世卫组织新冠病毒溯源联合研究报告（英）-世卫组织-2021.2-120正式版-WN4

WHO-convenedGlobalStudyofOriginsofSARS-CoV-2:

ChinaPart

JointWHO-ChinaStudy

January-10February2021JointReport

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LISTOFABBREVIATIONSANDACRONYMS

ARI

cDNA

ChinaCDC

CNCB

CoV

Ctvalues

DDBJ

EMBL-EBI

FAO

GISAID

GOARN

HongKongSAR

Huananmarket

IHR

ILI

INSD

MERS

MRCA

NAT

NCBI

NMDC

NNDRS

OIE

PCR

PHEIC

RT-PCR

SARI

SARS-CoV-2

SARSr-CoV-2

tMRCA

WHO

WIV

acuterespiratoryillness

complementaryDNA

ChineseCenterforDiseaseControlandPrevention

ChinaNationalCenterforBioinformation

coronavirus

cyclethresholdvalues

DNADatabaseofJapan

EuropeanMolecularBiologyLaboratoryandEuropeanBioinformatics

Institute

FoodandAgricultureOrganizationoftheUnitedNations

GlobalInitiativeonSharingAvianInfluenzaDatabase

GlobalOutbreakAlertandResponseNetwork

HongKongSpecialAdministrativeRegion

HuananSeafoodWholesaleMarket

InternationalHealthRegulations(2005)

influenza-likeillness

InternationalNucleotideSequenceDatabase

MiddleEastrespiratorysyndrome

mostrecentcommonancestor

nucleicacidtesting

NationalCenterforBiotechnologyInformation

NationalMicrobiologyDataCenter

NationalNotifiableDiseaseReportingSystem

WorldOrganisationforAnimalHealth(OfficeinternationaldesEpizooties)

polymerasechainreaction

publichealthemergencyofinternationalconcern

real-timepolymerasechainreaction

severeacuterespiratoryillness

Severeacuterespiratorysyndromecoronavirus2

Severeacuterespiratorysyndromecoronavirus2-relatedvirus

timetomostrecentcommonancestor

WorldHealthOrganization

WuhanInstituteofVirology

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Acknowledgements

WHOgratefullyacknowledgestheworkofthejointteam,includingChineseandinternationalscientistsandWHOexpertswhoworkedonthetechnicalsectionsofthisreport,andthosewhoworkedonstudiestopreparedataandinformationforthejointmission.Inaddition,manyhealthofficials,animal,environmentalandpublichealthexpertsfromWuhan,HubeiProvinceandacrossChinaworkedwiththejointteamontheoriginsstudies,andtheircontributionsarereflectedinthereport.Theinterpretationandtranslationteams,ledbyFuXijuan,providedcrucialsimultaneousandconsecutiveinterpretationforplenarymeetingsofthejointteamandforworkinggroups;supportedsitevisitsandinterviews;andprovidedrapidtranslationofworkingdocuments,presentations,reportsandkeydocumentstosupporttheworkofthejointteam.

WHOalsogratefullyacknowledgesthetechnical,administrativeandlogisticssupportofmanyagenciesandofficesinthepreparationsandconductofthejointmission.StaffatWHOCountryOfficeinBeijingandatWHOHeadquartersworkedcloselywithChinesecounterpartsandcolleaguesandwithpartnerorganizationsandagenciesondetailedpracticalarrangementsandlogisticsandprovidedstafftosupportthejointmission.Further,theWHOrapidreviewteamandOIEprovidedadatabaseofrelevantliteratureonSARS-CoV-2potentialoriginstocomplementthetechnicalworkinggroupsduringthejointstudy.

WHOacknowledgesthecontributionsofmanypeople,butinparticular(inalphabeticalorder)ChenZhongdan,GaudenGalea(WHORepresentative),C-KLee,QiaoJianrong,DannySheath,PaigeSnider,SunJiani,KhristeenUmaliDalangin,aswellasXuHuabing,PangXinxin,LiuXijuanandtheadministrativeteamattheWHOcountryofficeinChina.

Thereportsofplenaryandworkinggroupmeetings,andofsitevisitswerepreparedbyDavidFitzSimons(whoalsoeditedthereport),SunJianniandLisaScheuermann.

Wegratefullyacknowledgethefollowingexpertsfortheirinvaluablecontributionsduringthisjointstudy:Prof.HUANGFei(ChineseCenterforDiseaseControlandPrevention),Prof.LIUJiangmei(ChineseCenterforDiseaseControlandPrevention),Prof.HANJingxiu(ChineseCenterforDiseaseControlandPrevention),Prof.XUChunyu(ChineseCenterforDiseaseControlandPrevention),Prof.GENGMengjie(ChineseCenterforDiseaseControlandPrevention),Prof.HUYuehua(ChineseCenterforDiseaseControlandPrevention);Dr.WUYang(HubeiProvincialCenterforDiseaseControlandPrevention),Dr.CHENQi(HubeiProvincialCenterforDiseaseControlandPrevention),Dr.LIUManman(HubeiProvincialCenterforDiseaseControlandPrevention),Dr.ZHOUMengge(HubeiProvincialCenterforDiseaseControlandPrevention),Dr.MENGPai(WuhanPrefectureCenterforDiseaseControlandPrevention),Dr.ZHAOYuanyuan(WuhanPrefectureCenterforDiseaseControlandPrevention),Dr.WANGDashuai(WuhanPrefectureCenterforDiseaseControlandPrevention),Dr.ZHANGJiajing(WuhanPrefectureCenterforDiseaseControlandPrevention),Prof.WANGLinghang(BeijingDitanHospital),Prof.WUWenjuan(JinyintanHospital)Prof.XULei(TsinghuaUniversity),Prof.JIAZhiyuan(NationalInstituteforViralDiseaseControlandPrevention,ChineseCenterforDiseaseControlandPrevention),Prof.WUZhiqiang(InstituteofPathogenBiology,ChineseAcademyofMedicalSciencesandPekingUnionMedicalCollege),Dr.),Dr.HEXiaozhou(NationalInstituteforViralDiseaseControlandPrevention,ChineseCenterforDiseaseControlandPrevention),Prof.NIJianqiang(ChinaAnimalDiseaseControlCenter),Prof.JIANGJingkun(SchoolofEnvironment,TsinghuaUniversity),;Prof.LIDong(WuhanAnimalDiseaseControlCenter),Prof.Ming-KunLi(ChinaNationalCenterForBioinformation),Prof.HuaChen(ChinaNationalCenterforBioinformation),Prof.JianLu(PekingUniversity).

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Contents

SUMMARY

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BACKGROUND

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MEMBERSOFTHEJOINTINTERNATIONALTEAMANDMETHODSOFWORK

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MAINFINDINGS

16

EPIDEMIOLOGY

16

Surveillancedata–morbidity

16

Surveillancedata–mortality

30

ReviewofStoredBiologicalSamplesTesting

50

Summaryandrecommendations

53

References

56

MOLECULAREPIDEMIOLOGY

58

Backgroundonmolecularepidemiology

58

Approach

61

OverviewofglobaldatabasesofSARS-CoV-2

61

Overviewofthesequencesofearlycases,globaloverview

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ZoonoticoriginsofSARS-CoV-2

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GenomicsequencingdataofSARS-CoV-2virusesinnaturallyinfectedanimals

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Summariesandperspectives

87

References

88

ANIMALANDENVIRONMENTSTUDIES

92

Introduction

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Methods

93

Results

94

Conclusions

108

Recommendations

109

References

110

POSSIBLEPATHWAYSOFEMERGENCE

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Directzoonotictransmission

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Introductionthroughintermediatehostfollowedbyzoonotictransmission

114

Introductionthroughthecold/foodchain

116

Introductionthroughalaboratoryincident

118

References

120

CONCLUDINGREMARKS

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WHO-convenedglobalstudyoforiginsofSARS-CoV-2:ChinaPartJointWHO-ChinaStudyTeamreport14January-10February2021

SUMMARY

InMay2020,theWorldHealthAssemblyinresolutionWHA73.1requestedtheDirector-GeneraloftheWorldHealthOrganization(WHO)tocontinuetoworkcloselywiththeWorldOrganisationforAnimalHealth(OIE),theFoodandAgricultureOrganizationoftheUnitedNations(FAO)andcountries,aspartoftheOneHealthapproach,toidentifythezoonoticsourceofthevirusandtherouteofintroductiontothehumanpopulation,includingthepossibleroleofintermediatehosts.Theaimistopreventbothreinfectionwiththevirusinanimalsandhumansandtheestablishmentofnewzoonoticreservoirs,therebyreducingfurtherrisksoftheemergenceandtransmissionofzoonoticdiseases.

InJuly2020,WHOandChinabeganthegroundworkforstudiestobetterunderstandtheoriginsofthevirus.TermsofReference(TORs)wereagreedthatdefinedaphasedapproach,andthescopeofstudies,themainguidingprinciplesandexpecteddeliverables.TheTORsenvisagedaninitialPhase1ofshort-termstudiestobetterunderstandhowthevirusmighthavebeenintroducedandstartedtocirculateinWuhan,China.

WHOselectedaninternationalmultidisciplinaryteamofexpertstoworkcloselywithamultidisciplinaryteamofChineseexpertsinthedesign,supportandconductofthesestudiesandtoconductafollow-upvisittoreviewprogressandagreeuponaseriesoffurtherstudies.

Thejointinternationalteamcomprised17Chineseand17internationalexpertsfromothercountries,theWorldHealthOrganization(WHO),theGlobalOutbreakAlertandResponseNetwork(GOARN),andtheWorldOrganisationforAnimalHealth(OIE)(AnnexB).TheFoodandAgricultureOrganizationoftheUnitedNations(FAO)participatedasanobserver.Followinginitialonlinemeetings,ajointstudywasconductedovera28-dayperiodfrom14Januaryto10February2021inthecityofWuhan,People’sRepublicofChina.

TheteamagreedaworkplanandestablishedworkinggroupstoreviewtheprogressmadeinPhase1studiesintheareasof:epidemiology;animalsandtheenvironment;andmolecularepidemiologyandbioinformatics.Duringthecourseofthediscussions,theinternationalexpertsgaineddeeperunderstandingofthemethodsusedanddataobtained.Inresponsetorequestsduringthevisit,furtherdataandanalysesweregenerated,reflectingaproductiveiterativeapproachtorefiningthedesignandinterpretationofcomplexstudiesinallareas.

Inadditiontogroupwork,theteamsharedscientificandthematicpresentationsonrelevanttopicstohelpinformitswork,undertookaseriesofsitevisitstoimportantlocationsandconductedinterviewswithkeyinformants.

TheepidemiologyworkinggroupcloselyexaminedthepossibilitiesofidentifyingearliercasesofCOVID-19throughstudiesfromsurveillanceofmorbidityduetorespiratorydiseasesinandaroundWuhaninlate2019.Italsodrewonnationalsentinelsurveillancedata;laboratoryconfirmationsofdisease;reportsofretailpharmacypurchasesforantipyretics,coldandcoughmedications;aconveniencesubsetofstoredsamplesofmorethan4500researchprojectsamplesfromthesecondhalfof2019storedatvarioushospitalsinWuhan,therestofHubeiProvinceandotherprovinces.InnoneofthesestudieswasthereevidenceofanimpactofthecausativeagentofCOVID-19onmorbidityinthemonthsbeforetheoutbreakofCOVID-19.

Furthermore,surveillancedataonall-causemortalityandpneumonia-specificmortalityfromWuhancityandtherestofHubeiProvincewerereviewed.Thedocumentedrapidincreaseinall-causemortality

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andpneumonia-specificdeathsinthethirdweekof2020indicatedthatvirustransmissionwaswidespreadamongthepopulationofWuhanbythefirstweekof2020.ThesteepincreaseinmortalitythatoccurredonetotwoweekslateramongthepopulationintheHubeiProvinceoutsideWuhansuggestedthattheepidemicinWuhanprecededthespreadintherestofHubeiProvince.

BothsurveillancedataandcasesreportedtotheNationalNotifiableDiseaseReportingSystem(NNDRS)inChinaweresubjectedtoclinicalreview.TheNNDRSwasnotifiedof174COVID-19caseswithonsetofsymptomsinDecember2019.Inanextensiveexerciseby233healthinstitutionsinWuhan,some76,253recordsofcasesofrespiratoryconditionsinthetwomonthsofOctoberandNovemberbeforetheoutbreakinlate2019werescrutinizedclinically.Although92caseswereconsideredtobecompatiblewithSARS-CoV-2infectionafterreview,subsequenttestingandfurtherexternalmultidisciplinaryclinicalreviewdeterminedthatnonewasinfactduetoSARS-CoV-2infection.Basedontheanalysisofthisandothersurveillancedata,itisconsideredunlikelythatanysubstantialtransmissionofSARS-CoV-2infectionwasoccurringinWuhanduringthosetwomonths.

ManyoftheearlycaseswereassociatedwiththeHuananmarket,butasimilarnumberofcaseswereassociatedwithothermarketsandsomewerenotassociatedwithanymarkets.TransmissionwithinthewidercommunityinDecembercouldaccountforcasesnotassociatedwiththeHuananmarketwhich,togetherwiththepresenceofearlycasesnotassociatedwiththatmarket,couldsuggestthattheHuananmarketwasnottheoriginalsourceoftheoutbreak.Othermildercasesthatwerenotidentified,however,couldprovidethelinkbetweentheHuananmarketandearlycaseswithoutanapparentlinktothemarket.NofirmconclusionthereforeabouttheroleoftheHuananmarketintheoriginoftheoutbreak,orhowtheinfectionwasintroducedintothemarket,cancurrentlybedrawn.

Themolecularepidemiologyandbioinformaticsworkinggroupexaminedthegenomicdataofvirusescollectedfromanimals.EvidencefromsurveysandtargetedstudiessofarhaveshownthatthecoronavirusesmosthighlyrelatedtoSARS-CoV-2arefoundinbatsandpangolins,suggestingthatthesemammalsmaybethereservoirofthevirusthatcausesCOVID-19.However,neitherofthevirusesidentifiedsofarfromthesemammalianspeciesissufficientlysimilartoSARS-CoV-2toserveasitsdirectprogenitor.Inadditiontothesefindings,thehighsusceptibilityofminkandcatstoSARS-CoV-2suggeststhatadditionalspeciesofanimalsmayactasapotentialreservoir.

Toanalysetheviralgenomesandepidemiologicaldatafromtheearlyphaseoftheoutbreak,theteamrevieweddatacollectedthroughtheChinaNationalCentreforBioinformationintegrateddatabaseonallavailablecoronavirusessequencesandtheirmetadata.AllsequencedatafromsamplescollectedinDecember2019andJanuary2020weresubjectedtodeeperanalysistoseethediversityofvirusesinthefirstphasesoftheoutbreak.ForthecasesdetectedinWuhan,dataonsamplesfromcaseswithillnessonsetbefore31December2019werelinkedwithepidemiologicalbackgrounddata.SeveralsamplesfrompatientswithexposuretotheHuananmarkethadidenticalvirusgenomes,suggestingthattheymayhavebeenpartofacluster.However,thesequencedataalsoshowedthatsomediversityofvirusesalreadyexistedintheearlyphaseoftheoutbreakinWuhan,suggestingunsampledchainsoftransmissionbeyondtheHuananmarketcluster.Therewasnoobviousclusteringbytheepidemiologicalparametersofexposuretorawmeatorfurryanimals.

Inaddition,thetimetothemostrecentcommonancestoroftheSARS-CoV-2sequencesinthefinaldatasetwasestimatedandcomparedwithresultsfrompreviousstudies.Suchanalysescanbeconsideredestimatesbutdonotprovidedefinitiveproofoftimeoforigins.Basedonmolecularsequencedata,theresultssuggestedthattheoutbreakmayhavestartedsometimeinthemonthsbeforethemiddleofDecember2019.ThepointestimatesforthetimetothemostrecentancestorrangedfromlateSeptembertoearlyDecember,butmostestimateswerebetweenmid-NovemberandearlyDecember.

Finally,theteamrevieweddatafrompublishedstudiesfromdifferentcountriessuggestingearlycirculationofSARS-CoV-2.ThefindingssuggestthatcirculationofSARS-CoV-2precededtheinitialdetectionofcasesbyseveralweeks.Someofthesuspectedpositivesamplesweredetectedevenearlier

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thanthefirstcaseinWuhan,suggestingthepossibilityofmissedcirculationinothercountries.Sofar,however,thequalityofthestudiesislimited.Nonetheless,itisimportanttoinvestigatethesepotentialearlyevents.

TheanimalandenvironmentworkinggroupreviewedexistingknowledgeoncoronavirusesthatarephylogeneticallyrelatedtoSARS-CoV-2identifiedindifferentanimals,includinghorseshoebats(Rhinolophusspp)andpangolins.However,thepresenceofSARS-CoV-2hasnotbeendetectedthroughsamplingandtestingofbatsorofwildlifeacrossChina.Morethan80000wildlife,livestockandpoultrysampleswerecollectedfrom31provincesinChinaandnopositiveresultwasidentifiedforSARS-CoV-2antibodyornucleicacidbeforeandaftertheSARS-CoV-2outbreakinChina.ThroughextensivetestingofanimalproductsintheHuananmarket,noevidenceofanimalinfectionswasfound.

EnvironmentalsamplinginHuananmarketfromrightatthepointofitsclosingshowedoutof923environmentalsamplesinHuananmarket,73sampleswerepositive.ThisrevealedwidespreadcontaminationofsurfaceswithSARS-CoV-2,compatiblewithintroductionofthevirusthroughinfectedpeople,infectedanimalsorcontaminatedproducts.

ThesupplychainstoHuananmarketincludedcold-chainproductsandanimalproductsfrom20countries,includingthosewheresampleshavebeenreportedaspositiveforSARS-CoV-2beforetheendof2019andthosewherecloserelativesofSARS-CoV-2arefound.ThereisevidencethatsomedomesticatedwildlifetheproductsofwhichweresoldinthemarketaresusceptibletoSARS-CoV,butnoneoftheanimalproductssampledinthemarkettestedpositiveinthisstudy.Intheearlyphaseofpandemic,duetolackofawarenessofthepotentialroleofcoldchaininvirusintroductionandtransmission,thecold-chainproductswerenottested.Thesefindings,however,doraisethepossibilityofdifferentpotentialpathwaysofintroduction.PreliminarysamplingandtestingofothermarketsinWuhanandupstreamsupplierstotheHuananmarkettakenduring2020didnotrevealevidenceofSARS-CoV-2circulatinginanimals.

SARS-CoV-2hasbeenfoundtopersistinconditionsfoundinfrozenfood,packagingandcold-chainproducts.IndexcasesinrecentoutbreaksinChinahavebeenlinkedtothecoldchain;thevirushasbeenfoundonpackagesandproductsfromothercountriesthatsupplyChinawithcold-chainproducts,indicatingthatitcanbecarriedlongdistancesoncold-chainproducts.

Furtheranalysiswillexaminespatialandtemporalcorrelationsandcorrectforunderlyingbiasesinsampling,andalsototracefrozenproductsbacktotheHuananmarketfromsuppliers.

Theteamsuggestednext-phasestudiestohelptracingtheoriginofSARS-CoV-2andtheclosestcommonancestortothisvirus,includinganalysisoftradeandhistoryoftradeinanimalsandproductsinothermarkets,particularlyinmarketsepidemiologicallylinkedtoearlyhumancasesorsequencedata,surveysofsusceptibleanimalsinfarmsinSouth-EastAsiaandfurtherafieldforvirusesrelatedtoSARS-CoV-2,livestockfarmswherecoronavirus-susceptibleanimalsarepresent,andcontinued,targetedsurveysoffurfarmsforSARS-CoV-2andrelatedviruses.Farmers,suppliersandtheircontactscouldbefollowedup,andcohortsofworkerswhohaveanoccupationalriskofexposuretoanimalsandcold-chainproductscouldbeserologicallytestedforunusuallyhighantibodytitresthatmightsuggestariskforSARS-Cov-2emergence.

ThenextphasestudiesincludetestingwildlifesamplesforSARS-CoV-2relatedviralsequenceandantibodies;continuingsurveysofRhinolophusbatsinsouthernprovincesofChinaandcountriesaroundEastAsia,South-EastAsiaandanyotherregionswhereRhinolophusbatsaredistributed;tracingthecoldchainproductsuppliercountrieswhereSARS-CoV-2positivetestingwaspreliminarilyreportedbeforetheendof2019,andwhereevidenceofmoredistantlyrelatedSARSr-CoVinbatsoutsideAsiawerereported,iftherearecrediblelinks.Conductfurtherrelevanttraceabilityresearchstudiesincountriesandregionswithinitialreportsofpositiveresultsinsewage,serum,humanoranimaltissues/swabandotherSARS-CoV-2testbytheendof2019.Conveneaglobalexpertgrouptosupportfuturejointtraceabilityresearchontheoriginofepidemics.

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Thejointinternationalteammadeaseriesofrecommendationsforeacharea(seedetailsinthereport)andindoingsoassessedthelikelihoodofdifferentpossiblepathwaysfortheintroductionofthevirus.

Thejointinternationalteamexaminedfourscenariosforintroduction:

directzoonotictransmissiontohumans(spillover);

introductionthroughanintermediatehostfollowedbyspillover;

introductionthroughthe(cold)foodchain;

introductionthroughalaboratoryincident.

Foreachofthesepossiblepathwaysofemergence,thejointteamconductedaqualitativeriskassessment,consideringtheavailablescientificevidenceandfindings.Italsostatedtheargumentsagainsteachpossibility.Theteamassessedtherelativelikelihoodofthesepathwaysandprioritizedfurtherstudiesthatwouldpotentiallyincreaseknowledgeandunderstandingglobally. 

Thejointteam’sassessmentoflikelihoodofeachpossiblepathwaywasasfollows:

directzoonoticspilloverisconsideredtobeapossible-to-likelypathway;

introductionthroughanintermediatehostisconsideredtobealikelytoverylikelypathway;

introductionthroughcold/foodchainproductsisconsideredapossiblepathway;

introductionthroughalaboratoryincidentwasconsideredtobeanextremelyunlikelypathway.

BACKGROUND

TheemergenceofSARS-CoV-2wasfirstobservedwhencasesofunexplainedpneumoniawerenotedinthecityofWuhan,China.(1)DuringthefirstweeksoftheepidemicinWuhan,anassociationwasnotedbetweentheearlycasesandtheWuhanHuananSeafoodWholesaleMarket(hereafterreferredtoasthe“Huananmarket”);casesweremainlyreportedinoperatingdealersandvendors.(1)Theauthoritiesclosedthemarketon1January2020forenvironmentalsanitationanddisinfection.Themarket,whichpredominantlysoldaquaticproductsandseafoodaswellassomefarmedwildanimalproducts,wasinitiallysuspectedtobetheepicentreoftheepidemic,suggestinganeventatthehuman-animalinterface.RetrospectiveinvestigationsidentifiedadditionalcaseswithonsetofdiseaseinDecember2019,andnotalltheearlycasesreportedanassociationwiththeHuananMarket.(2)

Althoughtheroleofcivetsasintermediatehostsintheoutbreakofsevereacuterespiratorysyndrome(SARS)in2002-2004hadbeenfavouredandaroleforpangolinsintheoutbreakofCOVID-19wasinitiallyposited,subsequentepidemiologicalandepizooticstudieshavenotsubstantiatedthecontributionoftheseanimalsintransmissiontohumans.ThepossibleintermediatehostofSARS-CoV-2remainselusive.

Batshavebeenidentifiedasthehostsofaseriesofimportantzoonoticviruses(forexample,Nipahvirus,HendravirusandSARS-CoV),includingcoronaviruseswithconsiderablegeneticdiversity.(3,4)OfparticularrelevancewithregardtoCOVID-19arethosecoronavirusesthatwerefoundtobeassociatedwiththeoutbreaksinhumansofSARSin2002andtheMiddleEastrespiratorysyndrome(MERS)in2013.(5)

ThecausativevirusofCOVID-19wasrapidlyisolatedfrompatientsandsequenced,withtheresultsfromChinasubsequentlybeingsharedandpublishedinJanuary2020.(6)Thefindingsshowedthatitwasapositive-strandedRNAvirusbelongingtotheCoronaviridaefamily(asubgroupBbetacoronavirus)andwasnewtohumans.Intheearlywork,analysisofthegenomicsequenceofthenewvirus(SARS-CoV-2)showedhighhomologywiththatofthecoronavirusthatcausedSARSin2002-2004,namelySARS-CoV(anothersubgroupBbetacoronavirus).(5)OverthenextyearextensiveworkgloballyonsequencesandphylogenyfollowedandtheresultshavebeensharedinternationallyandstoredthroughtheGISAIDplatform.

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SARS-CoV-2alsosharesa96.2%homologywithasequenceofastrainofcoronavirus(RaTG13)previouslyidentifiedbygeneticsequencingfromahorseshoebatsample(Rhinolophusspecies)andtoalesserextentwithastrainisolatedfrompangolins.TheRaTG13virussequenceistheclosestknownsequencetoSARS-CoV-2.

AswiththecoronavirusesthatcauseSARSandMERS,human-to-humantransmissionofSARS-CoV-2wassoonestablished,(7)butthevirusdemonstratedmuchgreaterinfectivitythantheseothertwocoronaviruses.(8)SARS-CoV-2showsabroadtissuetropism,inparticularbindingthroughitsspikeproteintoangiotensin-convertingenzyme2(ACE2).Italsodirectlyinfectsendothelialcellsliningthebloodvessels,unusuallyforahumanrespiratoryvirus.Othernovelpathologicalfeaturesofthevirusarehypercoagulabilityandtheexcessivemulti-organimmunesystemresponseandlong-termsequelae.PeopleinfectedwithSARS-CoV-2appeartobemostinfectiousatthetimeofonsetofsymptomsbutwerealsoinfectiousinthedaysbeforeonset.Infectionscanbeasymptomatic,causeamildillnessorresultinseverediseaseanddeath.

InFebruary2020thejointWHO-ChinamissiononCOVID-19(9)wasconvenedtoinformplanninginChinaandinternationallyonthenextstepsintheresponsetotheongoingoutbreakofCOVID-19.Itsmajorobjectiveswere:

toenhanceunderstandingoftheevolvingCOVID-19outbreakinChinaandthenatureandimpactofongoingcontainmentmeasures;

toshareknowledgeontheCOVID-19responseandpreparednessmeasuresbeingimplementedincountriesaffectedbyoratriskofimportationsofCOVID-19;

togeneraterecommendationsforadjustingCOVID-19containmentandresponsemeasuresinChinaandinternationally;and

toestablishprioritiesforacollaborativeprogrammeofwork,researchanddevelopmenttoaddresscriticalgapsinknowledgeandresponseandreadinesstoolsandactivities.

InMay2020,theSeventy-thirdWorldHealthAssemblyadoptedresolutionWHA