布魯蓋爾研究所-降低非典冠狀病毒變異株的移動(dòng)性以遏制疫情（英文）-2021.5-8正式版

REDUCINGTHEMOBILITYOFSARS-COV-2VARIANTSTOSAFEGUARDCONTAINMENTMARTINHELLWIG,VIOLAPRIESEMANNANDGUNTRAMB.WOLFFEscapevariantscancausenewwavesofCOVID-19andputvaccinationstrategiesatrisk.Topreventordelaytheglobalspreadofthesewaves,virusmobilityneedstobeminimisedthroughscreeningandtestingstrategies,whichshouldalsocovervaccinatedpeople.ecostsofthesestrategiesareminimalcomparedtothecoststohealth,societyandeconomyfromanotherwave.MartinHellwigisDirectoroftheMaxPlanckInstituteforResearchonCollectiveGoodsViolaPriesemannisResearchGroupLeaderNeuralSystemseoryattheMaxPlanckInstituteforDynamicsandSelf-OrganizationGuntramB.Wol?(guntram.wol?@)isDirectorofBruegelRecommendedcitation:Hellwig,M.,V.PriesemannandG.B.Wol?(2021)‘ReducingthemobilityofSARS-CoV-2variantstosafeguardcontainment’,WorkingPaper07/2021,BruegelWhenthecoronaviruspandemicstartedin2019/2020,anumberofcountriesreactedearly,closingdownpubliclifeandreducingprivatecontactsbeforecontagionfullytookoff.Countriesthatfailedtodothissawlargespikesincases,stretchingoroverwhelmingtheirmedicalcapacities.Likewise,countriesthatignoredwarningsignalsofasecondwavewerehithardinautumn2020.Athirdwave,causedbythemorecontagiousB.1.1.7SARS-CoV-2coronavirusvariant,hasunfolded.ThisvariantwasfirstrecognisedinKent,UnitedKingdom,fromwhereitspreadquicklyacrosstheUKandbeyond.ItspreadtocountrieswithmoretraveltotheUKearlierthanothers.GermanywasaffectedrelativelylatewhilePortugalandIrelandwereaffectedearlybecauseofmoreintensivetravellinks.Anothervariant,P1,isalsospreadingrapidlyinBrazilandcountrieswithstrongtravelconnectionstoBrazil,suchasChile.PeopletravellingplayacentralroleinspreadingnewvariantsofSARS-CoV-2,withdevastatingconsequences.Stoppinganewvariantfromenteringfromabroad,oratleastslowingitdown,wouldfacilitatecontainmentandlimitthehuman,socialandeconomiccosts.TheexperiencewithB.1.1.7showshowslowerentryofavarianttoacountrydelaysthedeteriorationofthehealthsituationandtheintroductionofstrictandcostlylockdowns.Publicpolicyinadvancedeconomiesisfocusingonvaccinationinthehopethiswillbringdownthenumberofseverecasesanddeathswhileallowingrestrictionstobelifted(Daganetal,2021).Bytheendof2021,largepartsofthepopulationsofIsrael,Chile,theUS,theUKandtheEUwillhavereceivedthevaccineandwillbelargelyimmunetothewildstrainandsomevariantsofCOVID-19.However,additionalwavesofcontagionmustbeexpected,causedinparticularbyescapevariantsagainstwhichcurrentvaccinesarelesseffective(McCormicketal,2021).Evenifvaccinationcontinuesascurrentlyforeseen,theviruswillnotbefullyeliminated.Withincompleteuptakeofvaccines,waningimmunityandimperfecttransmissionprevention,itwillpersistincertainsub-populations(Phillips,2021).Moreover,inmanycountries,vaccinationisproceedingslowlyifatall.Thepersistentprevalenceofthevirusinvarioussub-populationsandvariousplacesprovidesabreedinggroundformutations.Withadvancesinvaccinationandimmunisation,variantsthatescapetheimmuneresponsewillhaveanevolutionaryadvantage.Theemergenceofescapevariantshasbeendocumentedinseveralregions,andasimilarevolutionhasalsobeenobservedin-vitro(Andreanoetal,2020).Withanescapevariant,contagionpersistsinthevaccinatedpopulationitselfandnewescape-variantwavescouldspreadveryquicklyifalargepartofthepopulationhasbeenvaccinatedandmovesabout1withoutrestraint.Newrestrictions,uptocompletelockdowns,mightthereforebecomeinevitable,untilanewvaccineisdevelopedandadministered,andimmunisationagainstthenewvariantissuccessful.Anystrategythatreliesonvaccinationonlywillthereforebeinsufficient.Whileeverythingshouldbedonetospeedupthesupplyofvaccinesandtheirroll-out,astrategythatrecognisesandslowsdowntheemergenceofnewvariantsandlimitstheirspreadisneeded.Suchstrategiesmustencompassthepartofthepopulationthathasacquiredimmunityagainstthewildstrain,throughvaccinationsorthroughinfections.Preparingforthispotentialdangerrequiresastrategywiththreecentralgoals:(1)minimisingtherateatwhichescapevariantsdevelop;(2)detectingthemearly,and(3)minimisingthemobilityofthevirus.Whileallthreegoalsareinprincipletechnicallyfeasible,theyrunagainstbasichumanandsocialneeds,inparticularinopensocieties.Measurestomeetthegoalsmustthereforebedesignedinawaythatrendersthemacceptable.Thesemeasureswillalsobesubstantiallycheapereconomicallythansustainedcontagionwaves.1Minimisetherateatwhichescapevariantsdevelop:minimisingSARS-CoV-2incidenceLowincidenceisthebestprotectionagainstthebreedingofnewvariants.Roughly,theprobabilitythatanescapevariantemergesisproportionaltothenumberofinfectedpeople,andtheexpectedtimeuntilavariantemergesisinverselyproportionaltothenumberofinfectedpeople.Reducingthenumberofinfectedpeopledelaystheexpectedemergenceofanewescapevariant.Lowcasenumbersalsohaveclearadvantagesforpublichealth,societyandtheeconomy(Priesemannetal,2021;Oliu-Bartonetal,2021).Moreover,atlowcasenumbers,contacttracingcontributesefficientlytocontainment,allowingthehealthauthoritytoconcentrateontheremaininginfectionchains(Contrerasetal,2021).Lastly,localoutbreaksofnewvariantsaredetectedearlyandnothiddenwithinagenerallyhighincidence.However,evenwithlowcasenumbers,escapevariantscanemerge.Oncethishashappened,anewvariant’seffectivereproductionratesintheimmunisedandnon-immunizedpartsofthepopulationdependnotonlyonthecharacteristicbasicreproductionnumbersRandR’,butalsoonthecontact00andhygienebehaviourinthetwopartsofthepopulation.Assumingthattheimmunisedpopulationislesscarefultoprotectitself,apotentvariantcouldspreadveryquickly,becausetheeffectivereproductionrateisveryhigh.Ifsuchanoutbreakisnotdetectedandfoughtearly,developmentofanewvaccinewillbelate,afterthewavehastakenitstoll.22Detectescapevariantsearly:screeningandsurveillanceTheearly,localdetectionofvirusvariantsisimportanttoslowtheirglobalspread.Regularscreeningofarepresentativesampleofthepopulation,asestablishedintheUKforexample,providesabetterbasisforinformedscientificevaluationofthepandemicthanonlythecurrent,moresymptom-basedtesting.Screeningwouldcontributetoanearlywarningsystemfortheemergenceofnewoutbreaksandnewvariants,withdatasharedrapidlyacrosstheglobe(Cyranoski,2021).ForCOVID-19,testingshouldalsoincludeimmuneandvaccinatedpeople,becauseinfectionofvaccinatedindividualsbyescapevariantscouldbeparticularlyfastbecauseoftheirhighernumbersofcontacts.Testingreportsshouldlisttheimmunisationstatusofthosetested(egdateandtypeofvaccine,earlierinfection).Thisfacilitatesdetectionofoutbreaksamongthevaccinatedpopulation–akeyindicatorforanescapevariant.Toreacharepresentativepartofthepopulation,testingshouldbeorganisedatschoolsandworkplaces,wheretestingwouldbeembeddedinanorganisedsettingandcanbeimplementedaspartofadailyorweeklyroutine.Inaddition,testingatschoolsandworkplaceswouldtargetpopulationgroupsthathaveregularcontactsoutsidethehousehold.Also,incentivesforregulartestingmatterforcompliance.Foremployers,thedesiretoavoidinterruptionsofproductionactivitiescausedbyemployeeillness,quarantineorlong-COVIDprovidesanincentivefortesting.Governmentsneedtotakelegalstepstofacilitateworkplacetestingandperhapsevenimposeit.Inschools,teachershaveaninterestintestingtoavoidself-infection.CompletetestingofentiregroupswithsinglePCRtests,whereallsamplesarejointlyandanonymouslyevaluated,couldforestallconcernsaboutprivacy,ensurehigheraccuracythanindividualself-tests,andreducecosts.Overall,easilyaccessibletesting,togetherwithsystematicvirusgenomesurveillance,isacoreactivitytodetectnewvariantsearly.3Reducingthevirusspread:testingandquarantineIfanescapevariantemergesandspreads,itmakesahugedifferencewhether,atthetimeitisrecognised,thenumberofinfectedindividualsis10or1000.AssuminganRof1.4andaserialintervaloffourdays,thenstartingfrom10,ratherthan1000individualsbuysalmosteightweekstoimplementmitigationstrategiesandadaptvaccinations.Thedifferencebetween10and1000initialcarrierscanbeachievedbyinstallingatestingstrategythatprevents99%ofviruscarriersfromenteringaregion.Systematictestingoftravellerswouldbea3centralpartofthis.Suchtestingmustencompassimmunisedandnon-immunisedpeople,asbothgroupsmighttransmitthevirus.Astrategytopreventavirus’srapidspreadviahumanmobilityshouldinprincipleapplytowithin-jurisdictiontravelaswellascross-bordertravel.Somemightobjectthatwedonotordinarilytestforasyetunknowndiseases.However,escapevariantsaredifferentfromasyetunknownviruses.Theyaresufficientlysimilartothevariantsweknowtobedetectablethroughtesting.Thatopportunityshouldbeused.Isthisstrategyfeasible?Noneofoursuggestionsinvolvesamajoreconomiccost.Relativetothecostoftravel,astandardtestwouldincreasethecostofaflightbyperhapsaround€40–anditwouldrequirethetimeoftheindividualtogettested.Thecostsarethusnotzerobutaresmallrelativetothecostsoffurtherwavesofcontagion:theeconomiccostsoflockdownsandsimilarrestrictions,letaloneanuncontrolledpandemic,aremanytimesthecostsofthemeasureswepropose(CutlerandSummers,2020).Therealchallengeissocietal.TestingrequirementsruncountertoasenseofindividualrightsdeeplyrootedinWesternsocieties.Thedismantlingofbordersandbordercontrolsareconsideredmajoradvancements.However,frictionlesstravelcomesatacostandinvolvesrisksofcontagion.Oncecontagiontakesoff,theimplicationsforindividualfreedomaremuchmoreseriousthantherestrictionsfromtestingrequirementsattachedtotravel.Certificationrequirementsforcross-bordermovementsofpeopledonotpreventtravel.Fortransportoffoodandanimals,suchrequirementsareconsiderednormal.Thepoliticalchallengeistocommunicatetothepublicthattestingforvirusesdoesnotendmobilitybutisawayofkeepingsocietiesopen.Theproposedtestingstrategybuyslimitedtime.Tousethistimesensibly,publichealthmeasuresarenecessarytoslowdownthespreadandflattenthecurve,whileincreasingresearchandproductioncapacityforeffectivevaccines(forexamplewithmarketdesign;seeCastilloetal,2021).4ConclusionOverall,itisofcriticalimportancetopreventfuturewavesofescapevariantshittingunpreparedsocietiesinthecomingmonths.Thebasicrequirementisrapidprogressonvaccinationandlowcasenumbersacrosstheworld(Priesemannetal,2021).Thisshouldbecomplementedbyarigoroustestingstrategythatstopsvirusesfromspreading,whilekeepingbordersopentohumantravel.Inthisway,repeatedlockdownsandtheirlargehealth,economic,socialandpersonalcosts,whichdwarfanycostsrelatedtotesting,canbeavoided.Giventheriskoffuturewaves,Westernsocietiesinparticularmustlearnthatunprotectedtravelcanhavemuchlargersocialcoststhanhithertoaccepted,andmusthencestartrigorouspreventionagainstthespreadofSARS-CoV-2variants.ReferencesAndreano,E.,G.Piccini,D.Licastro,L.Casalino,N.V.Johnson,I.Paciello...R.Rappuoli(2020)'SARS-CoV-2escapeinvitrofromahighlyneutralizingCOVID-19convalescentplasma',bioRxiv2024451,doi:/10.1101/2024451Castillo,J.C.,A.Ahuja,S.Athey,A.Baker,E.Budish,T.Chipty...W.Wiecek(2021)'MarketdesigntoaccelerateCOVID-19vaccinesupply',ScienceVol.371,Issue6534:1107-1109Contreras,S.,J.Dehning,M.Loidolt,J.Zierenberg,F.P.Spitzner,J.H.Urrea-Quintero...V.Priesemann(2021)'ThechallengesofcontainingSARS-CoV-2viatest-trace-and-isolate',NatureCommunications12,378,/10.1038/s41467-020-20699-8Cutler,D.M.andL.H.Summers