长新冠手册参考(2022)-Gez+Medinger-Danny+Altmann

GezMedinger&ProfessorDannyAltmannTHELONGCOVIDHANDBOOKContentsIntroductionChapter1:WhatIsLongCovid?Chapter2:WhoGetsLongCovidandWhy?Chapter3:CanChildrenGetLongCovid?Chapter4:WhatCausesLongCovid?Chapter5:ThePathologyofLongCovidChapter6:GenderBiasandHowtoTackleItChapter7:TheImpactofLongCovidonMentalHealthChapter8:HowtoHelpOthersHelpYouChapter9:TipsforManagingSymptomsChapter10:WhataboutTreatment?Chapter11:WhatDoesRecoveryLookLike?Chapter12:TheEmotionalJourneyChapter13:What’sNext?ConclusionAcknowledgementsNotesResourcesReferencesIndexAbouttheAuthorsGezMedingerisaninvestigativesciencejournalistandpatientadvocateforLongCovid.Hewasafilm-makerandmarathonrunnerwhenhebecameillwithCovidintheearlydaysofthepandemic.Whenhedidn’trecover,GezputhiseffortsintoresearchingthenovelconditionofLongCovid,interviewingsomeoftheworld’sleadingcliniciansandturninghisYouTubechannelintoahugeresourceforpatients,conductingoveradozenpatient-ledstudies–whichhavebeenquotedintheglobalpress,includingtheNewYorkTimes,NewScientistandMen’sHealth.Intheprocesshehasbuiltaworldwidecommunityandhisfilmscurrentlyhaveover5millionviews.ProfessorDannyAltmannisaProfessorofImmunologyatImperialCollegeLondon.Hiskeyresearchinterestsaretheimmunologyofinfectiousdiseaseincludingseverebacterialinfections,Zikavirus,chikungunyavirusandSARS-CoV-2.Hehasalsoworkedonautoimmunediseasesincludingmultiplesclerosisandrheumatoidarthritis.DuringtheCovid-19pandemichehasactedinseveraladvisoryroles,includingontheHouseofCommonsandHouseofLordsScienceCommitteesandtheImmunologyTaskForcetotheScientificAdvisoryGroupforEmergencies(SAGE).HespentsomeyearsworkingastheleadonstrategyinInfection,ImmunityandPopulationHealthattheWellcomeTrust,andhasservedmorethantwentyyearsaseditoronmedicaljournals,includingImmunology.IntroductionInearlyMarch2020,IwasinthehillsaboveLosAngeles–gettingasuntan,tryingtogetmysecondfeaturefilmoffthegroundandtrainingformyfourthmarathon.Theweatherwasdelightful,mylegswerestrong,andIwasconfidentofhittingmytwohoursfiftyminutestargetintheLondonMarathonthefollowingmonth.TheonlyproblemwasthatsomewhereincentralChinaapangolinhadpartiedtoohardwithabat,andnowapandemicwasbrewing.fn1Theworld–andmylife–wasabouttochangeimmeasurably.IflewbacktoLondonon6March,andlessthanaweeklaterhadmyfirstsymptom–apeculiarnausea.Thefollowingday,chillsandstomachupset.AllthecolleaguesI’dsharedameetingroomwithafewdayspriorwereilltoo.Therewerenotests,sonoonecouldbesure,butCovidwasexplodingacrossLondon.Myinitialillnesswasn’ttoosevere.Iwasabletoworkafewhoursadayandfeltfoolishlyandquietlysmugthatmyimmunesystemwasobviouslybetterthanmycolleagues’,whowerefeverish,coughingandhavingageneralshocker.TheLondonMarathonnowlookedlikeitwasgoingtobecancelled,butIwassokeennottolosemyhard-wonfitnessthatinthesecondweekoftheillnessItriedgoingforshortjogs.Bythispointmycolleagueswererecovering.IwasconfidentthatinafewdaysI’dberightasraintoo.Afterall,thegovernmentwassayingthatifyoudidn’tendupinhospital,thenyourisolationcouldendafteraweek,bywhichpointyou’dbefittogobacktowork.OnlyIdidn’tgetbetter.Ikeptrunning–goingslowly,tellingmyselfthatitwasonlyamatteroftime–buttheweekswentpastandstillIfeltawful.Andthen,fiveweeksin,Ifeltit:averyspecific‘grizzly’feelinginmythroatandchestthatI’dnotexperiencedfortwenty-twoyears.Thatfeelingwasthesignaturesymptomofpost-viralfatiguesyndrome(PVFS),whichIexperiencedforayearafterbeingillwithglandularfever.OhGodno,Ithought,Ican’tbedoingthatforanotherwholeyear.Notnow.So,IdecidedtomakeafilmformynascentYouTubechanneltoexaminethepotentiallinksbetweenthenovelcoronavirusandPVFS.Coulditbepossiblethatswathesofpeoplewouldbestruckdownwithacomplex,poorlyunderstoodandoftencompletelydebilitatingcondition,evenafteramildinitialCovidinfection?Iwasn’tsureifanyonewouldfindtheirwaytothefilm(especiallygivenmypaltrysubscriberbaseatthetime),butitgainedanaudienceinthetensofthousandsimmediately–peopleallaroundtheworld,whowerecryingoutforsomeonetorecognisewhatwashappeningtothem.IthoughtI’dmakeonlyonefilmonthesubject.ButthenImadeanother.Andwhynotonemore?It’llbeatrilogy,Ithought.AndnowhereIam,morethantwoyearsandeightyfilmslater.StillnotbacktowhereIwasatinLosAngeles,running20kmatracepaceeveryday,butabletoliveabusylifewithoutrelapsingeveryweekasIdidinthebeginning.ThevastimprovementinmyqualityoflifehasbeendueinlargeparttomakingmyselfGuineaPigNo.1,incorporatingeverypieceofexpertadviceandresearchaccumulatedonmyjourneyintomyownlifetoaidmyrecovery.Havingmadealotofprogress,mygoalnowistosharethelessonsthatI,andotherrecoveredlonghaulers,havelearnt–oftenthehardway.Icouldn’tbemorepleasedtobecollaboratingonthisprojectwithProfessorDannyAltmann,oneoftheUK’smostrespectedimmunologistsandanexpertonpost-viralconditionstoboot.Sinceearlyinthepandemic,hehasbeenpreparedtoputhisheadabovetheparapetandspeakonbehalfofpatientsstrugglingtogetrecognitionfromthemedicalestablishment.DannyisalsorunningalargeresearchprojectatImperialCollegeLondonthatisinvestigatingtheroleofimmunesystemabnormalitiesandautoimmunity(whichdescribeswhenourimmunesystemattacksourowncells)inLongCovid,andsoisattheveryforefrontofbiomedicalunderstandingoftheillness.Betweenus,wehopetopresentaspectrumoftheknowledgethatexistsatthetimeofwriting–fromtheanecdotalexperiencesthatIhaveobservedintheLongCovidcommunitythroughtomyownpatient-ledstudiesandthehardsciencethat’saccumulatingasmoreresearch,trialsandpublicationsreachthelightofday.Perhapsyou’reaLongCovidsuffereryourself,orafamilymemberorpartnerofsomeonewhois.Orperhapsyou’reaclinicianseeingpatientsandlookingforaresourcethatbringseverythingweknowaboutLongCovidtogether.Thisisthatresource.DannyandIhavetriedtomaketheknowledge,lessonsandsciencehereinasaccessibleaspossible,becauseifanyoneknowshowdifficultitistoabsorbinformationwithbrainfog,it’ssomeonewithLongCovid.Wewillbreakdownthekeytopicsintoshortchapters.Ratherthanpresentyouwithasolidwalloftext,Iwillbeyournarrator,whileDannywillbreakdowntheknottyandestablishedsciencerelevanttoeachtopicinseparate‘boxout’sections,likethatbelow.Attheendofmostchapters,thereisaquickQ&AwithDannyandotherkeycontributors,pickingupsomeoftheoutstandingquestions.LikeGez,myintroductiontotheworldofCovidalsocameinMarch2020,whenmyresearchteamoptedtopivotfromour‘dayjobs’investigatinginfectionandimmunitytoeffortsatdecodingimmunitytosevereacuterespiratorysyndromecoronavirus2(SARS-CoV-2),thevirusthatcausesCovid.Morethantwoyearsin,wehaveallbecomesoexpertinthetopicthatit’shardtothinkbacktothattimeofavirtuallyblankcanvas.AlthoughI’vespentmyliferesearchingthemolecularimmunologyofpathways(i.e.howthebody’simmunesystemrespondstoinfection)inawidevarietyofbacterial,viral,fungalandautoimmunediseases,herewasanewdiseaseaboutwhichweknewnothing.Sincethatperiod,we’veworkedonCovidimmunityprettymuchsevendaysaweek,publishingourfindingsinjournalssuchasTheLancet,ScienceandNature.Withinafewmonths,oneofmyoldestfriendswho’dbeeninfectedearlyinthatfirstwavegavemeadetailedandaccuratedescriptionofwhatwastobecomeknownasLongCovid.Previouslyanextremelybusy,activeperson,shefeltshe’dhadthewindknockedoutofher,couldbarelywalkaroundtheblockandfeltconstantlyfatigued.Thiswasvaguelyfamiliarandalarming.Oneoftheflagship‘day-job’projectswe’dhadtosuspendwasacollaborationacrossclinicalsitesinBrazil,whichaimedtoestablishwhysomanypatientsinfectedwiththemosquito-bornechikungunyavirusgoontodevelopachronic,disablingillnessthatcandragonforyears.Oneofournextpapers,publishedintheBritishMedicalJournal,wasakindofmanifestofortherouteforwardtounderstandLongCovid.I’dalwaysbeenquitemotivatedabouttheneedtocommunicateaboutresearchwiththepublic,pressandpolicymakers.Thiscommunicationbegantoseemreallycriticalinatimeofuncertaintyandpanic.Noonewantstocomeacrossasasmartalecormansplainer,butherewasasituationinwhichyoucouldn’tturnontheTVorradiowithoutapoliticianexpoundingon‘antibodies’or‘herdimmunity’,topicsthatI’dlivedandbreathedfromthefirstdayofmyPhDstudiesattheageoftwenty-one.Mydiarybegantofillupwithdailysessionswithjournalists,TVcrews,politiciansandpatientgroups.Duringoneofthesesessions,ImetGezmakingoneofhisfilms.We’vekeptinclosetoucheversince,oftenexchangingnewsofthelatestresearchfindings.TheLongCovidstoryisremarkableinthesensethatthemedicalagendahasbeendrivenentirelybypatientsthemselvesandtheircommunicationacrosssocialmediaplatforms.I’vemetterrific,medicallyarticulatepeoplethroughthosegroupsandacquiredfromthemacrashcourseinlivingwiththisdiseasethatnowinformsallourresearch.Withthatinmind,myaspirationhereistodorightbypeoplewithLongCovidintryingtoofferanhonestandaccessibledistillateofallI’velearntandanythingthatcouldbehelpful.ThepriceIpayforthisisthat,whileGez’snarrativewilloftencomeacrossasdramaticandexciting,I’mcastintheroleof‘ProfessorBoring’,asthevoiceofthemedicalestablishment.It’saroleI’mcontenttotakeifitoffersusefulillumination.Itwillbeself-evidentfromthisbookthatLongCovidresearchisinitsembryonicstage,sittingataninterfacebetweenthepatientadvocatesandthemedicalresearchprofessionals.Inthatcontextit’shopefullyusefulthatthisbookhastwodistinctvoicesfromthosedifferentperspectives.Thetwoviewscaninevitablybecomepolarisedattimes.Gezhashisroleindrawingtogetherthelivedexperienceofthesufferersincludingtheirsearchfortherapeuticanswers.Itisthisclamourforanswersthatwillintimewenditswayintoformalresearchstudies.Mycareerhasdrummedintometheparamountneedtoignoreanecdotesinfavourofalaser-focusonthestatistically-powered,controlledtrial.Thatis,whenhearingabout‘evidence’inLongCovid,IsetthebarinexactlythesameplaceasifIwereaskedtopeerreviewitforNatureorTheLancet.ThismeansthatsometimesGezandIwillnotagree.Idon’tendorseeverystatementhemakes,andviceversa.LongCovidhasyettoachieveconsensussoweseethisbreadthasaplus.Italsomeansthatmyformalitymaysometimesannoyyou–youmayfindthatthehypothesisortreatmentthatseemsmostcentraltoyourviewhasreceivedshortshriftfrommebecauseithasn’tyetcrossedthatbar.Whoknows,withtime(anddata)youmayhavethelastlaugh.So,withoutfurtherado,let’sbegin.CHAPTER1WhatIsLongCovid?OneofthehardestpartsoftryingtodescribeLongCovidisthatitmaybeverydifferentforyoufromhowitisforme.Butforalmostallofuswhoexperienceit–longhaulers,aswearesometimesknown–theillnessimpairsalmosteveryaspectofday-to-daylife.Mostlonghaulersareunabletosocialiseorworkastheycouldbefore,theyaremostcertainlyunabletoexerciseastheycouldbeforeandoftentheyareevenunabletoeatanddrinkastheycouldbefore.Otherthansomebagsundertheeyes,youmightlookprettynormal.Thosearoundyou–unlessthey’veexperiencedchronicillnessthemselves–maystruggletounderstandwhatyou’regoingthrough.Althoughperhapsthat’snotsurprising:LongCovidcomeswithabewilderingarrayofsymptoms–203ofthem,accordingtoapatient-ledstudypublishedbyTheLancetGroup.1Ofcourse,nooneexperiencesall203ofthesesymptoms.TheCovidlotteryissomethingofan(un)luckydip.LongCovidcanencompassasinglesymptomsuchasanosmia,throughtothemorecommonclusterofmultiple(usuallyaround5–20)symptoms.ThetermisalsoapplicabletosomeonewithaknowncomplicationafterCovid-19,suchasastrokeorseverelungdamage.Thisbookwon’ttakeadogmaticstanceonthedurationofpersistentsymptomsthatcountasaLongCovidcase–both4weeksor12weeksfromstartofinfectionhavebeenapplied.Sincemanydoimprovesignificantlyfrom4–12weeks,thelattercut-offisusefulfordemarcatingthosesetonmoreofa‘long-hauler’trajectory.WhatisLongCovidinasinglesentence?LongCovidisalong-termconsequenceofSARS-CoV-2infection,lastingbeyondtheinitial‘acute’phaseofinfection,affectingmultiplebodilyorgansandsystems,causingahugevarietyofsymptomsandofvaryingseverityandduration,potentiallyrelapsingandremittingovertime.Crucially,longhaulers’symptomsarenotlikelytobeconsistent.Theyvaryfromweektoweek,daytoday,evenminutetominute.Day-to-daytasksandplanningevenasfaraheadastomorrowaredifficultwhenyouhavenoideahowyou’llbefeelingatanypointinthefuture.LongCovidisdebilitatingbynature.Peoplewhohaven’texperiencedfatigue,themostcommonsymptomofLongCovid,oftenimagineittobeclosetothefeelingoftirednessafterheavyexerciseoranextremelylongday.Beforethepandemichit,ifyou’daskedme,IwouldhavesaidIknewwhatspendingeverylastdropofenergyfeltliketoo,assomeonewho’drunseveralmarathonsandranmyownbusiness,frequentlyputtinginconsecutiveall-nighters.ButthesystemicexhaustionthatLongCoviddealsupisonanentirelydifferentlevel–perhapsonlyfamiliartothosewithseverechronicillnesses,suchasmyalgicencephalomyelitis,alsoknownaschronicfatiguesyndrome(ME/CFS).Thisexhaustionreallyneedsanewwordtodescribeit,because‘fatigue’doesn’tdoitjustice.Inmypatient-ledresearch,this‘fatigue’isrepeatedlycitedasthemostcripplingsymptomforlonghaulersacrosstheboard.Fatigueisexhaustiondowntoyourverybones.EvensimpleactivitieslikereadingorwatchingTVaretoomuch,letalonetheabsurdideaofbeingabletoholdaconversation.OneAmericanstudycompared1,295Covidlonghaulerswith2,395patientswithcancer,andintheprocessfoundthatthelonghaulerswereroughlytwiceaslikelytoself-reportpoorphysicalhealthorpainasthosewithcancer.2Ofcourse,whilefatiguemightbethemostfrequentlyreported,there’sover200othersymptomswhich,onanygivenday,mightknockyouforsix.ThesymptomsWithoutmakinganexhaustivelistofall203symptoms,herearesomeofthemostcommon:fatiguebrainfog(akacognitivedysfunction)chestpainortightnessinsomniaheartpalpitationsdizzinessjointpaindepressionandanxietytinnitusandearachesnausea,diarrhoeaandstomachachesheadachesskinproblems(peeling,rashes,itching)continuedlossoftasteandsmell.Butthere’snoendofunusualstuffbeingreportedbylonghaulers,fromtheprofoundlydisablingtothemerely‘upsetting’,suchas:hairlosstinglingandnumbnessnervepainmenstrualchangeserectiledysfunctionurinaryincontinenceblurredvisionhallucinations.Ifyou’vegotmorethanoneofthesesymptoms(forthefirsttime)andhaverecentlyhadCovid,thenit’spossibleyou’resufferingfromLongCovid.Asyoumayhavegathered,there’sverylittlecorrelationbetweenthesymptomsyoumighthaveexperiencedinyouracuteinfectionandthoseyoucouldexperienceinLongCovid,whichcanpresentinalmostanysystemofthebody.And,intheUKatleast,wheresomanypeopledidnothaveaccesstoCovidtestsearlyinthepandemic,clinicianscannowdiagnosetheconditionwithoutneedingevidenceofinfection–or,forthatmatter,adiagnostictest.Because,atthetimeofwriting,areliable,easilyaccessibletestthatprovesyouhaveLongCoviddoesnotexist.Historicallythisabsenceof‘testability’hascontributedtopoorunderstandingofpost-viralconditions.It’ssimplytooeasytowriteoffthesymptomsasstress,anxietyorburnout,whichhashappenedtoinnumerablepeoplewithME/CFSandLymediseasefordecades.Long-termeffectsofCovid-193Fromaclinicalandacademicperspective,what’sdifferentorinterestingaboutLongCovid?Modernmedicineismeanttobeaboutpreventingpainfulanddebilitatingdisease.We’regrapplingwithanewviruswhich,dependingonwhichestimatesyouuse,hascausedatleast5milliondeathssofar.TheWorldHealthOrganizationrecentlyuppedtheestimatedglobaldeathtollto15millioninMay2022.Yetinmedicine,wedon’tjustcountdeaths,wecountsymptomsandqualityoflife.So,there’sactuallyamuchlargernumberofpeoplewhoareaffectedinthelongtermbyachronicdiseasethatimpairstheirlifeonaday-to-daybasis–whetherit’stheirabilitytofunctionnormally,worknormallyorevengetoutofbedinthemorning.Youcan’teasilyquantifyit,anditisoftenassignedlessimportancethandeath,butthepointI’veoftenmadeis:let’sjustsupposethatinanidealworldourvaccinesworksowellthatweceasetoworryaboutintensivecareunits(ICUs)beingoverrunandadailydeathtoll.WemightstillbetalkingaboutthispandemicintermsoftheLongCovidimpactforyearstocome,longafterwe’reworryingabouttryingtodealwiththeacutedisease.What’sparticularlychallengingisthat,aswelearnmoreandmore,it’simpossibleforanyonedoctororcliniciantounderstandabsolutelyeverythingaboutmodernmedicine.Ittakesalifetimejusttogetyourheadroundeverythingweknowabouttheimmunesystem,forexample.So,wegetincreasingdegreesofspecialisation,andknowledgegetssiloed.Youhavespecialistsforeachorgansystemordifferentpartsofphysiology.ButtheproblemwithLongCovidisthatitdoesn’t,inmostcases,neatlyfallintooneortwoofthosesilos.Itseemstoinvolveallofthem,andthusisoutsidetheremitofanyoneconventionalspecialist.Moretothepoint,LongCoviddefieseasytesting.Recentresearchhassuggestedthatlowcortisollevels(ahormoneresponsibleforregulatingstressresponseandsuppressinginflammation)maybeimplicatedinLongCovidandcouldatsomestageformpartofadiagnostictest,butthereisyettobewidespreadagreementonmarkersthatindicateseverityorwhatmightbegoingon.It’sevenpossiblethatasinglediagnostictestmightnoteverbedevelopedforsuchaheterogeneousdisorder.4SolvingthequestionofwhatLongCovidactuallyisseemstometoneedahelicopterviewatthesametimeasadeepdive.Howinthecurrentsystemdoyoudobothsimultaneously?What’sthesolutiontothisneedforbothadeepandbroadunderstandingofLongCovid,giventheconstraintsofthecurrentmedicalsystem?It’sunbelievablychallenging.Oneofthethingsthathappensisthat,inanyprofessionalspecialty,wealwaysthinkthatwe’rebetter,moreknowledgeableandbettertrainedthanthepreviousgeneration,andalsothat‘theyoungstersdon’tknowwhatthey’retalkingabout’.Theperennialwhingeoftheoldergenerationisthattheyoungdoctorsoftodayhavebeensoshoddilytrainedthattheybarelyunderstandtheirownspecialtyandareterrifiedofseeinganybodyoutsideit.But,tounderstandcomplexdiseases,youdoneedtounderstandthewholepersonandyouneedanexcellentcommandofgeneralinternalmedicine.IoftencompareLongCovidtolupus.Let’ssayyou’readoctorsittinginyourclinicandthemedicaltextbookchapteronlupushadneverbeenwritten.Apatientwalksin–let’ssayit’sayoungwomanwhodoesn’tknowwhattodobecauseshe’sgotaskinrash.Maybeifyouwerecleverorempatheticyou’dreferhertoadermatologistandyou’dthink,Wow,thatwasabittedious.Thenshecomesbackthreemonthslaterforarepeatappointment.Herrashhasclearedup,butshehasincrediblerespiratoryproblemsandtellsyouthatshecan’twalkuphillsanymore.Youthink,Lasttimeshesaiditwasherskin,thistimeshesaysit’sherlungs.Issheattention-seeking?What’sgoingonwithher?Soperhapsyoureferhertoarespiratoryteam.Threemonthslatersheturnsupagainandsaysshe’shavingtroublewalkingbecauseherjointsarereallyplayingup.Nowyou’reperhapswonderingifthiscouldbepsychosomatic,butyoureferhertoarheumatologist.PerhapsyoucanseewhereI’mheadingwiththis.Youmightassumethatthewomanwasanattention-seekerunlessyouunderstoodlupusandthefactthatthere’sacommonmechanismunderlyingallthesymptomsshehad.And,ofcourse,thispersonwasn’tmakingitup.Shehadabona-fideautoimmunediseasecalledsystemiclupuserythematosus,whichmeritsamulti-system,multi-organ,multi-specialtytreatmentapproach.So,attheendofmylabouredmetaphor,Ithinkthat’swherewearewithLongCovid.Peoplehavediversesymptomsthatareremittingandrelapsing,comingandgoing.Somepeoplearebeingempathetic,whereasothersarethinking,Aretheymakingitup?becausewehaven’tyetwrittenthetextbookchapteronLongCovid.Whilethere’sstillalongwaytogo,I’dliketothinkwe’remakingprogressandthatperhapsthisbookcanhelpfillsomeoftheknowledgegaps.Scientistsandcliniciansareusingfancy,high-techtoolkitstofigureouthowLongCovidworksatafunctional,cellularlevel.Intheend,thedevilisinthedetail,andwe’requitegoodatmeasuringdetail.I’moptimisticthatitwon’ttaketoolonguntilweunderstandLongCovidaswellas–ormaybeevenbetterthan–weunderstandlupus.Nomatterhowtired,exhaustedandsickyoumayfeelrightnow,orhowharditistogetthroughparagraphafterparagraph,Danny’soptimismismerited,despitewhatpeoplewithotherpost-viralconditionshaveexperiencedforthepasttwentyorthirtyyears.Moreonthereasonsforthatoptimismalittlelater.Butrightnow,let’sstayontopic.Thatwassymptoms.Nowlet’saddressphenotypes.ThephenotypesSomequestionstogetusgoing.IfyoulookateveryonewithLongCovid,isthereapatternaroundthegroupingofsymptoms?Forexample,whymightyouhavejointpainandshortnessofbreath,whileIhaveheadachesandpalpitations?Aretherelotsofpeoplewhohavethesesamecombinationsofsymptoms,andifso,whatcouldthattellusabouthowthediseaseworks?IsitpossiblethatunderstandingthesegroupingsandwhatcausesthemcouldhelppeopleavoidLongCovidaltogether?Itisthesegroupingsofsymptomsthatwecallphenotypes–literally,howthediseaseprocesslooks.Thesearehuge,importantquestionsthatmedicinehasn’tquiteansweredyet.Butresearchisongoingthatmightshinesomelightontheanswers.HoweasilycanwedemonstratephenotypesofsymptomsforLongCovid?Ithinkthejuryisstillout,simplybecauseyoucanlookatitinsomanydifferentways.Inmedicinewetendbreakitdownintothe‘lumpers’,whoareattemptingtounderstandthewholeofthisdisease,andthe‘splitters’,whoslicethediseaseintoaninfinitenumberofthinlittleslices.Untilyou’vegotaclearpictureofthediseasemechanism(i.e.howexactlythediseaseproducessymptomsonaphysiologicallevel),tryingtodelineatephenotypesisalwaysabitlikeputtingthecartbeforethehorse.Yousaytoyourself,‘I’vegottosimplifymyquestion,soI’mgoingtolookonlyatpatientswhoreportmainlyrespiratorysymptoms–thepeoplewhocan’thaveanykindofexertionandpermanentlyfeelbreathless.’Anditthenmightbeusefultosay,‘Let’slookattherespiratoryfolkwhoarepredominantlyexperiencingbreathlessnesscomparedtotheneurofolkwhoarepredominantlytroubledbybrainfogandword-findingproblems.’IhaveafeelingthatifItriedtodothat,Imightbebombedoutofthewaterbypeoplesaying,‘Well,I’mboth’or‘I’mrespiratorybuttherespiratorysymptomsonlycameaftermyjointandskinproblems.’Itmightturnoutthatmycategoriesarealoadofnonsense,becauseyoucan’tgettheansweruntilyou’vegottheanswer.Someofthelargeresearchprojectstodate5,6haveclusteredCovidlonghaulersintothefollowinggroupsbasedontheseverityoftheinitialinfection:milddisease,nothospitalisedhospitalisedadmittedtoICU.Butwhenitcomestounderstandingthedisease,thesegroupingscanonlytakeussofar.Forone,thevastmajorityoflonghaulersouttherefallintothefirstcategory.Furthermore,thoseinthethirdcategory–peoplewhowereadmittedtotheICU–aremorelikelytobeexperiencingtheeffectsoforgandamagethanthepotentiallymorediversedriversofLongCovidinothers.Soultimatelywewillneedafinerlevelofcategorisationbysymptomclusterstodeterminemechanismandthendevelopeffective,ideallyindividualisedtreatments.Thisfinercategorisationiscoming,withrecentresearch(usinghugevolumesofdatafromtheZOEapp)suggestingcertainsymptomclusters.7However,basedonwhatI’veobservedinmorethantwoyearsembeddedinthecommunityandfromsurveyingthousandsoflonghaulersinmyownpatient-ledresearch,Iwouldliketoproposesomephenotypeswhichmighthelpuswhenitcomestotreatingandmanagingsymptoms.Ifwebreakdownthefirstcategoryof‘milddisease,nothospitalised’intermsofsymptoms,Iwouldarguethreemaingroupingshaveemerged:increasedintolerancetofoods,allergies,headaches,skinissues,breathingproblemsandgutissuesbrainfog,fatigue,post-exertionalma