The Economist - 04.12.2021

24 BriefingTheOmicronvariant TheEconomistDecember4th 2021

travelfromsouthernAfrica.Some,likeIs­

raelandJapan,havebannedallforeigners

fromcomingin. Despitethis,byDecember

2ndovertwodozen countrieshadreported

thepresenceoftheOmicronvariantwithin

theirborders (see themap on thenext

page).Thatseemstosuggestthecatisal­

readyoutofthebag;ifOmicronhasthe

abilitytodisplaceDelta,itisprobablyal­

readyina positiontodoso.

Delayingtheinevitablecanstillprovide

realbenefits,becausehealthsystemsare

sensitivetotherateatwhichviralwaves

growandpeak:slowisbetter,fastisworse.

European countries, already struggling

witha winterwaveoftheDeltavariantand

worriedabouttheriskofflu,aretightening

measureslikemask­wearingandrestric­

tionsonmingling.Thereisevermoretalk

ofvaccinemandates.Theprospectofre­

newed distancing, working from home

andevenlockdownsisaddingtoa rangeof

othereconomicworriesaroundtheworld.

Westerncountries wheredoublevac­

cinationiscommonareprovidingmore

boostershots.Thatmakessenseevenifit

turnsoutthattheantibodiestheimmune

systemgeneratesinresponsetoexisting

vaccinesarenotaswell­tailoredtoOmi­

cronastheyweretoearliervariants.The

boosterswillnotmakebetterantibodies,

buttheywillspurthebodyintomaking

moreofthem,atleastfora while.Studies

havefoundthatthequantityofantibodies

against sars-cov­2 matters even if the

antibodiesarenotspecifictothevariant.

Vaccine­makers are looking at how to

change their offerings to dealwith the

newcomermoreeffectively—andtryingto

workoutwhethertheyactuallyneedto.

At the geneticlevel, Omicrondiffers

fromtheoriginalWuhanversioninmore

than 50 places.Butitisalsoverydifferent

fromotherrecentversionsofthevirus(see

chart1).Itsclosestrelativesareversionsof

thevirusfirstspottedatleasta yearagoand

rarely sequenced since. There are three

possibleexplanationsforthis.

OneisthatOmicron’sancestor man­

agedtocirculateforalmosta yearwithout

being detected by the genomic­surveil­

lanceapparatus,andwhilepickingupma­

nymoremutationsthananyothervariant

has.Thisseemsunlikely.Anotheristhat

Omicron’sancestorjumpedintoandoutof

ananimalpopulationoverthepastyear,

pickingupitslargenumberofmutations

there. Many ofthe mutations are com­

pletelynew,notseenbeforeinanyvariant,

lendingsomecredencetothishypothesis.

But it is the third possibility which

seemsmostlikely,notleastbecausesimi­

larthingshavebeendocumentedbefore.

Thisisfortheancestralsars­cov­2tohave

infected someone with a compromised

immunesystem.Becausesuchpeopleare

unabletogetridofit,theviruscanevolve

inside them for months, accumulating

mutationsasitdoesso.Theirbodiespro­

videwhatSharonPeacock ofCambridge

Universitycallsan“evolutionarygym”on

which variantscan both build up their

strengthandlearnsomenewtricks.

Omicronyou’resofine

The most worrying of Omicron’s muta­

tionsare inthegenethatdescribesthe

spikeprotein.Thisisthetoolthevirususes

tobinditselftocellsandenterthem.Delta

probablyowesitsgreatertransmissibility

inparttothefactthatitsticksbetterto

cells. Its mutations produce a spike in

whichnineoftheaminoacidsinthe1,273­

amino­acid­long chain from which the

proteinismadearedistinctivelydifferent.

The mutations in an unnamed variant

calledC.1.2,whichboastedoneofthemost

mutatedspikeeverseenuntilthepastfew

weeks,changed 14 oftheaminoacids.Om­

icron’smutationschange35;tenofthemu­

tationshaveneverbeenseeninanyofthe

variantsofconcerntodate.

Almosthalfofthe 35 changesareinthe

receptor­binding domain, the business

endoftheproteinwhenitcomestoenter­

ingcellsandalsotheparttargetedbythe

mosteffectiveantibodies.Bychangingthe

shapeofthispartoftheprotein,themuta­

tionscouldmakeOmicronbetteratgetting

intocellsandalsolesseasilyrecognisedby

antibodiesthat workagainsta different

versionofthespike.

A mutatedspikeisnotnecessarilya bet­

terspike.C.1.2derivednobenefitfromhav­

ingmoremutationstherethananyother

variant—itnever spread allthatfar and

maynowbeextinct.Butthelocationsof

Omicron’smutationsmakeitworrying.“If

youlookatthesequenceonpaper,because

ofthenumber of mutationsandwhere

theyare,itisveryconcerningbecauseof

the impact on neutralising antibodies,”

saysSusannaDunachie,animmunologist

attheUniversityofOxford.

Some other mutations are worrying,

too.Afterbindingtoa cell,thespikebreaks

intwoata juncturecalledthefurincleav­

agesite,allowingtheviralgenometoget

inside.RavindraGuptaofCambridgewor­

riesthatOmicron’sthreemutationsclose

tothissitewillgiveitanadvantageinrep­

licationsimilartothatenjoyedbyDelta.

Anothermutationmayallowittoconfuse

thewayinwhichtheimmunesystemuses

a chemicalmessengercalledinterferon.

ComputermodellingusingAlphaFold,

a programdevelopedbyDeepMind,a Brit­

ishartificial­intelligenceresearchcompa­

nyownedbyAlphabet,topredicttheshape

ofOmicron’sspikealsosuggeststhatanti­

bodieswillsticktoit atleasta bitlesswell,

saysColbyFord,a computationalbiologist

attheUniversityofNorthCarolinaatChar­

lotte.Experimentalapproachesthatcom­

paretheeffectoftheindividualmutations

involvedtendtoagree—butthecomplexity

ofprotein­foldingmeansthattheeffectsof

differentmutationsarenotstrictlyaddi­

tive;somewillreinforceeachother,others

will cancel each other out. The experi­

mentsthatshouldprovidea clearideaof

whatisgoingonwillbethosewhichpita

widerangeofantibodiesagainstthewhole

proteinasfoundonvirusparticles.Such

workisgoingonallovertheworld,no­

wheremoreurgentlythaninthelaborato­

Avariedapproach

Source:nextstrain.org *3,647genomestoNovember27th

EvolutionofSARS-CoV-2inAfrica,bydatesamplewastaken*

MutationsinspikeproteinS

0

5

10

15

20

25

30

2019 2020 2021

D J F MAM J J A S OND JF MAM J J A S ON

Omicron

Alpha Delta

Beta

= onegenome

Othervariants

Origin

1

Learning curve

World, lockdown-intensity index

Seven-day moving average, 100=max

Source:GoldmanSachsGlobalInvestmentResearch

60

40

20

0

2020 2021

Delta spreads

outside India

Alpha variant

spreads

2