarilyfromin-patientsandcomparedvirusisolationsinHongKongin2003withtheprecedingyears.Declinesinthenumberandproportionsofvirusisolationswereattributedtopopulationincreasesinhygienicmeasuresandwidespreaduseoffacemasks,aswellassocialdistancingduringtheSARSepidemic.However,thestudycouldnotdistinguishtherelativecontributionsofeachintervention.

DISCUSSION

Ourreviewhighlightsthelimitedevidencebasesupportingtheefficacyoreffectivenessoffacemaskstoreduceinfluenzavirustransmission.Animportantconcernwhendeterminingwhichpublichealthinterventionscouldbeusefulinmitigatinglocalinfluenzavirusepidemics,andwhichinfectioncontrolproceduresarenecessarytopreventnosocomialtransmission,isthemodeofinfluenzavirustransmissionbetweenpeopleandintheenvironment.Physicalbarrierswouldbemosteffectiveinlimitingshortdistancetransmissionbydirectorindirectcontactandlargedropletspread,whilemorecomprehensiveprecautionswouldberequiredtopreventinfectionatlongerdistancesviaairbornespreadofsmall(nuclei)dropletparticles[19].Inhealthcaresettings,stringentprecautionsarerecommendedtoprotectagainstpathogensthataretransmittedbytheairborneroute,includingtheuseofN95-typerespirators(whichrequirefittesting),otherpersonalprotectiveequipmentincludinggowns,gloves,headcoversandfaceshields,andisolationofpatientsinnegativepressurerooms[19].Thereremainsconsiderablecontroversyovertherelativeimportanceofthealternativemodesoftransmissionforinfluenzavirus.Inarecentreview,Brankstonandcolleaguesconcludedthatnaturalinfluenzatransmissioninhumanbeingsoccursgenerally

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overshortdistanceratherthanoverlongdistance[20].Basedonthesameevidence,Tellierhadearlierconcludedthataerosoltransmissionoccursatappreciablerates[21],andcitedfurtherevidenceinanupdatedreview[22].Weber&Stilianakis[23]foundthatcontact,largedropletandsmalldroplet(aerosol)transmissionareallpotentiallyimportantmodesoftransmissionforinfluenzavirus.Ifairbornetransmissionwereimportant,itwouldbelesslikelythatsurgicalmaskswillleadtoreductionsininfectiousnessorprotectionagainstinfection,ifwornbyilloruninfectedpeople,respectively.Theprimaryargumentagainstairbornetransmissionisasmuchoneofabsenceofevidenceasevidenceofabsence.Whiletherearedocumentedexamplesoflong-distanceairbornetransmissionofotherpathogensincludingvaricellazostervirusandMycobacteriumtuberculosis,theliteraturecontainfewcompellingexamplesofairbornetransmissionofinfluenzavirus[20],andseveralreportsofscenarioswhereairbornetransmissiondidnotoccur[24–27].Furtherindirectevidencesuchasthesubstantialbenefitofhandhygienetopreventinfluenzatransmission[14]issuggestiveofdirectorindirectcontactasoneofthemostimportantmodesoftransmissionforinfluenzavirusinsomesettings.Furtherobservationalorinterventionstudiesconductedindifferentlatitudesduringdifferenttimesoftheyearcouldhelptoelucidatetheroleoftemperatureandhumidityinmediatingmodesoftransmission[28].WedidnotidentifyanyexperimentalvolunteerstudiesthatinvestigatedwhethersurgicalmasksorN95respiratorscouldprotectagainstinfection.Weidentifiedoneexperimentalstudyoffacemaskperformancewhichinvolvedparticipantswithconfirmedinfluenzavirusinfection[7],andtheresultssuggestedthatsurgicalmasksmaybeabletoreduceinfectiousness.Infuturesimilarstudiesitwouldbeimportanttoconsiderthepotentialforleakagearoundthesidesofthemaskinadditiontodirectpenetrationofinfectiousviralparticlesthroughthemask,iftheresultsaretohavepracticalimplicationsforreductionoftransmissionincommunityandothersettings[29].Furtherstudiesareneededtoinvestigatehowmaskandrespiratorperformancevarieswithtemperatureandhumidity,orunderworkingconditionswhenmoistureinexhaledbreathorsweatmaybuildupinfacemasksandhinderfiltrationorfit[30].Fewstudieshavebeenconductedinhealthcaresettings,andthereislimitedevidencetosupporttheeffectivenessofeithersurgicalmasksorN95respiratorstoprotecthealthcarepersonnel[8–13].OnerecentlargetrialinnursesfoundnodifferenceineffectivenessbetweensurgicalmasksandN95respirators,although

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theconfidenceintervalswerewideenoughtoincludemoderateeffectsizes[8].Further,largerstudiesareneededtoconfirmthenoninferiorityofsurgicalmasks.GuidanceprovidedbytheWorldHealthOrganizationforprotectionofhealthcareworkersagainstpandemicinfluenzaA(H1N1)virusinfectionrecommendstheuseofstandardanddropletprecautions(includingsurgicalmasksorafaceshield)duringmostpatientinteractions,whileN95orequivalentrespiratorsarerecommendedforaerosol-generatingprocedures[31].Oneconcernovertheuseoffacemasksorrespiratorsinhealthcaresettingsisthepotentialfornegativepsychosocialimpactsonpatientsandchildreninparticular,especiallyinregionsoutsideAsiawheremasksarenotroutinelyworn[32].Long-termuseofN95-typerespiratorsislikelytoleadtophysicaldiscomfort[33],andhasbeenassociatedwithheadaches[34].ConsiderableresourcesmightberequiredtomakeavailableN95respiratorsandotherprotectiveequipmenttolargenumbersofhealthcarepersonnelthroughthecourseofinfluenzaepidemicsorpandemics.Finally,therearelikelytobedifficultiesinensuringcomplianceinhealthcareworkers[35].Neverthelesspersonalprotectiveequipmenthasledtomajorimprovementsingeneralinfectioncontrolproceduresinthehospitalsetting[36–38]andshouldnotbediscountedduetothelackofavailabledataexamininginfluenzavirusoutcomes.Threecontrolledstudiesoffacemaskeffectivenessinthecommunitysettingusedcase-ascertaineddesigns,whereillindexcaseswererecruitedfromoutpatientclinicsandhouseholdswerefollowedupfor7–10daystoobservesecondarytransmission[14–16].

TheHongKongstudyappliedsurgicalfacemaskstoindexcasesandtheirhouseholdcontacts[14,15],whiletheAustralianstudyappliedsurgicalmasksorN95-typerespiratorstohouseholdcontactsonly[16].Neitherstudyprovidesconclusiveevidencethatfacemasksareeffectiveinprimaryintention-to-treatanalyses,althoughstatisticalpowerwaslimited.Adherencewasmoderateinbothstudies,andaperprotocolanalysisoftheAustralianstudysuggeststhatmaskscouldbeeffectiveinreducingriskofinfection[16].IntheHongKongstudy,indexcasesnotallocatedtothefacemaskinterventionreporteduseoffacemasks,indicatingsomedegreeofcontaminationoftheintervention,whileadherencewaslowerinhouseholdcontactsandtheresultsmayprimarilysupporttheuseofmasksinillmemberstoreduceinfectiousness[14,15].Theeffectivenessoffacemasksisprobablyimpactedbycomplianceissuesinboththehealthcareand

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communitysetting[14,15,35].Variousstudiesshowalowerlevelofcompliancewithfacemasks[14,15]orfindlowerreportedacceptabilityoffacemasks[39]comparedtohandhygienebehavioursandothernon-pharmaceuticalinterventions.However,thesestudiesdonotseektoexplainthereducedcompliance,nordotheymeasurelevelsofcomplianceinthemidstofanoutbreakofpandemicinfluenza.Futureresearchendeavoursshouldinvestigatetheinfluenceofculturalandsocio-behaviouralfactors(e.g.fear,stigma,altruism)onlevelsofcomplianceduringapandemic.UseoffacemasksinthecommunitywasverycommonduringtheSARSepidemicinHongKong,butnotinSingapore[40],andculturaldifferencescouldalsoaffectcompliance.PandemicguidanceprovidedbytheWorldHealthOrganizationforcommunitysettingsadvisesthatmasksmaybewornalthougheffectivenessisuncertainparticularlyinopenspaces[41].Otherhealthagencies,suchastheUSCentersforDiseaseControlandPrevention,arenotrecommendingmasksinthecommunitysetting,withtheexceptionofhigh-riskindividualswhocareforthesickorspendtimeinlargecrowdsinareasaffectedbythepandemic[42].Wearingmasksincorrectlymayincreasetheriskoftransmission[41].Furtherstudiesoffacemaskusearenowunderway,includingsomewithprospectivedesignsthatfollowcohortsofinitiallyuninfectedpeople.Thesestudieswillbeparticularlyimportantinaddressingcompliancetoandeffectivenessassociatedwithsustaineduseoffacemasksbeyondtheacutescenariosofexistingstudies[14–16].Whilefewerresourcesarerequiredtoconductstudieswithoutcomesbasedonself-reportedsignsandsymptomsofacuterespiratoryinfection,futurestudiescouldincludeacuteandconvalescentserologyorrepeatedcollectionofclinicalspecimenstoprovideresultsspecifictoinfluenzavirusinfection.Inconclusionthereremainsasubstantialgapinthescientificliteratureontheeffectivenessoffacemaskstoreducetransmissionofinfluenzavirusinfection.Whilethereissomeexperimentalevidencethatmasksshouldbeabletoreduceinfectiousnessundercontrolledconditions[7],thereislessevidenceonwhetherthistranslatestoeffectivenessinnaturalsettings.Thereislittleevidencetosupporttheeffectivenessoffacemaskstoreducetheriskofinfection.Currentresearchhasseverallimitationsincludingunderpoweredsamples,limitedgeneralizability,narrowinterventiontargetingandinconsistenttestingprotocols,differentlaboratorymethods,andcasedefinitions.Furtherin-vivostudiesoffacemasksininfectiousindividualsarewarrantedtodeterminetheproportionofexhaledvirusthatistrappedbythe

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mask.Moredetailedvolunteerchallengeandvolunteertransmissionstudiescouldbedesignedtoincludebothinfectiousandsusceptibleparticipants,toevaluatetheefficacyoffacemasksbothinreducinginfectiousnessandreducingsusceptibility.However,suchstudieswouldrequiresubstantialresources,andcontrivedexperimentsmayhavelimitedgeneralizabilitytothenaturalsetting.Largeinterventionstudiesinhealthcareandcommunitysettingsarelikelytoprovidethebestevidenceoftheeffectivenessoffacemasksinreducingtransmissioninpandemicandinter-pandemicperiodsandareanurgentprioritytoguidepandemicpreparednessforsecondandsubsequentwavesofpandemicinfluenzaA(H1N1)andfuturepandemics.

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Aclusterrandomisedtrialofclothmaskscomparedwithmedicalmasksinhealthcareworkers

CRainaMacIntyre,HollySeale,ThamChiDung,NguyenTranHien,PhanThiNga,AbrarAhmadChughtai,BayzidurRahman,DominicEDwyer,andQuanyiWang

https://bmjopen.bmj.com/content/5/4/e006577

Objective

Theaimofthisstudywastocomparetheefficacyofclothmaskstomedicalmasksinhospitalhealthcareworkers(HCWs).Thenullhypothesisisthatthereisnodifferencebetweenmedicalmasksandclothmasks.Setting14secondary-level/tertiary-levelhospitalsinHanoi,Vietnam.Participants1607hospitalHCWsaged≥18yearsworkingfull-timeinselectedhigh-riskwards.

Intervention

Hospitalwardswererandomisedto:medicalmasks,clothmasksoracontrolgroup(usualpractice,whichincludedmaskwearing).Participantsusedthemaskoneveryshiftfor4consecutiveweeks.MainoutcomemeasureClinicalrespiratoryillness(CRI),influenza-likeillness(ILI)andlaboratory-confirmedrespiratoryvirusinfection.ResultsTheratesofallinfectionoutcomeswerehighestintheclothmaskarm,withtherateofILIstatisticallysignificantlyhigherintheclothmaskarm(relativerisk(RR)=13.00,95%CI1.69to100.07)comparedwiththemedicalmaskarm.ClothmasksalsohadsignificantlyhigherratesofILIcomparedwiththecontrolarm.AnanalysisbymaskuseshowedILI(RR=6.64,95%CI1.45to28.65)andlaboratoryconfirmedvirus(RR=1.72,95%CI1.01to2.94)weresignificantlyhigherintheclothmasksgroupcomparedwiththemedicalmasksgroup.Penetrationofclothmasksbyparticleswasalmost97%andmedicalmasks44%.ConclusionsThisstudyisthefirstRCTofclothmasks,andtheresultscautionagainsttheuseofclothmasks.Thisisanimportantfindingtoinformoccupationalhealthandsafety.Moistureretention,reuseofclothmasksandpoorfiltrationmayresultinincreasedriskofinfection.Furtherresearchisneededtoinformthewidespreaduseofclothmasksglobally.However,asa

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precautionarymeasure,clothmasksshouldnotberecommendedforHCWs,particularlyinhigh-risksituations,andguidelinesneedtobeupdated.

Strengthsandlimitationsofthisstudy

Theuseofclothmasksiswidespreadaroundtheworld,particularlyincountriesathigh-riskforemerginginfections,buttherehavebeennoefficacystudiestounderpintheiruse.

Thisstudyislarge,aprospectiverandomisedclinicaltrial(RCT)andthefirstRCTeverconductedofclothmasks.

Theuseofclothmasksarenotaddressedinmostguidelinesforhealthcareworkers—thisstudyprovidesdatatoupdateguidelines.

Thecontrolarmwas‘standardpractice’,whichcomprisedmaskuseinahighproportionofparticipants.Assuch(withoutano-maskcontrol),thefindingofamuchhigherrateofinfectionintheclothmaskarmcouldbeinterpretedasharmcausedbyclothmasks,efficacyofmedicalmasks,ormostlikelyacombinationofboth.

INTRODUCTION

Theuseoffacemasksandrespiratorsfortheprotectionofhealthcareworkers(HCWs)hasreceivedrenewedinterestfollowingthe2009influenzapandemic,andemerginginfectiousdiseasessuchasavianinfluenza,MiddleEastrespiratorysyndromecoronavirus(MERS-coronavirus)andEbolavirus.Historically,varioustypesofcloth/cottonmasks(referredtohereafteras‘clothmasks’)havebeenusedtoprotectHCWs.Disposablemedical/surgicalmasks(referredtohereafteras‘medicalmasks’)wereintroducedintohealthcareinthemid19thcentury,followedlaterbyrespirators.Comparedwithotherpartsoftheworld,theuseoffacemasksismoreprevalentinAsiancountries,suchasChinaandVietnam.Inhighresourcesettings,disposablemedicalmasksandrespiratorshavelongsincereplacedtheuseofclothmasksinhospitals.Yetclothmasksremainwidelyusedglobally,includinginAsiancountries,whichhavehistoricallybeenaffectedbyemerginginfectiousdiseases,aswellasinWestAfrica,inthecontextofshortagesofpersonalprotectiveequipment(PPE).Ithasbeenshownthatmedicalresearch

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disproportionatelyfavoursdiseasesofwealthycountries,andthereisalackofresearchonthehealthneedsofpoorercountries.Further,thereisalackofhigh-qualitystudiesaroundtheuseoffacemasksandrespiratorsinthehealthcaresetting,withonlyfourrandomisedclinicaltrials(RCTs)todate.Despitewidespreaduse,clothmasksarerarelymentionedinpolicydocuments,andhaveneverbeentestedforefficacyinaRCT.Veryfewstudieshavebeenconductedaroundtheclinicaleffectivenessofclothmasks,andmostavailablestudiesareobservationalorinvitro.Emerginginfectiousdiseasesarenotconstrainedwithingeographicalborders,soitisimportantforglobaldiseasecontrolthatuseofclothmasksbeunderpinnedbyevidence.TheaimofthisstudywastodeterminetheefficacyofclothmaskscomparedwithmedicalmasksinHCWsworkinginhigh-riskhospitalwards,againstthepreventionofrespiratoryinfections.

METHODS

Acluster-randomisedtrialofmedicalandclothmaskuseforHCWswasconductedin14hospitalsinHanoi,Vietnam.Thetrialstartedonthe3March2011,withrollingrecruitmentundertakenbetween3March2011and10March2011.Participantswerefollowedduringthesamecalendartimefor4weeksoffacemasksuseandthenoneadditionalweekforappearanceofsymptoms.Aninvitationletterwassentto32hospitalsinHanoi,ofwhich16agreedtoparticipate.Onehospitaldidnotmeettheeligibilitycriteria;therefore,74wardsin15hospitalswererandomised.Followingtherandomisationprocess,onehospitalwithdrewfromthestudybecauseofanosocomialoutbreakofrubella.Participantsprovidedwritteninformedconsentpriortoinitiationofthetrial.RandomisationSeventy-fourwards(emergency,infectious/respiratorydisease,intensivecareandpaediatrics)wereselectedashigh-risksettingsforoccupationalexposuretorespiratoryinfections.Clusterrandomisationwasusedbecausetheoutcomeofinterestwasrespiratoryinfectiousdiseases,wherepreventionofoneinfectioninanindividualcanpreventachainofsubsequenttransmissioninclosedsettings.EpiinfoV.6wasusedtogeneratearandomisationallocationand74wardswererandomlyallocatedtotheinterventions.Fromtheeligiblewards1868HCWswereapproachedtoparticipate.Afterprovidinginformedconsent,1607participantswererandomisedbywardtothreearms:(1)medicalmasksatalltimesontheirworkshift;(2)clothmasksatalltimesonshiftor(3)controlarm(standardpractice,whichmay12345678–111213141516689ormaynot

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includemaskuse).StandardpracticewasusedascontrolbecausetheIRBdeemeditunethicaltoaskparticipantstonotwearamask.Westudiedcontinuousmaskuse(definedaswearingmasksallthetimeduringaworkshift,exceptwhileinthetoiletorduringteaorlunchbreaks)becausethisreflectscurrentpracticeinhigh-risksettingsinAsia.Thelaboratoryresultswereblindedandlaboratorytestingwasconductedinablindedfashion.Asfacemaskuseisavisibleintervention,clinicalendpointscouldnotbeblinded.Figure1outlinestherecruitmentandrandomisationprocess.

Primaryendpoints

Therewerethreeprimaryendpointsforthisstudy,usedinourpreviousmaskRCTs:(1)Clinicalrespiratoryillness(CRI),definedastwoormorerespiratorysymptomsoronerespiratorysymptomandasystemicsymptom;(2)influenza-like

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illness(ILI),definedasfever≥38°Cplusonerespiratory88917symptomand(3)laboratory-confirmedviralrespiratoryinfection.LaboratoryconfirmationwasbynucleicaciddetectionusingmultiplexreversetranscriptasePCR(RT-PCR)for17respiratoryviruses:respiratorysyncytialvirus(RSV)AandB,humanmetapneumovirus(hMPV),influenzaA(H3N2),(H1N1)pdm09,influenzaB,parainfluenzaviruses1–4,influenzaC,rhinoviruses,severeacuterespiratorysyndrome(SARS)associatedcoronavirus(SARS-CoV),coronaviruses229E,NL63,OC43andHKU1,adenovirusesandhumanbocavirus(hBoV).Additionalendpointsincludedcompliancewithmaskuse,definedasusingthemaskduringtheshiftfor70%ormoreofworkshifthours.HCWswerecategorisedas‘compliant’iftheaverageusewasequalormorethan70%oftheworkingtime.HCWwerecategorisedas‘non-compliant’iftheaveragemaskusewaslessthan70%oftheworkingtime.EligibilityNursesordoctorsaged≥18yearsworkingfull-timewereeligible.Exclusioncriteriawere:(1)Unableorrefusedtoconsent;(2)Beards,longmoustachesorlongfacialhairstubble;(3)Currentrespiratoryillness,rhinitisand/orallergy.InterventionParticipantsworethemaskoneveryshiftforfourconsecutiveweeks.Participantsinthemedicalmaskarmweresuppliedwithtwomasksdailyforeach8hshift,whileparticipantsintheclothmaskarmwereprovidedwithfivemasksintotalforthestudyduration,whichtheywereaskedtowashandrotateoverthestudyperiod.Theywereaskedtowashclothmaskswithsoapandwatereverydayafterfinishingtheshifts.Participantsweresuppliedwithwritteninstructionsonhowtocleantheirclothmasks.Masksusedinthestudywerelocallymanufacturedmedical(threelayer,madeofnon-wovenmaterial)orclothmasks(twolayer,madeofcotton)commonlyusedinVietnamesehospitals.Thecontrolgroupwasaskedtocontinuewiththeirnormalpractices,whichmayormaynothaveincludedmaskwearing.Maskwearingwasmeasuredanddocumentedforallparticipants,includingthecontrolarm.Datacollectionandfollow-upDataonsociodemographic,clinicalandotherpotentialconfoundingfactorswerecollectedatbaseline.Participantswerefollowedupdailyfor4weeks(activeinterventionperiod),andforanextraweekofstandardpractice,inordertodocumentincidentinfectionafterincubation.Participantsreceivedathermometer(traditionalglassandmercury)tomeasuretheirtemperaturedailyandatsymptomonset.Dailydiarycardswereprovidedtorecordnumberofhoursworkedandmaskuse,estimatednumberofpatientcontacts(with/withoutILI)andnumber/typeofaerosol-generatingprocedures

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(AGPs)conducted,suchassuctioningofairways,sputuminduction,endotrachealintubationandbronchoscopy.Participantsintheclothmaskandcontrolgroup(iftheyusedclothmasks)werealsoaskedtodocumenttheprocessusedtocleantheirmaskafteruse.Wealsomonitoredcompliancewithmaskusebyapreviouslyvalidatedself-reportingmechanism.Participantswerecontacteddailytoidentifyincidentcasesofrespiratoryinfection.Ifparticipantsweresymptomatic,swabsofbothtonsilsandtheposteriorpharyngealwallwerecollectedonthedayofreporting.

Samplecollectionandlaboratorytesting18–2398Trainedcollectorsuseddoublerayon-tipped,plastic-shaftedswabstoscratchtonsillarareasaswellastheposteriorpharyngealwallofsymptomaticparticipants.TestingwasconductedusingRT-PCRapplyingpublishedmethods.ViralRNAwasextractedfromeachrespiratoryspecimenusingtheViralRNAMinikit(Qiagen,Germany),followingthemanufacturer'sinstructions.TheRNAextractionstepwascontrolledbyamplificationofaRNAhouse-keepinggene(amplifypGEM)usingreal-timeRT-PCR.Onlyextractedsampleswiththehousekeepinggenedetectedbyreal-timeRT-PCRweresubmittedformultiplexRT-PCRforviruses.ThereversetranscriptionandPCRswereperformedinOneStep(Qiagen,Germany)toamplifyviraltargetgenes,andtheninfivemultiplexRT-PCR:RSVA/B,influenzaA/H3N2,A(H1N1)andBviruses,hMPV(reactionmix1);parainfluenzaviruses1–4(reactionmix2);rhinoviruses,influenzaCvirus,SARS-CoV(reactionmix3);coronavirusesOC43,229E,NL63andHKU1(reactionmix4);andadenovirusesandhBoV(reactionmix5),usingamethodpublishedbyothers.AllsampleswithvirusesdetectedbymultiplexRT-PCRwereconfirmedbyvirus-specificmononestedorheminestedPCR.Positivecontrolswerepreparedbyinvitrotranscriptiontocontrolamplificationefficacyandmonitorforfalsenegatives,andincludedinallruns(exceptforNL63andHKU1).Eachrunalwaysincludedtwonegativestomonitoramplificationquality.Specimenprocessing,RNAextraction,PCRamplificationandPCRproductanalyseswereconductedindifferentroomstoavoidcross-contamination.

Filtrationtesting

ThefiltrationperformanceoftheclothandmedicalmaskswastestedaccordingtotherespiratorystandardAS/NZS1716.TheequipmentusedwasaTSI8110

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Filtertester.Totestthefiltrationperformance,thefilterischallengedbyaknownconcentrationofsodiumchlorideparticlesofaspecifiedsizerangeandatadefinedflowrate.Theparticleconcentrationismeasuredbeforeandafteraddingthefiltermaterialandtherelativefiltrationefficiencyiscalculated.Weexaminedtheperformanceofclothmaskscomparedwiththeperformancelevels—P1,P2(=N95)andP3,asusedforassessmentofallparticulatefiltersforrespiratoryprotection.The3M9320N95and3MVflex9105N95wereusedtocompareagainsttheclothandmedicalmasks.

Samplesizecalculation

Toobtain80%powerattwo-sided5%significancelevelfordetectingasignificantdifferenceofattackratebetweenmedicalmasksandclothmasks,andforarateofinfectionof13%forclothmaskwearerscomparedwith6%inmedicalmaskwearers,wewouldneedeightclustersperarmand530participantsineacharm,andintraclustercorrelationcoefficient(ICC)0.027,obtainedfromourpreviousstudy.Thedesigneffect(deff)forthisclusterrandomisationtrialwas1.65(deff=1+(m−1)×ICC=1+(25−1)×0.027=1.65).Assuch,weaimedtorecruitasamplesizeof1600participantsfromupto15hospitals.

Analysis

Descriptivestatisticswerecomparedamonginterventionandcontrolarms.Primaryendpointswereanalysedbyintentiontotreat.Wecomparedtheeventratesfortheprimaryoutcomesacrossstudyarmsandcalculatedpvaluesfromcluster-adjustedχtestsandICC.Wealsoestimatedrelativerisk(RR)afteradjustingforclusteringusingalog-binomialmodelundergeneralisedestimatingequation(GEE)framework.Wecheckedforvariableswhichwereunequallydistributedacrossarms,and19–23181920248225252627conductedanadjustedanalysisaccordingly.Wefittedamultivariablelog-binomialmodel,usingGEEtoaccountforclusteringbyward,toestimateRRafteradjustingforpotentialconfounders.Intheinitialmodel,weincludedallthevariablesthathadpvaluelessthan0.25intheunivariableanalysis,alongwiththemainexposurevariable(randomisationarm).Abackwardeliminationmethodwasusedtoremovethevariablesthatdidnothaveanyconfoundingeffect.Asmostparticipantsinthecontrolarmusedamaskduringthetrialperiod,wecarriedoutapost-hocanalysis

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comparingallparticipantswhousedonlyamedicalmask(fromthecontrolarmandthemedicalmaskarm)withallparticipantswhousedonlyaclothmask(fromthecontrolarmandtheclotharm).Forthisanalysis,controlswhousedbothtypesofmask(n=245)orusedN95respirators(n=3)ordidnotuseanymasks(n=2)wereexcluded.Wefittedamultivariablelog-binomialmodel,toestimateRRafteradjustingforpotentialconfounders.Aswepooleddataofparticipantsfromallthreearmsandanalysedbymasktype,nottrialarm,wedidnotadjustforclusteringhere.AllstatisticalanalyseswereconductedusingSTATAV.12.Owingtoaveryhighlevelofmaskuseinthecontrolarm,wewereunabletodeterminewhetherthedifferencesbetweenthemedicalandclothmaskarmswereduetoaprotectiveeffectofmedicalmasksoradetrimentaleffectofclothmasks.Toassistininterpretingthedata,wecomparedratesofinfectioninthemedicalmaskarmwithratesobservedinmedicalmaskarmsfromtwopreviousRCTs,inwhichnoefficacyofmedicalmaskscouldbedemonstratedwhencomparedwithcontrolorN95respirators,recognisingthatseasonalandgeographicvariationinvirusactivityaffectstheratesofexposure(andhenceratesofinfectionoutcomes)amongHCWs.Thisanalysiswaspossiblebecausethetrialdesignsweresimilarandthesameoutcomesweremeasuredinallthreetrials.Theanalysiswascarriedouttodetermineiftheobservedresultswereexplainedbyadetrimentaleffectofclothmasksoraprotectiveeffectofmedicalmasks.

RESULTS

Atotalof1607HCWswererecruitedintothestudy.Theparticipationratewas86%(1607/1868).Theaveragenumberofparticipantsperwardwas23andthemeanagewas36years.Onaverage,HCWswereincontactwith36patientsperdayduringthetrialperiod(range0–661patientsperday,median20patientsperday).Thedistributionofdemographicvariableswasgenerallysimilarbetweenarms(table1).Figure2showstheprimaryoutcomesforeachofthetrialarms.TheratesofCRI,ILIandlaboratory-confirmedvirusinfectionswerelowestinthemedicalmaskarm,followedbythecontrolarm,andhighestintheclothmaskarm.

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Onaverage,HCWsworkedfor25daysduringthetrialperiodandwashedtheirclothmasksfor23/25(92%)days.Themostcommonapproachtowashingclothmaskswasself-washing(456/569,80%),followedbycombinedself-washingandhospitallaundry(91/569,16%),andonlyhospitallaundry(22/569,4%).Adverseeventsassociatedwithfacemaskusewerereportedin40.4%(227/562)ofHCWsinthemedicalmaskarmand42.6%(242/568)intheclothmaskarm(pvalue0.450).Generaldiscomfort(35.1%,397/1130)andbreathingproblems(18.3%,207/1130)werethemostfrequentlyreportedadverseevents.Laboratorytestsshowedthepenetrationofparticlesthroughtheclothmaskstobeveryhigh(97%)comparedwithmedicalmasks(44%)(usedintrial)and3M9320N95(<0.01%),3MVflex9105N95(0.1%).

DISCUSSION

Wehaveprovidedthefirstclinicalefficacydataofclothmasks,whichsuggestHCWsshouldnotuseclothmasksasprotectionagainstrespiratoryinfection.Clothmasksresultedinsignificantlyhigherratesofinfectionthanmedicalmasks,

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andalsoperformedworsethanthecontrolarm.ThecontrolswereHCWswhoobservedstandardpractice,whichinvolvedmaskuseinthemajority,albeitwithlowercompliancethanintheinterventionarms.ThecontrolHCWsalsousedmedicalmasksmoreoftenthanclothmasks.Whenweanalysedallmask-wearersincludingcontrols,thehigherriskofclothmaskswasseenforlaboratory-confirmedrespiratoryviralinfection.89Thetrendforalloutcomesshowedthelowestratesofinfectioninthemedicalmaskgroupandthehighestratesintheclothmaskarm.ThestudydesigndoesnotallowustodeterminewhethermedicalmaskshadefficacyorwhetherclothmasksweredetrimentaltoHCWsbycausinganincreaseininfectionrisk.Eitherpossibility,oracombinationofbotheffects,couldexplainourresults.ItisalsounknownwhethertheratesofinfectionobservedintheclothmaskarmarethesameorhigherthaninHCWswhodonotwearamask,asalmostallparticipantsinthecontrolarmusedamask.Thephysicalpropertiesofaclothmask,reuse,thefrequencyandeffectivenessofcleaning,andincreasedmoistureretention,maypotentiallyincreasetheinfectionriskforHCWs.Thevirusmaysurviveonthesurfaceofthefacemasks,andmodellingstudieshavequantifiedthecontaminationlevelsofmasks.Selfcontaminationthroughrepeateduseandimproperdoffingispossible.Forexample,acontaminatedclothmaskmaytransferpathogenfromthemasktothebarehandsofthewearer.Wealsoshowedthatfiltrationwasextremelypoor(almost0%)fortheclothmasks.ObservationsduringSARSsuggesteddouble-maskingandotherpracticesincreasedtheriskofinfectionbecauseofmoisture,liquiddiffusionandpathogenretention.Theseeffectsmaybeassociatedwithclothmasks.WehavepreviouslyshownthatN95respiratorsprovidesuperiorefficacytomedicalmasks,butneedtobeworncontinuouslyinhigh-risksettingstoprotectHCWs.Althoughefficacyformedicalmaskswasnotshown,efficacyofamagnitudethatwastoosmalltobedetectedispossible.Themagnitudeofdifferencebetweenclothmasksandmedicalmasksinthecurrentstudy,ifexplainedbyefficacyofmedicalmasksalone,translatestoanefficacyof92%againstILI,whichispossible,butnotconsistentwiththelackofefficacyinthetwopreviousRCTs.Further,wefoundnosignificantdifferenceinratesofvirusisolationinmedicalmaskusersbetweenthethreetrials,suggestingthattheresultsofthisstudycouldbeinterpretedaspartlybeingexplainedbyadetrimentaleffectofclothmasks.Thisisfurthersupportedbythefactthattherateofvirusisolationintheno-maskcontrolgroupinthefirstChineseRCTwas

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3.1%,whichwasnotsignificantlydifferenttotheratesofvirusisolationinthemedicalmaskarmsinanyofthethreetrialsincludingthisone.UnlikethepreviousRCTs,circulatinginfluenzaandRSVwerealmostcompletelyabsentduringthisstudy,withrhinovirusescomprising85%ofisolatedpathogens,whichmeansthemeasuredefficacyisagainstadifferentrangeofcirculatingrespiratorypathogens.InfluenzaandRSVpredominantlytransmitthroughdropletandcontactroutes,whileRhinovirustransmitsthroughmultipleroutes,includingairborneanddropletroutes.ThedataalsoshowthattheclinicalcasedefinitionofILIisnon-specific,andcapturesarangeofpathogensotherthaninfluenza.Thestudysuggestsmedicalmasksmaybeprotective,butthemagnitudeofdifferenceraisesthepossibilitythatclothmaskscauseanincreaseininfectionriskinHCWs.Further,thefiltrationofthemedicalmaskusedinthistrialwaspoor,makingextremelyhighefficacyofmedicalmasksunlikely,particularlygiventhepredominantpathogenwasrhinovirus,whichspreadsbytheairborneroute.GiventheobligationstoHCWoccupationalhealthandsafety,itisimportanttoconsiderthepotentialriskofusingclothmasks.Inmanypartsoftheworld,clothmasksandmedicalmasksmaybetheonlyoptionsavailableforHCWs.ClothmaskshavebeenusedinWestAfricaduringtheEbolaoutbreakin2014,duetoshortagesofPPE,(personalcommunication,MJalloh).Theuseofclothmasksisrecommendedbysomehealthorganisations,withcaveats.Inlightofourstudy,andtheobligationtoensureoccupationalhealthandsafetyofHCWs,clothmasksshouldnotberecommendedforHCWs,particularlyduringAGPsandinhigh-risksettingssuchasemergency,infectious/respiratorydiseaseandintensivecarewards.Infectioncontrolguidelinesneedtoacknowledgethewidespreadreal-worldpracticeofclothmasksandshouldcomprehensivelyaddresstheiruse.Inaddition,otherimportant2930318998989323334–36infectioncontrolmeasuresuchashandhygieneshouldnotbecompromised.Weconfirmedtheprotectiveeffectsofhandhygieneagainstlaboratory-confirmedviralinfectioninthisstudy,butmasktypewasanindependentpredictorofclinicalillness,evenadjustedforhandhygiene.Alimitationofthisstudyisthatwedidnotmeasurecompliancewithhandhygiene,andtheresultsreflectself-reportedcompliance,whichmaybesubjecttorecallorothertypesofbias.Anotherlimitationofthisstudyisthelackofano-maskcontrolgroupandthehighuseofmasksinthecontrols,whichmakesinterpretationoftheresultsmoredifficult.Inaddition,thequalityofpaperandclothmasksvarieswidelyaroundtheworld,sotheresults

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maynotbegeneralisabletoallsettings.ThelackofinfluenzaandRSV(orasymptomaticinfections)duringthestudyisalsoalimitation,althoughthepredominanceofrhinovirusisinformativeaboutpathogenstransmittedbythedropletandairborneroutesinthissetting.Asinpreviousstudies,exposuretoinfectionoutsidetheworkplacecouldnotbeestimated,butwewouldassumeittobeequallydistributedbetweentrialarms.Themajorstrengthoftherandomisedtrialstudydesignisinensuringequaldistributionofconfoundersandeffectmodifiers(suchasexposureoutsidetheworkplace)betweentrialarms.Clothmasksareusedinresource-poorsettingsbecauseofthereducedcostofareusableoption.Varioustypesofclothmasks(madeofcotton,gauzeandotherfibres)havebeentestedinvitrointhepastandshowlowerfiltrationcapacitycomparedwithdisposablemasks.Theprotectionaffordedbygauzemasksincreaseswiththefinenessoftheclothandthenumberoflayers,indicatingpotentialtodevelopamoreeffectiveclothmask,forexample,withfinerweave,morelayersandabetterfit.Clothmasksaregenerallyretainedlongtermandreusedmultipletimes,withavarietyofcleaningmethodsandwidelydifferentintervalsofcleaning.Furtherstudiesarerequiredtodetermineifvariationsinfrequencyandtypeofcleaningaffecttheefficacyofclothmasks.Pandemicsandemerginginfectionsaremorelikelytoariseinlow-incomeormiddle-incomesettingsthaninwealthycountries.Intheinterestsofglobalpublichealth,adequateattentionshouldbepaidtoclothmaskuseinsuchsettings.Thedatafromthisstudyprovidesomereassuranceaboutmedicalmasks,andarethefirstdatatoshowpotentialclinicalefficacyofmedicalmasks.Medicalmasksareusedtoprovideprotectionagainstdropletspread,splashandsprayofbloodandbodyfluids.MedicalmasksorrespiratorsarerecommendedbydifferentorganisationstopreventtransmissionofEbolavirus,yetshortagesofPPEmayresultinHCWsbeingforcedtouseclothmasks.Intheinterestofprovidingsafe,low-costoptionsinlowincomecountries,thereisscopeforresearchintomoreeffectivelydesignedclothmasks,butuntilsuchresearchiscarriedout,clothmasksshouldnotberecommended.WealsorecommendthatinfectioncontrolguidelinesbeupdatedaboutclothmaskusetoprotecttheoccupationalhealthandsafetyofHCWs.

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N95RespiratorsvsMedicalMasksforPreventingInfluenzaAmongHealthCarePersonnelARandomizedClinicalTrial

LewisJ.RadonovichJr,MD;MichaelS.Simberkoff,MD;MaryT.Bessesen,MD;AlexandriaC.Brown,PhD;DerekA.T.Cummings,PhD;CharlotteA.Gaydos,MD;JennaG.Los,MLA;AmandaE.Krosche,BS;CynthiaL.Gibert,MD;GeoffreyJ.Gorse,MD;Ann-ChristineNyquist,MD;NicholasG.Reich,PhD;MariaC.Rodriguez-Barradas,MD;ConnieSavorPrice,MD;TrishM.Perl,MD;fortheResPECTinvestigators

https://jamanetwork.com/journals/jama/fullarticle/2749214

IMPORTANCEClinicalstudieshavebeeninconclusiveabouttheeffectivenessofN95respiratorsandmedicalmasksinpreventinghealthcarepersonnel(HCP)fromacquiringworkplaceviralrespiratoryinfections.OBJECTIVETocomparetheeffectofN95respiratorsvsmedicalmasksforpreventionofinfluenzaandotherviralrespiratoryinfectionsamongHCP.

DESIGN,SETTING,ANDPARTICIPANTSAclusterrandomizedpragmaticeffectivenessstudyconductedat137outpatientstudysitesat7USmedicalcentersbetweenSeptember2011andMay2015,withfinalfollow-upinJune2016.Eachyearfor4years,duringthe12-weekperiodofpeakviralrespiratoryillness,pairsofoutpatientsites(clusters)withineachcenterwerematchedandrandomlyassignedtotheN95respiratorormedicalmaskgroups.

INTERVENTIONSOverall,1993participantsin189clusterswererandomlyassignedtowearN95respirators(2512HCP-seasonsofobservation)and2058in191clusterswererandomlyassignedtowearmedicalmasks(2668HCP-seasons)whennearpatientswithrespiratoryillness.

MAINOUTCOMESANDMEASURESTheprimaryoutcomewastheincidenceoflaboratory-confirmedinfluenza.Secondaryoutcomesincludedincidenceofacuterespiratoryillness,laboratory-detectedrespiratoryinfections,laboratory-confirmedrespiratoryillness,andinfluenzalikeillness.Adherencetointerventionswasassessed.RESULTSAmong2862randomizedparticipants(mean[SD]age,43[11.5]years;2369[82.8%])women),2371completedthestudyandaccountedfor5180HCP-seasons.Therewere207laboratory-confirmedinfluenzainfectionevents(8.2%ofHCP-seasons)intheN95respiratorgroupand193(7.2%ofHCP-seasons)inthemedicalmaskgroup(difference,1.0%,[95%CI,−0.5%to2.5%];P=.18)(adjustedoddsratio[OR],1.18[95%CI,0.95-1.45]).Therewere1556acuterespiratoryillnesseventsintherespiratorgroupvs1711inthemaskgroup(difference,−21.9per1000HCP-seasons[95%CI,−48.2to4.4];P=.10);679laboratory-detectedrespiratoryinfectionsintherespiratorgroupvs745inthemaskgroup(difference,−8.9per1000HCP-seasons,[95%CI,−33.3to15.4];P=.47);371laboratory-confirmedrespiratoryillnesseventsintherespiratorgroupvs417inthemaskgroup(difference,−8.6per1000HCP-seasons[95%CI,−28.2to10.9];P=.39);and128influenzalikeillnesseventsintherespiratorgroupvs166inthemaskgroup(difference,−11.3per1000HCP-seasons[95%CI,−23.8to1.3];P=.08).Intherespiratorgroup,

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89.4%ofparticipantsreported“always”or“sometimes”wearingtheirassigneddevicesvs90.2%inthemaskgroup.

CONCLUSIONSANDRELEVANCEAmongoutpatienthealthcarepersonnel,N95respiratorsvsmedicalmasksaswornbyparticipantsinthistrialresultedinnosignificantdifferenceintheincidenceoflaboratory-confirmedinfluenza.

Healthcarepersonnel(HCP)whoareroutinelyexposedtoviralrespiratoryinfectionsintheworkplace1maytransmitinfectiontoothers.ItiswidelyrecognizedthatHCP,asagroup,incompletelyadheretoinfectionpreventionrecommendationsandpracticestandards.Inpatientrespiratoryprotectionstudiessuggestadherenceratesvaryfrom10%to84%.2-4Whilelaboratorystudiesdesignedtoachieve100%interventionadherencehaveshownthatN95filteringfacepiecerespiratorsaremoreefficaciousthanmedicalmasksatreducingexposuretoaerosols,5comparativeclinicaleffectivenessstudieshavebeeninconclusive.3,4,6SomeexpertsarguethatN95respiratorsandmedicalmasksareequivalentinclinicalsettings.2,7Pragmaticeffectivenesstrialsareincreasinglyrecognizedasanessentialcomponentofmedicalevidence,inpartbecauseefficacystudiesmayoverestimateeffectivenessandtrueadherence.8DisposableN95respiratorsandmedicalmasksarebothwornbyHCPforself-protection;however,thesemaskshavedifferentintendeduses.N95respiratorsaredesignedtopreventthewearerfrominhalingsmallairborneparticles,9mustmeetfiltrationrequirements,10andfittightlytothewearer’sface,limitingfacialsealleakage.Medicalmasks,frequentlycalledsurgicalmasks,areintendedtopreventmicroorganismtransmissionfromthewearertothepatient.Medicalmasksfitthefacelooselyanddonotreliablypreventinhalationofsmallairborneparticles.However,medicalmaskspreventhand-to-facecontactandfacialcontactwithlargedropletsandsprays.11ClinicalevidenceisinconclusiveregardingwhetherN95respiratorsaremoreeffectivethanmedicalmasksforpreventingviralrespiratoryinfectionamongHCP,includinginfluenza,3,4,6,12accountingfordifferingpractices2andpositionsheldbyclinical,7publichealth,13,14andregulatoryorganizations.15Theobjectiveofthisstudywastocompare13theeffectivenessofN95respiratorsvsmedicalmaskswornbyHCPinclinicalpracticeforpreventionofworkplace-acquiredinfluenzaandotherviralrespiratoryinfectionsingeographicallydiverse,high-exposure,outpatientsettings.

METHODS

StudySitesandInstitutionalReviewBoardsTheRespiratoryProtectionEffectivenessClinicalTrial(ResPECT)wasapprovedbythehumansubjectsresearchboardattheNationalInstituteforOccupationalSafetyandHealth(protocol#10-NPPTL-O5XP)andtheinstitutionalreviewboards(IRBs)atthe7participatinghealthsystems,aspreviouslydescribed,16andapprovedorexemptedbyIRBsattheanalysisandsamplestoragesites.Allparticipantswerepermittedtoparticipatefor1ormoreyearsandgavewrittenconsentforeachyearofparticipation.StudyinterventionsitesincludedoutpatientsettingsattheChildren’sHospitalColorado(Aurora),

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DenverHealthMedicalCenter(Denver,Colorado),JohnsHopkinsHealthSystem(Baltimore,Maryland),MichaelE.DeBakeyVeteransAffairs(VA)MedicalCenter(Houston,Texas),VAEasternColoradoHealthcareSystem(Denver),WashingtonDCVAMedicalCenter,andVANewYorkHarborHealthcareSystem(NewYork).SamplestorageanddataanalysissitesweretheVAStLouisHealthcareSystemandStLouisUniversity(StLouis,Missouri),UniversityofFlorida(Gainesville),UniversityofMassachusetts(Amherst),andUniversityofTexasSouthwesternMedicalCenter(Dallas).

DesignandOversight

Thisclusterrandomized,multicenter,pragmaticeffectivenesstrial16conductedbetweenSeptember2011andMay2015,withfinalfollow-uponJune28,2016,comparedtheeffectofN95respirators,usedasrecommendedduringthe2009H1N1pandemic,13andmedicalmasks,usedasrecommendedtopreventseasonalinfluenza17,18andotherviralrespiratoryinfectionsandillnesses,amongHCP.17Theinvestigatorswereblindedtotherandomizationuntilcompletionofthestudyandanalysis.Anindependentdataandsafetymonitoringboardassessedthedata.AdditionaldetailsareincludedinSupplement1,includingthestatisticalanalysisplanandthefullprotocolthatwaspreviouslypublishedinanabridgedformat.16

ParticipantsandSetting

Thistrialwasconductedindiverseoutpatientsettingsservingadultandpediatricpatientswithahighprevalenceofacuterespiratoryillness,includingprimarycarefacilities,dentalclinics,adultandpediatricclinics,dialysisunits,urgentcarefacilitiesandemergencydepartments,andemergencytransportservices.Allparticipantsinaclusterworkedinthesameoutpatientclinicoroutpatientsetting.Aclusterrandomizeddesignwasusedtoimproveadherenceandincreaseindirecteffectsassociatedwithparticipantsinaclusterusingthesameintervention.Participantswereagedatleast18years,employedatoneofthe7participatinghealthsystems,andself-identifiedasroutinelypositionedwithin6feet(1.83m)ofpatients.Participantswerefull-timeemployees(definedasdirectpatientcareforapproximately≥24hoursweekly)andworkedprimarilyatthestudysite(definedas≥75%ofworkinghours).Exclusioncriteriaweremedicalconditionsprecludingsafeparticipationoranatomicfeaturesthatcouldinterferewithrespiratorfit,suchasfacialhairorthird-trimesterpregnancy.Participantsself-identifiedraceandsexusingfixedcategories;thesevariableswerecollectedbecausefacialanthropometricsrelatedtoraceandsexmayinfluenceN95respiratorfit.Participantskeptdiariesthatincludedsignsandsymptomsofrespiratoryillness,annualinfluenzavaccinationstatus,andexposuretohouseholdandcommunitymemberswithrespiratoryillness.Participantsalsorecordedtheirparticipationinaerosol-generatingproceduresandexposuretopatients,coworkers,orbothwithrespiratoryillnessdaily.Participantswerecategorizedforexposureriskbyoccupationalroles.

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Procedures,Interventions,andGroupAllocation

Eachyear,participatingsiteswereclusterrandomizedtohaveparticipantswearN95respirators13ormedicalmasks,17,18aspreviouslydescribed.16N95respiratormodelsstudiedwerethe3MCorporation1860,1860S,and1870(StPaul,Minnesota)andtheKimberlyClarkTechnolFluidshieldPFR95-270,PFR95-274(Dallas,Texas);medicalmaskmodelswerethePrecept15320(Arden,NorthCarolina)andKimberlyClarkTechnolFluidshield47107(Dallas,Texas).Withineachmedicalcenter,foreachstudyyear,pairsofclusters(clinicsandothersettings)werematchedbythenumberofparticipants,healthservicesdelivered,patientpopulationserved,andadditionalpersonalprotectiveequipment.OneclusterwasrandomlyassignedtothemedicalmaskgroupandonetotheN95respiratorgroup.Randomallocationofclustersrequiredusingconstrainedrandomization,aprocessthatmaintainsrandomassignmentandbalancebetweengroups.19Computer-generatedrandomsequencesofgroupassignmentsweregeneratedbyanindividualnotinvolvedinthestudyimplementationanddataanalyses.RandomsequencesofassignmentassuredthateveryparticipantineachseasonhadanequalprobabilityofbeingassignedtotheN95respiratorandmedicalmaskgroupsandallowedparticipantstoswitchgroupsbetweenseasons.OccupationalSafetyandHealthAdministration–acceptedfittesting15ofN95respiratorswasconductedannuallyforallstudyparticipants.Participantswereinstructedtoweartheirassignedprotectivedevices(ie,N95respiratorsormedicalmasks)duringthe12-weekperiod(theinterventionperiod)duringwhichtheincidenceofviralrespiratoryillnessandinfectionswasexpectedtobehighestthatyear,aspredictedbytheALERTalgorithm20developedforthistrial.Participantswereinstructedtoputonanewdevicewhenevertheywerepositionedwithin6feet(1.83m)ofpatientswithsuspectedorconfirmedrespiratoryillness.HandhygienewasrecommendedtoallparticipantsinaccordancewithCentersforDiseaseControlandPreventionguidelines.13,17,18Infectionpreventionpolicieswerefollowedateachstudysite.Participantsvolunteeredtoparticipateforupto12weekseachinterventionperiod,foratotalof48weeksofinterventionspanning4consecutiveviralrespiratoryseasons.

Surveillance,Outcomes,andMeasuresofEffectiveness

Studypersonnelobtainedswabsoftheanteriornaresandoropharynx21(FLOQSwabsUTM,DiagnosticHybrids)fromparticipantswhoself-reportedsymptomsofrespiratoryillness(Box1).Symptomaticswabswerecollectedwithin24hoursofself-report,andagainifsignsorsymptomspersistedbeyond7days.Ifsymptomaticparticipantswerenotatwork,sampleswereself-obtainedusingastructuredprocessandshippedtothestudylaboratory.Duringeach12-weekinterventionperiod,2randomswabswereobtainedfromallparticipants,typicallywhileasymptomatic.Additionally,eachyear,pairedserumsamplesobtainedfromallparticipantswereassayedforinfluenzahemagglutininlevelsbeforeandafterpeakviralrespiratoryseason.Theprespecifiedprimaryoutcomewastheincidenceoflaboratory-confirmedinfluenza,definedasdetectionofinfluenzaAorBvirusbyreverse-transcriptionpolymerasechainreaction22inanupperrespiratoryspecimencollectedwithin7daysof

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symptomonset;detectionofinfluenzafromarandomlyobtainedswabfromanasymptomaticparticipant;orinfluenzaseroconversion(symptomaticorasymptomatic),definedasatleasta4-foldriseinhemagglutinationinhibitionantibodytiterstoinfluenzaAorBvirusbetweenpreseasonandpostseasonserologicalsamplesdeemednotattributabletovaccination.Individualsexperiencingseroconversionwerenotrequiredtohaveadetectedsymptomaticillnesstomeetthedefinedoutcome.InfluenzareagentsusedinthehemagglutinationinhibitionantibodyassayswereobtainedfromtheInternationalReagentResourceProgram,establishedbytheCentersforDiseaseControlandPrevention.

Secondaryoutcomemeasuresweretheincidenceof4measuresofviralrespiratoryillnessandinfection:(1)acuterespiratoryillness(Box1)withorwithoutlaboratoryconfirmation;(2)laboratory-detectedrespiratoryinfection,definedasdetectionofarespiratorypathogenbypolymerasechainreactionorserologicalevidenceofinfectionwitharespiratorypathogenduringthestudysurveillanceperiod(s),whichwasaddedtotheprotocolpriortodataanalysis;(3)laboratoryconfirmedrespiratoryillness,identifiedaspreviouslydescribed,23definedasself-reportedacuterespiratoryillnessplusthepresenceofatleast1polymerasechainreaction–confirmedviralpathogen(Box2)inaspecimencollectedfromtheupperrespiratorytractwithin7daysofthereportedsymptomsand/oratleasta4-foldrisefrompreinterventiontopostinterventionserumantibodytiterstoinfluenzaAorBvirus;and(4)influenzalikeillness,definedastemperatureofatleast100°F(37.8°C)pluscoughand/orasorethroat,withorwithoutlaboratoryconfirmation.

AdherencetoGroupAssignmentandInfectionPreventionandControlPractices

Participantswereremindedtoadheretoprotectivedeviceandhandhygieneinstructionsbysignagepostedatstudysites,email,andbystudypersonnelinperson.Adherencetoassigneddeviceswerereporteddailybyparticipantsas“always,”“sometimes,”“never,”or“didnotrecall.”Inaddition,studypersonnelobservedparticipants’device-wearingbehaviorsastheyenteredandexitedpatientcareroomsbyconductingunannounced,inconspicuousvisitstorandomlyselectedstudysitesthroughouttheinterventionperiod.However,topreservepatientconfidentiality,monitorswerenotpermittedtoenterpatientcarerooms.

StatisticalAnalyses

Althoughweidentifiednostandarddefinitionofa“clinicallysignificantdifference,”thisstudy16wasdesignedtodetecta25%relativereductionintheincidenceoflaboratoryconfirmedinfluenzaorrespiratoryillness,basedonexpertopinion,ratherthananabsolutereduction,whichhasbeendescribedinapreviousstudy.6Thetotalsamplesizerequiredtoprovide80%powertoshowa25%reductionintheincidenceoflaboratory-confirmedinfluenzaintheN95respiratorgroupcomparedwiththemedicalmaskgroup,withatypeIerrorrateof.05,was10024participant-sessions,andthesamplesizeneededtoprovide80%powertoshowa25%reductionintheincidenceoflaboratory-confirmedrespiratoryillnesswas5104participant-seasons.Comparativeeffectsoftheinterventionswereestimatedforthe

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primaryandsecondaryoutcomesbycalculatingoddsratios(ORs;forbinaryoutcomes)andincidencerateratios(IRRs;forcountoutcomes)betweenparticipantclustersrandomlyassignedtowearN95respiratorsormedicalmasks.Laboratory-confirmedinfluenzawasmodeledusinglogisticregressionandviralrespiratoryinfectionandillnessoutcomesweremodeledusingPoissonregression.Unadjustedandadjustedanalyses(bothprespecified)wereconductedaccordingtothestatisticalanalysisplan(Supplement2).Theprimaryoutcomewasanadjustedanalysis,asspecifiedinthestatisticalanalysisplan.Prespecifiedcovariatesusedinadjustedanalysesincludedage,sex,race,numberofhouseholdmembersyoungerthan5years,occupationrisklevel(definedaslow,medium,orhigh),binaryseason-specificinfluenzavaccinationstatus,theproportionofdailyexposurestootherswithrespiratoryillness,categoricalself-reportedadherencetohandhygiene,andinterventiongroupassignment.Prespecifiedadherencerateswerecalculatedastheproportionofreportsofadherenceineachgroupreporting“always,”“sometimes,”“never,”or“didnotrecall.”Comparisonofproportionsbetweengroupsweredoneusingχ2statisticsandcomparisonsofbinomialproportions.Analysesincludedrandomeffectstoaccountforcorrelationofoutcomesatsite-levelandindividual-levelrandomeffectstoaccountforcorrelationofoutcomesattheindividuallevelforparticipantswhoparticipatedformultipleseasons.Theprimaryanalysisusedavailabledataonallrandomizedparticipantsfortheprimarycomparisonoftheintervention.Aper-protocolanalysis,conductedatthesametimeastheprimaryanalysis,includedonlyindividualswhocompletedatleast8weeksofstudyparticipation.Asensitivityanalysiswasconductedusingimputationtoassignoutcomestoparticipantswhodidnotcompletethestudy.Missingoutcomeswereimputedusingstandardmultipleimputationtechniques,creatingmultipleimputeddatasetswithnomissingvaluesforeachanalysis.23DetailsofthisanalysisaredescribedinSupplement2.Interventiongroupwithdrawalratesandtimetowithdrawalwerecomparedtoassessforpotentialbias.Inanadditionalsensitivityanalysis,observedandself-reportedexposuresandadherencewerecomparedusingPearsonχ2tests.Meanworkplaceandhouseholdratesofexposuretorespiratoryillnesswerecomparedusingmixed-effectslogisticregression.Forallcalculations,a2-sidedtypeIerrorprobabilityof.05wasused.BecauseofthepotentialfortypeIerrorduetomultiplecomparisons,findingsforanalysesofsecondaryendpointsshouldbeinterpretedasexploratory.AllstatisticalanalyseswereperformedinRversion3.3.3(RFoundation).

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Results

Participants

Thestudysiteswererandomizedtoprovide380clusterseasonsofobservationover4consecutiveinterventionperiods.Ofthe2862participants,1416participatedformorethan1yearorinterventionperiod.Among2862uniquerandomizedparticipants(mean[SD]age,43[11.5]years;2369[82.8%]women),2371completedtheResPECTprotocoloverthecourseof48weeksofinterventionspanning4years.Amongtheseindividuals,1446participatedinone12-weekinterventionperiod,723participatedintwo12-weekinterventionperiods,and693participatedin3ormore12-weekinterventionperiods,accountingfor5180HCP-seasonsenrolledandrandomizedfrom137medicalcenters.Followingrandomization,491participants

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withdreworwereexcludedbecausetheclustersizewasbelowapreestablishedthresholdof2.Overall,4689HCP-seasonswereincludedintheper-protocolanalysis(2243intheN95respiratorgroupand2446inthemedicalmaskgroup;Figure1).Somemembersoftheprimaryanalyticcohortdidnotcompleteallweeksofthestudyandweremissingserologicaloutcomes.Dataweremissingbecauseofearlywithdrawalin189of2512participants(7.5%)intheN95respiratorgroupand145of2668(5.4%)inthemedicalmaskgroup.Intheper-protocolanalysis,dataweremissingfrom16of2243participants(0.7%)intheN95respiratorgroupand28of2446(1.1%)inthemedicalmaskgroup.BaselinecharacteristicsoftheparticipantsintheN95respiratorandmedicalmaskgroupsweresimilar(Table1).Dailyworkplaceexposuretorespiratoryillnesswasreported22.5%ofthetimeintheN95groupand21.6%ofthetimeinthemedicalmaskgroup,whileweeklyhouseholdexposuretorespiratoryillnesswasreported3.6%ofthetimeintheN95respiratorgroupand3.4%ofthetimeinthemedicalmaskgroup(Table1).

IllnessSurveillanceandEffectiveness

Intheprimaryanalysis,theincidenceoflaboratoryconfirmedinfluenzainfectioneventsoccurredin207of2512HCP-seasons(8.2%)intheN95respiratorgroupand193of2668HCP-seasons(7.2%)inthemedicalmaskgroup,(difference,1.0%[95%CI,−0.5%to2.5%];P=.18)(adjustedOR,1.18[95%CI,0.95-1.45]).Regardingsecondaryoutcomes,therewere1556acuterespiratoryillnesseventsintheN95respiratorgroup(incidencerate[IR],619.4per1000HCP-seasons)vs1711inthemedicalmaskgroup(IR,641.3per1000HCP-seasons)(difference,−21.9per1000HCP-seasons[95%CI,−48.2to4.4];P=.10;adjustedIRR,0.99[95%CI,0.92-1.06]).Therewere679laboratory-detectedrespiratoryinfectioneventsintheN95respiratorgroup(IR,270.3per1000HCP-seasons)vs745inthemedicalmaskgroup(IR,279.2per1000HCPseasons)(difference,−8.9per1000HCP-seasons[95%CI,−33.3to15.4];P=.47;adjustedIRR,0.99[95%CI,0.89-1.09])(Table2andFigure2).Overall,371laboratoryconfirmedrespiratoryillnesseventsoccurredintheN95respiratorgroup(IR,147.7per1000HCP-seasons)vs417inthemedicalmaskgroup(IR,156.3per1000HCP-seasons)(difference,−8.6per1000HCP-seasons[95%CI,−28.2to10.9];P=.39;adjustedIRR,0.96[95%CI,0.83-1.11]).Therewere128influenzalikeillnesseventsintheN95respiratorgroup(IR,51.0per1000HCP-seasons)vs166inthemedicalmaskgroup(IR,62.2per1000HCP-seasons)(difference,−11.3per1000HCP-seasons[95%CI,−23.8to1.3];P=.08;adjustedIRR,0.86[95%CI,0.68-1.10]).Resultsweresimilarintheadjustedprimaryanalysisandper-protocolanalyses(Figure2).

Intervention,Adherence,andAdverseEvents

Adherencewasreportedondailysurveys22330timesintheN95respiratorgroupand23315timesinthemedicalmaskgroup.“Always”wasreported14566(65.2%)timesintheN95respiratorgroupand15186(65.1%)timesinthemedicalmaskgroup;“sometimes,”5407(24.2%)timesintheN95respiratorgroupand5853(25.1%)timesinthemedicalmaskgroup;“never,”2272(10.2%)timesintheN95respiratorgroupand2207(9.5%)timesinthemedicalmaskgroup;and“didnotrecall,”85(0.4%)timesintheN95respiratorgroupand69(0.3%)

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timesinthemedicalmaskgroup.Participant-reportedadherencecouldnotbeassessedin784participants(31.2%)intheN95respiratorgroupand822(30.8%)inthemedicalmaskgroup(P=.84)

becauseoflackofresponsetosurveysorlackofadherenceopportunities(ie,participantsdidnotencounteranindividualwithrespiratorysignsorsymptoms).Analyzedposthoc,participantadherencewasreportedasalwaysorsometimes89.4%ofthetimeintheN95respiratorgroupand90.2%ofthetimeinthemedicalmaskgroup.AdditionaldetailsaboutadherenceareincludedinSupplement1.Noseriousstudy-relatedadverseeventswerereported.Nineteenparticipantsreportedskinirritationorworseningacneduringyears3and4atonestudysiteintheN95respiratorgroup.

Per-ProtocolAnalysisandSensitivityAnalysis

Resultsoftheper-protocolanalysiscanbeseeninFigure2.Asensitivityanalysisassessedwhethertherewasevidenceforbiasinself-reportedoutcomesbasedongroupassignment.Inaprespecifiedmultiple-imputationanalysis,theratesoflaboratory-confirmedinfluenzainfectioneventswere204of2243HCPseasons(9.1%)intheN95respiratorgroupand190of2446HCP-seasons(7.8%)inthemedicalmaskgroup.QuantitativedataareavailableinSupplement3.

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DISCUSSION

Inthispragmatic,clusterrandomizedtrialthatinvolvedmultipleoutpatientsitesat7healthcaredeliverysystemsacrossawidegeographicareaover4seasonsofpeakviralrespiratoryillness,therewasnosignificantdifferencebetweentheeffectivenessofN95respiratorsandmedicalmasksinpreventinglaboratory-confirmedinfluenzaamongparticipantsroutinelyexposedtorespiratoryillnessesintheworkplace.Inaddition,therewerenosignificantdifferencesbetweenN95respiratorsandmedicalmasksintheratesofacuterespiratoryillness,laboratory-detectedrespiratoryinfections,laboratory-confirmedrespiratoryillness,andinfluenzalikeillnessamongparticipants.Asensitivityanalysissuggestedthattheprimaryanalysisreportedwasfairlyrobusttothemissingoutcomedatawithquantitativeoutcomesvaryingbylessthan5%.ThissupportsthefindingthatneitherN95respiratorsnormedicalmasksweremoreeffectiveinpreventinglaboratoryconfirmedinfluenzaorotherviral

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respiratoryinfectionorillnessamongparticipantswhenworninafashionconsistentwithcurrentUSclinicalpractice.Respiratoryvirusesareprimarilytransmittedbylargedroplets.Becauseafractionofrespiratoryvirusesmaybetransmittedbyaerosol,N95respiratorshavebeenpresumedtoprovidebetterprotectionthanmedicalmasksagainstviralrespiratoryinfectionsinhealthcaresettings.2However,definitiveevidenceofgreaterclinicaleffectivenessofN95respiratorsislacking.Awell-designedtrial6foundtheeffectivenessofmedicalmaskstobenoninferiortoN95respirators,butthetrialwasstoppedprematurelyandwaslimitedbysmallsamplesize.Twoadditionalstudies3,4(andapooledanalysis12)concludedthatN95respiratorsmaybemoreeffectivethanmedicalmasks;however,thesestudieswerelimitedbyuncertainclinicalsignificanceofendpoints.24Thecurrentstudywasundertakenbecauseofremaininguncertaintybasedonpreviousstudies,whichmadeitchallengingforinfectioncontrolclinicianstoeffectivelyimplementrespiratoryprotectionprogramsinhealthcaresettings.2,7,13,18,24,25Thistrialwasdesignedtoassessclinicaleffectiveness,takingintoaccountmanychallengesofworkinginoutpatienthealthcaresettings.Thisstudyhadseveralstrengths,includingthepragmaticdesign;wideUSgeographicandclimaticdistribution;variedadultandpediatricoutpatientsettings,includingemergencydepartments;andenrollmentspanning4seasonsofpeakviralrespiratoryillness.Respiratorysampleswereobtainedfromsymptomaticandasymptomaticparticipantstodeterminetheincidenceofviralrespiratoryinfection,includingindividualsthatweresubclinicalbutstillpotentiallytransmissible.Influenzavaccinationstatusinformationwascollected.Thistrialwasclusterrandomizedtoavoidmixingofinterventionsineachclinicandclinicalsettingandtominimizecross-contaminationfromdifferentHCPbehaviors,conductedat7medicalcentersamongfrontlineHCPinvariedclinicalsettingswithhighexposurerisk,andsufficientlypoweredtodetectthepredefineddifferenceinlaboratory-confirmedrespiratoryillness.Previouseffectivenessstudies3,4,6,12,26-28havemetsome,butnotall,ofthesecharacteristicsandhavebeeninconclusive,contributingtotheuncertaintyandcontroversyamongexpertsdeterminingpublichealthguidance,regulatoryrequirements,andhealthcaredeliverypractices.2,7,14,17,29Inthecurrentstudy,findingswereconsistentacrossalllaboratory-basedoutcomesandclinicalsyndromes.Resultsfortheprimaryandsecondaryoutcomeswereinoppositedirections(ie,oneIRRwasassociatedwithincreasedriskandtheotherwithdecreasedrisk),althoughthedifferenceswerenonsignificant,furthersupportingafindingofnosignificantdifferenceintheeffectivenessofN95respiratorsvsmedicalmasksforpreventionofinfluenzaorotherrespiratoryillness.

Limitations

Thisstudyhasseverallimitations.First,thecriteriaforviralpolymerasechainreactiontestingmayhavemissedparticipantswhowereinfectedbutasymptomatic.Unrecognizedinfectionsmayhaveincreasedtheprobabilityoffindingnodifferencebetweeninterventions,evenifadifferenceexisted.Second,self-reportingofsymptomsindailydiarieslikelyunderestimatedillnessamongHCPwhooftenworkwhileill.30Third,despitebeingintentionallyconductedasapragmaticeffectivenesstrial,8incompleteparticipantadherencetoassignedprotectivedevicescouldhavecontributedtomoreunprotectedexposures,increasingtheprobabilityoffindingno

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differencebetweeninterventionsevenifadifferenceexisted.However,participant-reporteddataindicatesthisdidnotdifferbystudygroup.Fourth,participantswerenotinstructedtowearprotectivedevicesoutsidetheworkplace,whichmayhavebiasedtheresultstowardfindingnodifferencebetweengroups,althoughtheratesofadherencedidnotdifferbystudygroupandhouseholdexposurewasreportedasmuchlowerthanworkplaceexposure.Fifth,only2N95respiratorandmedicalmaskmodelswerestudied,limitingtheabilitytogeneralizeabouttheprotectivenessofothermodels.Sixth,thesamplesizerequiredtodefinitivelydeterminewhetherN95respiratorsormedicalmasksaremoreeffectiveforprotectionfromlaboratory-confirmedinfluenzainthehealthcaresettingrequiredapproximately10000participantseasons,whichwasnotfeasiblewiththeavailablefundingorresources.However,themorbidityandmortalityassociatedwithawiderangeofviralrespiratoryinfections,includingnovelandemergingpathogens,rendersasecondaryoutcomeinthisstudy,laboratory-confirmedrespiratoryillness,important.

CONCLUSIONS

AmongoutpatientHCP,N95respiratorsvsmedicalmasksaswornbyparticipantsinthistrialresultedinnosignificantdifferenceintheincidenceoflaboratory-confirmedinfluenza.

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SurgicalMaskvsN95RespiratorforPreventingInfluenzaAmongHealthCareWorkers

MarkLoeb1,NancyDafoe,JamesMahony,MichaelJohn,AliciaSarabia,VerneGlavin,RichardWebby,MarekSmieja,DavidJDEarn,SylviaChong,AshleyWebb,StephenDWalter

https://pubmed.ncbi.nlm.nih.gov/19797474/

ContextDataabouttheeffectivenessofthesurgicalmaskcomparedwiththeN95respiratorforprotectinghealthcareworkersagainstinfluenzaaresparse.GiventhelikelihoodthatN95respiratorswillbeinshortsupplyduringapandemicandnotavailableinmanycountries,knowingtheeffectivenessofthesurgicalmaskisofpublichealthimportance.

ObjectiveTocomparethesurgicalmaskwiththeN95respiratorinprotectinghealthcareworkersagainstinfluenza.

Design,Setting,andParticipantsNoninferiorityrandomizedcontrolledtrialof446nursesinemergencydepartments,medicalunits,andpediatricunitsin8tertiarycareOntariohospitals.

InterventionAssignmenttoeitherafit-testedN95respiratororasurgicalmaskwhenprovidingcaretopatientswithfebrilerespiratoryillnessduringthe2008-2009influenzaseason.

MainOutcomeMeasuresTheprimaryoutcomewaslaboratory-confirmedinfluenzameasuredbypolymerasechainreactionora4-foldriseinhemagglutinintiters.EffectivenessofthesurgicalmaskwasassessedasnoninferiorityofthesurgicalmaskcomparedwiththeN95respirator.Thecriterionfornoninferioritywasmetifthelowerlimitofthe95%confidenceinterval(CI)forthereductioninincidence(N95respiratorminussurgicalgroup)wasgreaterthan−9%.

ResultsBetweenSeptember23,2008,andDecember8,2008,478nurseswereassessedforeligibilityand446nurseswereenrolledandrandomlyassignedtheintervention;225wereallocatedtoreceivesurgicalmasksand221toN95respirators.Influenzainfectionoccurredin50nurses(23.6%)inthesurgicalmaskgroupandin48(22.9%)intheN95respiratorgroup(absoluteriskdifference,

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−0.73%;95%CI,−8.8%to7.3%;P=.86),thelowerconfidencelimitbeinginsidethenoninferioritylimitof−9%.

ConclusionAmongnursesinOntariotertiarycarehospitals,useofasurgicalmaskcomparedwithanN95respiratorresultedinnoninferiorratesoflaboratoryconfirmedinfluenza.

INFLUENZACAUSESANNUALEPIDEMICSofrespiratoryillnessworldwideandisthemostimportantcauseofmedicallyattendedacuterespiratoryillness.1,2Moreover,thereisincreasingconcernabouttherecentlydeclaredinfluenzapandemicdueto2009influenzaA(H1N1)inhumans.3-5Transmissionofinfluenzacanoccurbycoughingorsneezingwhereinfectiousparticlesofvariablesize,rangingfromapproximately0.1to100µm,maybeinhaled.6Thisrangeofparticleshasayetundefinedbutpossiblyimportantroleintransmission.Althoughdatafromanimalmodelsandhumanexperimentalstudiessuggestthatshort-rangeinhalationaltransmissionwithsmalldropletnuclei(10µm)canoccur,7-11theexactnatureoftransmissionofinfluenzathatoccursinnonexperimentalsettingsisnotwellunderstood.12Asaconsequence,considerableuncertaintyexistsabouttheeffectivenessofpersonalrespiratorydevicesagainstinfluenzaforhealthcareworkers.Duringapandemic,reducingtransmissionofinfluenzatohealthcareworkersmaynotonlyhelpsupportthehealthcareworkforce,butmayalsopreventinfluenzatransmissiontopatients.Otherpersonalprotectivestrategies,suchaseffectivevaccinesorantiviraldrugs,maybelimitedinavailability.GiventhelikelihoodthatN95respiratorswillbeinshortsupplyduringapandemicandunavailableinmanycountries,understandingtherelativeeffectivenessofpersonalrespiratoryprotectiveequipmentisimportant.Therearefewcomparativestudiesofrespiratoryprotectivedevices,13-15anddatacomparingthesurgicalmaskwiththeN95respiratoramonghealthcareworkersaresparse.WeconductedarandomizedtrialtocomparethesurgicalmaskwiththeN95respiratorinhealthcareworkers.Wehypothesizedthatthesurgicalmask,whichislessexpensiveandmorewidelyavailablethantheN95respirator,offerssimilarprotectiontotheN95respiratoramonghealthcareworkersathighestriskforexposuretoinfluenza.

METHODSParticipantsWeenrollednurseswhoworkedinemergencydepartments,medicalunits,andpediatricunitsin8Ontariotertiarycare

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hospitals,ofwhich6werewithinthegreaterTorontoarea.Sixofthe8hospitalswereuniversityaffiliatedteachinghospitals(rangeofbedsize,310-400)and2werecommunityhospitals(bedsizes,256and400).Participantswereenrolledfromatotalof22units,whichincluded9acutemedicalunits,7emergencydepartments,and6pediatricunits.Therewereanaverageof34beds(range,14-60beds)onthemedicalunitsandanaverageof27beds(range,19-38)onthepediatricunits.Nursesexpectedtoworkfull-time(definedas37hoursperweek)onstudyunitsduringthe2008-2009influenzaseasonwereeligible.Nurseshadtoprovidecurrentfit-testcertification.Nurseswhocouldnotpassafittestwereexcludedfromthestudy.TheresearchprotocolwasapprovedbytheMcMasterUniversityresearchethicsreviewboard.Allparticipantsgavewritteninformedconsent.InterventionsRandomizationwasperformedcentrallybyanindependentclinicaltrialscoordinatinggroupsuchthatinvestigatorswereblindtotherandomizationprocedureandgroupassignmentandwasstratifiedbycenterinpermutedblocksof4participants.ItwasnotpossibletoconcealtheidentityoftheN95respiratororthesurgicalmasksincemanipulatingthesedeviceswouldinterferewiththeirfunction.Laboratorypersonnelconductinghemagglutinininhibitionassays,polymerasechainreaction(PCR),andviralcultureforinfluenzawereblindedtoallocation.Nursesallocatedtothesurgicalmaskgroupwererequiredtowearthebrandofsurgicalmaskalreadyinuseattheirhospital.Followingthesevereacuterespiratorysyndrome(SARS)outbreakinOntario,useofsuchasurgicalmaskwasrequiredbytheMinistryofHealthandLong-TermCarewhenprovidingcaretoorwhenwithin1mofapatientwithfebrilerespiratoryillness,definedassymptomsofabodytemperature38°Corgreaterandneworworseningcoughorshortnessofbreath.16Nurseswereinstructedinproperplacementofthesurgicalmaskaccordingtothemanufacturer’srecommendations.SincefittestingismandatoryfornursesinOntario,themajorityofnursesinthestudyhadbeenfittestedpriortoenrollment;additionalfittestingwasconductedfornurseswhohadnotbeenfittestedin2008.Usingastandardprotocol,atechnicianshowedtheparticipanthowtopositiontherespiratorandfastenthestrapanddeterminewhetheritprovidedanacceptablefit.Thenursewasaskedtowearthemostcomfortablemaskforatleast5minutestoassessfit.Adequacyoftherespiratoryfitwasassessedusingstandardcriteria,includingchinplacement,adequatestraptension,appropriaterespiratorsize,fitacrossnosebridge,tendencyofrespirator

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toslip,andpositionofmaskonfaceandcheeks.Thenursethenconductedausersealcheck.17NurseshadaqualitativefittestingusingthesaccharinorBitrexprotocol.17NurseswereaskedtobeginusingthesurgicalmaskorN95respiratorwhencaringforpatientswithfebrilerespiratoryillnessatthebeginningoftheinfluenzaseason,whichwasdefinedas2ormoreconsecutiveisolationsofinfluenzaperweekineachstudyregion.Nursesworeglovesandgownswhenenteringtheroomofapatientwithfebrilerespiratoryillness,whichwasroutinepractice.Foraerosol-generatingprocedures(suchasintubationorbronchoscopy),aslongastuberculosiswasnotsuspected,nursescontinuedtousetherespiratorydevicetheywereassignedto.Wehadplannedtostopthestudyattheendofinfluenzaseason.However,becauseofthe2009influenzaA(H1N1)pandemic,thestudywasstoppedonApril23,2009,whentheOntarioMinistryofHealthandLong-TermCarerecommendedN95respiratorsforallhealthcareworkerstakingcareofpatientswithfebrilerespiratoryillness.Follow-upAllparticipantswereassessedforsignsandsymptomsofinfluenzatwiceweeklyusingWeb-basedquestionnaires.Responsetothequestionnairewasmonitoredcentrallyandparticipantswhofailedtoprovidearesponsewerecontactedandaskedtocompletethequestionnaire.Ifanewsymptomwasreported,thestudynursewasnotifiedandaflockednasalspecimen(CopanItalia,Brescia,Italy)wasobtainedbytheparticipants.Theyweretrainedtoinserttheswabintotheleftorrightnostrilandrotatetheswabatleast3timesandtoconductself-swabbingifanyof1ofthefollowingsymptomsorsignswerepresent:fever(temperature

38°C),cough,nasalcongestion,sorethroat,headache,sinusproblems,muscleaches,fatigue,earache,earinfection,orchills.Wealsoprovidedparticipantswithtympanicthermometers.Toassesshouseholdexposuresbetweenstudygroups,weaskedparticipantswhetherhouseholdmembers(spouses,roommates,orchildren)hadexperiencedinfluenza-likeillnessoverthestudyperiod.OutcomesTheprimaryoutcomeofthisstudywaslaboratory-confirmedinfluenza.ThiswasdefinedbyeitherthedetectionofviralRNAusingreverse-transcriptase(RT)PCRfromnasopharyngealandflockednasalspecimensoratleasta4-foldriseinserumantibodiestocirculatinginfluenzastrainantigens.AllnasopharyngealornasalspecimensweretestedforinfluenzaandotherrespiratoryviruseswiththexTAGRespiratoryVirusPaneltest(LuminexMolecularDiagnostics,Toronto,Ontario,Canada).18ThismultiplexPCRassaydetectsinfluenzaAvirussubtypes

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H1(seasonal),H3,andH5aswellasthemajorityofothervirusesthatcauserespiratoryillnessinhumans.Bloodspecimensforserologywereobtainedpriortoenrollmentandattheendofthefollow-upperiod.Serologicalinfectionwasdefinedbydetectionof4-foldorgreaterincreaseininfluenza-specifichemagglutinininhibitionassaytiterbetweenbaselineandconvalescentserumsamplesusingguineapigerythrocytesandtheantigenscirculatingA/Brisbane/59/2007(H1N1)-likevirus;A/Brisbane/10/2007(H3N2)-likevirus;B/Florida/4/2006-likevirus;andA/TN/1560/09(H1N1),thecirculatingpandemicinfluenzavirus.ForA/Brisbane/59/2007(H1N1)-likevirus,A/Brisbane/10/2007(H3N2)-likevirus,andB/Florida/4/2006-likevirus,werestrictedserologicalcriteriaofinfectiontonurseswhodidnotreceivethetrivalent2008-2009influenzavaccinetoreducemisclassificationduetovaccineresponse.SecondaryoutcomesincludeddetectionofthefollowingnoninfluenzavirusesbyPCR:parainfluenzavirustypes1,2,3,and4;respiratorysyncytialvirustypesAandB;adenovirus;metapneumovirus;rhinovirus-enterovirus;andcoronavirusesOC43,229E,SARS,NL63,andHKU1.Influenza-likeillnesswasdefinedasthepresenceofcoughandfever(temperature

38°C).19Work-relatedabsenteeismandphysicianvisitsforrespiratoryillnesswerealsoassessed.AuditsToassesscomplianceofparticipantswiththeassignedmaskorN95respirator,weconductedauditsduringwhatweanticipatedwaspeakinfluenzaperiod,fromMarch11toApril3,2009.Medicalandpediatrichospitalstudyunitsatallcenterswithnursesparticipatinginthestudywerecontactedbytelephonedailybyaresearchassistanttoassesswhethertherewerepatientsadmittedtotheunitindropletprecautionsforinfluenzaorfebrilerespiratoryillness.Ifthereweresuchcasesandiftheprimarynurseforthepatientwasenrolledinourstudy,atrainedauditorwassenttotheunittoobserveforcompliance.Theauditorwasinstructedtostandashortdistancefromthepatientisolationroomtoremaininconspicuousbutwithindistancetoaccuratelyrecordtheaudit.Auditorswereaskedtoremainontheunituntiltheyrecordedthetypeofprotectiveequipmentwornbytheparticipantpriortotheparticipantenteringtheisolationroom.Tomaintainpatientconfidentialityandtoremainanonymoustothestudyparticipant,noauditswereconductedwithinthepatient’sroom.Onceanauditwasconducted,thesessionwascompleted.Auditswereconductedbothonweekdaysandonweekendsduringdayandevening

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shifts.Assessmentofhandhygienewasnotconducted.StatisticalAnalysisTheeffectivenessofthesurgicalmaskwasassessedthroughanoninferiorityanalysisrelativetotheN95respirator.20Fortheprimaryanalysis,thedifferenceintheincidenceoflaboratoryconfirmedinfluenzabetweentheN95respiratorgroupandsurgicalmaskgroupwasestimatedandthecorresponding2-sided95%confidenceinterval(CI)wascalculated.WeusedtheFisherexacttesttoassessstatisticalsignificanceincontingencytableshavingexpectedcellfrequencieslessthan5.NoninferioritytotheN95respiratorwasachievedifthelowerlimitofthe95%CIforthereductioninincidence(N95respiratorminussurgicalgroup)wasgreaterthantheprespecifiednoninferioritylimitof−9%.Assuminganeventrateof20%incontrols,thislimitwasselectedonaclinicalbasisconsideringthatlaboratoryconfirmedinfluenzawouldincludeasymptomaticcasesinadditiontosymptomaticcasesofinfluenza.Infectiondetectedbyserologycanaccountforupto75%ofcasesoflaboratoryconfirmedinfluenzawherefebrileillnessisnotpresent.21Sincewedidnotanticipatesevereoutcomes(eg,mortality)inthestudysample,weusedasimilarapproachforinfluenza-likeillness,work-relatedabsenteeism,andphysicianvisitsforrespiratoryillness.Allparticipantswhohadfollow-updatacollected(ie,hadnotwithdrawnpriortoanyfollow-upaftertheyhadbeenrandomized)wereincludedintheanalysis.Sinceintentionto-treatanalysesinnoninferioritytrialsmaybebiasedtowardfindingnodifference,wealsoconductedananalysisofourprimaryoutcomeusingonlydatafromparticipantswithcompletefollow-up.22Toavoidlackofindependenceassociatedwithcountingmultipleoutcomes,eachspecificoutcomeinaparticipantwasonlycountedonce.Withapowerof90%anda2-sidedtype-Ierrorrateof5%,therequiredsamplewouldbe191participantsineachgroupforanoninferioritytestassuminganabsoluteriskreductionof12%intheN95respiratorgroupcomparedwiththesurgicalmask.Iftheabsolutereductionwasassumedtobe10%,astatisticalpowerof80%wouldbemaintained.Theabsoluteriskreductionsselectedwerebasedonconsensusbyclinicianinvestigators.Assuminga10%dropoutrate,weestimatedthatatotalof420participantswouldbeneeded.SASversion9.1.3(SASInstitute,Cary,NorthCarolina)wasusedtoconducttheanalyses.RESULTSBetweenSeptember23,2008,andDecember8,2008,478nurseswereassessedforeligibilityand446participantsfrom8centersinOntariowereenrolled.Theywerethenrandomlyassignedtheintervention,225tothesurgicalmaskand221totheN95respirator(FIGURE).Themeanageof

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participantswas36.2years,94%ofthemwerefemale,andstudygroupswerewellbalancedintermsofdemographics(TABLE1).Vaccinationstatuswassimilar:68participants(30.2%)inthesurgicalmaskgroupand62(28.1%)intheN95respiratorgrouphadreceived2008-2009trivalentinactivatedinfluenzavaccine.Follow-upbeganJanuary12,2009,andendedApril23,2009.Mean(SD)durationoffollow-upwassimilarbetweengroups:97.9(16.1)daysinthesurgicalgroupand97.2(18.0)daysintheN95respiratorgroup.Therewere24participantswhowithdrewfromthestudywithnofollow-up—13inthesurgicalmaskgroupand11intheN95respiratorgroup—becauseofresignationortransfer(n=5),workingpart-time(n=1),noresponse(n=13),orillness(n=5)(Figure).Noneofthehealthcareworkerswithdrewbecauseofrespiratoryillness.Oftheresulting422(allofwhomwereintheanalysis),follow-upwascompletein386(91.4%),and403(95.5%)hadacuteandconvalescentseracollected.Therewere223nasalspecimensobtained(115inthesurgicalmaskgroupand108intheN95respiratorgroup).Laboratory-confirmedinfluenza(byRT-PCRor

4-foldriseinserumtiters)occurredin50nurses(23.6%)inthesurgicalmaskgroupandin48(22.9%)intheN95respiratorgroup(absoluteriskdifference,−0.73%;95%CI,−8.8%to7.3%;P=.86),indicatingnoninferiorityofthesurgicalmask(TABLE2).ThediagnosisofinfluenzawasmadebyRT-PCRin6nurses(2.8%)inthesurgicalmaskgroup(5influenzaAand1influenzaB)and4(1.8%)intheN95respiratorgroup(1influenzaAand3influenzaB)(absoluteriskdifference,−0.93%;95%CI,−3.82%to1.97%;P=.75).FouroftheinfluenzaAcasesdetectedbyPCRwereH1(allinthesurgicalmaskgroup).TheserologyresultsaresummarizedinTable2.Notably,8.0%inthesurgicalmaskgroupand11.9%intheN95respiratorgrouphada4-foldorgreaterriseinserumtiterstoA/TN/1560/09(H1N1),thecirculatingpandemicswineinfluenzastrain.NoninferioritywasdemonstratedbetweenthesurgicalmaskgroupandtheN95respiratorgroupfor2009influenzaA(H1N1)(absoluteriskdifference,3.89%;95%CI,−1.82%to9.59%;P=.18).Whentheanalysiswasconductedusingonlythedatafromparticipantswithcompletefollow-upvisits,laboratory-confirmedinfluenza(byRTPCRor

4-foldriseinserumtiters)occurredin66nurses(33.9%)inthesurgicalmaskgroupandin72(37.7%)intheN95respiratorgroup(absoluteriskdifference,

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3.85%;95%CI,−5.71%to13.41%;P=.43),indicatingnoninferiority.Noadenoviruses;norespiratorysyncytialvirustypeA;andnoparainfluenza1,2,and4virusesweredetectedbyPCR.TherewerenosignificantdifferencesbetweenthesurgicalmaskandN95respiratorgroupsinrespiratorysyncytialvirustypeB,metapneumovirus,parainfluenza3,rhinovirusenterovirus,orcoronoviruses.ThelowerCIsforthedifferencesweregreaterthan−9%,meetingourcriteriafornoninferiority(TABLE3).All52(100%)ofthosehavinginfectionwitharespiratoryvirusotherthaninfluenzahad1ormoresymptoms,buttheydidnotmeettheinfluenza-likeillnessdefinition.Ninenurses(4.2%)inthesurgicalmaskgroupand2nurses(1.0%)intheN95respiratorgroupmetourcriteriaforinfluenza-likeillness(absoluteriskdifference,−3.29%;95%CI,−6.31%to0.28%;P=.06)(TABLE4).All11hadlaboratory-confirmedinfluenza.Asignificantlygreaternumberofnursesinthesurgicalmaskgroup(12,or5.66%)reportedfevercomparedwiththeN95respiratorgroup(2,or0.9%;P=.007).Therewasnosignificantdifferenceinnurseswhoreportedcough,nasalcongestion,headache,sorethroat,myalgia,fatigue,earache,orearinfection.Ofthe44nursesineachgroupwhohadinfluenzadiagnosedbyserology,29(65.9%)inthesurgicalmaskgroupand31(70.5%)intheN95respiratorgrouphadnosymptoms.Therewere13physicianvisits(6.1%)forrespiratoryillnessamongthoseinthesurgicalmaskgroupcomparedwith13(6.2%)intheN95respiratorgroup(absoluteriskdifference,−0.06%;95%CI,−4.53%to4.65%;P=.98).Fortytwoparticipants(19.8%)inthesurgicalmaskgroupreportedanepisodeofwork-relatedabsenteeismcomparedwith39(18.6%)intheN95respiratorygroup(absoluteriskdifference,−1.24%;95%CI,−8.75%to6.27%;P=.75)(Table4).Therewerenoepisodesoflowerrespiratorytractinfectionamongparticipants.Therewerenoadverseeventsreportedbyparticipants.Fifty-fiveparticipants(25.9%)inthesurgicalmaskgroupvs47(22.4%)intheN95respiratorgroupreportedaspouseorroommatewithinfluenzalikeillness(P=.39).Forty-eightparticipants(22.6%)inthesurgicalmaskgroupvs43(20.5%)intheN95respiratorgroupreportedachildwithinfluenza-likeillness(P=.59).Overthe2-weekauditperiod,therewere18episodesofpatientsadmittedtounitsindropletprecautionsforinfluenzaorfebrilerespiratoryillnesswherethenurseprovidingcareforthepatienthadbeenenrolledinourstudy.Theresultsoftheauditdemonstratedthatall11participants(100%)allocatedtosurgicalmasksand6of7participants(85.7%)

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allocatedtoN95respiratorswerewearingthedevicetowhichtheyhadbeenassigned.

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COMMENT

Ourdatashowthattheincidenceoflaboratory-confirmedinfluenzawassimilarinnurseswearingthesurgicalmaskandthosewearingtheN95respirator.Surgicalmaskshadanestimatedefficacywithin1%ofN95respirators.Basedontheprespecifieddefinition,thelowerCIforthedifferenceineffectivenessofthesurgicalmaskandN95maskwaswithin−9%andthestatisticalcriterionofnoninferioritywasmet.Thatis,surgicalmasksappearedtobenoworse,withinaprespecifiedmargin,thanN95respiratorsinpreventinginfluenza.Transmissionbysmalldropletspreadwouldbecompatiblewithgreaterprotectionwiththe

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N95maskcomparedwiththesurgicalmaskwhereefficiencyestimatesrangefrom2%to92%forparticlessmallerthan20µmindiameter.23-28Thefactthatattackratesweresimilarmaysuggestthatsmallaerosolsdidnotdominatetransmission.OnefrequentlycitedconcernaboutthesurgicalmaskisitsinabilitytoobtainanappropriatesealcomparedwiththeN95respirator.29Basedontheresultsofthistrial,thisconcerndoesnotseemtobeassociatedwithanincreasedrateofinfectionofinfluenzaorotherrespiratoryviruses.Influenzaattackratesamonghealthcareworkersinnon-outbreaksettingsaresparse.Ourdataprovideestimatesofanattackrate(23%)inalargelyunvaccinatedcohortofnursesfollowedcloselyduringaperiodofrelativelymildinfluenza-likeillnessandintothebeginningofwhatisnowconsideredapandemicperiod.Giventhatserologycapturesexposureovertheentireseasonandthatnurseshaverepeatedexposures,thisrateofinfectionwasnotunexpected.Ourserologicaldatainunvaccinatednurseswere20%forH3N2,10%forH1N1,and8%forinfluenzaB.Inacommunity-basedstudy,agespecificratesofinfectionforthoseaged30to39yearsbyserologywas16%forH3N2,approximately5%forH1N1,and5%forinfluenzaB.21Itisforthisreasonthatthenumberofparticipantswithinfluenza-likeillness,definedbyfeverandcoughalone,19wererelativelyfewcomparedwiththenumberwithlaboratory-confirmedinfluenza.Giventhattherewasnodifferenceinlaboratory-confirmedinfluenzabetweenstudygroups,thehigherproportionofnursesinthesurgicalmaskgroupwithinfluenza-likeillness,althoughnotstatisticallysignificant,wasunexpected.Theresultsofseroconversionto2009influenzaA(H1N1)(10%)wasunexpectedgiventhattheconvalescentspecimenswereobtainedfromApril23toMay15,2009.Thisattackratemaysuggestthat2009influenzaA(H1N1)wascirculatinginOntariobeforeApril2009.Analternativeexplanationforthishighrateofseroconversionmaybecross-reactionduetoexposuretoseasonalH1N1.Strengthsofthisstudyincludeindividual-levelrandomization,comprehensivelaboratory-confirmedoutcomeassessmentwithPCRandserologicalevaluation,follow-upoveranentireinfluenzaseason,andexcellentparticipantfollow-up.Thereareanumberoflimitationsofthisstudy.Compliancewiththeinterventioncouldnotbeassessedforallparticipants.Only1roomentrywasrecordedperobservationandtheauditordidnotentertheisolationroomtoassesswhethertheparticipantremovedtherespiratorprotection.Auditswereonlyconductedonmedicalandpediatricunits,notintheemergencydepartment.Hadtherebeenpoor

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compliancewiththeN95respirator,thiscouldhavebiasedthestudytowardnoninferiority.However,theresultsfromourauditedsamplesuggestexcellentadherence.ThisisinkeepingwiththefactthatallhospitalsinthestudywereinOntario,whichwasaffectedbytheSARSoutbreakandwhereuseofpersonalprotectiveequipmentismandatedandauditedbytheOntarioMinistryofLabour.Weacknowledgethatourprotocoldidnotaccountfortheeffectofindirectcontactbecausehandhygieneanduseofglovesandgownswerenotmonitored.Animbalanceinhandhygienebetweenstudygroups,withworseadherenceintheN95group,wouldhavebiasedthestudytowardnoninferiority.However,individual-levelrandomizationandstratifiedrandomizationwithinhospitalswouldhelpbalanceanydifferencesinadherencetohandhygienebetweenstudygroups.Becausetheuseofglovesandgownswhenenteringtheroomofapatientwithfebrilerespiratoryillnesswasstandardpracticeinourstudyhospitals,variabilityofusewouldlikelyhavebeenminimal.Itisalsoimpossibletodeterminewhetherparticipantsacquiredinfluenzaduetohospitalorcommunityexposure.However,ourdataonhouseholdexposuresuggestthatsuchexposureswerebalancedbetweeninterventiongroups.Weacknowledgethatnotsurveyingparticipants’coworkersaboutinfluenza-likeillnesswasalimitation.Sincewedidnotcollectinformationondropletisolationprecautions,agreaterexposureofN95respiratornursesvssurgicalmasknursestopatientsondropletprecautionswouldhavebiasedthestudytowardnoninferiority.However,thefactthatthenurseswerewellbalancedoneachwardandinthenumberofspecimensobtainedoneachunitwouldminimizethechanceofsuchdifferentialexposurehavingoccurred.ThemajorimplicationofthisstudyisthatprotectionwithasurgicalmaskagainstinfluenzaappearstobesimilartotheN95respirator,meetingcriteriafornoninferiority.Ourfindingsapplytoroutinecareinthehealthcaresetting.Theyshouldnotbegeneralizedtosettingswherethereisahighriskforaerosolization,suchasintubationorbronchoscopy,whereuseofanN95respiratorwouldbeprudent.Inroutinehealthcaresettings,particularlywheretheavailabilityofN95respiratorsislimited,surgicalmasksappeartobenoninferiortoN95respiratorsforprotectinghealthcareworkersagainstinfluenza.

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UniversalMaskinginHospitalsintheCovid-19EraTheNewEnglandJournalofMedicine

MichaelKlompas,M.D.,M.P.H.,CharlesA.Morris,M.D.,M.P.H.,JuliaSinclair,M.B.A.,MadelynPearson,D.N.P.,R.N.,andEricaS.Shenoy,M.D.,Ph.D.

May21,2020

https://www.nejm.org/doi/full/10.1056/nejmp2006372

AstheSARS-CoV-2pandemiccontinuestoexplode,hospitalsystemsarescramblingtointensifytheirmeasuresforprotectingpatientsandhealthcareworkersfromthevirus.Anincreasingnumberoffrontlineprovidersarewonderingwhetherthiseffortshouldincludeuniversaluseofmasksbyallhealthcareworkers.UniversalmaskingisalreadystandardpracticeinHongKong,Singapore,andotherpartsofAsiaandhasrecentlybeenadoptedbyahandfulofU.S.hospitals.Weknowthatwearingamaskoutsidehealthcarefacilitiesofferslittle,ifany,protectionfrominfection.PublichealthauthoritiesdefineasignificantexposuretoCovid-19asface-to-facecontactwithin6feetwithapatientwithsymptomaticCovid-19thatissustainedforatleastafewminutes(andsomesaymorethan10minutesoreven30minutes).ThechanceofcatchingCovid-19fromapassinginteractioninapublicspaceisthereforeminimal.Inmanycases,thedesireforwidespreadmaskingisareflexivereactiontoanxietyoverthepandemic.Thecalculusmaybedifferent,however,inhealthcaresettings.Firstandforemost,amaskisacorecomponentofthepersonalprotectiveequipment(PPE)cliniciansneedwhencaringforsymptomaticpatientswithrespiratoryviralinfections,inconjunctionwithgown,gloves,andeyeprotection.Maskinginthiscontextisalreadypartofroutineoperationsformosthospitals.Whatislesscleariswhetheramaskoffersanyfurtherprotectioninhealthcaresettingsinwhichthewearerhasnodirectinteractionswithsymptomaticpatients.Therearetwoscenariosinwhichtheremaybepossiblebenefits.ThefirstisduringthecareofapatientwithunrecognizedCovid-19.Amaskaloneinthissettingwillreduceriskonlyslightly,however,sinceitdoesnotprovideprotectionfromdropletsthatmayentertheeyesorfromfomitesonthepatientorintheenvironmentthatprovidersmaypickupontheirhandsandcarrytotheirmucousmembranes(particularlygiventheconcernthatmaskwearersmayhaveanincreasedtendencytotouchtheirfaces).Morecompellingisthe

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possibilitythatwearingamaskmayreducethelikelihoodoftransmissionfromasymptomaticandminimallysymptomatichealthcareworkerswithCovid-19tootherprovidersandpatients.ThisconcernincreasesasCovid-19becomesmorewidespreadinthecommunity.Wefaceaconstantriskthatahealthcareworkerwithearlyinfectionmaybringthevirusintoourfacilitiesandtransmitittoothers.Transmissionfrompeoplewithasymptomaticinfectionhasbeenwelldocumented,althoughitisuncleartowhatextentsuchtransmissioncontributestotheoverallspreadofinfection.1-3Moreinsidiousmaybethehealthcareworkerwhocomestoworkwithmildandambiguoussymptoms,suchasfatigueormuscleaches,orascratchythroatandmildnasalcongestion,thattheyattributetoworkinglonghoursorstressorseasonalallergies,ratherthanrecognizingthattheymayhaveearlyormildCovid-19.Inourhospitals,wehavealreadyseenanumberofinstancesinwhichstaffmemberseithercametoworkwellbutdevelopedsymptomsofCovid-19partwaythroughtheirshiftsorworkedwithmildandambiguoussymptomsthatweresubsequentlydiagnosedasCovid-19.Thesecaseshaveledtolargenumbersofourpatientsandstaffmembersbeingexposedtothevirusandahandfulofpotentiallylinkedinfectionsinhealthcareworkers.Maskingallprovidersmightlimittransmissionfromthesesourcesbystoppingasymptomaticandminimallysymptomatichealthcareworkersfromspreadingvirus-ladenoralandnasaldroplets.Whatisclear,however,isthatuniversalmaskingaloneisnotapanacea.AmaskwillnotprotectproviderscaringforapatientwithactiveCovid-19ifit’snotaccompaniedbymeticuloushandhygiene,eyeprotection,gloves,andagown.AmaskalonewillnotpreventhealthcareworkerswithearlyCovid-19fromcontaminatingtheirhandsandspreadingthevirustopatientsandcolleagues.Focusingonuniversalmaskingalonemay,paradoxically,leadtomoretransmissionofCovid-19ifitdivertsattentionfromimplementingmorefundamentalinfectioncontrolmeasures.SuchmeasuresincludevigorousscreeningofallpatientscomingtoafacilityforsymptomsofCovid-19andimmediatelygettingthemmaskedandintoaroom;earlyimplementationofcontactanddropletprecautions,includingeyeprotection,forallsymptomaticpatientsanderringonthesideofcautionwhenindoubt;rescreeningalladmittedpatientsdailyforsignsandsymptomsofCovid-19incaseaninfectionwasincubatingonadmissionortheywereexposedtothevirusinthehospital;havingalowthresholdfortestingpatientswithevenmildsymptomspotentiallyattributabletoaviralrespiratoryinfection(thisincludespatientswith

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pneumonia,giventhatathirdormoreofpneumoniasarecausedbyvirusesratherthanbacteria);requiringemployeestoattestthattheyhavenosymptomsbeforestartingworkeachday;beingattentivetophysicaldistancingbetweenstaffmembersinallsettings(includingpotentiallyneglectedsettingssuchaselevators,hospitalshuttlebuses,clinicalrounds,andworkrooms);restrictingandscreeningvisitors;andincreasingthefrequencyandreliabilityofhandhygiene.Theextentofmarginalbenefitofuniversalmaskingoverandabovethesefoundationalmeasuresisdebatable.Itdependsontheprevalenceofhealthcareworkerswithasymptomaticandminimallysymptomaticinfectionsaswellastherelativecontributionofthispopulationtothespreadofinfection.Itisinformative,inthisregard,thattheprevalenceofCovid-19amongasymptomaticevacueesfromWuhanduringtheheightoftheepidemictherewasonly1to3%.4,5ModelersassessingthespreadofinfectioninWuhanhavenotedtheimportanceofundiagnosedinfectionsinfuelingthespreadofCovid-19whilealsoacknowledgingthatthetransmissionriskfromthispopulationislikelytobelowerthantheriskofspreadfromsymptomaticpatients.3Andthenthepotentialbenefitsofuniversalmaskingneedtobebalancedagainstthefutureriskofrunningoutofmasksandtherebyexposingclinicianstothemuchgreaterriskofcaringforsymptomaticpatientswithoutamask.Providingeachhealthcareworkerwithonemaskperdayforextendeduse,however,mayparadoxicallyimproveinventorycontrolbyreducingone-timeusesandfacilitatingcentralizedworkflowsforallocatingmaskswithoutriskassessmentsattheindividual-employeelevel.Theremaybeadditionalbenefitstobroadmaskingpoliciesthatextendbeyondtheirtechnicalcontributiontoreducingpathogentransmission.Masksarevisibleremindersofanotherwiseinvisibleyetwidelyprevalentpathogenandmayremindpeopleoftheimportanceofsocialdistancingandotherinfection-controlmeasures.Itisalsoclearthatmasksservesymbolicroles.Masksarenotonlytools,theyarealsotalismansthatmayhelpincreasehealthcareworkers’perceivedsenseofsafety,well-being,andtrustintheirhospitals.Althoughsuchreactionsmaynotbestrictlylogical,weareallsubjecttofearandanxiety,especiallyduringtimesofcrisis.Onemightarguethatfearandanxietyarebettercounteredwithdataandeducationthanwithamarginallybeneficialmask,particularlyinlightoftheworldwidemaskshortage,butitisdifficulttogetclinicianstohearthismessageintheheatofthecurrentcrisis.Expandedmaskingprotocols’greatestcontributionmaybetoreducethetransmissionofanxiety,

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overandabovewhateverroletheymayplayinreducingtransmissionofCovid-19.Thepotentialvalueofuniversalmaskingingivinghealthcareworkerstheconfidencetoabsorbandimplementthemorefoundationalinfection-preventionpracticesdescribedabovemaybeitsgreatestcontribution.

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EffectivenessofN95respiratorsversussurgicalmasksagainstinfluenza:Asystematicreviewandmeta-analysis

YoulinLongTengyueHuLiqinLiuRuiChenQiongGuoLiuYangYifanChengJinHuangLiang

https://onlinelibrary.wiley.com/doi/full/10.1111/jebm.12381

Abstract

Objective

Previousmeta-analysesconcludedthattherewasinsufficientevidencetodeterminetheeffectofN95respirators.WeaimedtoassesstheeffectivenessofN95respiratorsversussurgicalmasksforpreventionofinfluenzabycollectingrandomizedcontrolledtrials(RCTs).

Methods

WesearchedPubMed,EMbaseandTheCochraneLibraryfromtheinceptiontoJanuary27,2020toidentifyrelevantsystematicreviews.TheRCTsincludedinsystematicreviewswereidentified.ThenwesearchedthelatestpublishedRCTsfromtheabovethreedatabasesandsearchedClinicalTrials.govforunpublishedRCTs.Tworeviewersindependentlyextractedthedataandassessedriskofbias.Meta-analyseswereconductedtocalculatepooledestimatesbyusingRevMan5.3software.

Results

AtotalofsixRCTsinvolving9171participantswereincluded.Therewerenostatisticallysignificantdifferencesinpreventinglaboratory-confirmedinfluenza(RR=1.09,95%CI0.92-1.28,P>.05),laboratory-confirmedrespiratoryviralinfections(RR=0.89,95%CI0.70-1.11),laboratory-confirmedrespiratoryinfection(RR=0.74,95%CI0.42-1.29)andinfluenzalikeillness(RR=0.61,95%CI0.33-1.14)usingN95respiratorsandsurgicalmasks.Meta-analysisindicatedaprotectiveeffectofN95respiratorsagainstlaboratory-confirmedbacterialcolonization(RR=0.58,95%CI0.43-0.78).

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Conclusion

TheuseofN95respiratorscomparedwithsurgicalmasksisnotassociatedwithalowerriskoflaboratory-confirmedinfluenza.ItsuggeststhatN95respiratorsshouldnotberecommendedforgeneralpublicandnonhigh-riskmedicalstaffthosearenotinclosecontactwithinfluenzapatientsorsuspectedpatients.

1INTRODUCTION

Severeacuterespiratorysyndromecoronavirus(SARS-CoV)andMiddleEastrespiratorysyndromecoronavirus(MERS-CoV)havemortalityratesabout10%and37%,respectively.1Sincetheoutbreakofsevereacuterespiratorysyndromecoronavirus2(SARS-CoV-2),facemaskshavebeenconsideredtobevitallyimportanttoreducetheriskofinfectionbecausevaccinationorspecificanti-infectivetreatmentsareunavailable.2,3N95respiratorsareusedtopreventusersfrominhalingsmallairborneparticlesandmustfittightlytotheuser'sface.Surgicalmasksaredesignedtoprotectwearersfrommicroorganismtransmissionandfitlooselytotheuser'sface.5,6Althoughsurgicalmaskscannotpreventinhalationofsmallairborneparticles,bothofthemcanprotectusersfromlargedropletsandsprays.7,8

Thereareconflictingrecommendationsforsevereacuterespiratorysyndrome(SARS)andpandemicinfluenza:theWorldHealthOrganization(WHO)recommendsusingmasksinlow-risksituationsandrespiratorsinhigh-risksituations,buttheCentersforDiseaseControlandPrevention(CDC)recommendsusingrespiratorsinbothlowandhigh-risksituations.9However,N95respiratorsmayplayalimitedroleinlow-resourcesettings,wherethereareafinitenumberofN95respirators,oritmaybeunaffordable.9Also,previousmeta-analysesconcludedtherewasinsufficientevidencetodeterminetheeffectofN95respiratorsduetoasmallnumberofstudiesthatispronetolackofstatisticalpower.10,11Additionally,thesemeta-analyseswerelimitedbythesmallnumberofincludedrandomizedcontroltrials(RCTs).MorerigorousRCTsofcomparingN95respiratorswithsurgicalmasksagainstinfluenzapublishedinrecentyearswerenotincludedinpreviousmeta-analyses.12-14

InlightofthegrowingnumberofRCTsofmasksuseforprotectingagainstinfluenza,thissystematicreviewandmeta-analysisaimedtoassesstheeffectivenessofN95respiratorsversussurgicalmasksforpreventionofinfluenza.

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2METHODS

Thismeta-analysiswasconductedbasedonthepreferredreportingitemsforsystematicreviewsandmeta-analyses(PRISMA)guidelines.15

2.1Inclusionandexclusioncriteria

Inclusioncriteriawere(1)studytype:RCT(includingcluster-randomizedtrial)andnonrandomizedcontrolledstudy;(2)participants:humanswithinfluenza(includingpandemicstrains,seasonalinfluenzaAorBvirusesandzoonoticvirusessuchasswineoravianinfluenza),andotherrespiratoryviralinfections(asaproxyforinfluenza);(3)interventionandcomparator:N95respiratorsversussurgicalmasks;(4)primaryoutcome:laboratory-confirmedinfluenza;(5)secondaryoutcomes:laboratory-confirmedrespiratoryviralinfections,laboratory-confirmedbacterialcolonization,laboratory-confirmedrespiratoryinfection,andinfluenzalikeillness;and(6)settings:hospitalorcommunity.RCTswereselectedduetothepotentialpossibilityofhighevidencelevel.Exclusioncriteriawere(1)theoreticalmodels;(2)human⁄nonhumanexperimentallaboratorystudies;and(3)conferenceabstract.

2.2Searchstrategy

WesearchedPubMed,EMBASE,andTheCochraneLibrarydatabasesfrominceptiontoJanuary27,2020,toidentifypublishedsystematicreviewsonevaluatingtheuseofmasksforpreventinginfluenza.SearchstrategyinPubMedcouldbefoundinTable1,andthestrategywasadequatelyadjustedtouseinotherdatabases.Then,primaryRCTsincludedinthesystematicreviewswereidentified.Additionally,weconductedanadditionalsearchtoidentifyRCTspublishedinthepastfiveyearsfromJanuary27,2015,toJanuary27,2020,usingthedatabasesandsearchstrategiesdescribedabove.WealsosearchedforClinicalTrials.govtoobtainunpublisheddata.Therewerenopublicationstatusandlanguagerestrictionsonselectingthestudies.

2.3Studyselectionanddataextraction

Tworeviewersindependentlyscreenedthearticlesbasedonthetitles,abstractsandfulltexts.Then,tworeviewersindependentlyexactedthefollowingdatafromincludedstudies:firstauthor,publicationyear,country,disease,detailsofstudy

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populationandintervention,studydesign,samplesize,settings,andresults.Alldisagreementswereresolvedbydiscussion.

2.4Riskofbiasassessment

TworeviewersindependentlyassessedtheriskofbiasoftheselectedRCTsusingtheCochraneRiskofBiastool,16whichincludesdomainsonrandomsequencegeneration,allocationconcealment,blindingofparticipantsandpersonnel,blindingofoutcomeassessors,incompleteoutcomedata,andselectivereporting.ForeachRCT,everydomainwasjudgedamong3levels:highrisk,unclearrisk,andlowrisk.Disagreementswereresolvedbydiscussion.

2.5Dataanalysis

AllstatisticalanalyseswereperformedusingReviewManager(RevMan)version5.3.Comparabledatafromstudieswithsimilarinterventionsandoutcomeswerepooledusingforestplots.Relativerisk(RR)with95%confidenceintervals(CIs)fordichotomousdatawasusedastheeffectmeasure.Between-studyheterogeneitywasassessedusingtheI2foreachpooledestimate.17Weadoptedarandom-effectsmodelforheterogeneityP<.10.Weperformedasubgroupanalysisbasedonthesettings(hospital,community)duetothepossibilityofclinicalheterogeneity.Asensitivityanalysiswasconductedtoevaluatetherobustnessoftheresultsbyexcludingindividualstudiesforeachforestplot.Funnelplotswereplannedtoassessedpublicationbias.Becauseofthesmallnumberofstudiesavailableforeachpooledestimate,wefailedtoassesspublicationbias.

3RESULTS

3.1Searchresultsandstudycharacteristics

ThedetailsontheliteraturesearchandscreeningprocesscanbefoundinFigure1.ExcludedstudiesandreasonsforexclusionwereshowninTable2.Intotal,weincludedsixRCTs12,18-22andfoundnounpublisheddataofRCTsfromClinicalTrials.gov.ThecharacteristicsoftheseRCTswerepresentedinTable3.Theincludedstudiespublishedbetween2009and2019.Atotalof9171participantsinCanada,Australia,China,orAmericawereincluded,andthenumberofparticipantsineachRCTrangedfrom435to5180patients.Thefollow-updurationvariedfrom2to15weeks.Fivestudiesincludedparticipantsinhospitals,12,18,20-22andoneinhouseholds.19Becauseofdifferentdefinitions

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ofoutcomeinincludedstudies,weredefinedthelaboratory-confirmedrespiratoryinfectionasrespiratoryinfluenza,othervirusesorbacteriainfection.

3.2Riskofbias

TheresultsoftheriskofbiasassessmentcanbefoundinFigure2.Fivestudiesreportedthecomputer-generatedrandomsequences,whileonlyonementionedrandomization.Allstudiesdidnotmentionallocationconcealment.Participantsandtrialstaffwerenotblindedintwostudies,andtheothertwostudiesfailedtomentiontheblindingofparticipantsandpersonnel.Fourstudiesdidnotreportwhethertheoutcomeassessorswereblinded.Allstudieshadcompleteoutcomedataordescribedcomparablenumbersandreasonsforwithdrawalacrossgroupsandprespecifiedoutcomes.

3.3Effectiveness

FiveRCTsinvolving8444participantsreportedlaboratory-confirmedinfluenza.12,18-21Meta-analysiswithfixed-effectsmodelrevealedthattherewasnostatisticallysignificantdifferencesinpreventinginfluenzausingN95respiratorsandsurgicalmasks(RR=1.09,95%CI0.92-1.28,P>.05)(Figure3).Theresultsofsubgroupanalyseswereconsistentwiththisregardlessofthehospitalorthecommunity.Theresultsofthesensitivityanalysiswerenotalteredafterexcludingeachtrial.

FourRCTs18-21involving3264participantsreportedlaboratory-confirmedrespiratoryviralinfections.Meta-analysiswithfixed-effectsmodelrevealedthattherewerenostatisticallysignificantdifferencesinpreventingrespiratoryviralinfectionsusingN95respiratorsandsurgicalmasks(RR=0.89,95%CI0.70-1.11,P>.05)(Figure4).Theresultsofsubgroupanalyseswereconsistentregardlessofthehospitalorthecommunity.However,thesensitivityanalysisafterexcludingthetrialbyLoebetal18showedasignificanteffectofN95respiratorsonpreventingrespiratoryviralinfections(RR=0.61,95%CI0.39-0.98,P<.05).

TwoRCTs21,22involving2538participantsreportedlaboratory-confirmedbacterialcolonization.Meta-analysiswithfixed-effectsmodelrevealedthatcomparedwithsurgicalmasks,N95respiratorssignificantlyreducedbacterialcolonizationinhospitals(RR=0.58,95%CI0.43-0.78,P<.05)(Figure5).The

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sensitivityanalysisshowedthattheresultsdidnotchangeafterexcludingeachtrial.

TwoRCTs12,22involving6621participantsreportedlaboratory-confirmedrespiratoryinfection.Meta-analysiswithrandom-effectsmodelrevealedthattherewerenostatisticallysignificantdifferencesinpreventingrespiratoryinfectionusingN95respiratorsandsurgicalmasksinhospitals(RR=0.74,95%CI0.42-1.29,P>.05)(Figure6).However,thesensitivityanalysisafterexcludingthetrialbyRadonovichetal12showedasignificanteffectofN95respiratorsonpreventingrespiratoryinfection(RR=0.53,95%CI0.35-0.82,P<.05).

FiveRCTsinvolving8444participantsreportedinfluenzalikeillness.12,18-21Meta-analysiswithrandom-effectsmodelrevealedthattherewerenostatisticallysignificantdifferencesinpreventinginfluenzalikeillnessusingN95respiratorsandsurgicalmasks(RR=0.61,95%CI0.33-1.14,P>.05)(Figure7).TheresultsofsubgroupanalysesindicatedthatstatisticallysignificantsuperiorityofN95respiratorsoversurgicalmasksagainstinfluenzalikeillness(RR=0.37,95%CI0.20-0.71,P<.05)inthecommunity(onlyoneRCT).Thesensitivityanalysisshowedresultsremainedunchangedafterexcludingeachtrial.

4DISCUSSION

Thismeta-analysisshowedthattherewerenostatisticallysignificantdifferencesinpreventinglaboratory-confirmedinfluenza,laboratory-confirmedrespiratoryviralinfections,laboratory-confirmedrespiratoryinfectionandinfluenza-likeillnessusingN95respiratorsandsurgicalmasks.N95respiratorsprovidedaprotectiveeffectagainstlaboratory-confirmedbacterialcolonization.Insubgroupanalysis,similarresultscouldbefoundinthehospitalandcommunityforlaboratory-confirmedinfluenzaandlaboratory-confirmedrespiratoryviralinfections.However,sensitivityanalysisshowedunstableresultsforthepreventionoflaboratory-confirmedrespiratoryviralinfectionsandlaboratory-confirmedrespiratoryinfection.

Throughthecourseofinfluenzapandemics,largenumbersoffacemasksmayberequiredtouseinlongperiodstoprotectpeoplefrominfections.23UsingN95respiratorsislikelytoresultindiscomfort,forexample,headaches.23Apreviousstudy3reportedthattherewasaninverserelationshipbetweenthelevelofcompliancewithwearinganN95respiratorandtheriskofclinicalrespiratory

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illness.ItisdifficulttoensurehighcomplianceduetothisdiscomfortofN95respiratorsinallstudies.

ThereasonforthesimilareffectsonpreventinginfluenzafortheuseofN95respiratorsversussurgicalmasksmayberelatedtolowcompliancetoN95respiratorswear,23whichmayleadtomorefrequentdoffingcomparedwithsurgicalmasks.13AlthoughN95respiratorsmayconfersuperiorprotectioninlaboratorystudiesdesigningtoachieve100%interventionadherence,24theroutineuseofN95respiratorsseemstobelessacceptableduetomoresignificantdiscomfortinreal-worldpractice.11Therefore,thebenefitofN95respiratorsoffittingtightlytofacesisoffsetorsubjugated.13However,itshouldbenotedthatthesurgicalmasksareprimarilydesignedtoprotecttheenvironmentfromthewearer,whereastherespiratorsaresupposedtoprotectthewearerfromtheenvironment.25

Thereareseverallimitationstothisstudy.First,someRCTshadahighriskofbiasduetolackofallocationconcealmentandblinding;althoughitisimpracticaltoblindparticipantswhowouldknowthetypeofmaskstheyarewearing.Second,thenumberofincludedstudiesfocusingonthecommunitywassmall.Consequently,theresultsofthesubgroupanalysismightbeunreliable.Third,weidentifiedRCTsfrompublishedsystematicreviews,whichmayresultintheomissionofrelativeRCTs.Finally,theremightbepublicationbias,andwecannotassessitduetoaninsufficientnumberofincludedRCTs.

Inconclusion,thecurrentmeta-analysisshowstheuseofN95respiratorscomparedwithsurgicalmasksisnotassociatedwithalowerriskoflaboratory-confirmedinfluenza.ItsuggeststhatN95respiratorsshouldnotberecommendedforthegeneralpublicandnonhighriskmedicalstaffsthosearenotinclosecontactwithinfluenzapatientsorsuspectedpatients.