COVID-19:Firstlargegenome-widestudyworldwideonriskgenes
ResearchteamfromKielfindsgenevariantsforseverecourseofCovid-19:ThebloodgroupmighthaveaninfluenceontheseverityofCovid-19symptoms.
WhydosomepeoplebecomeseverelyillwithCovid-19whileothersshowhardlyanysymptoms?Oneanswermightlieintheirdifferentbloodgroups.ScientistsattheUniversityMedicalCenterSchleswig-Holstein(UKSH)andtheKielUniversity(CAU),incooperationwitharesearchgroupfromNorway,havefoundgenevariantsintheworld'sfirstlarge-scalegenome-widestudythatsignificantlyinfluencethecourseofthedisease-oneofthemconcernsthegeneforthebloodgrouptrait.Prof.Dr.AndreFranke,DirectoroftheInstituteofClinicalMolecularBiology(IKMB)andmemberofthesteeringcommitteeoftheclusterofexcellence"PrecisionMedicineinChronicInflammation"(PMI),aswellasthefirstauthorsProf.Dr.DavidEllinghausandFraukeDegenhardt,bothofwhomarealsoactiveintheIKMB,areinchargeofthissensationalproject.ThestudyhasbeenpublishedonlineinTheNewEnglandJournalofMedicine(NEJM).
ThestudyhadshownthatpeoplewithbloodgroupAhaveanapproximately50percenthigherriskofsevereCovid-19progressionthanpeoplewithotherbloodgroups.Incontrast,peoplewithtype0bloodgroupswerealmost50percentbetterprotectedagainstseriouscovid-19disease.Thestudythusconfirmed-forthefirsttimebymeansofacomprehensivegenome-wideanalysis-twoearlierstudiesbyinternationalresearcherswhohadalreadydescribedapossiblecorrelationbetweenbloodgroupcharacteristicsandthediseaseusingthebloodserumofCovid-19patients.AnanalysisbytheAmericancompany23andMevalidatedtheresultsoftheKielresearchersinanindependentpatientcohort.
ForthestudygroupledbythemolecularbiologistProf.FrankeandtheNorwegianinternistProf.Dr.TomKarlsen,doctorsfromseveralhospitalsofthecoronaepicentersinNorthernItalyandSpain,sentbloodsamplesoftheirCovid-19patientstoKiel-atotalof1,980intensivecarepatientswhohadtobetreatedwithoxygenorconnectedtoaventilator.Forthecontrolgroup,2,205randomlyselectedwomenandmenfromthepopulationofthesecountrieswereobtained.Withinonlythreeweeks,DNAwasisolatedfromthebloodsamplesattheInstituteofClinicalMolecularBiologyinKieland8.5millionpositionsofthegeneticmaterialfromeachindividualweremeasuredwithso-calledbiochips(SNParrays)."Usingthislargeamountofdata,wehaveidentifiedtrulyinterestingregionsinthegenomethatincreaseordecreasetheriskofsevereCovid-19progression,"saidProf.Ellinghaus,whocarriedoutthebioinformaticsandstatisticalanalyses."Insimpleterms,wewereabletoshowwherethemusicisplayingonaverylargemap."Intotal,thestudytooklessthantwomonths."ThisspeedwasonlypossiblebecauseeveryoneintheKielteamworkedhardontheprojecteverysingledayoftheweek-wewantedtogivesomethingbackforthetrustthattheclinicalpartnersandpatientsinSpainandItalyhaveplacedinus,"saidbiostatisticianFraukeDegenhardt.
InadditiontothesignificantabnormalityintheAB0bloodgrouplocus,thegenelocusbywhichtheindividualbloodgroupisdetermined,theresearchersfoundanevenhighereffectstrengthforageneticvariationonchromosome3.Whichoftheseveralcandidategeneslocatedinthislocusisresponsibleforthiscannotbedeterminedpreciselyatpresent,buttheanalysiswasabletoshowthatcarriersofthegeneareatatwofoldhigherriskofcontractingsevereCovid-19thanpeoplewhodonotcarrythisvariation.AmongtheItalianandSpanishpatientswhoweresoillthattheynotonlyhadtobesuppliedwithoxygenbutalsoconnectedtoaventilator,aparticularlyhighnumbercarriedthisgeneticdisposition.Aresultthatwasalsoevidentinthedistributionofbloodgroups:Amongtheparticularlyseriouslyill,therewerealsoaparticularlylargenumberofpeoplewithbloodgroupA.
Theresultswereveryexcitingandsurprisingforus,"saysProf.Franke.Theregiononchromosome3inparticularhadnotpreviouslybeenassociatedwithCovid-19byscientists.Inotherregionsofthegenomeforwhichaneffectonthediseasehadbeensuspected,nostatisticallysignificantdifferenceswerefoundbetweenthehealthyvolunteersandthepatients;neitherinthechromosomesection6p21,whichisassociatedwiththeimmunesystemandmanyinfectiousdiseases,norinthegeneIFITM3,whichisassociatedwithinfluenza.
"Withchromosome3andtheAB0bloodgrouplocuswedescriberealcausesforaseverecourseofCovid-19,"saysProf.Franke."Ourresultsthereforecreateanexcellentbasisforthedevelopmentofactivesubstancesthatcantargetthecandidategenesfound.Ithasbeenproventhataclinicalstudyinwhichadrugistestedhastwiceasmuchsuccessifgeneticevidenceforthetargetisalreadyavailable.TheresultscouldalsocontributetoanimprovedriskassessmentforaseverecourseofCovid-19inpatients.
Theoriginalpublicationisentitled"Genome-wideassociationstudyofsevereCovid-19withrespiratoryfailure".ThestudywassupportedbytheGermanFederalMinistryofEducationandResearchandtheUKSHFoundation.
Contakt:
Prof.Dr.AndreFranke
InstituteofClinicalMolecularBiology,CAUandUKSH
 +49431500-15110
 a.franke@ikmb.uni-kiel.de
Prof.Dr.AndreFranke,memberoftheSteeringCommitteeoftheClusterofExcellence"PrecisionMedicineinChronicInflammation"(PMI)andDirectorattheInstituteforClinicalMolecularBiology(IKMB)oftheCAUandtheUKSH,withhisresearchgroup.
Prof.Dr.DavidEllinghausandFraukeDegenhardt,bothfirstauthorsofthestudy.
Originalpublication
DavidEllinghaus,FraukeDegenhardtet.al:GenomewideAssociationStudyofSevereCovid-19withRespiratoryFailure.NEJM(2020).DOI:10.1056/NEJMoa2020283
AbouttheClusterofExcellencePMI
TheClusterofExcellence"PrecisionMedicineinChronicInflammation"(PMI)isbeingfundedfrom2019to2025throughtheGermanExcellenceStrategy(ExStra).Itsucceedsthe"InflammationatInterfacesCluster,whichwasalreadyfundedintwoperiodsoftheExcellenceInitiative(2007-2018).Around300membersfromeightinstitutionsatfourlocationsareinvolved:Kiel(KielUniversity,UniversityMedicalCenterSchleswig-Holstein(UKSH),MuthesiusUniversityofFineArtsandDesign,KielInstitutefortheWorldEconomy(IfW),LeibnizInstituteforScienceandMathematicsEducation(IPN)),Lbeck(UniversityofLbeck,UniversityMedicalCenterSchleswig-Holstein(UKSH)),Pln(MaxPlanckInstituteforEvolutionaryBiology)andBorstel(ResearchCenterBorstel-LeibnizLungCenter).
Thegoalistotranslateinterdisciplinaryresearchfindingsonchronicinflammatorydiseasesofbarrierorganstohealthcaremoreintensively,aswellastofulfilpreviouslyunsatisfiedneedsofthepatients.Threepointsareimportantinthecontextofsuccessfultreatment,andarethereforeattheheartofPMIresearch:theearlydetectionofchronicinflammatorydiseases,thepredictionofdiseaseprogressionandcomplications,andthepredictionofindividualresponsestotreatment.
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ClusterofExcellence "PrecisionMedicineinChronicInflammation"
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Contact:SonjaPetermann
 +49(0)431880-4850,fax:+49(0)431880-4894
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