COVID-19origintracingtimeline:Studiesshowearlieremergenceworldwide_GuangmingOnlineTodeterminetheoriginofCOVID-19isthoughtcriticaltopreventingfutureresurgenceofthevirusanddevelopingefficienttreatmentsforthedisease.Sincetheoutbreakofthepandemic,intensiveeffortshavebeenmadebyscientiststotracethecausativeagent,SARS-CoV-2,andinvestigateitstransmission,pathogenesis,andtherapeutics.FollowingitsreleaseoftheWHO-Chinajointreportfindingalab-leakoftheSARS-CoV-2"extremelyunlikely",theWHO'scallforfurtherretrospectiveandsystematicresearcharoundearliercasesandpossiblehostshasintensifiedglobalcollaborationinorigintracing.Asstudiesgodeep,agrowingbodyofevidencesuggeststhenovelcoronaviruswasspreadinggloballymonthsbeforetheoutbreakinChina.AstudypublishedinthejournalClinicalInfectiousDiseasesonJune15,2021showedevidenceofcoronavirusinfectionsinfiveAmericanstatesasearlyasDecember2019--weeksbeforethefirstofficiallyreportedcases.ThefindingsinAmericaarethelatestamongstudiesworldwidethatdatetheemergenceandcirculationofCOVID-19earlierthanwasrecordedandreshapetheCOVID-19timelineofmanycountries.AstudypublishedbyaresearchteamfromtheUniversityofBarcelonaonJune26,2020showedthepresenceofthevirusgenomeinasewagesamplecollectedonMarch12,2019.TheteamhadbeentestingwastewatersamplestakenbetweenJanuary2018andDecember2019intheSpaincityBarcelonatoidentifypotentialnewoutbreaks.ThelevelsofSARS-CoV-2werelowbutwerepositive,implyingthediseasemayhaveappearedninemonthsinSpainbeforethefirstcaseswereofficiallyidentifiedinWuhan,ChinainearlyDecember2019.AstudypublishedbytheItalianscientificmagazineTumoriJournalinNovember2020showedSARS-CoV-2RBD-specificantibodiesweredetectedin111of959(11.6%)volunteersenrolledinalungcancerscreeningtrialbetweenSeptember2019andMarch2020.AfurtherSARS-CoV-2antibodiestestcarriedoutbytheUniversityofSienashowedthatfourcasesdatingbacktothefirstweekofOctoberwerepositiveforantibodies,meaningtheyhadgotinfectedinthepreviousmonthandthecoronavirushadbeencirculatinginItalyinSeptember2019.AccordingtoastudypublishedbytheBritishJournalofDermatologyonJanuary7,2021,aresearchteamfromtheUniversityofMilandetectedtheSARS-CoV-2virusinskincellsfroma25-year-oldwomanwhohadabiopsyforanunusualskinconditiononNovember10,2019inItaly.Thefindingtracedtheappearanceof"patientzero"inItalybacktoNovember2019.AnotherresearchteamfromtheUniversityofMilanreportedintheEmergingInfectiousDiseasesjournalthattheyidentifiedSARS-CoV-2RNAinanoropharyngealswabspecimencollectedfroma4-year-oldboywithsuspectedmeaslesinearlyDecember2019.AsCOVID-19symptomscanappearaslateas14daysafterinfection,thecoronavirusmayhavebeencirculatinginItalyasearlyastheendofNovember2019.TheFederalUniversityofSantaCatarinainBrazilreportedonJuly2,2020thatitfoundparticlesofSARS-CoV-2intwosamplesofsewagecollectedinFlorianopolis,thecountry’ssecondlargestcity,onNovember27,2019.Anauthorofthestudyaddedthatpeoplemighthavebeeninfectedwiththenovelcoronavirusafewweeksbeforetheycollectedthewastewatersamples.ThepresenceofthevirusisaboutthreemonthsearlierthanthefirstofficiallyconfirmedcaseinBrazilonFebruary26,2020.ThehealthdepartmentofthestateofEspiritoSanto,Brazil,announcedonJanuary1,2021thatthepresenceofIgGantibodies,specificforSARS-CoV-2virus,wasdetectedinserumsamplesfromDecember2019.Thehealthdepartmentstatedthatittakesabout20daysforapatienttoreachdetectablelevelsofIgGafterinfection,soitcouldhaveoccurredbetweenlateNovemberandearlyDecember2019.AccordingtoastudypublishedinthejournalClinicalInfectiousDiseasesonNovember30,2020,scientistsattheCentersforDiseaseControlandPrevention(CDC)testedAmericanRedCrossblooddonationscollectedbetweenDecember13,2019,andJanuary17,2020,andfoundevidenceofcoronavirusantibodiesin106outof7,389blooddonations.ThesesuggestedthattheviruswaspresentintheUnitedStatesasearlyasDecember2019,aboutamonthearlierthanthefirstUScasewasofficiallyconfirmedinJanuary2020.InanotherstudypublishedinthejournalClinicalInfectiousDiseasesonJune15,2021,researchersoftheU.S.NationalInstitutesofHealth’sAllofUsResearchProgramreportedtohaveanalyzedmorethan24,000storedbloodsamplescontributedbyprogramparticipantsacrossall50statesbetweenJanuary2andMarch18,2020.SARS-CoV-2antibodiesweredetectedinsamplescollectedasearlyasJanuary7,2020frompatientsinIllinois,Massachusetts,Mississippi,PennsylvaniaandWisconsin,suggestingthattheviruswaspresentintheU.S.inDecember2019.AnanalysisreleasedbytheItalianNationalInstituteofHealthonJune18,2020showedthepresenceoftheSARS-Cov-2virusinwastewater.Afterlookingat40compositeinfluentwastewatersamplescollectedbetweenOctober2019andFebruary2020fromfivewastewatertreatmentplantsinthreecitiesandregionsinnorthernItaly,researchersfoundtheearliestofpositivesamplesdatebacktoDecember18,2019inMilanandTurin,suggestingCOVID-19wasalreadycirculatinginnorthernItalyaftermid-December,2019.Aretrospectiveanalysisofsamplestakenfrom24patientstreatedinDecember2019andJanuary2020withinfluenza-likesymptomsattheAvicenneandJean-VerdierhospitalsinFrancefoundonepatientpositiveforCOVID-19onDecember27,2019.ThereportmeansthatthevirushadbeenpresentnearlyamonthbeforethefirstCOVID-19casewasconfirmedinbothEuropeandFranceon24January2020.Editor: