COVID-19 pandemic. What have we learned? 夽

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www.analesdepediatria.org

SPANISH ASSOCIATION OF PAEDIATRICS

COVID-19 pandemic. What have we learned? ^夽

Cristina Calvo

^a,b,^∗

, Alfredo Tagarro

^b,c

, Ana Méndez Echevarría

^a,b

,

Belén Fernández Colomer

^d

, M. Rosa Alba˜ nil Ballesteros

^e

, Quique Bassat

^f,g,h,i,j

, M. José Mellado Pe˜ na

^a,b

aServiciodePediatría,EnfermedadesInfecciosasyTropicales,HospitalUniversitarioLaPaz,Madrid,Spain

bReddeInvestigacióntraslacionaleninfectologíaPediátrica(RITIP),Spain

cUnidaddePediatríaInvestigaciónyEnsayosClínicos(UPIC),InstitutodeInvestigaciónSanitariaHospital12deOctubre (IMAS12),Madrid;FundaciónparalaInvestigaciónBiomédicadelHospital12deOctubre,Madrid;ServiciodePediatría,Hospital UniversitarioInfantaSofía,UniversidadEuropeadeMadrid,Madrid,Spain

dComisióndeInfección,SociedadEspa˜noladeNeonatología(SENeo),Spain

eCentrodeSaludCuzco,Fuenlabrada,Madrid;GrupodePatologíaInfecciosadelaAsociaciónEspa˜noladePediatríadeAtención Primaria(AEPap),Spain

fISGlobal,HospitalClínic-UniversitatdeBarcelona,Barcelona,Spain

gCentrodeInvestigac¸ãoemSaúdedeManhic¸a(CISM),Maputo,Mozambique

hICREA,Barcelona,Spain

iPediatricsDepartment,HospitalSantJoandeDéu,UniversitatdeBarcelona,EspluguesdeLlobregat,Barcelona,Spain

jConsorciodeInvestigaciónBiomédicaenReddeEpidemiologíaySaludPública(CIBERESP),Madrid,Spain

Received6September2021;accepted20September2021 Availableonline21October2021

KEYWORDS COVID-19;

SARS-CoV-2;

Schools;

Neonates

Abstract SincetheCOVID-19pandemicwasdeclaredinMarch2020,we havelearnedalot abouttheSARS-CoV-2coronavirus,anditsroleinpediatricpathology.

Childrenareinfectedinaratequitesimilartoadults,althoughinmostcasestheysuffermild orasymptomaticsymptoms.Around1%ofthoseinfectedrequirehospitalization,lessthan0.02%

requireintensivecare,andmortalityisverylowandgenerallyinchildrenwithcomorbidities.

Themostcommonclinicaldiagnosesareupperorlowerrespiratoryinfections,gastrointestinal infectionand,moreseriously,multisystemicinflammatorysyndrome(MIS-C).Mostepisodesdo notrequiretreatment,exceptforMIS-C.Remdesivirhasbeenwidelyusedasacompassionate treatmentanditsrolehasyettobedefined.

Thenewborncanbecomeinfected,althoughvertical transmissionisvery low(<1%)andit hasbeenshownthatthebabycansafelycohabitwithitsmotherandbebreastfed.Ingeneral, neonatalinfectionshavebeenmild.

夽 Pleasecitethisarticleas:Calvo C,TagarroA,MéndezEchevarría A,FernándezColomerB,Alba˜nil BallesterosMR,BassatQ,etal.

PandemiaCOVID-19.¿Quéhemosaprendidoenestetiempo?AnPediatr(Barc).2021;95:382.

∗Correspondingauthor.

E-mailaddress:[email protected](C.Calvo).

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Primarycarehassupportedaveryimportantpartofthemanagementofthepandemicinpedi- atrics. Therehasbeen numerouscollateraldamagederivedfrom thedifficultyofaccess to careandtheisolationsufferedbychildren.Thementalhealthofthepediatricpopulationhas beenseriouslyaffected.Althoughithasbeenshownthatschoolinghasnotledtoanincreasein infections,butrathertheopposite.Itisessentialtocontinuemaintainingthesecuritymeasures thatmakeschoolsasafe place,sonecessarynotonlyforchildren’seducation,butfortheir healthingeneral.

4.0/).

PALABRASCLAVE COVID-19;

SARS-CoV-2;

Colegios;

Neonatos

PandemiaCOVID-19.¿Quéhemosaprendidoenestetiempo?

Resumen Desdequeenmarzode2020sedeclararalapandemiaCOVID-19hemosaprendido muchascosasdelcoronavirusSARS-CoV-2,ydesupapelenlaenfermedadpediátrica.

Losni˜nosseinfectanenunporcentajebastantesimilaralosadultos,sibienenlamayoríade lasocasionessufrencuadroslevesoasintomáticos.Alrededordeun1%deinfectadosprecisan hospitalización,menosdeun0,02%precisancuidadosintensivos,ylamortalidadesmuybajay generalmenteenni˜nosconcomorbilidades.Loscuadrosclínicosmáshabitualessoninfecciones respiratoriasdevíasaltasobajas,cuadrosgastrointestinalesyconmayorgravedadelsíndrome inflamatoriomultisistémico(MIS-C).Lamayoríadelosepisodiosnoprecisantratamiento,salvo elMIS-C.Elremdesivirsehaempleadogeneralmentecomotratamientocompasivoyaúnestá pordefinirsupapel.

Elreciénnacidopuedeinfectarse,sibienlatransmisiónverticalesmuybaja(<1%),yseha demostradoqueelbebépuedecohabitardemaneraseguraconsumadreyrecibirlactancia materna.Engenerallasinfeccionesneonataleshansidoleves.

Laatenciónprimariahasoportadounapartemuyimportantedelmanejodelapandemiaen pediatría.Sehanproducidonumerososda˜noscolateralesderivadosdeladificultaddeacceso ala asistenciay delaislamientoquehansufrido losni˜nos.Lasaludmentaldelapoblación pediátricasehavistoseriamenteafectada.Apesardequesehademostradoquelaescolar- ización nohasupuestounincrementode loscontagios,sinomás bientodolocontrario.Es fundamentalseguirmanteniendolasmedidasdeseguridadquepermitanhacerdelasescuelas unlugarseguro,tannecesarionosoloparalaeducacióninfantil,sinoparasusaludengeneral.

Epidemiology

OnDecember31,2019,theWuhanMunicipalHealthCommis- sion(Hubeiprovince,China)reportedthedetectionofcases of severe pneumonia witha common history of visiting a seafoodandwild animal market.On January7,2020, the Chineseauthoritiesinformedthatthecausativeagenthad beenidentified,anewvirusintheCoronaviridaefamilythat waseventually named SARS-CoV-2.The genomesequence wasdivulgated onJanuary 12, 2020.¹ On January 30, the WorldHealthOrganization declaredtheoutbreak apublic healthemergencyofinternationalconcern,²andonMarch 30aglobalpandemic.

In Spain,fromthat pointthroughAugust 18,2021, the COVID-19 pandemic has unfolded in 5 waves or periods³ (Fig.1):

- Firstwaveofthepandemic:fromtheoutsetuntilJune21, 2020,whenthestateofalertwascalledoffinSpain.

- Second wave: from June 22 to December 6, 2020, the inflection point of the 14-day cumulativeincidence betweenwaves.

- Thirdwave: fromDecember7,2020 toMarch14,2021, the inflection point of the 14-day cumulativeincidence ofcoronavirusdisease2019(COVID-19)betweenthethird andfourthwaves.

- Fourthwave:fromMarch15,2021throughJune19,the inflection point of the 14-day cumulative incidence of COVID-19betweenthefourthandfifthwaves.

- Fifthwave:fromJune20,2021topresent.

The impact on the paediatric population has changed throughtime in terms of both its characteristics and the perceptionofknowledgeofthedisease,due,amongother things, to the varying availability of diagnostic tests. At thebeginningofthepandemic,thepolymerasechainreac- tion(PCR)testwasonlyperformed inchildrenwithsevere disease managed at the hospital level. Thus, in the first waveofthe pandemicin Spain,approximately1400cases 382.e2

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Figure1 WavesoftheCOVID-19pandemicinSpain.

ofinfectionbySARS-CoV-2weredetectedinchildrenunder 14years,whichamountedto1%ofthetotalcasesdiagnosed.

Amongthesechildren,26%requiredinpatientcare,and54 childrenrequiredadmissiontothepaediatricintensivecare unit (PICU) and 3 died (0.2% of the total). In the second wave,whendiagnostictestsbecamewidelyavailable,with performanceofantigenandantibodytestsandcontacttrac- ing,thenumberofpaediatriccasesincreasedsharplyuntil theyamountedto12%ofthetotaldiagnosed,withahospi- talizationrateinchildrenof0.8%,aPICUadmissionrateof 0.02%andamortalityoflessthan0.01%.³Themortalityis estimatedat0.21per100000childrenaged0---9yearsand 0.34per100000childrenaged10---19years.⁴Thistemporal trendhasbeen similarinSpain andtherest of developed countries.⁵

The fourth report of the National Study on the Sero- logical Epidemiology of SARS-COV-2 Infection in Spain (ENE-COVID),⁶ of December 2020, suggests that 400000 children in Spain had seroconverted at that point. Taking intoaccountthat at least 25%of children donotdevelop detectablelevelsofantibodies,theactualnumberthatgot infectedisprobablyhigher.

In the Barcelona area, the data showed that the rate of infection was similar in children and adults sharing a household,although,asitisknown,thecourse inthefor- merismuchmilderorasymptomatic.⁷Thepresentationof detected caseshaschanged betweenthe firstandsecond waves,withadecreasingproportionofpatientswithsevere respiratorydisease(pneumonia)andan increasingpropor- tion of febrile illness and mild infection.⁸ Although there arefewerdata forthe thirdand fourthwaves, it appears thatseverityandthefrequencyofhospitalizationcontinue todecline,anditisunclearwhetherthesechangesaredue totheemergenceofnewvariantsortoourimprovedknowl- edgeofthedisease.

Clinical characteristics and underlying diseases of infected individuals

The clinical spectrum of COVID-19 in children is broad, withsymptomsincluding,inorderofdecreasingfrequency, fever and low-grade fever, cough, rhinorrhoea, vomiting, abdominalpain,diarrhoea,fatigue,headache,sorethroat, breathing difficulty, myalgia and, more rarely, rash, con- junctivitis, enanthema, wheezing, chest pain, arthralgia andchangesintasteandsmell.Thefollowingbroadersyn- dromes or phenotypes have been described: mild disease (upper respiratory tract infection indistinguishable from otheraetiologies,flu-likeillness),feverwithoutsource,lung disease(usuallyviralpneumoniaand,muchlessfrequently, bronchitis,asthmaattacksorbronchiolitis),gastrointestinal disease(abdominalpain,vomiting,diarrhoea)andmultisys- teminflammatorysyndromeinchildren(MIS-C).⁹Thelatter isasevereformofillnessfollowinginfectionbySARS-CoV- 2 that is due to immune dysregulation and that usually requiresintensivecare.Thrombosis,ontheotherhand,has notbeenafrequentcomplicationinchildren.¹⁰Inthesubset of children that require hospital admission, the risk fac- torsforseverityincludeelevationofinflammatorymarkers, targetorgandamage(elevatedcreatinine,lowoxygensatu- ration),leucocytosis,neutrophilia,lymphopaenia,anaemia andthrombocytopenia.Onlinemodelsareavailabletopre- dict which patients are at high risk of severe COVID-19⁹ (https://rserver.h12o.es/pediatria/EPICOAPP/,username:

user,password:0000).

The paediatricstudy ofinfections bynovel coronavirus SARS-CoV-2 (EPICO-AEP), which encompasses 10% of the 800 public and private hospitals in Spain, had recruited approximately650 hospitalisedpatientsasofMarch2021.

In Spain, 19% of children withCOVID-19 managed at the hospitallevelhadsome formof comorbidity,a proportion

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that rose to28% inthe case of patients admitted tohos- pital and 60% in patients admitted to the PICU. Most of the patients that died (90%) had a severe underlying disease. There is evidence that underlying cardiac disease, liver disease and asthma is associated with an increased risk of admission tothe PICU. Interestingly,patients with asthma were admitted tothe PICUdue topneumonia, as opposed toasthma exacerbations. In addition, neurologic comorbidities,obesityandimmunosuppressivetherapyhave beenassociatedwithanincreasedriskofMIS-C.Incontrast, cancer,rheumaticdiseaseanddiabeteshavenotbeenasso- ciatedtoanincreasedriskofsevereCOVID-19inchildrenin Spain.⁹Inotherregions,type1diabeteshasbeenassociated withseveredisease.¹¹

In children, acute disease can be diagnosed by means oftherapidantigentestorthePCRtestinanappropriate sample.Nasopharyngeal(NP)swabsarethemostfrequently usedsamples,butrecentdatafromtheEPICO-AEPsuggest thatthePCRtestinbuccalswabsalivaspecimensprocessed and analysed the same way as NP swabs have a similar diagnosticyieldthatisalsogreatercomparedtotherapid antigentest.Inchildren,therapidantigentestislessaccu- ratethaninadults(sensitivityof60%---72%comparedtothe PCRtest).¹²

Nevertheless,itisimportanttotakeintoaccountthata positivePCRtest doesnotalwayscorrespondtotheacute phaseofinfection.ThemeantimetoPCR-negativeconver- sioninchildrenis17days,independentlyofage,severity, phenotypeorimmunosuppression.¹³

Treatment of infection by SARS-CoV-2

ThedecisiontoinitiatetreatmentinchildrenwithCOVID-19 iscomplicated,asmostchildrenhavemild symptomsthat resolvewithsymptomatictreatmentandthereislittleevi- denceontheuseofdifferenttreatmentsinthepaediatric population.¹⁴

In children who develop moderate to severe disease within a few days of infection, when the viral load is still high, administration of antivirals could curtail replication.^14,15Remdesiviristheonlyantiviraltodatethat has achieved a reductionin the length of stay in clinical trials,especiallywhen administeredearly.^14,15 Ithasbeen approvedforuseinchildrenover12years.Inyoungerchil- dren,itisusedonacompassionatebasis.^14,16Previouscase series report few adverse events in children with severe COVID-19andresolutioninmostcases.^14,15

Dexamethasone could be beneficial to some patients with severe disease.¹⁶ This drug reduces morbidity and mortalityinseriouslyillpatientsreceivingmechanicalven- tilation, while in patients with milder presentations it does notimproveoutcomescomparedtoplacebo.¹⁶ Other immunomodulatorydrugs,suchastocilizumab,baricitinibor anakinra,havebeenusedinadults,butthecurrentevidence oftheiruseinchildrenwithCOVID-19isscarce.¹⁴

In hospitalised adults, administration of convalescent plasmahasbeenfound toreduce morbidityandmortality, especially if given early on and if it contains high anti- body titres of antibodies.^14,17 In patients with COVID-19 withriskfactorsthatarenothospitalised,earlyoutpatient treatment withneutralisingantibodies (bamlanivimaband

casirivimab-imdevimab[REGN-COV2])hasproveneffective in reducingthe progression tosevere disease.¹⁸ However, the use of convalescent plasma and monoclonal antibodies in children is controversial, the efficacy data in this populationisscarce,theymaycauseinfusion-relatedreac- tionsanditisdifficult todetermine whichpatientsareat risk of developing severe disease and could benefit from theirearlyadministration.^14,18Althoughtheyshouldnotbe usedroutinely,their use could be individualisedin select patients.^14,18

As for the management of MIS-C, the most frequent approaches have been steroid therapy, in boluses or at lowerdoses,andintravenous immunoglobulin,onaccount ofthesimilaritiestoKawasakidisease.¹⁹Someauthorshave usedthemincombination,althoughrecentlypublisheddata obtainedin614childrenwithMIS-Cfailedtoevincethesupe- riority of any of these 3 options compared to the rest.¹⁹ Therefore,anyoftheseapproachescouldbeusedwhilewe awaitstrongerevidence.

Inshort,inchildrenwithmoderatesymptoms,especially iftheyhaveanunderlyingdiseasethatputsthematriskof severeCOVID-19,theuseofremdesivirintheearlydaysof infectioncouldbebeneficial.Furthermore,dexamethasone isrecommendedinchildrenwithprolongeddisease,espe- ciallythoserequiringrespiratory support.Inchildren with MIS-C,initialtreatmentmayconsistofimmunoglobulinsor steroidsasmonotherapyoracombinationofboth.

Impact of COVID-19 on neonatal clinical practice

NeonatescanalsobecomeinfectedbySARS-CoV-2,but,in additiontothemechanismsoftransmissionatplayinallage groups,inthisparticularpopulationthereisaspecificmech- anismwhichisverticaltransmissionfromamotherinfected bySARS-CoV-2tothefoetusor neonate,whichmayoccur inutero(congenitalinfection),duringchildbirth(perinatal infection)orpostnatallythroughthebreastmilk.²⁰

WhenweanalysedtheimpactofCOVID-19onthemother- childdyad,we foundthatpregnantwomenwithCOVID-19 areat greater risk of severe disease (admission tointen- sive care unit), general and obstetric complications and death.^21,22Thus,thereisevidenceofasignificantincreasein thefrequencyofpretermbirthininfectedpregnantwomen, inmostcasesassociatedwithseverematernaldisease(med- ically indicated early-term delivery to improve maternal health),whichresultsinpoorerneonataloutcomesinchil- drenofmotherswithCOVID-19.²³

Whenitcomestoverticaltransmission,casesofcongen- italinfectionhavebeenrare,withaverylowincidenceof perinatal infection (<1%), and there has been no proven case of transmission through breast milk. In fact, most cases reported in infants were of postnatal transmission throughtheusualmechanismsandfromtheclosecontacts oftheinfant(mother,otherrelativesetc).Inaddition,the presentation in infants tends tobeasymptomatic or mild (symptomsofupperrespiratorytractinfectionand/orfever and/ordiarrhoea)ordoesnotdifferinanywayfromthepre- sentationofotherneonataldiseases(preterminfants).^24,25

Thelowimpactoninfantscouldberelatedtomaternal passiveimmunity,asthereisevidenceofthetransplacental

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transferof IgGantibodies againstSARS-CoV-2ininfants of infected or vaccinated mothers,and neutralisingantibod- iesagainstSARS-CoV-2(IgGandIgA)havebeendetectedin humanmilk.^26,27

Atthebeginningofthepandemic,theSociedadEspa˜nola de Neonatología (Spanish Society of Neonatology, SENeo) publishedguidelinesforthemanagementofneonatesinthe context of SARS-CoV-2, and especiallyfor infants born to motherswithCOVID-19.Ourstancefromtheoutset,despite thescarcityoftheevidence,wastoavoidtheseparationof thenewborninfantandthemother(aslongastheclinical conditionofbothallowedit,andirrespectiveofSARS-CoV- 2test resultsintheinfant)andtomaintainbreastfeeding (Fig.2).Atthesametime,toobtainevidenceofourown, weinstitutedtheCOVID-19-SENeoregistertocollectdataon infectedpregnantwomenandtheirinfantsandoncasesof postnatalinfectionbySARS-CoV-2(nosocomialoracquired in the community). Having analysed 15 months’worth of datacollectedinmorethan3700mother-infantdyads,we didnotfindanyconfirmedcaseofcongenitalinfection,and found an incidenceof perinatalinfection ofless than 1%.

When itcametocasesofpostnatal infection,withatotal of 138 recorded cases included in theanalysis, we found that20%wereasymptomatic,72weremildand8%required admissiontotheintensivecareunit.

Lastly,thispandemichasalsohadacollateralimpacton infantsderivedfromthelimitsplacedonparentalpresence inneonatalunits(restrictionsonfamily-centredcare,etc) andthestressexperiencedbyhealthcareworkers.

COVID-19 and primary care (Table 1)

Diseasemanagement

From the early daysof the pandemic, primarycare pae- diatricians (PCPs) identified possible COVID-19 cases in patients and their contacts, recommendedisolation measures,followeduppatientsandwatchedforwarningsigns and symptoms (MIS-Cand severe respiratory disease) and assessedtheneedforreferral.OncePCRandantigentests became available,it waspossiblefor PCPs toconfirm the diagnosis,whichmadeitpossibletolimitlossesofschool- ing or work timetoconfirmed cases andtothe minimum necessaryduration.²⁸

It was assumed that the start of the school year and theexpectedincreaseinseasonalinfectiousdiseaseswould complicatecaredelivery,buttherehasbeenasubstantial decreaseintheincidenceofnon-COVIDinfectiousdiseases, includingtheabsenceoftheflu season,²⁹ probablyassoci- atedwiththelockdownandhygiene(frequenthandwashing anduseofmasks)andsocialdistancingmeasures.

Collateralimpact

The decreased delivery of in-person care at the PC level and in hospitals, theprioritization of the management of COVID-19patients,theclosureofschoolsandrecreational activitiesandrehabilitationservicesandhomeconfinement havehadanimpactonhealth.Themostimportantare:

Table1 Roleofprimarycarepaediatriciansinthecontext ofCOVID-19.

Detection,identificationsanddiagnosisofcases Contacttracing/testing

Recommendationofisolationmeasures Treatmentandfollow-up

Monitoringforwarningsigns Updatingimmunizationschedules

Resumingdiagnosticevaluationsintheprimarycare settingthathadbeeninterrupted

Resumingdeliveryoftheroutinehealthy-child programme,withspecialemphasison Breastfeedingpromotion

Recommendationofphysicalactivity Supportofsocialinteraction/communication

Preventionofinfectiousdiseases:handhygiene,social distancing.

Revisionofdiagnosticandtreatmentprotocolsatother levelsofcare

Continuationoffollow-upofpatientswithchronicdisease Detectionandmanagementofoverweightandobesity Monitoringofpotentialconflictinthehousehold Carefulwatchingfor

Problemsinsocialinteractions/communication Moodchanges

Behaviouralchanges Eatingdisorders Learningdisorders

Excessiveuseofelectronicdevices

- Important decrease in vaccine coverage in the early monthsofthepandemic.³⁰Wedonotknowwhetherinter- ruptedvaccinationscheduleshavebeengenerallycaught upwithbynow.

- Delaysintesting,diagnosisandtreatmentinitiation.Ade- quatecoordinationbetweenlevelsofcareisnecessaryto remedythissituation.

- Children who require early intervention services and stimulation,physicaltherapy,occupationaltherapy,psy- chotherapy, speech therapy, etc, access to which is significantly delayed under normal circumstances, have experienced interruptionsincare,andtherehasbeena significantdelayintheassessmentofchildrenreferredto determine theneed oftheseservices.Thisconstitutesa significantlossofopportunitytoimprovetheirsituation.

- Inadditiontothegenerallockdown,therehavebeenmany other localconfinementmeasures, withclosureofparks andrecreationalactivities.This,combinedwiththeanx- iety of families, has severely limited opportunities for social interaction outside the household. Depending on the developmental stage at which these measures took place,theymayhaveaffectedthedevelopmentofsocial skills in children. Close follow-up of these children is required todifferentiate delaysin skillacquisition from actualdisorders.

- Anincreaseinobesity,probablyrelatedtowhatwasnoted inthepreviouspointandtheincreaseinsedentaryhabits.

- As has been the case at other levels of care, we have detected a significant increase in the number of vis- its relatedtomental health complaints, some involving

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Figure2 ManagementofneonatesborntomotherswithsuspectedSARS-CoV-2infection.

*Incaseofmothersundergoingevaluationorthattestedpositive,ifthemotherisoligosymptomaticorasymptomatic,rooming inofmotherandinfantisrecommendedwithcontactanddropletisolationmeasures(handhygiene,facemaskandcrib2mapart frommother’sbed)andpromotionofbreastfeeding.

**Insymptomaticinfantsborntomotherswithconfirmedinfectionorstrongsuspicionofinfectionbasedonclinical/epidemiological factors,rulingoutinfectionrequires2negativeviralPCRtests(atbirthandat24−48h).Inasymptomaticinfants,1or2PCRtests willbedonedependingontestavailability.

excessive use of electronic devices.^31---33 We must take intoaccountthatmanyfamilieshavelostmembersunder conditions of isolation and loneliness, that others have becomeimpoverishedandthatconfinementmeasuresmay havebeentriggersinviolentordysfunctionalhouseholds.

Theresourcesdevotedtomanagingmentalhealthissues areclearlyinsufficient.

- Thepandemichasimpoverishedmanyfamilies.Duetothe saturationofsocialservicesandtheclosureofschoolmeal services,thebasicneedsofchildrenarenotbeingmet.

During theCOVID-19pandemic, therehave been situa- tions that threatened the physical and mental health of children,theimpactof whichwillbefeltin theshortand thelongterm.Wemustremainwatchfulattheprimarycare leveltodetectanypossibledisorders.³⁴

Transmission of SARS-CoV-2 by children and implications for in-person schooling

Until theexplosivefifth wavein summerof2021, Spanish childrenandadolescentseemedtohavebeencomparatively sparedbytheCOVID-19pandemic,despitebeingassuscep-

tibletoinfectionasadults.⁷ Althoughat the beginningof thepandemicitwashypothesisedthattheyoungestinthe populationcouldplayaroleassuperspreaders,asisthecase whenitcomestootherrespiratoryviruses,suchasinfluenza, itsoonbecameclearthatchildrenhadamorelimitedrole inthetransmissionofSARS-CoV-2tootherindividuals.The few studies onthe subjectavailable todate suggest that childrenarerarelythesourceofsuperspreadingevents,that largeoutbreaksareinfrequentin childrenunder12years, and that children seemed tobe less infectious compared toadults,^35,36 with the ability to infect others increasing withage,reaching thetransmission potentialof adultsin lateadolescence.Aschool-basedstudyconductedinCatalo- niaallowedestimationofthesedifferencesintransmission potentialintermsofthereproductionnumber(R*),anepi- demiologicalparameterthatstandsfortheaveragenumber of secondary infections produced by one case, and found Rvalues that were30% (for young children) and 60% (for olderchildren)thereferenceRvalueinadults.³⁷Thismea- surewascalculatedinchildrenattendingschoolsthathad implementedstrict preventive measures, so the resulting valuesmustbeinterpretedinthecontextofatransmission containmentstrategy.

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The reopening of schools for in-person learning in September 2020wasperceivedasariskychoice (thathas beenextensivelycontested)bylargesegmentsofthepop- ulation in the context of the incipient second wave that was ravaging the country. However, a careful analysis of data on infections in the school-age population indicates thatschoolshavenotbeenhotbedsoftransmission(ifany- thing,theyappeartohavedonetheopposite)andthatthe measures implemented in the facilities have dramatically containedoutbreaks in thissetting and reducedtransmis- sionintheclassroom.Evenattimeswhenthetransmission ratewasalarminglyhighinSpain,reachinganincidenceof nearly1000casesper100000inhabitants,schoolswereable tocontinuetheiractivitywithoutmajorchanges,withfewer than 5%of theestablishedbubblesneeding tobequaran- tinedduetodetectionofapositivecaseandapproximately 75%ofdetectedinfectionsnotgivingrisetoanysecondary cases(unpublished data).These dataarereassuring when it comes to the return to school in September 2021, but the high transmissionrate recorded in children in recent monthsandtheemergenceofvariantsthataremuchmore infectioussuggesttheneedtomaintainthestrictmeasures appliedinthepreviousschoolyearandofincludingchildren aged12ormoreyearsinthenationalSARS-CoV-2vaccination campaigntomakevaccinationarequisitetoattendschools, thusmakingthereturntotheclassroom,ifatallpossible, evensafer.

Conflicts of interest

Theauthorshavenoconflictsofinteresttodeclare.

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