《自然》：
https://www.nature.com/articles/d41586-022-00007-8
Omicron'sfeebleattackonthelungscouldmakeitlessdangerous
MountingevidencefromanimalstudiessuggeststhatOmicrondoesnotmultiplyreadilyinlungtissue,whichcanbebadlydamagedinpeopleinfectedwithothervariants.
EarlyindicationsfromSouthAfricaandtheUnitedKingdomsignalthatthefast-spreadingOmicronvariantofthecoronavirusSARS-CoV-2islessdangerousthanitspredecessorDelta.Now,aseriesoflaboratorystudiesoffersatantalizingexplanationforthedifference:Omicrondoesnotinfectcellsdeepinthelungasreadilyasitdoesthoseintheupperairways.
“It’saveryattractiveobservationthatmightexplainwhatweseeinpatients,”saysMelanieOtt,avirologistattheGladstoneInstituteofVirologyinSanFrancisco,California,whowasnotinvolvedintheresearch.ButsheaddsthatOmicron’shyper-transmissibilitymeansthathospitalsarefillingquickly—despiteanydecreaseintheseverityofthediseaseitcauses.
AuthoritiesinSouthAfricaannouncedon30DecemberthatthecountryhadpasseditsOmicronpeakwithoutamajorspikeindeaths.Anda31DecemberUKgovernmentreportsaidthatpeopleinEnglandwhowereinfectedwithOmicronwereabouthalfaslikelytorequirehospitalizationoremergencycareaswerethoseinfectedwithDelta.
ButthenumberofpeoplewhohavegainedimmuneprotectionagainstCOVID-19throughvaccination,infectionorbothhasgrownovertime,makingitdifficulttodeterminewhetherOmicronintrinsicallycausesmilderdiseasethanearliervariants.Foranswers,researchershaveturnedtoanimalsandtocellsinlaboratorydishes.
Howthecoronavirusinfectscells—andwhyDeltaissodangerous
MichaelDiamond,avirologistatWashingtonUniversityinSt.Louis,Missouri,andhiscolleaguesinfectedhamstersandmicewithOmicronandothervariantstotrackdiseaseprogression.Thedifferenceswerestaggering:afterafewdays,theconcentrationofvirusinthelungsofanimalsinfectedwithOmicronwasatleasttentimeslowerthanthatinrodentsinfectedwithothervariants1.Otherteamshavealsonotedthatcomparedwithpreviousvariants,Omicronisfoundatreducedlevelsinlungtissue2,3.
DiamondsayshewasespeciallyshockedtoseethattheOmicron-infectedanimalsnearlymaintainedtheirbodyweight,whereastheothersquicklylostweight—asignthattheirinfectionswerecausingseveredisease.“EverystrainofSARS-CoV-2hasinfectedhamstersveryeasily,tohighlevels,”hesays,“andit’sclearthatthisoneisdifferentforhamsters.”Thelungsarewherethecoronavirusdoesmuchofitsdamage,andlunginfectioncansetoffaninflammatoryimmuneresponsethatravagesinfectedanduninfectedcellsalike,leadingtotissuescarringandoxygendeprivation.Fewerinfectedlungcellscouldmeanmilderillness.
AnothergroupfoundthatOmicronismuchlesssuccessfulthanpreviousvariantsatinfectinglungcellsandminiaturelungmodelscalledorganoids4.Theseexperimentsalsoidentifiedaplausibleplayerinthedifference:aproteincalledTMPRSS2,whichprotrudesfromthesurfacesofmanycellsinthelungsandotherorgans,butisnotablyabsentfromthesurfacesofmostnoseandthroatcells.
Previousvariantshaveexploitedthisproteintoinfectcells,buttheresearchersnoticedthatOmicrondoesn’tbindtoTMPRSS2sowell.Instead,ittendstoentercellswhenitisingestedbythem5,6.
Upperairwaypreferred
DifficultyenteringlungcellscouldhelptoexplainwhyOmicrondoesbetterintheupperairwaysthaninthelungs,saysRavindraGupta,avirologistattheUniversityofCambridge,UK,whoco-authoredoneoftheTMPRSS2studies4.Thistheorycouldalsoexplainwhy,bysomeestimates,Omicronisnearlyastransmissibleasmeasles,whichisthebenchmarkforhightransmissibility,saysDiamond.Ifthevariantlingersintheupperairways,viralparticlesmightfinditeasytohitcharideonmaterialexpelledfromthenoseandmouth,allowingthevirustofindnewhosts,saysGupta.OtherdataprovidedirectevidencethatOmicronreplicatesmorereadilyintheupperairwaysthaninthelungs2,5.
Thelatestresultscouldmeanthat“thevirusestablishesaverylocalinfectionintheupperairwaysandhaslesschancetogoandwreakhavocinthelungs”,Ottsays.Thatwouldbewelcomenews—butahost’simmuneresponseplaysanimportantpartindiseaseseverity,andscientistsneedmoreclinicaldataiftheyaretounderstandhowOmicron’sbasicbiologyinfluencesitsdiseaseprogressioninhumans.
Omicron’scourseofinfectioncouldalsohaveimplicationsforchildren,saysAudreyJohn,aspecialistinpaediatricinfectiousdiseaseattheChildren’sHospitalofPhiladelphiainPennsylvania.Youngchildrenhaverelativelysmallnasalpassages,andbabiesbreatheonlythroughtheirnoses.Suchfactorscanmakeupperrespiratoryconditionsmoreseriousforchildrenthanforadults,Johnsays.Butsheaddsthatshehasnotseendatasuggestinganuptickinthenumbersofyoungchildrenhospitalizedforcroupandotherconditionsthatcouldindicateasevereinfectionoftheupperrespiratorytract.

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