Coronavirus vaccine - summary of Yellow Card reporting

The Yellow Card scheme is a mechanism by which anybody can voluntarily report any suspected adverse reactions or side effects to the vaccine. It ... Skiptomaincontent CookiesonGOV.UK Weusesomeessentialcookiestomakethiswebsitework. We’dliketosetadditionalcookiestounderstandhowyouuseGOV.UK,rememberyoursettingsandimprovegovernmentservices. Wealsousecookiessetbyothersitestohelpusdelivercontentfromtheirservices. Acceptadditionalcookies Rejectadditionalcookies Viewcookies Youcanchangeyourcookiesettingsatanytime. Hidethismessage Home Vigilance,safetyalertsandguidance Coronavirus(COVID-19)vaccinesadversereactions Medicines&HealthcareproductsRegulatoryAgency Contents Updateonpublicationfrequency Summary 1.Introduction 2.YellowCardreports 3.AnalysisofData 4.Conclusion Annex1VaccineAnalysisPrint Annex2Glossary Printthispage ©Crowncopyright2022 ThispublicationislicensedunderthetermsoftheOpenGovernmentLicencev3.0exceptwhereotherwisestated.Toviewthislicence,visitnationalarchives.gov.uk/doc/open-government-licence/version/3orwritetotheInformationPolicyTeam,TheNationalArchives,Kew,LondonTW94DU,oremail:[email protected]. Wherewehaveidentifiedanythirdpartycopyrightinformationyouwillneedtoobtainpermissionfromthecopyrightholdersconcerned. Thispublicationisavailableathttps://www.gov.uk/government/publications/coronavirus-covid-19-vaccine-adverse-reactions/coronavirus-vaccine-summary-of-yellow-card-reporting Updateonpublicationfrequency TheweeklysummaryofYellowCardreportinghasprovidedtimelyandrelevantinformationtopatientsandhealthcareprofessionalsonthesafetyoftheCOVID-19vaccinesastheyweredeployedintheUKthroughoutthepandemic. Inlinewiththewidergovernment’sLivingwithCOVID-19agendastrategy,thefrequencyofpublicationoftheupdatedsummaryhaschangedtoeveryotherweek,beforetransitioningtooncepermonthfromAugust.Ourrobustsafetymonitoringandsurveillancewillcontinueinthenormalwaybetweenpublicationsandwewillcontinuetocommunicatepromptlyonanyupdatedsafetyinformation. Summary Overthefirst26monthsofthepandemicover178,231peopleacrosstheUKhavediedwithin28daysofapositivetestforcoronavirus(COVID-19).VaccinationisthesinglemosteffectivewaytoreducedeathsandsevereillnessfromCOVID-19.AnationalimmunisationcampaignhasbeenunderwaysinceearlyDecember2020. ThreeCOVID-19vaccines-themonovalentCOVID-19VaccinePfizer/BioNTech,COVID-19VaccineAstraZenecaandmonovalentCOVID-19VaccineModerna–wereusedintheprimaryandboostervaccinationcampaignsuptotheendofAugust2022.AllhavebeenauthorisedforsupplybytheMedicinesandHealthcareproductsRegulatoryAgency(MHRA)followingathoroughreviewofsafety,qualityandefficacyinformationfromclinicaltrials.Inclinicaltrials,thesevaccinesshowedveryhighlevelsofprotectionagainstsymptomaticinfectionswithCOVID-19.Dataareavailableontheimpactofthevaccinationcampaigninreducinginfections,illnessandmortalityintheUK. TheMHRAconfirmedon9September2021thattheCOVID-19vaccinesmadebyPfizerandAstraZenecacanbeusedassafeandeffectiveboosterdoses.FollowingreviewofdatafortheCOVID-19VaccineModerna,theMHRAandCommissiononHumanMedicine(CHM)expertsalsoconcludedthatthisvaccinecanbeusedasasafeandeffectiveboosterdose. Allvaccinesandmedicineshavesomesideeffects.Thesesideeffectsneedtobecontinuouslybalancedagainsttheexpectedbenefitsinpreventingillness. On15Augustand3September2022respectively,theModernabivalentvaccine(SpikevaxbivalentOriginal/Omicron)andthePfizer/BioNTechbivalentvaccine(ComirnatyOriginal/OmicronBA.1)wereapprovedbytheMHRAasboostervaccines.Bothbivalentvaccinesareactiveagainsttheoriginal(Wuhan)strainoftheSARS-CoV-2virusandtheOmicronBA.1variant.Theywerefoundtomeettherequiredstandardsofsafety,qualityandefficacy.COVID-19vaccineNovavax(Nuvaxovid)isalsobeingusedasaboosterdoseinthesmallproportionofpatientswhoareunabletoreceivemRNAvaccines.AspartoftheMHRA’sresponsibilitytoensurethatthebenefitsoftheCOVID-19vaccinesusedintheUKcontinuetooutweightherisks,theMHRAiscloselymonitoringthebivalentmRNAvaccinesandCOVID-19vaccineNovavaxusingtheproactivepharmacovigilancesurveillancestrategyinplacefortheinitialvaccinerollout.OurongoingreviewofsuspectedadverseeventsfollowingthelaunchoftheNationalAutumnboostercampaignhasnotrevealedanynewsafetyconcerns.Itshouldbenotedthatunlessotherwisespecified,thenumbersofADRreportsforthemRNACOVIDvaccinesincludesreportsforboththemono-andbivalentCOVID-19mRNAvaccines. ThemonovalentCOVID-19VaccinePfizer/BioNTechwasevaluatedinclinicaltrialsinvolvingmorethan44,000participants.Themostfrequentadversereactionsinthesetrialswerepainattheinjectionsite,fatigue,headache,myalgia(musclepains),chills,arthralgia(jointpains),andfever;thesewereeachreportedinmorethan1in10people.Thesereactionswereusuallymildormoderateinintensityandresolvedwithinafewdaysaftervaccination.Adversereactionswerereportedlessfrequentlyinolderadults(over55years)thaninyoungerpeople. TheCOVID-19VaccineAstraZenecawasevaluatedinclinicaltrialsinvolvingmorethan23,000participants.Themostfrequentlyreportedadversereactionsinthesetrialswereinjection-sitetenderness,injection-sitepain,headache,fatigue,myalgia,malaise,pyrexia(fever),chills,andarthralgia,andnausea;thesewereeachreportedinmorethan1in10people.Themajorityofadversereactionsweremildtomoderateinseverityandusuallyresolvedwithinafewdaysaftervaccination.Adversereactionsweregenerallymilderandreportedlessfrequentlyinolderadults(65yearsandolder)thaninyoungerpeople. ThemonovalentCOVID-19VaccineModernawasevaluatedinclinicaltrialsinvolvingmorethan30,000participants.Themostfrequentadversereactionsinthesetrialswerepainattheinjectionsite,fatigue,headache,myalgia(musclepains),arthralgia(jointpains),chills,nausea/vomiting,axillaryswelling/tenderness(swelling/tendernessofglandsinthearmpit),fever,injectionsiteswellingandredness;thesewereeachreportedinmorethan1in10people.Thesereactionswereusuallymildormoderateinintensityandresolvedwithinafewdaysaftervaccination.Adversereactionswerereportedlessfrequentlyinolderadults(over65years)thaninyoungerpeople. TheCOVID-19VaccineNovavaxwasevaluatedinclinicaltrialsinvolvingmorethan30,000participants.Themostfrequentlyreportedadversereactionsinthesetrialswereheadache,feelingsick(nausea)orgettingsick(vomiting),muscleache,jointpain,tendernessorpainwheretheinjectionisgiven,feelingverytired(fatigue)andgenerallyfeelingunwell;thesewereeachreportedinmorethan1in10people.Thesereactionswereusuallymildormoderateinintensityandresolvedwithinafewdaysaftervaccination.Adversereactionswerereportedlessfrequentlyinolderadults(over65years)thaninyoungerpeople. TheMHRAcontinuallymonitorssafetyduringwidespreaduseofavaccine.Wehaveinplaceaproactivestrategytodothis.Wealsoworkcloselywithourpublichealthpartnersinreviewingtheeffectivenessandimpactofthevaccinestoensurethebenefitscontinuetooutweighanypossiblesideeffects. Partofourmonitoringroleincludesreviewingreportsofsuspectedsideeffects.AnymemberofthepublicorhealthprofessionalcansubmitsuspectedsideeffectsthroughtheYellowCardscheme.ThenatureofYellowCardreportingmeansthatreportedeventsarenotalwaysprovensideeffects.Someeventsmayhavehappenedanyway,regardlessofvaccination.Thisisparticularlythecasewhenmillionsofpeoplearevaccinated,andespeciallywhenvaccinesarebeinggiventothemostelderlypeopleandpeoplewhohaveunderlyingillness. Asof28September2022,fortheUK,173,381YellowCardshavebeenreportedforthemonovalentandbivalentCOVID-19VaccinePfizer/BioNTech,246,393havebeenreportedfortheCOVID-19VaccineAstraZeneca,42,436forthemonovalentandbivalentCOVID-19VaccineModerna,14fortheCOVID-19VaccineNovavaxand1,848havebeenreportedwherethebrandofthevaccinewasnotspecified. ForthemonovalentandbivalentCOVID-19VaccinePfizer/BioNTech,COVID-19VaccineAstraZenecaandmonovalentandbivalentCOVID-19VaccineModernatheoverallreportingrateisaround2to5YellowCardsper1,000dosesadministered. Inthe28dayssincetheprevioussummaryfor24August2022wehavereceivedafurther480YellowCardsforthemonovalentandbivalentCOVID-19VaccinePfizer/BioNTech,210fortheCOVID-19VaccineAstraZeneca,1,860forthemonovalentandbivalentCOVID-19VaccineModerna,14fortheCOVID-19VaccineNovavaxand29wherethebrandwasnotspecified.TheincreaseinreportsforCOVID-19VaccinesModernaisduetothebivalentvaccineuseinthenationalautumnboostercampaign.Ourreviewtodateofsuspectedadverseeventssincethelaunchofthecampaignhasnotrevealedanynewsafetyconcerns. ItisimportanttonotethatYellowCarddatacannotbeusedtoderiveside-effectratesorcomparethesafetyprofileofCOVID-19vaccinesasmanyfactorscaninfluenceADRreporting.Additionally,itisimportanttoconsiderthataYellowCardreportcanincludereferencetomorethanonevaccineassociatedwithasuspectedreactionwheredifferentvaccineshavebeenusedasthirdorboosterdoses. ForallCOVID-19vaccines,theoverwhelmingmajorityofreportsrelatetoinjection-sitereactions(sorearmforexample)andgeneralisedsymptomssuchas‘flu-like’illness,headache,chills,fatigue(tiredness),nausea(feelingsick),fever,dizziness,weakness,achingmuscles,andrapidheartbeat.Generally,thesehappenshortlyafterthevaccinationandarenotassociatedwithmoreseriousorlastingillness. Thesetypesofreactionsreflectthenormalimmuneresponsetriggeredbythebodytothevaccines.Theyaretypicallyseenwithmosttypesofvaccineandtendtoresolvewithinadayortwo.Thenatureofreportedsuspectedsideeffectsisbroadlysimilaracrossagegroups,although,aswasseeninclinicaltrialsandasisusuallyseenwithothervaccines,theymaybereportedmorefrequentlyinyoungeradults. Anumberofdetailedassessmentsofsafetytopicshavebeenundertakenandwehaveupdatedouradviceonthesetopicsaccordingly.Overall,ouradviceremainsthatthebenefitsofthevaccinesoutweightherisksinthemajorityofpeople.FurthercommentsonuseinspecificpopulationsanddetailsonthespecificsafetytopicscanbefoundwithinSectiontitledAnalysisofdata. Conclusion VaccinesarethebestwaytoprotectpeoplefromCOVID-19andhavealreadysavedtensofthousandsoflives.Everyoneshouldcontinuetogettheirvaccinationwheninvitedtodosounlessspecificallyadvisedotherwise. Aswithallvaccinesandmedicines,thesafetyofCOVID-19vaccinesisbeingcontinuouslymonitored. ThebenefitsofthevaccinesinpreventingCOVID-19andseriouscomplicationsassociatedwithCOVID-19faroutweighanycurrentlyknownsideeffectsinthemajorityofpatients. Furtherinformationonthetypeofsuspectedadversereactions(ADRs)reportedforthemonovalentandbivalentCOVID-19VaccinePfizer/BioNTech,theCOVID-19VaccineAstraZeneca,themonovalentandbivalentCOVID-19VaccineModernaandCOVID-19VaccineNovavaxisprovidedinAnnex1.Itisimportanttoreadtheattachedguidancenotestoensureappropriateinterpretationofthedata. 1.Introduction TheMedicinesandHealthcareproductsRegulatoryAgency(MHRA)istheexecutiveAgencyoftheDepartmentofHealthandSocialCarethatactstoprotectandpromotepublichealthandpatientsafety,byensuringthatmedicinesandmedicaldevicesmeetappropriatestandardsofsafety,qualityandefficacy. TheMHRAoperatestheYellowCardschemeonbehalfoftheCommissiononHumanMedicines(CHM).Theschemecollectsandmonitorsinformationonsuspectedsafetyconcernsorincidentsinvolvingvaccines,medicines,medicaldevices,ande-cigarettes.Theschemereliesonvoluntaryreportingofsuspectedadverseincidentsbyhealthcareprofessionalsandmembersofthepublic(patients,users,orcarers).Thepurposeoftheschemeistoprovideanearlywarningthatthesafetyofaproductmayrequirefurtherinvestigation.FurtherinformationabouttheYellowCardscheme,includingitscontributiontoidentifyingsafetyissuescanbefoundontheYellowCardwebsite. TheMHRAisplayinganactiveroleinrespondingtothecoronaviruspandemic.InrelationtoCOVID-19vaccines,theMHRAhasauthorisedtheirsupplyfollowingarigorousreviewoftheirsafety,qualityandefficacy;however,aspartofitsstatutoryfunctions,theMHRAisresponsibleformonitoringallvaccinesonanongoingbasistoensuretheirbenefitscontinuetooutweighanyrisks.ThisisarequirementforallauthorisedmedicinesandvaccinesintheUK.Thismonitoringstrategyiscontinuous,proactiveandbasedonawiderangeofinformationsources,withadedicatedteamofscientistsreviewinginformationdailytolookforsafetyissuesorunexpected,rareevents. ThisreportsummarisesinformationreceivedviatheYellowCardschemeandispublishedregularlytoincludeothersafetyinvestigationscarriedoutbytheMHRAundertheCOVID-19VaccineSurveillanceStrategy. WhatisaYellowCard? TheYellowCardschemeisamechanismbywhichanybodycanvoluntarilyreportanysuspectedadversereactionsorsideeffectstothevaccine.ItisveryimportanttonotethataYellowCardreportdoesnotnecessarilymeanthevaccinecausedthatreactionorevent.Weaskforanysuspicionstobereported,evenifthereporterisn’tsureifitwascausedbythevaccine.Reportstotheschemeareknownassuspectedadversedrugreactions(ADRs). ManysuspectedADRsreportedonaYellowCarddonothaveanyrelationtothevaccineormedicineanditisoftencoincidentalthatsymptomsoccurredaroundthesametimeasvaccination.Thereportsarecontinuallyreviewedtodetectpossiblenewsideeffectsthatmayrequireregulatoryaction,andtodifferentiatethesefromthingsthatwouldhavehappenedregardlessofthevaccineormedicinebeingadministered,forinstanceduetounderlyingorundiagnosedillness. ItisthereforeimportantthatthesuspectedADRsdescribedinthisreportarenotinterpretedasbeingprovensideeffectsofCOVID-19vaccines.AlistofthepossiblesideeffectsofCOVID-19vaccinesareprovidedintheproductinformationdocumentforhealthcareprofessionalsandtheUKrecipientinformation. COVID-19VaccinePfizer/BioNTech. COVID-19Pfizer/BioNTechbivalent(BA.1) COVID-19VaccineAstraZeneca COVID-19VaccineModerna COVID-19VaccineModernabivalent(BA.1) COVID-19VaccineNovavax ThesecanalsobefoundontheCoronavirusYellowCardreportingsite. ThispublicsummaryprovidesanoverviewofallUKsuspectedADRsassociatedwiththeCOVID-19vaccines(themonovalentandbivalentCOVID-19VaccinePfizer/BioNTech,COVID-19VaccineAstraZeneca,monovalentandbivalentCOVID-19VaccineModernaandCOVID-19VaccineNovavax),andtheMHRA’sanalysisofthedata,between9December2020and28September2022(inclusive).AglossaryofkeytermsisprovidedinAnnex2. Ifidentified,informationonnewandemergingsafetyconcernswillbeprovidedinfutureeditionsofthisreporttogetherwithdetailsofanyresultingregulatoryactionorchangestoadviceonuseofthevaccines. 2.YellowCardreports Vaccinedosesadministered DatafromtheUKPublicHealthagenciesshowthatatleast53,832,410peoplehavereceivedtheirfirstvaccinationintheUKby28September2022,with50,800,539seconddosesadministered[footnote1].Everyoneaged5andoveriseligibletoreceiveafirstandseconddoseoftheCOVID-19vaccine.Peopleaged16andover,andsomechildrenaged12to15,arealsoeligibletoreceiveaboosterdose.Peopleaged5andoverwhohadaseverelyweakenedimmunesystemwhentheyhadtheirfirst2doses,willbeofferedathirddosebeforeanyboosterdoses.Peopleaged50yearsandolder,residentsincarehomesforolderpeople,thoseaged5yearsandoverinaclinicalriskgroupandhealthandsocialcarestaffwillbeofferedanautumnboosterofCOVID-19vaccine.Atpresent,thevaccinationuptakedataonAutumn(2022)boostersisnotavailable. Table1:NumberofpeoplewhohavereceivedthefirstdoseofavaccineforCOVID-19intheUKbetween8December2020andendof28September2022. Country Numberofdoses England 45,265,434 Wales 2,588,296 NorthernIreland 1,429,124 Scotland 4,549,556 Table2:NumberofpeoplewhohavereceivedtheseconddoseofavaccineforCOVID-19intheUKbetween8December2020andendof28September2022. Country Numberofdoses England 42,700,117 Wales 2,457,975 NorthernIreland 1,356,501 Scotland 4,285,946 Asof28September2022,anestimated27.2millionfirstdosesoftheCOVID-19VaccinePfizer/BioNTechand24.9millionfirstdosesoftheCOVID-19VaccineAstraZenecahadbeenadministered,andaround25.0and24.2millionseconddoseseachoftheCOVID-19VaccinePfizer/BioNTechandCOVID-19VaccineAstraZenecarespectively.Anapproximate1.7millionfirstdosesandapproximately1.6millionseconddosesoftheCOVID-19VaccineModernahavealsonowbeenadministered.Anestimated30.9millionthirdorboosterdosesofCOVID-19VaccinePfizer/BioNTech,59,000thirdorboosterdosesofCOVID-19VaccineAstraZenecaand9.4milliondosesofCOVID-19VaccineModernahavebeengiven.Thesefiguresarebasedonnumbersofexposuresreportedindividuallybytheindividualnationswhichareextrapolatedtoproduceanestimateofthetotalnumberofdoses.ThefiguresforboosterdosesdonotincludeanyAutumn2022boosters.Dataarenotalwaysreportedweeklyandcanbeupdatedforhistoricaldateswhenvaccinationsarerecordedontherelevantsystem.Therefore,dataforthismaybeincompleteandtheresultingestimatesareapproximate. Theestimatednumberofdosesadministereddiffersfromtheestimatednumberofpeoplevaccinatedduetothedifferentdatasourcesused. Asof28September2022,anestimated40,453,549peoplehadreceivedtheirboosteroradditionalvaccinationintheUK.Peopleaged16andover,andsomechildrenaged12to15,areeligibletoreceiveaboosterdose.ThesedatadonotincludeanydosesadministeredaspartoftheAutumn(2022)boostercampaign. Table3:NumberofpeoplewhohavereceivedthethirdorboosterdoseofavaccineforCOVID-19intheUKbetween8December2020andendof28September2022. Country Numberofdoses England 33,587,779 Wales 2,072,464 NorthernIreland 1,198,471 Scotland 3,594,835 YellowCardreportingtrends AreportofasuspectedADRtotheYellowCardschemedoesnotnecessarilymeanthatitwascausedbythevaccine,onlythatthereporterhasasuspicionitmayhavebeen.Underlyingorpreviouslyundiagnosedillnessunrelatedtovaccinationcanalsobefactorsinsuchreports.Therelativenumberandnatureofreportsshouldthereforenotbeusedtocomparethesafetyofthedifferentvaccines. TheMHRAmayalsoreferto‘cases’asopposedto‘reports’withintheanalysisoftheYellowCarddata;thesetypicallyrefertoADRreportsthathaveundergonemedicalassessmentandareconsideredtomeetcertaincriteriafordiagnosisofthereportedeventandhaveatleastaplausibleassociationwiththevaccine.Allcasesandreportsarekeptundercontinualreviewinordertoidentifypossiblenewrisks. Uptoandincluding28September2022,theMHRAreceivedandanalysed173,381UKYellowCardsfrompeoplewhohavereceivedthemonovalentorbivalentCOVID-19VaccinePfizer/BioNTech.Thesereportsincludeatotalof499,965suspectedreactions(i.e.,asinglereportmaycontainmorethanonesymptom).Thefirstreportwasreceivedon9December2020. Uptoandincluding28September2022,theMHRAreceivedandanalysedatotalof246,393UKreportsofsuspectedADRstotheCOVID-19VaccineAstraZeneca.Thesereportsincludeatotalof873,051suspectedreactions(asinglereportmaycontainmorethanonesymptom).Thefirstreportwasreceivedon4January2021. Uptoandincluding28September2022,theMHRAreceivedandanalysedatotalof42,436UKreportsofsuspectedADRstothemonovalentandbivalentCOVID-19VaccineModerna.Theseincludeatotal138,950suspectedreactions(asinglereportmaycontainmorethanonesymptom).Thefirstreportwasreceivedon7April2021. Uptoandincluding28September2022,theMHRAreceivedandanalysedatotalof14UKreportsofsuspectedADRstotheCOVID-19VaccineNovavax.Theseincludeatotalof28suspectedreactions(asinglereportmaycontainmorethanonesymptom).Thefirstreportwasreceivedon21November2021. Additionally,uptoandincluding28September2022,theMHRAreceived1,848YellowCardreportswherethebrandofvaccinewasnotspecifiedbythereporter. Inthe28dayssincetheprevioussummaryfor24August2022wehavereceivedafurther480YellowCardsforthemonovalentandbivalentCOVID-19VaccinePfizer/BioNTech,210fortheCOVID-19VaccineAstraZeneca,1,860forthemonovalentandbivalentCOVID-19VaccineModernaand29wherethebrandwasnotspecified.PleasenotethataYellowCardreportcanincludemorethanonevaccinesuspectedtohavecausedareactionwheredifferentvaccineshavebeenusedasthirdorboosterdoses. ItisimportanttonotethatYellowCarddatacannotbeusedtoderivesideeffectratesorcomparethesafetyprofileofCOVID-19vaccinesasmanyfactorscaninfluenceADRreporting. Table4:NumberofsuspectedADRreportsreceivedintheUKuptoandincluding28September2022. Numberofreports Country COVID-19Pfizer/BioNTechVaccine(monovalentandbivalent) COVID-19VaccineAstraZeneca COVID-19VaccineModerna(monovalentandbivalent) Brandunspecified England 134,957 202,748 33,881 1,070 Wales 8,417 10,912 2,508 102 NorthernIreland 3,046 3,014 180 22 Scotland 13,019 17,576 3,567 187 ThefiguresinTable4arebaseduponthepostcodeprovidedbythereporter.Thesumsofthereportsinthetablewillnotequalthetotalreportsreceivedforthevaccinesasapostcodemaynothavealwaysbeenprovidedormayhavebeenenteredincorrectly.Itisimportanttonotethatthenumberofreportsreceivedforeachcountrydoesnotdirectlyequatetothenumberofpeoplewhomayhaveexperiencedadversereactionsandthereforecannotbeusedtodeterminetheincidenceofreactions.ADRreportingratesareinfluencedbymanyaspects,includingtheextentofuse. WeareworkingwithpublichealthbodiesandencouragingallhealthcareprofessionalsandpatientsaliketoreportanysuspectedADRstotheYellowCardscheme.Asexpected,reportsgraduallyincreaseinlinewithanincreaseindosesadministered. Theoverallreportingrateforfirst,secondandthirdorboosterdosesisintheorderof2to5YellowCardsper1,000dosesadministeredforthemonovalentandbivalentCOVID-19VaccinePfizer/BioNTech,COVID-19VaccineAstraZenecaandmonovalentandbivalentCOVID-19VaccineModerna.Itisknownfromtheclinicaltrialsthatthemorecommonsideeffectsforallvaccinescanoccuratarateofmorethanonein10doses(forexample,localreactionsorsymptomsresemblingtransientflu-likesymptoms). 3.AnalysisofData OneoftheMHRA’smainrolesistocontinuallymonitorthesafetyofmedicinesandvaccinesduringwidespreaduse,andwehaveinplaceaproactivestrategytodothisforCOVID-19vaccines.Wealsoworkcloselywithourpublichealthpartnersinreviewingtheeffectivenessandimpactthatthevaccinesarehavingtoensurebenefitscontinuetooutweighanypossiblesideeffects.Inaddition,weworkwithourinternationalcounterpartstogatherinformationonthesafetyofvaccinesinothercountries. GiventhehugescaleoftheCOVID-19immunisationprogramme,withmanymillionsofdosesofvaccinesadministeredoverarelativelyshorttimeperiod,vigilanceneedstobecontinuous,proactiveandasnearreal-timeasispossible.Theimportanceofthisistwo-fold.First,weneedtorapidlydetect,confirm,andquantifyanynewrisksandweightheseagainsttheexpectedbenefits.Wecanthentakeanynecessaryactiontominimiseriskstoindividuals. Secondly,weneedtoveryquicklyestablishifanyseriousmedicaleventswhicharetemporallyrelatedtovaccinationaremerelyacoincidentalassociation.Theseassociationsarelikelywhilewearestillinthemidstofamajornationalvaccinationprogramme,andbecausemanyofthemillionsofpeopleofferedthevaccineintheearlyphaseofavaccinationcampaignwereelderlyand/orhadunderlyingmedicalconditions,whichincreasesthelikelihoodofunrelatedillnessesoccurringsoonaftervaccination.Asmentionedabove,thenatureofYellowCardreportingmeansthatreportedeventsarenotalwaysprovenadversereactions,andsomemayhavehappenedregardlessofvaccination. YellowCardreportsofsuspectedADRsareevaluated,togetherwithadditionalsourcesofevidence,byateamofsafetyexpertstoidentifyanynewsafetyissuesorsideeffects.Weapplystatisticaltechniquesthatcantellusifweareseeingmoreeventsthanwewouldexpecttosee,basedonwhatisknownaboutbackgroundratesofillnessintheabsenceofvaccination.Thisaimstoaccountforfactorssuchascoincidentalillness.Wealsolookattheclinicalcharacteristicstoseeifnewpatternsofillnessareemergingthatcouldindicateanewsafetyconcern. Wesupplementthisformofsafetymonitoringwithotherepidemiologystudiesincludinganalysisofdataonnationalvaccineusage,anonymisedGP-basedelectronichealthcarerecordsandotherhealthcaredatatoproactivelymonitorsafety.Wealsotakeintoaccounttheinternationalexperiencebasedondatafromothercountriesusingthesamevaccines.ThesecombinedsafetydataenablestheMHRAtodetectsideeffectsorsafetyissuesassociatedwithCOVID-19vaccines.Aswellasconfirmingnewrisks,anequallyimportantobjectiveofmonitoringwillbetoquicklyruleoutrisks–inotherwordstoconfirmthatthevaccineisnotresponsibleforasuspectedsideeffectandtoprovidereassuranceonitssafety. Overallsafety Aswithanyvaccine,COVID-19vaccineswillcausesideeffectsinsomepeople.ThetotalnumberandthenatureofthemajorityofYellowCardsreportsreceivedsofarisnotunusualforanewvaccineforwhichmembersofthepublicandhealthcareprofessionalsareencouragedtoreportanysuspectedadversereaction. Ashighlightedabove,itisknownfromtheclinicaltrialsthatthemostcommonsideeffectsforallvaccinescanoccuratarateofmorethanoneper10doses(suchaslocalreactions,symptomsresemblingtransientflu-likesymptoms).Overall,YellowCardreportingisthereforelowerthanthereportingrateofpossiblesideeffectsfromtheclinicaltrials,althoughwegenerallydonotexpectallsuspectedsideeffectstobereportedonYellowCards.TheprimarypurposeofYellowCardreportingistodetectnewsafetyconcerns. ForalloftheoriginalCOVID-19vaccines,detailedreviewofallreportshasfoundthattheoverwhelmingmajorityrelatetoinjection-sitereactions(sorearmforexample)andgeneralisedsymptomssuchasa‘flu-like’illness,headache,chills,fatigue(tiredness),nausea(feelingsick),fever,dizziness,weakness,achingmuscles,andrapidheartbeat.Generally,thesehappenshortlyafterthevaccinationandarenotassociatedwithmoreseriousorlastingillness. Thesetypesofreactionreflecttheacuteimmuneresponsetriggeredbythebodytothevaccines,aretypicallyseenwithmosttypesofvaccineandtendtoresolvewithinadayortwo.ThenatureofreportedsuspectedADRsacrossallagesisbroadlysimilar,although,asseenintheclinicaltrialsandasisusuallyseenwithothervaccines,theymaybereportedmorefrequentlyinyoungeradults. AswereceivemorereportsofthesetypesofreactionswithmoreexposuretotheCOVID-19vaccines,wehavebuiltapictureofhowindividualsareexperiencingthemandthedifferentwaysthatsideeffectsmaypresentinpeople.Somepeoplehavereportedasuddenfeelingofcoldwithshivering/shakingaccompaniedbyariseintemperature,oftenwithsweating,headache(includingmigraine-likeheadaches),nausea,muscleachesandfeelingunwell,startingwithinadayofhavingthevaccine.Similartotheflulikeillnessreportedinclinicaltrials,theseeffectsmaylastadayortwo. ItisimportanttonotethatitispossibletohavecaughtCOVID-19andnotrealiseuntilaftervaccination.IfotherCOVIDsymptomsareexperiencedorfeverishighandlastslongerthantwoorthreedays,vaccinerecipientsshouldstayathomeandarrangetohaveatest. Anumberofdetailedassessmentsofsafetytopicshavebeenundertakenandwehaveupdatedouradviceonthesetopicsaccordingly.Overall,ouradviceremainsthatthebenefitsofthevaccinesoutweightherisksinthemajorityofpeople.Furthercommentsonuseinspecificpopulationsanddetailsonthefollowingsafetytopicscanbefoundbelow. Inadditiontothespecificsafetytopicssummarisedinthisreport,arangeofotherisolatedeventsorseriesofreportsofnon-fatal,serioussuspectedADRshavebeenreported.Theseallremainundercontinualreview,includingthoroughanalysisofexpectedratesintheabsenceofvaccine.Therearecurrentlynoindicationsofspecificpatternsorratesofreportingthatwouldsuggestthevaccinehasplayedarole. Commentsonsafetyinspecificpopulations SafetyofCOVID-19vaccinesinpregnancy TheMHRAcloselymonitorsthesafetyofCOVID-19vaccineexposuresinpregnancy,includingpublishedinformationaswellasYellowCardreportsforCOVID-19vaccinesusedinpregnancy.ThesereportshavebeenreviewedbytheindependentexpertsoftheCHM’sCOVID-19VaccinesBenefitRiskExpertWorkingGroupandbytheMedicinesforWomen’sHealthExpertAdvisoryGroup(MWHEAG). PregnantwomenhavethesameriskofgettingCOVID-19asnon-pregnantwomen,buttheymaybeatanincreasedriskofbecomingseverelyill,particularlyiftheygetinfectedinthethirdtrimesteroriftheyalsohaveunderlyingmedicalproblems,comparedtonon-pregnantwomen.ThecurrentadviceoftheJointCommitteeonVaccinationandImmunisation(JCVI)isthattheCOVID-19vaccines,includingboosterdoses,shouldbeofferedtothosewhoarepregnantasaclinicalriskgroupintheCOVID-19vaccinationprogrammeandcanbegivenatanystageinpregnancy. ThenumberofYellowCardreportsforpregnantwomenarelowinrelationtothenumberofpregnantwomenwhohavereceivedCOVID-19vaccinestodate(about135,000womeninEnglandhavegivenbirthuptoendofMay2022[footnote2]afterreceivingatleast1doseofCOVID-19vaccineduringorshortlybeforepregnancyandabout47,000womeninScotlandandWaleshavereceivedatleast1dosewhilstpregnantuptoendJuly2022).Pregnantwomenhavereportedsimilarsuspectedreactionstothevaccinesaspeoplewhoarenotpregnant.ReportsofmiscarriageandstillbirtharealsolowincomparisontohowcommonlytheseeventsoccurredintheUKoutsideofthepandemic.Afewreportsofcommonlyoccurringcongenitalanomaliesandobstetriceventshavealsobeenreceived.ThereisnopatternfromthereportstosuggestthatanyoftheCOVID-19vaccinesusedintheUK,oranyreactionstothesevaccines,increasetheriskofmiscarriage,stillbirths,congenitalanomaliesorbirthcomplications. Sadly,miscarriageisestimatedtooccurinabout20to25in100pregnanciesintheUKandmostoccurinthefirst12to13weeksofpregnancy(thefirsttrimester).PublishedstudiesfromtheUSA[footnote3]andNorway[footnote4]havecomparedmiscarriageratesforvaccinatedandunvaccinatedwomenwhowerepregnantoverthesametimeperiods.Thestudiesincludeddatafromalargenumberofwomen(morethan15,000)whoreceivedthemonovalentCOVID-19VaccinePfizer/BioNTechormonovalentCOVID-19VaccineModerna.Bothstudiesfoundthattheoccurrenceofmiscarriagewasequallylikelyamongstunvaccinatedwomenasamongstwomenatthesamestageofpregnancywhowerevaccinatedintheprevious3to5weeks.RecentevidencefromtheCOVID-19inPregnancyScotland(COPS)study[footnote5]comparedratesofmiscarriageamongstvaccinatedandunvaccinatedwomeninScotland.ThestudyfoundnodifferencesinratesofmiscarriageorectopicpregnancyamongstwomenvaccinatedwithmonovalentCOVID-19VaccinePfizer/BioNTech,monovalentCOVID-19VaccineModernaorCOVID-19VaccineAstraZeneca,comparedtoratesforwomenofthesameageandgeneralhealthstatuswhowereeitherpregnantatasimilartimeofyearpriortothepandemicorwhobecamepregnantataroundthesametime(duringthepandemic)andwereunvaccinated.ThesestudiesprovidestrongevidencefornoincreasedriskofmiscarriageinassociationwiththemRNAvaccinesincurrentuse. Evidenceforpregnancyoutcomesotherthanmiscarriageisaccumulatingasmorepregnanciesreachfullterm.Currentlyavailableevidencedoesnotsuggestanyincreasedrisksofpregnancycomplications,stillbirths,pretermbirthsoradverseneonataloutcomesfollowingvaccinationinlaterpregnancy. Stillbirthsaresadlyestimatedtooccurinabout1in200pregnanciesintheUK.InformationfromsurveillancebyUKHSA(formerlyPublicHealthEngland)hasfoundsimilarratesofstillbirthamongst(morethan125,000)womenwhowerevaccinatedbeforeorduringpregnancyandthosewhogavebirthoverthesameperiodandwereunvaccinated.Likewise,surveillancebyPublicHealthScotland[footnote6]andtheCOPSstudy[footnote7]hasfoundsimilarratesofperinatalmortality(includingstillbirths)amongst(morethan15,700)womenwhowerevaccinatedduringpregnancyandthosewhogavebirthoverthesameperiodandwhowereunvaccinatedandnotinfectedwithCOVID-19. AdditionalevidenceonthesafetyofmonovalentCOVID-19VaccinePfizer/BioNTechexposuresinearlypregnancyisavailablefromapublishedstudyfromIsrael[footnote8].Thisstudylookedatlivebirthoutcomesformorethan2,000womenwhowerevaccinatedintheirfirsttrimestercomparedtomorethan3,500unvaccinatedwomenwhobecamepregnantaroundthesametime.Thestudyfoundnodifferencesbetweenvaccinatedandunvaccinatedwomeninratesofpre-termbirths,neonatalhospitalisationormortality,orbabiesbornwithbirthdefects.ThisstudyprovidesfurtherevidencefornoincreasedriskofbirthdefectsfollowingmonovalentCOVID-19VaccinePfizer/BioNTech. Although,likemostvaccinesandmedicines,clinicaltrialsofCOVID-19vaccinesinpregnantwomenwerenotcarriedoutpriortouseofthevaccinesinthegeneralpopulation,thereisnowgrowingevidencefromclinicalusewhichprovidesreassuranceonthesafetyofthevaccinesinpregnancy.Thisaddstotheevidencefromnon-clinicalstudiesoftheCOVID-19vaccineswhichhavenotraisedanyconcernsaboutsafetyinpregnancy.TheCOVID-19vaccinesdonotcontainorganismsthatcanmultiplyinthebody,sotheycannotinfectanunbornbabyinthewomb.TheproductinformationforCOVID-19VaccinePfizer/BioNTechandCOVID-19VaccineModernahasbeenupdatedtoreflectthenewsafetydataandthatthevaccinescanbeusedduringpregnancy. TheproductinformationformonovalentandbivalentCOVID-19VaccinePfizer/BioNTechandCOVID-19VaccineModernareflectsthattheavailabledataarereassuringonsafetyandthatthevaccinescanbeusedduringpregnancy. TheMHRAwillcontinuetocloselymonitorsafetydatafollowinguseoftheCOVID-19vaccinesinpregnancy,includingthroughevaluationofelectronichealthcarerecorddata. SafetyofCOVID-19vaccinesinthosebreastfeeding TheMHRAcloselymonitorsthesafetyofCOVID-19vaccinesduringbreastfeeding,includingevaluationofYellowCardreportsforCOVID-19vaccinesfrombreastfeedingwomen.ThesereportshavebeenreviewedbytheindependentexpertsoftheCHM’sCOVID-19VaccinesBenefitRiskExpertWorkingGroup,bypaediatricandbreastfeedingexperts. ThereisnocurrentevidencethatCOVID-19vaccinationwhilebreastfeedingcausesanyharmtobreastfedchildrenoraffectstheabilitytobreastfeed. COVID-19vaccinesdonotcontainlivecomponentsandthereisnoknownriskassociatedwithbeinggivenanon-livevaccinewhilstbreastfeeding.ThecurrentadviceoftheJointCommitteeonVaccinationandImmunisation(JCVI)isthatbreastfeedingparentsmaybeofferedanysuitableCOVID-19vaccinedependingontheirage. Wehavereceivedabout4,000YellowCardreportsfromwomenbreastfeedingatthetimeofvaccination.Mostofthesewomenreportedonlysuspectedreactionsinthemselveswhichweresimilartoreportsforthegeneralpopulation,withnoeffectsreportedontheirmilksupplyorintheirbreastfedchildren. Asmallnumberofwomenhavereporteddecreasesintheirmilksupply,mostofwhichweretransient,orpossiblereactionsintheirbreastfedchild.Anumberoffactorscanaffectmilksupplyandinfantbehaviour,includinggeneralmaternalhealth,amountofsleep,andanxiety.Thesymptomsreportedforthechildren(hightemperature,rash,diarrhoea,vomitingandgeneralirritability)arecommonconditionsinchildrenofthisage,sosomeoftheeffectsreportedmayhaveoccurredbycoincidence. TheproductinformationformonovalentandbivalentCOVID-19VaccinePfizer/BioNTechandCOVID-19VaccineModernareflectsthattheavailabledataarereassuringonsafetyandthatthevaccinescanbeusedduringbreastfeeding. Asmallnumberofwomenmayexperienceareductionintheirbreastmilkproductionanditmaybehelpfulforbreastfeedingwomentoknowhowtomaintaintheirbreastmilksupply,particularlyiftheyarefeelingunwell.TheNHSwebsitehasagoodresourceforthis. Suspectedsideeffectsreportedinindividualsunder18yearsold TheMHRAcloselymonitorsthesafetyofCOVID-19vaccineexposuresinindividualsunder18yearsold,includingYellowCardreportsforCOVID-19vaccinesusedinthisagegroup. Uptothe28September2022therehavebeenanestimated4.2millionfirstdoses,2.9millionseconddoses,and0.2millionadditionalorboosterdosesofthemonovalentCOVID-19VaccinePfizer/BioNTechgiventounder18s;approximately11,500firstdosesand8,700seconddosesoftheCOVID-19VaccineAstraZenecagiventothispopulation;and2,200firstdosesand2,100seconddoses,and2,400additionalorboosterdosesofthemonovalentCOVID-19VaccineModernagiventoindividualsunder18.TherehasbeenextremelylimiteduseofCOVID-19VaccineAstraZenecaasboostersinthoseunder18years. TheMHRAhasreceived4,121UKreportsofsuspectedADRsfortheCOVID-19VaccinePfizer/BioNTechinwhichtheindividualwasreportedtobeunder18yearsold,266reportsfortheCOVID-19VaccineAstraZeneca,37fortheCOVID-19VaccineModernaand35wherethebrandofvaccinewasunspecified. ForthemonovalentCOVID-19VaccinePfizer/BioNTech,whichiscurrentlythepreferredCOVID-19vaccinefortheunder18sagegroupintheUKvaccinationprogrammeforprimaryimmunisation,theexperiencereportedinunder18sissimilartothatidentifiedinthegeneralpopulation.Areviewofthesereportsdoesnotraiseanyadditionalsafetytopicsspecifictothisagegroup.Thisincludesthedifferentagesubgroups(5-11,12-15and16-17yearolds).Reportingratesfor5-11yearolds,12-15yearoldsand16-17yearoldsarealllessthan1per1,000doses.ThisisapproximatelyhalfthereportingratefortheCOVID-19VaccinePfizer/BioNTechforthose18yearsandover,whichisaround2per1,000doses. AsCOVID-19VaccineAstraZenecaandmonovalentCOVID-19VaccineModernaarenotthepreferredvaccinesinunder18sthereisinsufficientexperienceinthisagegrouptobeabletomakesimilarestimates. Therehasbeenasmallnumberofreportsformyocarditisandpericarditis(inflammationoftheheart)inindividualsunder18yearsbothintheUKandinternationally.ThisisarecognisedpotentialriskwiththemonovalentandbivalentCOVID-19VaccinePfizer/BioNTechandmonovalentandbivalentCOVID-19VaccineModernaandtheMHRAcontinuestocloselymonitortheseevents.Furtherinformationsurroundingtheseveryrarereportsofmyocarditisandpericarditiswithinthispopulationcanbefoundwithinthespecificsectiononthissafetytopiclaterinthesummary.WewillcontinuetocloselymonitorthesafetyoftheCOVID-19vaccinesinthoseunder18yearsold. Suspectedsideeffectsreportedinindividualsreceivingaboostervaccination Safetymonitoringplanshavebeenagreedtoensureactioncanbetakenonanyemergingsafetyconcernsfromsupplementaryorboosterdoses. Asof28September2022,anestimated40.5millionCOVID-19thirddosesandboosterdoseshavebeenadministeredintheUK.ThemonovalentCOVID-19VaccinePfizer/BioNTechandmonovalentCOVID-19VaccineModernawerethepreferredvaccinesintheUKboosterprogrammepriortoAutumn2022andmadeupthevastmajorityofdosesadministered.TheseboosterfiguresdonotyetincludedatafromtheAutumn(2022)boosterprogramme. Upto28September2022theMHRAhasreceived32,299UKreportsofsuspectedADRswherethemonovalentandbivalentCOVID-19VaccinePfizer/BioNTechwasreportedtobetheboosterdose,615reportswheretheCOVID-19VaccineAstraZenecawasreportedtobetheboosterdose,19,479reportswherethemonovalentandbivalentCOVID-19VaccineModernawasreportedtobetheboosterdoseand222reportswherethebrandofvaccineboosterwasunspecified. ForthemonovalentandbivalentCOVID-19VaccinePfizer/BioNTechcombinedthisrepresentsareportingrateof1reportper1,000thirdorboosterdosesandmonovalentandbivalentfortheCOVID-19VaccineModernacombinedthereisanestimated2reportsper1,000thirdorboosterdoses.BothofthesearelowerthanthereportingrateforallCOVID-19vaccinedosescombined,whichisbetween2-5reportsper1,000doses.FortheCOVID-19VaccineAstraZenecatherehasbeenverylimitednumberofboosterdosesintheUKandaverysmallnumberofreports.ThereisinsufficientexperiencewithCOVID-19VaccineAstraZenecaasaboostervaccinetobeabletomakesimilarestimatesofreportingrates. ThenatureofeventsreportedwiththirdandboosterdosesuptoAutumn2022issimilartothatreportedforthefirsttwodosesoftheCOVID-19vaccines,andthevastmajorityofreportsrelatetoexpectedreactogenicityevents.Reviewofthirdandboosterdosereportsdoesnotraiseanynewsafetyconcerns.AspartoftheMHRA’sboostersafetymonitoringstrategy,reportsofsuspectedadverseeventsfollowingCOVID-19boostersgivenatthesametimeasseasonalfluvaccineshavebeencloselymonitored,andnonewsafetyconcernshavebeenidentifiedinthisdataeither. Therehavebeenasmallnumberofreportsofsuspectedmyocarditisandpericarditis(inflammationoftheheart)followingboosterdoseswithmonovalentPfizer/BioNTechandModernaCOVID-19vaccines.ThisisarecognisedpotentialriskwiththemRNACOVID-19vaccinesandtheMHRAiscloselymonitoringtheseevents.Thereportsafterboosterdosesareextremelyrareandthereisnoindicationthattheseeventsaremoreseriousafterboosters.Furtherinformationsurroundingtheseveryrarereportsofsuspectedmyocarditisandpericarditiscanbefoundwithinthespecificsectiononthissafetytopiclaterinthesummary. FortheAutumn2022COVID-19vaccinationboostercampaign,thebivalentCOVID-19Pfizer/BioNTechboostervaccine(ComirnatyOriginal/OmicronBA.1)andthebivalentCOVID-19Modernaboostervaccine(SpikevaxbivalentOriginal/Omicron)aremainlybeingused.TheoriginalmonovalentPfizer-BioNTechvaccineisrecommendedforeligiblepersonsaged5-11yearswhiletheCOVID-19vaccineNovavax(Nuvaxovid)isrecommendedforthosewhocannotreceiveanmRNAvaccine.ReviewoftheYellowCarddatareceivedforthesevaccinessofardoesnotindicateanynewsafetyconcerns.WewillcontinuetocloselymonitorthesafetyofalldosesoftheCOVID-19vaccines. Commentsonspecificsafetytopics Thefollowingreportsreflectdataupto28September2022.Theglossaryprovidesanexplanationoftheclinicaltermsused. Anaphylaxis(severeallergicreactions) On9December2020,theMHRAissuedpreliminaryguidanceonsevereallergicreactionsafteradministrationofthemonovalentCOVID-19VaccinePfizer/BioNTechduetoearlyreportsofanaphylaxis.Followingfurtherdetailedreview,thisadvicewasamendedon30December2020tothecurrentadvice.Theadviceisthatpeoplewithaprevioushistoryofsevereallergicreactionstoanyingredientsofthevaccineshouldnotreceiveit.On14December2021itwasannouncedthatfollowingaCHMreviewoftheYellowCarddataonanaphylaxisaftertheprimarycourseandboosterstherewouldbeatemporarysuspensionofthepostvaccination15-minutemonitoringtimeforthemajorityofindividuals.ThishelpedtoacceleratethepublichealthresponsetotheOmicronvariant.On5May2022the15-minuteobservationperiodaftervaccinationwiththemonovalentCOVID-19Pfizer/BioNTechorModernavaccineswasremovedforindividualsaged12yearsandoverandwhohavenohistoryofasevereallergicreaction(asoutlinedintheGreenBookadvice)[footnote8].ThisfollowedcarefulreviewofthesafetydatabyMHRAandadvicefromtheCHM.Atemporarysuspensionofthe15-minuteobservationperiodforchildrenaged5-11yearsremainsinplaceandthiswillbereviewedonaregularbasis.The15-minuteobservationperiodwillremaininplaceforthesmallnumberofpeoplewhomayhavepreviouslysufferedanaphylaxisorotherallergicreactionstoafood,insectstingandmostmedicinesorvaccines.Thetemporarysuspensionofthe15-minuteobservationtimeforchildrenaged5-11yearsisunderregularreviewbytheCHMandtheCOVID-19VaccinesBenefitRiskExpertWorkingGroup. WidespreaduseofthevaccinesuggeststhatsevereallergicreactionstothemonovalentCOVID-19VaccinePfizer/BioNTechandmonovalentCOVID-19VaccineModernaareveryrare.Anaphylaxiscanalsobeaveryraresideeffectassociatedwithmostothervaccines. TheMHRAcontinuestomonitorreportsofsevereallergicreactionswiththemonovalentandbivalentCOVID-19VaccinePfizer/BioNTechandhasreceived669UKspontaneousadversereactionsassociatedwithanaphylaxisoranaphylactoidreactions.SevereallergicreactionstothemonovalentCOVID-19VaccinePfizer/BioNTechremainveryrare.TheMHRA’sguidanceremainsthatthosewithaprevioushistoryofallergicreactionstotheingredientsofthevaccineshouldnotreceiveit. TheMHRAiscloselymonitoringreportsofanaphylaxiswiththemonovalentandbivalentCOVID-19VaccineModernaandhasreceived99reportsofanaphylaxisinassociationwiththevaccines.AnaphylaxisisapotentialsideeffectoftheModernavaccines,anditisrecommendedthatthosewithknownhypersensitivitytotheingredientsofthesevaccinesshouldnotreceiveit. PriortoAutumn2022themonovalentCOVID-19VaccinePfizer/BioNTechandmonovalentCOVID-19VaccineModernawerethepreferredvaccinesintheUKboosterprogramme.FromSeptember2022,thebivalentoriginal/OmicronBA.1vaccinesfromPfizer/BioNTechandModernaarethemainproductsbeingusedintheAutumn2022boosterprogram.Reportsofanaphylaxisoranaphylactoidreactionsremainveryrareafterboosterdoses.Analysisofthedatashowsthattheseeventsareabout5timeslowerafterboosterdosescomparedtothefirstdose. TheMHRAalsocloselymonitorsreportsofanaphylaxisoranaphylactoidreactionswiththeCOVID-19VaccineAstraZenecaandhasreceived888UKspontaneousadversereactionsassociatedwithanaphylaxisoranaphylactoidreactionsreportedandsuchreportsareveryrare.TheproductinformationreflectsthefactthatreportsofanaphylaxishavebeenreceivedfortheCOVID-19VaccineAstraZeneca. Bell’sPalsy Bell’spalsy(BP)istemporaryweaknessorparalysisaffectingonesideofthefacethatdevelopsgradually;mostpeoplerecoverfromthisconditionwithinafewmonths.BPisknowntobeassociatedwithanumberofinfectiousdiseases,includingtheSARS-CoV-2virus.ReportsofsuspectedBPfollowingCOVID-19vaccinationhavebeencontinuouslyreviewedbytheMHRA.WhilstreportingofBPfollowingCOVID-19vaccinationisrare,evidencebasedonthelatestavailabledatashowsthattheremaybeanincreasedriskofBPfollowingCOVID-19vaccination.Toraiseawarenessofthispotentialadverseeventamongsthealthcareprofessionalsandpatients,facialparalysishasbeenincludedintheproductinformationforCOVID-19VaccineAstraZeneca,monovalentandbivalentCOVID-19VaccinePfizer/BioNTechandmonovalentandbivalentCOVID-19VaccineModerna.WewillcontinuetomonitortheseeventsfollowingCOVID-19vaccination. Transversemyelitis Transversemyelitis(TM)isarareacuteneurologicaldisorderwherepartsofthespinalcordareinflamed.TMisknowntobeassociatedwithanumberofviruses,suchastheherpesandinfluenzavirus.TheMHRAhascontinuallymonitoredreportsofsuspectedtransversemyelitisfollowingCOVID-19vaccinationsincethestartofthevaccinationprogramme. Asof28September2022,wehavereceived128reportsofsuspectedTMfollowingadministrationofCOVID-19VaccineAstraZeneca,41reportsfollowingadministrationofmonovalentCOVID-19VaccinePfizer/BioNTechand7reportsfollowingadministrationofmonovalentCOVID-19VaccineModerna.TherewerenoreportsreceivedwithafataloutcomefollowingsuspectedTM.WhilsttheincidencerateofthisadverseeventwithanyoftheCOVID-19vaccinesusedintheUKremainsextremelyrare(lessthan1reportper100,000dosesofeachvaccine),theavailableevidencereviewedbytheMHRAsuggestsanassociationbetweenTMandCOVID-19VaccineAstraZenecaispossible. Duetotheseriousnatureofthisadverseeventandasaprecaution,theproductinformationhasbeenupdatedtoraisehealthcareprofessionals’andpatients’awarenessofthesignsandsymptomsassociatedwithTMwhichmayincludemuscleweakness,localisedorradiatingbackpain,bladderandbowelsymptomsandchangesinsensation.ItisrecommendedthatpatientswhohadanepisodeoftransversemyelitisfollowingthefirstdoseofCOVID-19VaccineAstraZenecashouldnotreceiveaseconddoseofthisvaccine. Thrombo-embolic(bloodclotting)eventswithconcurrentlowplatelets TheMHRAhasundertakenathoroughreviewintoUKcasesofanextremelyrareandunlikelytooccurspecifictypeofbloodclotinthebrain,knownascerebralvenoussinusthrombosis(CVST)occurringtogetherwithlowlevelsofplatelets(thrombocytopenia)followingvaccinationwiththeCOVID-19VaccineAstraZeneca.Ithasalsoconsideredotherbloodclottingreports(thromboembolicevents)alongsidelowplateletlevels. ThisscientificreviewconcludedthattheevidenceofalinkwithCOVID-19VaccineAstraZenecaislikelyandanannouncementwasmadeon7April2021withafurtherstatementon7May2021.Wehavecontinuedtopublishthelatestbreakdownofallcasesoftheseextremelyraresideeffectsonaweeklybasis. AnyonewhoexperiencedcerebralorothermajorbloodclotsoccurringwithlowlevelsofplateletsaftertheirfirstvaccinedoseofCOVID-19VaccineAstraZenecashouldnothavefurtherdoses.Anyonewhodidnothavethesesideeffectsshouldcomeforwardfortheirseconddosewheninvited. Anyonewhoexperiencesanyofthefollowingfromaround4daysaftervaccinationshouldseekmedicaladviceurgently: asevereheadachethatisnotrelievedwithsimplepainkillersorgetsworseorfeelsworsewhenyouliedownorbendover anunusualheadachethatmaybeaccompaniedbyblurredvision,confusion,difficultywithspeech,weakness,drowsinessorseizures(fits) rashthatlookslikesmallbruisesorbleedingundertheskinbeyondtheinjectionsite shortnessofbreath,chestpain,legswellingorpersistentabdominal(tummy)pain. Upto28September2022,theMHRAhadreceivedYellowCardreportsof446 casesofmajorthromboembolicevents(bloodclots)withconcurrentthrombocytopenia(lowplateletcounts)intheUKfollowingvaccinationwithCOVID-19VaccineAstraZeneca.Fifty-oneofthe446reportshavebeenreportedafteraseconddose.Ofthe446reports,220occurredinfemales,and221occurredinmalesagedfrom18to93years.Theoverallcasefatalityratewas18%with80deaths,sixofwhichoccurredaftertheseconddose. Cerebralvenoussinusthrombosiswasreportedin163cases(averageage46years)and283hadothermajorthromboembolicevents(averageage54years)withconcurrentthrombocytopenia.TheestimatednumberoffirstdosesofCOVID-19VaccineAstraZenecaadministeredintheUKby28September2022was24.9millionandtheestimatednumberofseconddoseswas24.2million. Theoverallincidenceafterfirstorunknowndoseswas15.9permilliondoses.ConsideringthedifferentnumbersofpatientsvaccinatedwithCOVID-19VaccineAstraZeneca indifferentagegroups, thedata indicatesthat thereisahigher reported incidence rate intheyoungeradultagegroups followingthefirstdosecomparedtotheoldergroups(21.7permilliondosesinthoseaged18-49yearscomparedto11.3permilliondosesinthoseaged50yearsandover).Thenumberoffirstdosesgiventothoseinthe18-49yearsagegroupisestimatedtobe8.5millionwhileanestimated16.4millionfirstdoseshavebeengiventopatientsaged50+years.TheMHRA advisesthatthisevidenceshouldbetakenintoaccountwhenconsideringtheuseofthevaccine. Thereissomeevidencethatthereportedincidencerateishigherinfemalescomparedtomenalthoughthisisnotseenacrossallagegroupsandthedifferenceremainssmall. Theoverallincidenceofthromboemboliceventswithconcurrentlowplateletsafterseconddoseswas2.1casespermilliondoses.TakingintoaccountthedifferentnumbersofpatientsvaccinatedwithCOVID-19VaccineAstraZeneca indifferentagegroups, thedata indicatesthat thereisalowerreportedincidencerateinyoungeradultagegroupsfollowingtheseconddosecomparedtotheoldergroups(1.0permilliondosesinthoseaged18-49yearscomparedto2.1permilliondosesinthoseaged50yearsandover).Thenumberofseconddosesgiventothoseinthe18-49yearsagegroupisestimatedtobe8.1millionwhileanestimated16.1millionseconddoseshavebeengiventopatientsaged50+years.Theseratesafterseconddosesshouldnotbedirectlycomparedtotheincidenceratesreportedafterthefirstdoseasthetimeforfollow-upandidentificationofcasesafterseconddosesismorelimitedanddiffersacrossagegroups.However,thedataarereassuring,particularlyregardingyoungerrecipientswherethereisasignificantlylowerincidenceaftertheseconddosecomparedtothefirst,andthereisoverallnoindicationofanincreasedriskoftheseeventsaftertheseconddoseinanyagegroup.Anyonewhodidnothavethesesideeffectsshouldcomeforwardfortheirseconddosewheninvited. Thesecaseshavealsobeenanalysedbytheindependentadvisorybody,theCHM’sCOVID-19VaccinesBenefitRiskExpertWorkingGroup,whichincludeslayrepresentativesandadvicefromleadinghaematologists. Onthebasisofthisongoingreview,theadviceremainsthatthebenefitsofthevaccineoutweightherisksinthemajorityofpeople. Table5:Numberofsuspectedthrombo-emboliceventswithconcurrentthrombocytopeniaADRcasesreceivedfortheCOVID-19VaccineAstraZenecaintheUKuptoandincluding28September2022. Country Numberofcases England 353 Wales 14 NorthernIreland 11 Scotland 38 Unknown 30 Table6:NumberofUKsuspectedthrombo-emboliceventswithconcurrentthrombocytopeniaADRcasesreceivedfortheCOVID-19VaccineAstraZenecabypatientageuptoandincluding28September2022. Agerange(years) Numberofcases Numberoffatalcases 18-29 31 7 30-39 49 10 40-49 113 16 50-59 109 21 60-69 62 11 70-79 40 7 80-89 6 3 90-99 2 1 Unknown 34 4 Total 446 80 Table7:NumberofUKsuspectedthrombo-emboliceventswithconcurrentthrombocytopeniaADRcasesreceivedfortheCOVID-19VaccineAstraZenecabypatientsexuptoandincluding28September2022. Sex Numberofcases Numberoffatalcases Male 221 35 Female 220 44 Unknown 5 1 Total 446 80 Upto28September2022,theMHRAhadreceivedYellowCardreportsof32casesofmajorthromboembolicevents(bloodclots)withconcurrentthrombocytopenia(lowplateletcounts)intheUKfollowinguseofthemonovalentCOVID-19VaccinePfizer/BioNTech.Theseeventsoccurredin13females,18males,and1unknownagedfrom18to91years,andtheoverallcasefatalityratewas13%withfourdeathsreported. Upto28September2022,theMHRAhadreceivedYellowCardreportsof8casesofmajorthromboembolicevents(bloodclots)withconcurrentthrombocytopenia(lowplateletcounts)intheUKfollowingtheuseofmonovalentCOVID-19VaccineModerna.Theseeventsoccurredin6adultmalesand2adultfemalesbetweentheagesof28-95.Theoverallcasefatalityratewas13%withonedeathreported. Tonote,directcomparisonofthesummaryprovidedhere,andtheanalysisprintsisnotpossible.ThisreviewincludesreportsofCVSTorotherthrombo-emboliceventswithconcurrentthrombocytopenia.Bloodclottingeventswithoutloweredplateletsaredescribedbelow. YellowCardreportsmaycontainmorethanonereportedreactionandtheanalysisprintsarelistedbyindividualreactionsratherthanwholereports.Therefore,summingthereactionslistedintheprintswillnotequatetothetotalcasesincludedwithinthissummary. Thrombo-embolic(bloodclotting)eventswithoutconcurrentlowplatelets TheMHRAhasconductedathoroughreviewofeventsofcerebralvenoussinusthrombosis(CVST)withoutconcurrentlowplateletlevelsfollowingvaccinationwiththeCOVID-19VaccineAstraZenecaandsoughtadvicefromtheCHM’sVaccineBenefitRiskExpertWorkingGroup.Bloodclottingeventswithloweredplateletsaredescribedinaseparatesection(above).ThescientificreviewconcludedthatthereisapossiblelinkbetweenCVSTwithoutlowplateletsandCOVID-19VaccineAstraZeneca.TheproductinformationforCOVID-19VaccineAstraZenecahasbeenupdatedtoincludeinformationthatCVSTeventsnotassociatedwithlowlevelsofbloodplateletsoccurredextremelyrarely.ThemajorityoftheCVSTeventsoccurredwithinthefirstfourweeksfollowingvaccination.Apotentialcausehasnotbeenidentified. TheMHRAhasalsoconfirmedthattheevidencetodatedoesnotsuggestthattheCOVID-19VaccineAstraZenecaincreasestheriskofvenousthromboembolism(i.e,deepveinthrombosis/pulmonaryembolism)intheabsenceofalowplateletcount.TheMHRAwillcontinuetocloselymonitorreportsofvenousthromboembolismfollowingCOVID-19vaccination. Immunethrombocytopenia Immunethrombocytopenia(ITP)isaconditionwheretheimmunesystemdoesnotfunctioncorrectlyandbecomesinvolvedindestroyingplatelets,whichcanleadtobleeding;theseeventsareusuallyshort-livedandofminorseverity.ReportsofITPfollowingCOVID-19vaccinationhavebeencloselymonitoredbytheMHRA.ArecentthoroughreviewofalltheavailableevidenceconfirmedthatthistypeofeventisreportedextremelyrarelyforCOVID-19VaccineAstraZenecaintheUK,atapproximately5reportspermilliondoses.Inapproximately10-20%ofthereportspatientshadahistoryofITPoranunderlyingconditionknowntobeassociatedwithITP.Followingthemostrecentreview,theavailabledatasuggestedapossiblelinkbetweenCOVID-19VaccineAstraZenecaandITP,andtheproductinformationforthisvaccinehasbeenupdatedtoincludeinformationontheoccurrenceofITP. CapillaryLeakSyndrome TheMHRAhasreceived18reportsofsuspectedcapillaryleaksyndrome(aconditionwherefluidleaksfromthesmallbloodvesselsintothebody)inthecontextofmorethan49.2milliondosesofCOVID-19VaccineAstraZenecagiven.Ofthesereports,3peoplehadahistoryofcapillaryleaksyndrome.Thisisanextremelyrarerelapsing-remittingconditionandtriggersforrelapsesarenotwellunderstood.Asaprecautionarymeasure,theMHRAisadvisingthatCOVID-19VaccineAstraZenecaisnotusedinpeoplewhohavepreviouslyexperiencedepisodesofcapillaryleaksyndrome.Theproductinformationhasbeenupdatedtoreflectthisadvice. TheMHRAhasalsoreviewedreportsofcapillaryleaksyndromefortheCOVID-19ModernaandPfizer/BioNTechvaccines.ForthemonovalentCOVID-19VaccineModerna,whilenoassociationwithnew-onsetofcapillaryleaksyndromewasfound,apotentialriskofflare-upofexistingcapillaryleaksyndromewasidentifiedfollowingvaccination.TheproductinformationfortheCOVID-19VaccinesModernahighlightsthepotentialriskofflare-upofcapillaryleaksyndrometohealthcareprofessionalsandpatients.ForthemonovalentCOVID-19VaccinePfizer/BioNTech,noassociationbetweennew-onsetorflare-upofcapillaryleaksyndromewasidentified.TheMHRAhasreceivedatotalof2reportsofcapillaryleaksyndromefollowingadministrationofthemonovalentCOVID-19VaccineModernaand1reportfollowingtheadministrationofthemonovalentCOVID-19VaccinePfizer/BioNTech. Menstrualdisorders(periodproblems)andunexpectedvaginalbleeding TheMHRAisreviewingreportsofsuspectedsideeffectsofmenstrualdisorders(periodproblems)andunexpectedvaginalbleedingfollowingvaccinationagainstCOVID-19intheUK.ThesereportsarealsobeingreviewedbytheindependentexpertsoftheCHM’sCOVID-19VaccinesBenefitRiskExpertWorkingGroupandtheMedicinesforWomen’sHealthExpertAdvisoryGroup.TherigorousevaluationcompletedtodatedoesnotsupportalinkbetweenchangestomenstrualperiodsandrelatedsymptomsandCOVID-19vaccines. Upto28September2022atotalof51,500suspectedreactionsrelatingtoavarietyofmenstrualdisordershavebeenreportedafteradministrationofCOVID-19vaccinesincludingheavierthanusualperiods,delayedperiodsandunexpectedvaginalbleeding.Thesesuspectedreactionshavebeenreportedin40,143individualYellowCardreports(aseachreportmaycontainmorethanonesuspectedreaction).Thisisfollowingapproximately75.2millionmonovalentCOVID-19vaccinedosesadministeredtowomenupto28September2022.ThenumberofreportsofmenstrualdisordersandvaginalbleedingislowinrelationtoboththenumberofpeoplewhohavereceivedCOVID-19vaccinestodateandhowcommonmenstrualdisordersaregenerally. Themenstrualchangesreportedaremostlytransientinnature.ThereisnoevidencetosuggestthatCOVID-19vaccineswillaffectfertilityandyourabilitytohavechildren. Whilstuncomfortableordistressing,periodproblemsareextremelycommonandstressfullifeeventscandisruptmenstrualperiods.ChangestothemenstrualcyclehavealsobeenreportedfollowinginfectionwithCOVID-19andinpeopleaffectedbylong-COVID.Generaladviceaboutperiodproblemsand/orunexpectedvaginalbleedingisavailablefromtheNHSwebsite.Itisimportantthatanyoneexperiencingchangestotheirperiodsthatareunusualforthem,persistovertime,orhasanynewvaginalbleedingafterthemenopause,followingCOVID-19vaccination,shouldcontacttheirdoctor.Anyonepresentingwithmenstrualdisordersand/orunexpectedvaginalbleedingfollowingCOVID-19vaccinationshouldbetreatedaccordingtoclinicalguidelinesfortheseconditions,asusual. TheMHRAcontinuestocloselyreviewreportsofsuspectedsideeffectsofmenstrualdisordersandunexpectedvaginalbleeding. Myocarditisandpericarditis(Inflammationoftheheart) TheMHRAhasundertakenathoroughreviewofbothUKandinternationalreportsofsuspectedmyocarditisandpericarditisfollowingvaccinationagainstCOVID-19.TherehasbeenaconsistentpatternofhigherreportingofthesesuspectedeventswithboththemonovalentCOVID-19VaccinePfizer/BioNTechandCOVID-19VaccineModerna,andoftheseoccurringmorefrequentlyinmales.Thesereportshavealsobeenanalysedbythegovernment’sindependentadvisorybody,theCHManditsCOVID-19VaccinesBenefitRiskExpertWorkingGroup.Followingtheiradvice,theproductinformationforbothmonovalentCOVID-19VaccineModernaandCOVID-19VaccinePfizer/BioNTechwasupdatedtoinformhealthcareprofessionalsandpatientsofthesereportsandprovideadvicetobeawareofimportantsymptomsformyocarditisandpericarditis.Thisadvicehasalsobeenincludedintheproductinformationforthebivalent(original/OmicronBA.1)COVID-19vaccinesforModernaandPfizer/BioNTech. Thesereportsareveryrare,andtheeventsreportedaretypicallymildwithindividualsusuallyrecoveringwithinashorttimewithstandardtreatmentandrest. Peopleshouldcomeforwardfortheirsecondandboostervaccinationwheninvitedtodoso,unlessadvisedotherwise. Itisimportantthatanyonewhoexperiencesnewonsetofsymptomssuchaschestpain,shortnessofbreathorfeelingsofhavingafast-beating,fluttering,orpoundingheartseeksmedicalattention. Uptoandincluding28September2022,wehavereceived828reportsofmyocarditisand560reportsofpericarditisfollowinguseofthemonovalentCOVID-19VaccinePfizer/BioNTech,aswellastenreportsofcarditis,fivereportseachforviralmyocarditisandendocarditis,fourreportseachforinfectivepericarditisandviralpericarditis,tworeportseachformyocarditismycoticandmyocarditispostinfection,andonereporteachofinfectiousmyocarditis,constrictivepericarditis,pleuropericarditis,lupuspericarditis,non-infectiveendocarditis,eosinophilicmyocarditis,hypersensitivitymyocarditis,,bacterialmyocarditis,septicmyocarditisandstreptococcalendocarditis. ForCOVID-19VaccineAstraZenecatherehavebeen240reportsofmyocarditisand225reportsofpericarditisfollowingvaccinationuptoandincluding28September2022aswellasninereportsforendocarditis,fivereportsforviralpericarditis,threereportseachforviralmyocarditisandcarditis,tworeportseachforbacterialendocarditisandacuteendocarditis,andonereporteachforinfectiousmyocarditis,myocarditispostinfection,autoimmunepericarditisandautoimmunemyocarditis. Therehavebeen234reportsofmyocarditis,138reportsofpericarditis,threereportsofcarditisandonereporteachofhypersensitivitymyocarditis,pleuropericarditis,viralmyocarditisandendocarditisfollowinguseofbothCOVID-19VaccinesModernauptothesamedate. SevensuspectedmyocarditisorpericarditisreportswithafataloutcomehavebeenreportedfollowingthemonovalentCOVID-19VaccinePfizer/BioNTechandsixreportswithafataloutcomefollowingtheCOVID-19VaccineAstraZeneca.TherehavebeennosuspectedmyocarditisorpericarditisreportswithafataloutcomereportedfollowingthemonovalentCOVID-19VaccineModernatodate.Therehavealsobeennomyocarditis/pericarditisreportswithafataloutcomefollowingthebivalent(original/OmicronBA.1)ModernaandPfizer/BioNTechCOVID-19vaccinestodate.Reportswithafataloutcomearebeingmonitoredcloselyandarecarefullyfolloweduptogatherrelevantinformation.Themajorityofreportswithafataloutcomedescribeunderlyingillnessesinthesepatientsthatcouldprovidealternativeexplanationsfortheeventsreported. BasedonreportsofsuspectedADRsintheUK,theoverallreportingrateacrossallagegroupsforsuspectedmyocarditis(includingviralmyocarditis),afterfirst,secondandboosterorthirddoses,is10reportspermilliondosesofmonovalentCOVID-19VaccinePfizer/BioNTechandforsuspectedpericarditis(includingviralpericarditisandinfectivepericarditis)theoverallreportingrateis7reportspermilliondoses.FormonovalentCOVID-19VaccineModerna,theoverallreportingrateforsuspectedmyocarditis(includinghypersensitivitymyocarditisandviralmyocarditis)is18permilliondosesandforsuspectedpericarditis(includingpleuropericarditis)is11permilliondoses.ForCOVID-19VaccineAstraZenecatheoverallreportingrateforsuspectedmyocarditis(includingviralmyocarditisandinfectiousmyocarditis)is5permilliondosesandforsuspectedpericarditis(includingviralpericarditis)is5permilliondoses.Itshouldbenotedthatanindividualreportcancontainmorethanoneeventandthereforethetotalnumberofreportswillnotbeequaltothenumberofevents. Whenthereportingrateiscalculatedbyagegroup(seeTable8)thereportingrateforsuspectedmyocarditisandpericarditisishighestinthe18-29-yearagegroupforthemonovalentPfizer/BioNTechandModernaCOVID-19vaccines.AmoreevenspreadinreportingratesacrosstheagegroupsisseenforAstraZenecaCOVID-19vaccine.Forallvaccinesthereisatrendfordecreasedreportingintheolderagegroups. ThemonovalentCOVID-19vaccinePfizer/BioNTechwasthepreferredCOVID-19vaccinefortheunder18sagegroupintheUKvaccinationprogrammeuptoAutumn2022.FortheNationalAutumnboostercampaignthemonovalentandbivalent(original/OmicronBA.1)Pfizer/BioNTechvaccineswererecommendedforeligiblepeopleaged12-17yearsandthemonovalentPfizer/BioNTechvaccinewasrecommendedforthoseaged5to11years.ForthemonovalentPfizer/BioNTechvaccine,whichhasbeenthemostcommonlyusedvaccineintheunder18sagegroup,thereisnoindicationinthecurrentdatathatthereisanincreasedreportingrateofsuspectedmyocarditisandpericarditisinthisagegroupoverallcomparedtoyoungadults.Furthermore,thereportingratesforthe5-11year,12-15yearand16-17yearagegrouparelowerthanthatintheyoungadult18-29agegroupafterthefirstandseconddoses. PriortoAutumn2022,bothmonovalentCOVID-19VaccinePfizer/BioNTechandCOVID-19VaccineModernawerethepreferredvaccinesintheUKboosterprogramme,andthereportingratesforsuspectedmyocarditisandpericarditisfollowingboosterorthirddosesofthesevaccinesarelowerthanthoseestimatedforthefirstandseconddoses;theseeventsareveryrareafterboosterdoses.Thereisnoindicationthattheseeventsaremoresevereafterboosterdosescomparedtofirstandseconddoses;mostreportsdescribemildeventswitharapidrecoveryandaresimilartothoseexperiencedafterthefirstandseconddoses.ThereisextremelylimitedusageofCOVID-19VaccineAstraZenecaasabooster.Duetothislimitedusageandverysmallnumbersofreportsofsuspectedmyocarditisandpericarditisafterboosterdoses,itisnotpossibletocalculateareliablereportingratefortheCOVID-19VaccineAstraZenecawhenusedasabooster;noassociationhasbeenestablishedbetweenmyocarditisorpericarditisandtheCOVID-19VaccineAstraZeneca. ItisimportanttonotethatYellowCarddatacannotbeusedtocomparethesafetyprofileofCOVID-19vaccinesasmanyfactorscaninfluenceADRreporting. ThesereportingratesmayalsobesubjecttochangeasmoreexperienceisgatheredintheUK. Table8:ReportingratespermilliondosesforUKADRreportsofsuspectedmyocarditisandpericarditisassociatedwithCOVID-19Vaccines,bypatientageanddose,uptoandincluding28September2022. AgeRange(years) #COVID-19Pfizer/BioNTech(monovalent)1storunknowndose COVID-19Pfizer/BioNTech(monovalent)2nddose COVID-19Pfizer/BioNTech(monovalent)3rdorboosterdose COVID-19VaccineModerna(monovalent)-1storunknowndose COVID-19VaccineModerna(monovalent)-2nddose COVID-19VaccineModerna(monovalent)-3rdorboosterdose COVID-19VaccineAstraZeneca-1storunknowndose COVID-19VaccineAstraZeneca-2nddose Under18 12 9 Notcalculated* Notapplicable** Notapplicable** Notapplicable** Notapplicable** Notapplicable** 18-29 23 29 17 61 68 23 10 16 30-39 19 25 16 58 51 22 14 12 40-49 18 19 13 48 30 16 13 10 50-59 9 18 8 Notcalculated* Notcalculated* 8 8 8 60-69 5 14 7 Notcalculated* Notapplicable** 8 7 6 70+ 2 5 5 Notcalculated* Notapplicable** 3 4 5 *ThereiscurrentlyinsufficientdatatocalculateareliableestimateofthereportingrateintheUKduetotherelativelylimitedexposureandsmallnumbersofsuspectedreportsintheseindividuals. **Therehavebeennoreportsofsuspectedheartinflammationeventsreceivedforindividualsintheseagegroups Table9*:NumberofUKADRreportsassociatedwithsuspectedmyocarditis,pericarditisandotherrelatedtermsreceivedfortheCOVID-19Vaccinesbypatientageuptoandincluding28September2022. Numberofreports Agerange(years) COVID-19VaccinePfizer/BioNTech(monovalent) COVID-19VaccineModerna(monovalent) COVID-19VaccineAstraZeneca Under18 83 0 0 18-29 394 124 31 30-39 323 97 49 40-49 146 53 122 50-59 105 24 107 60+ 165 26 109 Unknown 152 39 55 Total 1373 363 472 *DuetothedynamicnatureoftheYellowCarddatathesefiguresmaychangebothasnewcasesarereceived,andasduplicatecasesareidentifiedandmanaged. Table10*:NumberofUKADRreportsassociatedwithsuspectedmyocarditis,pericarditisandotherrelatedtermsreceivedfortheCOVID-19Vaccinesbypatientsexuptoandincluding28September2022. Numberofreports Sex COVID-19VaccinePfizer/BioNTech(monovalent) COVID-19VaccineModerna(monovalent) COVID-19VaccineAstraZeneca Female 540 119 210 Male 790 234 250 Unknown 43 10 13 Total 1373 363 473 *DuetothedynamicnatureoftheYellowCarddatathesefiguresmaychangebothasnewcasesarereceived,andasduplicatecasesareidentifiedandmanaged. TwolargeEuropeanepidemiologicalstudieshaveestimatedtheexcessriskofmyocarditisfollowingvaccinationwithbothmonovalentCOVID-19VaccinePfizer/BioNTechandCOVID-19VaccineModerna.Onestudyshowedthatinaperiodof7daysaftertheseconddoseofthemonovalentCOVID-19VaccinePfizer/BioNTechtherewereabout27(95%CI26-28)extracasesofmyocarditisin12-29yearoldmalespermillioncomparedtounvaccinatedindividuals,andforthemonovalentCOVID-19VaccineModernatherewereabout132(95%CI130–133)extracasesofmyocarditisin12-29yearoldmalespermillion.Inanotherstudy,inaperiodof28daysaftertheseconddoseofthemonovalentCOVID-19VaccinePfizer/BioNTechtherewere57[95%CI39–75]extracasesofmyocarditisin16-24yearoldmalespermillioncomparedtounvaccinatedpersons,andforthemonovalentCOVID-19VaccineModernatherewere188(95%CI96–280)extracasesofmyocarditisin16-24yearoldmalespermillionindividualscomparedtounvaccinatedindividuals.ThesestudieshaveshownthattheseeventsareveryrarepostvaccinationwiththemRNAvaccines,andthattheseeventsaremorefrequentinyoungermales.ThefindingsofthesestudiesareconsistentwiththetrendsseenintheYellowCarddata. Internationaldatahasshownthatthesesuspectedeventshavebeenobservedtooccurmostfrequentlyapproximately3daysafterthefirstvaccineand2daysafterthesecondvaccine,andbothUKandinternationaldatahaveidentifiedthatthelargemajorityofsuspectedeventsoccurwithin7daysofvaccination.IntheUKthebodyofevidenceshowsthatthereissimilarfrequencyofreportingafterthefirstandseconddose. Longertermfollow-upinboththeUKandUStoatleast90daysfollowingidentificationofcasesofsuspectedmyocarditisafterbothmonovalentCOVID-19VaccinePfizer/BioNTechandModernafoundthatthemajorityofindividualswerefullyrecoveredandbacktonormalactivities. Myocarditisandpericarditishappenveryrarelyinthegeneralpopulation,anditisestimatedthatintheUKthereareabout60newcasesofmyocarditisdiagnosedpermillionpatientsperyearandabout100newcasesofpericarditisdiagnosedpermillionpatientsperyear.MyocarditisisalsoknowntobeassociatedwithCOVID-19infection,withanestimated1,500casesofmyocarditispermillionpatientswithCOVID-19. TheMHRAwillcontinuetocloselymonitorreportsofsuspectedmyocarditisandpericarditiswithallcurrentlyauthorisedCOVID-19vaccines. Delayedhypersensitivityreactions The MHRA hasbeenreviewingreportsofskinreactionsoccurringaroundthevaccinationsitethatappearalittlewhileaftervaccination.Thesereactionsaresuggestiveofadelayedhypersensitivityreactionthatoccurs4-11daysaftervaccination.Thereactionsarecharacterizedbyarash,swellingandtendernessthatcancoverthewholeupperarmandmaybeitchyand/orpainfulandwarmtothetouch.ThemajorityofthereportsreceivedhavebeenwiththemonovalentCOVID-19VaccineModernaandtheproductinformationforthisvaccinehasbeenupdatedtohighlightthepossibilityofdelayedinjectionsitereactions.Thisinformationhasalsobeenincludedintheproductinformationforthebivalent(original/OmicronBA.1)COVID-19VaccineModerna. Thereactionsareusuallyself-limitingandresolvewithinadayortwo,althoughinsomepatientsitcantakeslightlylongertodisappear.Individualswhoexperiencethisreactionaftertheirfirstdosemayexperienceasimilarreactioninshortertimeframefollowingtheseconddose,however,noneofthereportsreceivedhavebeenseriousandpeopleshouldstilltaketheirseconddosewheninvited.ThosewhoexperiencedelayedskinreactionsaftertheirCOVID-19vaccinationwhichdonotresolvewithinafewdaysshouldseekmedicaladvice. Guillain-BarréSyndrome Guillain-BarréSyndromeisaveryrareconditionwhichcausesinflammationofthenervesandcanleadtonumbness,weaknessandpain,usuallyinthefeet,handsandlimbsandcanspreadtothechestandface.Guillain-BarréSyndrometendstoaffectbothsidesofthebodyatonce.Thisconditionisknowntobeassociatedwithcertaininfectiousdiseases. Uptoandincludingthe28September2022,theMHRAhasreceived509reportsofsuspectedGuillain-BarréSyndromewiththeCOVID-19VaccineAstraZenecaand29reportsofarelateddiseasecalledMillerFishersyndrome.Uptothesamedate,theMHRAhasreceived111reportsofGuillain-BarréSyndromefollowinguseofthemonovalentCOVID-19VaccinePfizer/BioNTechand6reportsofMillerFishersyndromeandforthemonovalentCOVID-19VaccineModernatherehavebeen25reportsofGuillain-BarréSyndrome. TheMHRAhasbeencloselymonitoringandassessingreportsofsuspectedGuillain-BarréSyndrome(GBS)receivedfollowingadministrationoftheCOVID-19vaccine.Followingthemostrecentreviewoftheavailabledatatheevidenceofapossibleassociationhasstrengthened.Therefore,followingadvicefromthegovernment’sindependentadvisorybody,theCHManditsCOVID-19VaccinesBenefitRiskExpertWorkingGroup,theproductinformationfortheCOVID-19VaccineAstraZenecawasfurtherupdatedtoincludeGBSinthetabulatedlistofadversereactionsassociatedwiththeCOVID-19VaccineAstraZenecaandtoencouragehealthcareprofessionalsandthepublictolookoutforsignsofGBS. TheMHRAwillcontinuetoreviewreportsofGuillain-BarréSyndromereceivedfollowingvaccinationwithCOVID-19vaccinestofurtherassessapossibleassociation,withindependentadvicefromitsVaccineBenefit-RiskWorkingGroup. Swellingofthevaccinatedlimb TherehavebeenrarereportsofextensiveswellingofthevaccinatedlimbafterreceivingthemonovalentCOVID-19VaccinePfizer/BioNTech.Theproductinformationhasbeenupdatedtoinclude“extensiveswellingofthevaccinatedlimb”asasideeffectofthevaccine.Thisinformationhasalsobeenaddedtotheproductinformationforthebivalent(original/OmicronBA.1)COVID-19VaccinePfizer/BioNTech.Thistypeofswellingisalsorecognisedtooccurwithother(non-COVID-19)vaccines. Facialswellinginthosewithahistoryoffacialdermalfillers Rarereportsoffacialswellingoccurring1-2daysaftervaccinationinvaccinerecipientswithahistoryofinjectionoffacialdermalfillerswereobservedintheclinicaltrialsforthemonovalentCOVID-19VaccineModerna.InformationaboutthispossiblesideeffecthasbeenincludedintheproductinformationforthemonovalentCOVID-19VaccineModernasinceitwasfirstauthorisedforuse.Ithasalsobeenaddedtotheproductinformationforthebivalent(original/OmicronBA.1)COVID-19VaccineModerna. TheMHRAhasalsoreceivedYellowCardreportsoffacialswellinginthosewithahistoryofinjectionoffacialdermalfillersforthemonovalentCOVID-19VaccinePfizer/BioNTech.Areviewoftheworld-wideADRdataforthemonovalentCOVID-19VaccinePfizer/BioNTechfoundthat,inmostinstances,thefacialswellingwasmild,transientandwaslocalisedtothesiteofthedermalfiller.TheproductinformationforthemonovalentCOVID-19VaccinePfizer/BioNTechhasbeenupdatedtoincludefacialswellinginthosewithahistoryofinjectionoffacialdermatologicalfillersasasideeffectofthevaccine.Ithasalsobeenaddedtotheproductinformationforthebivalent(original/OmicronBA.1)COVID-19VaccinePfizer/BioNTech. Reportswithafataloutcome Vaccinationandsurveillanceoflargepopulationsmeansthat,bychance,somepeoplewillexperienceandreportanewillnessoreventsinthedaysandweeksaftervaccination.Ahighproportionofpeoplevaccinatedearlyinthevaccinationcampaignwereveryelderly,and/orhadpre-existingmedicalconditions.Olderageandchronicunderlyingillnessesmakeitmorelikelythatcoincidentaladverseeventsincludingthosewithafataloutcomewilloccur,especiallygiventhemillionsofpeoplevaccinated. Partofourcontinuousanalysisincludesanevaluationofnaturaldeathratesovertime,todetermineifanyspecifictrendsorpatternsareoccurringthatmightindicateavaccinesafetyconcern.Basedonage-stratifiedall-causemortalityinEnglandandWalestakenfromthe OfficeforNationalStatistics(ONS)deathregistrations,severalthousanddeathsareexpectedtohaveoccurrednaturally,mostlyintheelderly,within7daysofthemanymillionsofdosesofvaccinesadministeredsofar. Forreference,weeklydeathregistrationswithinEngland,Wales,ScotlandandNorthernIrelandareavailablefromrelevantstatisticalauthorities.ThemostrecentdataduringthepreparationofthesummaryofYellowCardreportingissummarisedasfollows: EnglandandWales(ONS):Intheweekending16September2022,10,673deathswereregistered;ofthesedeaths,301citedCOVID-19,accountingfor2.8%ofalldeaths. Scotland(TheNationalRecordsofScotland):Intheweekending25September2022,988deathswereregistered;ofthesedeaths,33citedCOVID-19,accountingfor3.3%ofalldeaths. NorthernIreland(TheNorthernIrelandStatisticsandResearchAgency):Intheweekending23September2022,276deathswereregistered;ofthesedeaths,6citedCOVID-19,accountingfor2.2%ofalldeaths. TheMHRAtakesallreportswithafataloutcomeinpatientswhohavereceivedaCOVID-19vaccineveryseriouslyandeveryreportwithafataloutcomeisreviewedcarefully.Allreportswithafataloutcomeregardlessofthetimeperiodbetweenreceivingthesuspectvaccineandthereporteddeatharereviewed.Allavailableinformationisassessedtoconsiderwhetherthevaccinemayhavecausedthereporteddeath.Cumulatively,theYellowCarddataisthoroughlyanalysedforpatternsorevidencewhichmightsuggestacausallinkbetweenthevaccinationandthereporteddeathalongsidedataavailablefrominternationalsources.ThisisfurtherconsideredbytheCommissiononHumanMedicinesanditsExpertAdvisoryGroups. TheMHRAhasreceived826UKreportsofsuspectedADRstobothCOVID-19Pfizer/BioNTechVaccinesinwhichthepatientdiedaftervaccination,1,314reportsfortheCOVID-19VaccineAstraZeneca,82reportsforbothCOVID-19VaccinesModernaand50reportswherethebrandofvaccinewasunspecified. AreportwithafataloutcometotheYellowCardschemedoesnotnecessarilymeanthatitwascausedbythevaccine,onlythatthereporterhasasuspicionitmayhavebeen.Underlyingorpreviouslyundiagnosedillnessunrelatedtovaccinationcanalsobefactorsinsuchreports.TherelativenumberandnatureofUKreportswithafataloutcomearesubjecttomanyfactorsthatinfluenceADRreporting.Theyshouldthereforenotbeusedtodirectlycomparethesafetyofthedifferentvaccines. ThenumberofUKreportswithafataloutcomefollowingaspecificCOVID-19vaccineshouldnotbedirectlycomparedwitheachother.Table11andTable12provideabreakdownbyageandsexforallUKreportswithafataloutcomefollowingCOVID-19vaccinationreceivedbytheMHRA. Table11*/**:NumberofUKreportswithafataloutcomereceivedforCOVID-19Vaccinesbypatientageuptoandincluding28September2022 Agegroup(years) COVID-19VaccineAstraZeneca COVID-19VaccinePfizer/BioNTech COVID-19VaccineModerna Brandunspecified Allvaccines Under18 ^ ^ - ^ 7 18-29 29 19 ^ - 49 30-39 48 33 6 ^ 88 40-49 95 30 6 ^ 134 50-59 158 43 ^ 8 213 60-69 198 73 10 6 287 70-79 267 174 14 ^ 459 80+ 325 320 21 16 682 Unknown 192 130 20 11 353 Total 1,314 826 82 50 2,272 *DuetothedynamicnatureoftheYellowCarddatathesefiguresmaychangebothasnewcasesarereceived,andasduplicatecasesareidentifiedandmanaged.Allreportswithafataloutcomeregardlessofthetimeperiodbetweenreceivingthesuspectvaccineandthereporteddeathareincluded. **‘-’denotesnoreportsreceived. ‘^’denotescensoreddatafieldforprivacyreasonsasthenumberofreportswithanamedvaccineis5orless. Table12*:NumberofUKreportswithafataloutcomereceivedforCOVID-19Vaccinesbypatientsexuptoandincluding28September2022. Sex COVID-19VaccineAstraZeneca COVID-19VaccinePfizer/BioNTech COVID-19VaccineModerna Brandunspecified Allvaccines Female 613 345 32 20 1,010 Male 641 425 44 27 1,137 Unknown 60 56 6 ^ 125 Total 1,314 826 82 50 2,272 *DuetothedynamicnatureoftheYellowCarddatathesefiguresmaychangebothasnewcasesarereceived,andasduplicatecasesareidentifiedandmanaged.Allreportswithafataloutcomeregardlessofthetimeperiodbetweenreceivingthesuspectvaccineandthereporteddeathareincluded. ‘^’denotescensoreddatafieldforprivacyreasonsasthenumberofreportswithanamedvaccineis5orless. AsdemonstratedinTable11,reportswithafataloutcomeareconcentratedinolderagegroupswithdecreasingnumbersinyoungeragegroups.ThisfindingisconsistentwithdatafromtheONSoutliningweeklyprovisionalfiguresondeathregistrationsinEnglandandWalesbysexandagegroup.Asanexample,intheweekending12February202115,354deathswereregisteredinEnglandandWales.Inthatweek,8,488deaths(55.3%)occurredinthoseaged80yearsandolder. ThepatternofreportswithafataloutcomefollowingCOVID-19vaccinationshowedapeakinreportingforbothCOVID-19VaccineAstraZenecaandmonovalentCOVID-19Pfizer/BioNTechVaccineatthestartoftheUKrolloutsofthesevaccineswhentheJCVIprioritisedCOVID-19vaccinationfortheelderlyandthosemostatriskofmorbidityandmortalityfromCOVID-19.AsecondpeakofreportingwasalsoidentifiedforCOVID-19VaccineAstraZenecawhichcoincidedwiththeUK’ssecondwaveofCOVID-19andtheidentificationoftheveryrareriskofthrombo-embolic(bloodclotting)eventswithconcurrentlowplatelets.AsoutlinedintheabovesafetysummaryofthisrisktheMHRAundertookathoroughreviewofUKcasesincludingreportswithafataloutcomeandprovidedupdatedguidanceforhealthcareprofessionalsonhowtominimiserisks,aswellasfurtheradviceonsymptomsforvaccinerecipients. Reviewsofreportswithafataloutcomeassociatedwithspecificadverseeventsareprovidedinthesummariesabove.Apossiblelinkbetweenthrombo-embolic(bloodclotting)eventswithconcurrentlowplateletsincludingreportswithafataloutcomeandCOVID-19VaccineAstraZenecawasidentifiedinMarch2021.Thepatternofreportingforallotherreportswithafataloutcomedoesnotsuggestthevaccinesplayedaroleinthesedeaths.TheMHRAwillcontinuetoreviewrelevantdatawhilstworkingalongsideotherregulatorybodiestopromoteandprotectpublichealth. Asthenumberofvaccinedosesadministeredhasincreased,sohasthenumberofreportswithfataloutcomesfollowingvaccination.However,thisdoesnotmeanthatthereisalinkbetweenvaccinationandthefatalitiesreported.TheUKHealthSecurityAgencyhaspreviouslyanalysedthedirectandindirectimpactofthevaccinationprogrammeoninfectionsandmortality.Ithasbeenestimatedthatupto26September2021,theUKvaccinationprogrammepreventedbetween23.9and24.3millioninfectionsandbetween123,600and131,300deaths. AstudypublishedbytheONSandtheOfficeofHealthImprovementandDisparities(OHID)analyseddataonCOVID-19vaccinationandmortalityinyoungpeopleduringthecoronaviruspandemic.Thestudyfoundnoindicationofanincreasedriskofdeathfromcardiac-relatedorothercausesinthoseaged12-29years,inthesixweeksfollowingCOVID-19vaccination.Thisisconsistentwithfindingsfromourrigoroussafetymonitoringactivities.Thestudyalsosuggestedthattheexcessindeathregistrationsinyoungpeoplein2021wasduetodelaysintheregistrationprocessandearlyindicationsofincreasednumbersofdeathsduetonon-vaccinerelatedexternalcauses.ThestudydatawerereviewedbytheindependentexpertsoftheCHM’sCOVID-19VaccinesBenefitRiskExpertWorkingGroupwhoagreedwiththeconclusionofthereportthatCOVID-19vaccineswerenotassociatedwithanincreasedriskofdeathinyoungpeople. TheMHRAwillcontinuetocarefullyreviewandmonitorallreportssubmittedtousincludingthosethatciteafataloutcomefollowingCOVID-19vaccination.WhenasafetyissueisconfirmedtheMHRAwillactpromptlytoinformpatientsandhealthcareprofessionalsandtakeappropriatestepstomitigateanyidentifiedrisk. 4.Conclusion Overthefirst26monthsofthepandemicover178,231peopleacrosstheUKhavediedwithin28daysofapositivetestforcoronavirus. VaccinationisthesinglemosteffectivewaytoreducedeathsandsevereillnessfromCOVID-19.AnationalimmunisationcampaignhasbeenunderwaysinceearlyDecember2020. Inclinicaltrials,themonovalentCOVID-19VaccinePfizer/BioNTech,theCOVID-19VaccineAstraZenecaandthemonovalentCOVID-19VaccineModernahavedemonstratedveryhighlevelsofprotectionagainstsymptomaticinfection.DataisavailableontheimpactofthevaccinationcampaigninreducinginfectionsandillnessintheUK. Allvaccinesandmedicineshavesomesideeffects.Thesesideeffectsneedtobecontinuouslybalancedagainsttheexpectedbenefitsinpreventingillness. FollowingwidespreaduseofthesevaccinesacrosstheUK,thevastmajorityofsuspectedadversereactionreportsconfirmthesafetyprofileseeninclinicaltrials.Mostreportsrelatetoinjection-sitereactions(sorearmforexample)andgeneralisedsymptomssuchasa‘flu-like’illness,headache,chills,fatigue,nausea,fever,dizziness,weakness,achingmuscles,andrapidheartbeat.Generally,thesereactionsarenotassociatedwithmoreseriousillnessandlikelyreflectanexpected,normalimmuneresponsetothevaccines. ThebenefitsofthevaccinesinpreventingCOVID-19andseriouscomplicationsassociatedwithCOVID-19faroutweighanycurrentlyknownsideeffects.Aswithallvaccinesandmedicines,thesafetyofCOVID-19vaccinesiscontinuouslymonitored,andbenefitsandpossiblerisksremainunderreview. WetakeeveryreportofasuspectedADRseriouslyandencourageeveryonetoreportthroughtheYellowCardscheme. Annex1VaccineAnalysisPrint TheattachedVaccineAnalysisPrintscontainacompletelistingofallsuspectedadversereactionsthathavebeenreportedtotheMHRAviatheYellowCardschemeforthemonovalentandbivalentCOVID-19VaccinePfizer/BioNTech,theCOVID-19VaccineAstraZeneca,themonovalentandbivalentCOVID-19VaccineModerna,theCOVID-19NovavaxVaccineandwherethebrandofthevaccinewasnotspecified.Thisincludesallreportsreceivedfromhealthcareprofessionals,membersofthepublic,andpharmaceuticalcompanies. Thisinformationdoesnotrepresentanoverviewofthepotentialsideeffectsassociatedwiththevaccines.AlistoftherecognisedadverseeffectsofCOVID-19vaccinesisprovidedintheinformationforhealthcareprofessionalsandtherecipientinformationhere.ThesecanalsobefoundontheCoronavirusYellowCardreportingsite.ConclusionsonthesafetyandrisksofthevaccinescannotbemadeonthedatashowninthePrintalone. Whenviewingthevaccineanalysisprintyoushouldrememberthat: reportersareaskedtosubmitYellowCardreportseveniftheyonlyhaveasuspicionthatthemedicineorvaccinemayhavecausedtheadversereaction.Theexistenceofanadversereactionreportintheprintdoesnotnecessarilymeanthatthevaccinehascausedthesuspectedreaction. itmaybedifficulttotellthedifferencebetweensomethingthathasoccurrednaturallyandasuspectedadversereaction.Sometimestheseeventscanbepartoftheconditionbeingtreatedratherthanbeingcausedbythevaccine. manyfactorshavetobeconsideredwhenassessingwhetherthevaccinehascausedareportedadversereaction.Whenmonitoringthesafetyofvaccinesandmedicines,MHRAstaffcarryoutcarefulanalysisofthesefactors. Foramedicineorvaccinetobeconsideredsafe,theexpectedbenefitswillbegreaterthantheriskofhavingharmfulreactions.Itisimportanttonotethatmostpeopletakemedicinesandvaccineswithouthavinganyserioussideeffects. VaccineAnalysisPrint-COVID-19VaccinePfizer/BioNTech VaccineAnalysisPrint-COVID-19VaccineAstraZeneca VaccineAnalysisPrint-COVID-19VaccineModerna VaccineAnalysisPrint-COVID-19VaccineNovavax VaccineAnalysisPrint-Brandunspecified Annex2Glossary Anaphylaxisoranaphylactoidreactions Anaphylaxisisasevereandpotentiallylife-threateningallergicreaction.Thesereactionscanoccurafteranexposuretoatrigger,suchasacertainingredientinfoodsormedicinesoraninsectsting.Anaphylaxisandanaphylactoidreactionscanbetreatedwithadrenaline. Bell’spalsy Bell’spalsyisaconditionthatcausestemporaryweaknessorparalysis(lackofmovement)ofthemusclesinonesideoftheface.Itisthemostcommoncauseoffacialparalysis.Formostpeople,thefacialparalysisistemporary.ViralinfectionssuchasthosewithherpesviruseshavebeenlinkedtoBell’spalsy. Bivalentvaccine Avaccinewhichstimulatesanimmuneresponsetotwoviralstrains. Boosterdose/vaccination ACOVID-19boostervaccinedosehelpsimprovetheprotectionobtainedfromthefirsttwodosesofthevaccine.Ithelpsgivelonger-termprotectionagainstgettingseriouslyillfromCOVID-19. CapillaryLeakSyndrome(CLS) CapillaryLeakSyndrome(CLS)occurswhenfluidleaksfromthesmallbloodvesselsintothebody. Cerebralvenoussinusthrombosis(CVST) Cerebralvenoussinusthrombosisoccurswhenthebrain’svenoussinusesorthesmallerveinsdrainingintothemarepartiallyorcompletelyblockedbyabloodclot.Thispreventsbloodfromdrainingoutofthebrain.Asaresult,theoxygensupplytonervecellsmaybeimpairedandbloodcellscanleakintothebraintissuecausingdamagetothebrain(haemorrhagicinfarction). ClinicalPracticeResearchDatalink(CPRD) ClinicalPracticeResearchDatalink(CPRD)isareal-worldresearchservicetosupportpublichealthandclinicalstudies.CPRDisjointlysponsoredbytheMedicinesandHealthcareproductsRegulatoryAgencyandtheNationalInstituteforHealthResearch(NIHR),aspartoftheDepartmentofHealthandSocialCare.CPRDcollectsanonymisedpatientdatafromanetworkofGPpracticesacrosstheUK. CommissiononHumanMedicines(CHM) TheCommissiononHumanMedicines(CHM)advisesministersonthesafety,efficacyandqualityofmedicinalproducts.ForCOVID-19vaccines,theCHMhasaCOVID-19VaccinesSafetySurveillanceMethodologiesExpertWorkingGroupandaCOVID-19VaccinesBenefitRiskExpertWorkingGroup. Endocarditis Endocarditisisinflammationoftheinnerliningoftheheart(endocardium). Epidemiologystudies Epidemiologicalstudiesincludelargenumbersofpeopleandaredesignedtocomparetheriskofaparticulareventinanexposedpopulation,inthiscasethosewhohavereceivedavaccine,tothosewhohavenot.Theyattempttoaccountfordifferencesinthedifferentgroupstohelpusunderstandifanydifferenceinriskiscausedbytheexposure.Epidemiologicalstudiesmeasuretheriskofillnessordeathinanexposedpopulationcomparedtothatriskinanidentical,unexposedpopulation. Guillain-BarréSyndrome Guillain-BarréSyndromeisinflammationofthenervesandcanleadtonumbness,weaknessandpain,usuallyinthefeet,handsandlimbsandcanspreadtothechestandface.Thissyndromehasbeenassociatedwithviralinfectionssuchastheflu. Immunethrombocytopenia Immunethrombocytopenia(ITP)isanauto-immuneconditioncharacterisedbylowbloodplateletcount(thrombocytopenia)andisassociatedwithanincreasedriskinbleedingwhichoftenpresentsasbruisingorpetechia/purpura. Miller-FisherSyndrome Miller-FishersyndromeisavariationofGuillain-BarréSyndromethataffectsthenervoussystemandcancauseweaknessinthefaceandalackofbalanceandco-ordination.SimilartoGuillain-BarréSyndrome,thissyndromehasbeenassociatedwithviralinfectionssuchastheflu. Miscarriage Thelossofapregnancyduringthefirst23weeks. Monovalentvaccine Avaccinewhichstimulatesanimmuneresponsetooneviralstrain. Myocarditis Myocarditisistheinflammationoftheheartmuscle(myocardium). Non-clinicalstudies Non-clinicalstudiesrefertostudiesthatarenotperformedonthehumanbody.Thesearelargelydonebeforeclinicaltrialsinhumansandcanincludeanimalsafetyandefficacystudies,humantissuesamplestudiesortoxicology. Pericarditis Pericarditisisinflammationofthepericardium,theprotectivesacthatsurroundsyourheart. Regulation174authorisation TemporaryauthorisationforsupplyofamedicineorvaccinebytheUKDepartmentofHealthandSocialCareandtheMedicinesandHealthcareproductsRegulatoryAgency.Thistemporaryauthorisationgrantspermissionforamedicine(vaccine)tobeusedforactiveimmunisationtopreventCOVID-19diseasecausedbySARS-CoV-2virus.Authorisationissubjecttoanumberofconditions.TheseareavailableforeachvaccineontheMHRAwebsite. Suspectedadversereactions Alsoknownassideeffects.Allmedicinesorvaccinescancauseadversereactionsinsomepeople.AdversedrugreactionsreportedtotheMHRAarelookedatandusedtoassessthebalanceofrisksandbenefitsofmedicinesandvaccines. Stillbirth Astillbirthiswhenababyisborndeadafter24completedweeksofpregnancy.Ifthebabydiesbefore24completedweeks,it’sknownasamiscarriage. TemporalAssociation Eventsoccurringfollowingvaccinationbutmayormaynotbecausedbythevaccine. Thirddose/vaccination ACOVID-19thirdvaccineisbeingofferedtothosewhohadaweakenedimmunesystemwhentheyhadthefirsttwodosesoftheCOVID-19vaccination.Thethirddosemayhelptoimproveimmuneresponseandgivebetterprotection. Thrombocytopenia Thrombocytopeniaiswherethebloodcontainsalowerthannormalnumberofplatelets.Plateletsarethesmallestofthebloodcellsandareinvolvedintheclottingprocess. TransverseMyelitis Transversemyelitisisarareacuteneurologicaldisordercausinginflammationofthespinalcord,thepartofthecentralnervoussystemthatsendsimpulsesfromthebraintonervesinthebody. YellowCardscheme TheMHRA’sschemeforhealthcareprofessionalsandmembersofthepublictoreportsuspectedadversereactionsforamedicineorvaccine,aswellasmedicaldevicesandotherproducts.ThededicatedCoronavirusYellowCardreportingsitewaslaunchedinMay2020specificallyformedicinesandmedicaldevicesusedinCOVID-19,aswellasCOVID-19vaccineswhenauthorised. Asaresultofchangestothepublicationschedulesofvaccineusagedatathisreportusesdatafromthedateclosesttoourdatalockpoint.ThisreportincludesdatafromEnglandupto25September2022,Scotlandupto11September2022,Walesupto21stSeptember2022andNorthernIrelanduptothe28September2022.Pleasenotethisappliestoallvaccinationdosagedatathroughoutthereport. ↩ NumberofvaccinationsduringpregnancyareupdatedwhendataismadeavailablebytheUKPublicHealthbodies ↩ KharbandaEO,etal.SpontaneousabortionfollowingCOVID-19vaccinationduringpregnancy.JAMA.doi:10.1001/jama.2021.15494. ↩ Magnus,MCetal.Covid-19VaccinationduringPregnancyandFirst-TrimesterMiscarriage.NEnglJMed2021;385:2008-2010DOI:10.1056/NEJMc2114466. ↩ StockSJ,etalEarlypregnancyoutcomesfollowingCOVID-19vaccinationandSARS-CoV-2infection:anationalpopulation-basedmatchedcohortstudyhttps://www.researchsquare.com/article/rs-1955486/v1 ↩ PublicHealthScotland,COVID-19Statisticalreport. ↩ StockSJ,etalSARS-CoV-2infectionandCOVID-19vaccinationratesinpregnantwomeninScotlandNatureMedicine2022https://www.nature.com/articles/s41591-021-01666-2. ↩ GoldshteinetalAssociationofBNT162b2COVID-19VaccinationDuringPregnancyWithNeonatalandEarlyInfantOutcomesJAMAPediatrics(2022)doi:10.1001/jamapediatrics.2022.0001 ↩ ↩2 Backtotop Isthispageuseful? 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