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AcceleratingDiagnostics inaTimeofCrisis
Accelerating DiagnosticsinaTime ofCrisis
Editedby StevenC.Schachter
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www.cambridge.org
Informationonthistitle: www.cambridge.org/9781009396981
DOI: 10.1017/9781009396998
©CambridgeUniversityPress&Assessment2024
Thispublicationisincopyright.Subjecttostatutoryexceptionandtotheprovisions ofrelevantcollectivelicensingagreements,noreproductionofanypartmaytake placewithoutthewrittenpermissionofCambridgeUniversityPress&Assessment.
Firstpublished2024
AcataloguerecordforthispublicationisavailablefromtheBritishLibrary.
LibraryofCongressCataloging-in-PublicationData
Names:Schachter,StevenC.,editor.|Bolton,WadeE.,1947– editor.
Title:Acceleratingdiagnosticsinatimeofcrisis:theresponsetoCOVID-19andaroadmapforfuturepandemics/ editedbyStevenC.Schachter,WadeE.Bolton.
Description:Cambridge,UnitedKingdom;NewYork,NY:CambridgeUniversityPress,2023.|Includes bibliographicalreferencesandindex.
Identifiers:LCCN2023023826(print)|LCCN2023023827(ebook)|ISBN9781009396981(paperback)|ISBN 9781009396998(ebook)
Subjects:MESH:COVID-19 – diagnosis|Pandemics|Emergencies|RapidDiagnosticTests|ProcessAssessment, HealthCare|UnitedStates
Classification:LCCRA644.C67(print)|LCCRA644.C67(ebook)|NLMWC506.1|DDC616.2/4144–dc23/eng/ 20230828
LCrecordavailableat https://lccn.loc.gov/2023023826
LCebookrecordavailableat https://lccn.loc.gov/2023023827
ISBN978-1-009-39698-1Paperback
CambridgeUniversityPress&Assessmenthasnoresponsibilityforthepersistence oraccuracyofURLsforexternalorthird-partyinternetwebsitesreferredtointhis publicationanddoesnotguaranteethatanycontentonsuchwebsitesis,orwill remain,accurateorappropriate.
Everyeff orthasbeenmadeinpreparingthisbooktoprovideaccurateandup-to-dateinformationthatisin accordwithacceptedstandardsandpracticeatthetimeofpublication.Althoughcasehistoriesaredrawn fromactualcases,everyeff orthasbeenmadetodisguisetheidentitiesoftheindividualsinvolved. Nevertheless,theauthors,editors,andpublisherscanmakenowarrantiesthattheinformationcontained hereinistotallyfreefromerror,notleastbecauseclinicalstandardsareconstantlychangingthrough researchandregulation.Theauthors,editors,andpublishersthereforedisclaimallliabilityfordirector consequentialdamagesresultingfromtheuseofmaterialcontainedinthisbook.Readersarestrongly advisedtopaycarefulattentiontoinformationprovidedbythemanufacturerofanydrugsorequipment thattheyplantouse.
DedicatedtoLindleyHallforhismentorship,JohnParrishforhispioneeringworkto acceleratehealth-caresolutionsandtoWallaceandJoeCoulterandtheirspiritofScience ServingHumanity.
ThisworkwassupportedbytheNationalInstituteofBiomedicalImagingand BioengineeringunderGrant5U54EB015408-06.Theviewsexpressedinthismanuscript arethoseoftheauthorsanddonotnecessarilyrepresenttheviewsoftheNationalInstitute ofBiomedicalImagingandBioengineering;theNationalHeart,Lung,andBloodInstitute; theNationalInstitutesofHealth;ortheUSDepartmentofHealthandHumanServices.
TheeditorsandchapterauthorsarethankfulforthevisionaryleadershipofFrancis Collins,BruceTromberg,JillHeemskerk,TiffaniLash,andToddMerchakinguidingthe developmentandimplementationoftheRapidAccelerationofDiagnostics(RADx®)Tech programandfacilitatingtheclosecollaborationofcruciallyessentialgovernmentagencies andnongovernmentalorganizationsinthiseffort.
ListofContributors ix
Foreword xiii
HarveyV.Fineberg
Preface xv
WadeE.Bolton
Acknowledgments xvii
Introduction 1
TaniaFernandez
1 EarlyDetection,Response, andSurveillanceoftheCOVID-19 PandemicCrisis 6
EnriqueM.Rabellino,Alexandra Smith,andMartaC.Cohen
2 ImmunologyofCOVID-19 andIneffectiveImmunity 31
AdolfoFirpo-BetancourtandEnrique M.Rabellino
3 ClinicalManagement:ARoadmap BasedonOneNewYorkCity Hospital’sResponsetotheCOVID-19 Pandemic 50
BarbaraBarnett,YvetteCalderon, BethanyKranitzky,YoungImLee,Erick Eiting,LinaMiyakawa,WaleedJavaid, andSaralynneBrown
4 ContributionofRADx® Tech totheRapidDevelopment ofCOVID-19DiagnosticTests 74
StevenC.Schachter,JohnM.Collins, MichaelK.Dempsey,LauraL. Gibson,MatthewL.Robinson,and PaulTessier
5 CoordinationofResourcesforthe ManufacturingandDeploymentof COVID-19DiagnosticAssays 88
MarenDowning,MiaCirrincione, AdamSamuta,KevinLeite,Sam
Dolphin,EmilyMuth,JoseValdesuso, andBrianWalsh
6 QualityandRiskManagement ProcessesforDiagnosticAssays duringanEmergencyPandemic Response 103
DevonC.CampbellandChristieJohnson
7 DevelopmentofAssaystoDiagnose COVID-19 125
YukariC.ManabeandWilliamClarke
8 LaboratoryVerificationandClinical ValidationofCOVID-19Diagnostic Assays 143
AnuradhaRao,LedaBassit,Julie Sullivan,WilburLam,andJennifer K.Frediani
9 ImportanceofTimelySequencing, Tracking,andSurveillance ofEmergentVariants 166
JessicaLin,MorganGreenleaf,Yang Lu,LedaBassit,CassandraWesselman, andAnnePiantadosi
10 TheRADx® RegulatoryCore andItsRoleinCOVID-19Emergency UseAuthorizations 194
ErikaTyburskiandCathrynCambria
11 CommercializationandMarket AssessmentofCOVID-19Assays 211 ManuelKingsley,SunshineMoore, HeathNaquin,EliseoVelasquez,Emily Kennedy,andGraceBendinger vii
TestingStrategiestoMitigate COVID-19DiseaseSpread 236
PaulTessierandAnette E.Hosoi 13 APandemicNotJustofInfection butofInequality:TheSocial ImpactofCOVID-19 250 MaraAspinallandLizRuark 14 SummaryandPathForward forFuturePandemics 263 WadeE.BoltonandSteven C.Schachter
Index 274
Contributors
MaraAspinall
HealthCatalysts,Tucson,AZ,USA
BarbaraBarnett
MountSinaiHealthSystem,NewYork, NY,USA
LedaBassit
EmoryUniversity,Atlanta,GA,USA
GraceBendinger
RapidAccelerationofDiagnostics (RADx®)–VentureWell,Hadley, MA,USAFrindleHealth,Newnan, GA,USA
WadeE.Bolton
RADx–VentureWell,Hadley,MA,USA
BoltonConsulting&Services,Delray Beach,FL,USA
SaralynneBrown
MountSinaiHealthSystem,NewYork, NY,USA
YvetteCalderon
MountSinaiHealthSystem,NewYork, NY,USA
CathrynCambria
CambriaRegulatoryConsulting,Atlanta, GA,USA
DevonC.Campbell Prodct,Boston,MA,USA
MiaCirrincione
RADx–VentureWell,Hadley, MA,USA
WilliamClarke
JohnsHopkinsUniversitySchoolof Medicine,Baltimore,MD,USA
MartaC.Cohen
SheffieldChildren’sHospital,Sheffield,UK
JohnM.Collins CIMIT,Boston,MA,USA
MichaelK.Dempsey CIMIT,Boston,MA,USA MassachusettsInstituteofTechnology, Cambridge,MA,USA
SamDolphin RADx–VentureWell,Hadley,MA,USA
MarenDowning
RADx–VentureWell,Hadley,MA,USA
ErickEiting
MountSinaiHealthSystem,NewYork, NY,USA
TaniaFernandez
DreamCatcherVentures,SanFrancisco, CA,USA
RADx-VentureWell,Hadley,MA,USA
HarveyV.Fineburg
Gordon&BettyMooreFoundation,Palo Alto,CA,USA
AdolfoFirpo-Betancourt
MountSinaiHealthSystem,NewYork, NY,USA
JenniferK.Frediani EmoryUniversity,Atlanta,GA,USA
LauraL.Gibson
UniversityofMassachusettsMedical School,Worcester,MA,USA
MorganGreenleaf
EmoryUniversity,Atlanta,GA,USA
AnetteE.Hosoi
MassachusettsInstituteofTechnology, Boston,MA,USA
WaleedJavaid
MountSinaiHealthSystem,NewYork, NY,USA
ChristieJohnson Prodct,Boston,MA,USA
EmilyKennedy
RADx–VentureWell,Hadley,MA,USA
ManuelKingsley
QuestusHealthcare,Atlanta,GA,USA
RADx–VentureWell,Hadley,MA,USA
BethanyKranitzky
TheOhioStateUniversityWexner MedicalCenter,Columbus, OH,USA
WilburLam EmoryUniversity,Atlanta,GA,USA
YoungImLee
MountSinaiHealthSystem,NewYork, NY,USA
KevinLeite
RADx – VentureWell,Hadley,MA,USA
JessicaLin
GeorgiaInstituteofTechnology,Atlanta, GA,USA
YangLu IcahnSchoolofMedicineatMountSinai, NewYork,NY,USA
YukariC.Manabe
JohnsHopkinsUniversitySchool ofMedicine,Baltimore, MD,USA
LinaMiyakawa
MountSinaiHealthSystem,NewYork, NY,USA
SunshineMoore
SunshineMooreConsulting,Madison,WI, USA
RADx–VentureWell,Hadley,MA,USA
EmilyMuth
RADx–VentureWell,Hadley,MA,USA
HeathNaquin UniversityCityScienceCenter, Philadelphia,PA,USA
RADx–VentureWell,Hadley,MA,USA
AnnePiantadosi EmoryUniversity,Atlanta,GA,USA
EnriqueM.Rabellino MedScienceServices,Miami,FL,USA
AnuradhaRao EmoryUniversity,Atlanta,GA,USA
MatthewL.Robinson
JohnsHopkinsUniversitySchoolof Medicine,Baltimore,MD,USA
LizRuark covidsafeschools.org,Boston,MA,USA
AdamSamuta
RADx–VentureWell,Hadley,MA,USA
StevenC.Schachter
HarvardMedicalSchool,Boston,MA,USA CIMIT,Boston,MA,USA
AlexandraSmith
RADx–VentureWell,Hadley,MA,USA UniversityofSouthCarolinaSchoolof MedicineGreenville,Greenville, SC,USA
JulieSullivan
EmoryUniversity,Atlanta, GA,USA
PaulTessier CIMIT,Boston,MA,USA
ErikaTyburski
AtlantaCenterforMicrosystems EngineeredPoint-of-Care Technologies,Atlanta, GA,USA
JoseValdesuso RADx–VentureWell,Hadley,MA,USA
EliseoVelasquez
InvestorsofColorNetwork,Boston,MA, USARADx–VentureWell,Hadley,MA,USA
BrianWalsh RADx – VentureWell,Hadley,MA,USA
CassandraWesselman ROSALINDInc.,SanDiego,CA,USA
Foreword
HarveyV.Fineberg
Adeadlypandemicdemandsaresponseatmultiplelevelsofgovernmentandsocietyand acrossmyriadneedsforpublichealthandmedicalcare.AstheCOVID-19pandemictook holdinearly2020,theUSresponsefaltered.Hospitalslackedsufficientpersonalprotective equipmentforstaff and,ascasessurged,somewereoverwhelmedbysickpatients.Optimal careforextremelyillpatientswasuncertain.Thefederalresponselackedaclearleadership structureandchainofcommand.Antiviralswerelacking,andaneffectivevaccinewasyetto bedeveloped.Moreover,theCentersforDiseaseControlandPreventioninitiallydistributedatestkitwithafaultyreagent,settingbackthenationaltestingstrategyforCOVID-19.
Thenation’spremierbiomedicalresearchorganization,theNationalInstitutesofHealth (NIH),focuseditsCOVID-19effortsonthreemaingoalsofresearch:vaccines,therapeutics, anddiagnostics.ByApril2020,theNIHhadactivatedapublic–privatepartnershipto acceleratethedevelopmentofCOVID-19therapeuticsandvaccines.Throughfundingand activecollaboration,theNIHwasinstrumentalinthedevelopmentoftheModernavaccine. Withtheactiveengagementof20companiesandscoresofscientists,theNIHscreened hundredsoftherapeuticcandidates,embarkedonclinicaltrialsformorethanthreedozenof themostpromising,andobtainedsixtherapeuticsapprovedforclinicaluse.Fueledby aspecialcongressionalappropriationinApril2020,theNIHlaunchedtheRapid AccelerationofDiagnostics(RADx®)initiative.Withinsixmonths,theFoodandDrug Administrationgrantedemergencyuseauthorizationtothe firstpoint-of-care – rapid COVID-19testsfundedthroughRADx – andsincethenmorethanfourdozenRADxsupportedtests(20point-of-care,16laboratory-based,and13home-basedtests)have receivedemergencyuseauthorization.
Thepandemicdemandedunaccustomedspeed,intensity,and flexibilityinresearch.All oftheinstitutesoftheNIHrespondedtothesepandemicexigencies.However,RADxstands outforitsdegreeofinnovativenessandreadinesstoembracenon-traditionalwaysofdoing businessattheNIH.
LedbytheNationalInstituteofBiomedicalImagingandBioengineering,RADxbuilton yearsofexperiencegainedthroughCIMITandthePoint-of-CareTechnologyResearch NetworkthatiscoordinatedbyCIMIT.Ratherthanconsidertheaimtobefundingbrilliant research,RADxadoptedanoutcomes-orientedapproachthatembracedeverystage,from scientificideathroughproofofconcept,productdevelopment,manufacturing,clinical evaluation,regulatoryreview,andauthorizationforuse.Ratherthantraditionalpeer review,RADxdevelopedashark-tankapproachofpresentation,assessmentofpromise, andinvestment,followedbyaninnovationfunnelwithdevelopmentmilestonesand sequentialwinnowingorintensifyinginvestment.Ratherthanahands-off approachafter grantapproval,RADxadoptedventure-capital-likecontinuedsupportandcoachingto overcomeanyobstaclesalongtheway.
TheseinnovationsmeantthatRADxwouldseekandfosterideasthathadthepromiseof successandnotsimplylookforreasonsthataprojectmightfail.Thus,RADxdidnotaccept aninevitable “valleyofdeath” forbiomedicalproductdevelopment;RADxestablishedoases ofsupportthatcarriedeasier-to-use,faster,andmorereliablediagnostictestsfromscientific
ideastoclinicallaboratories,sitesofclinicalcare,andhomes.BecauseofRADx,asmanyas 3billionCOVID-19testshaveenteredtheUSmarket,andrapidhomeandpoint-of-care testshavebecomethenorm.
Thisbookdescribestheconcept,organization,implementation,andresultsoftheRADx initiative.ItprovidesmanycasestoillustratethevariedwaysthattheRADxmodel, combiningthebestofpublicandprivatecapacities,contributedtothesuccess.Itshows howRADxadaptedandlearnedfromfailuresinrealtimetostrengthenitsapproach.The bookpositionsthequestformoreandbetterdiagnostictests – accurate,easytouse,and widelyavailable – againstthebackdropofmultiplepandemicdemandsonclinicalcareand publichealth.TheRADxexperienceholdslessonsnotonlyforthedevelopmentoffuture diagnosticsbutalsoforanysituationinwhichmultiplescientificscenariosmayyield technologiestohelpmeetanurgenthealthneed.
MorethanthreeyearsafterthestartofCOVID-19,theUnitedStatesandmuchofthe worldappeartohaveweatheredthebruntofthepandemic,althoughthetollonlivesandthe financialimpactcontinuetomount,andpost-acutesequelaeofsevereacuterespiratory syndromecoronavirus2(SARS-CoV-2)remainanongoingclinicaldilemma.China,whose zero-tolerancepoliciesheldoff thefullforceofCOVID-19foracoupleofyears,hassince founditselfinthethroesofthepandemicandhaslentitsweighttothegrowing,global burdenofdisease.
Withtime,wecananticipatemanyassessmentsofthepandemicresponseattheglobal, national,andsubnationallevels.Manywillprofferlessons,andsomewillbeworthheeding. TheRADxstorytoldheremeetsthathighstandard,worthyofheeding,inpreparingforthe nextpandemicorforanysimilarlysevereandurgenthealththreat.
Preface
WadeE.Bolton
In2019,auniquevirusemergedontheworldscenethatwouldcauseaglobalaffronttoour health-caresystems.Hundredsofmillionsofindividualsbecameinfectedwiththevirus, resultinginmillionsofliveslostandcatastrophic financialdamage.IntheUnitedStates alone,thepandemicwasthemostsignificantmedicalcalamityinthehistoryofournation, surpassingtheliveslostinWorldWarIandWorldWarIIcombinedandevenoutnumberingthecasualtiesofthe1918Spanish flupandemic.Asamemberofthecoronavirusfamily, whichwaslaternamedSARS-CoV-2,thisragingvirusat firstappearedtoresembletwoof itspredecessors,SARSandMiddleEastrespiratorysyndrome(MERS).Thescientific communitysoonlearned,however,thatthedifferencesamongthemwerestark.
ThroughtheNIH’sRADxinitiative,anetworkofprofessionalswasestablishedto respondtothevirusthroughthedevelopmentanddistributionofdiagnosticteststhat couldaccuratelydiagnosethepresenceofthevirusinpatientsamples.Ourassignmenthad noboundaries.Wereachedacrossinternationalborders,collaboratedwiththebravemen andwomeninthe field,andwerewelcomedbyacademicandgovernmentinstitutions willingandabletojoininthe fightagainstthiscommonfoe.Weunderstoodthatthiswas ourabsolutepriority – anationalandglobalmandatewithmillionsoflivesatstake.
Thisbookdocumentshowthelimitsofscienceanddiscoverywerepushedinacollective efforttocontainandmanagethispandemic,fromthedevelopmentofdiagnosticassaysto thesurveillanceofandresponsetoemergingvariants.Theauthorsdescribewhatwasdone differentlytoidentify,develop,anddistributediagnostictestsinrecordtimeandvolume. Weprovidetheframeworkfortechnical,organizational,practical,andoperationalaction itemsthatareessentialtothemanagementofanemergencyhealthcrisis.Wedescribeour lessonslearnedandwhatwewouldhavedonedifferentlytoimprovetheoutcomes.And, critically,eachchapterincludesaroadmapthatdetailsthestepsnecessarytooptimally respondtothepandemic.(Foracompleteroadmapcomprisingalloftheactionsteps plottedovertime,readerswillbeabletoturntoourwebsite, pandemicresponseroadmap .org,onceitislive.)Webelievethiscollectionofroadmapsisthe firstcomprehensive responseplanbasedonreal-lifepandemicexperiences.
Thepublicationofthisbookistimely,astheimpactofCOVID-19iscurrentlyundergoingoverallevaluation.Wearehopefulthattheexperiences,roadmaps,approaches,and frameworkshereinwillserveasscaffoldinguponwhichourcolleaguescanbuildwhenthey begintoplantheirresponsetothenexthealthcrisis.
TheWebsite
The pandemicresponseroadmap.org websitewillofferavaluableresourceforindividuals seekingtoenhancetheirunderstandingofpandemicresponsestrategies.Throughan interactiveandcustomizablepandemicresponseroadmap,userswillbeabletogaininsights intothecomplexandevolvingnatureofpandemicsanddevelopcustomizedstrategiesto navigatethemeffectively.Ourauthorbiosketcheswillprovidedetailedaccountsofthe trainingandexperiencesofeachauthor,enablingreaderstotrustinandappreciatetheir
uniqueperspectivesandexpertise.Additionally,ourcompiledlistoflessonslearnedduring theCOVID-19pandemicwillofferinsightsintosuccessfulpandemicresponsestrategies andareasforimprovement.Byleveragingthecollectiveknowledgeandexperiencesofour authors,ourwebsiteaimstoexpandupontheknowledgeprovidedwithinthebookpagesto furthercontributetoamoreinformedandeffectiveglobalpandemicresponse.
Acknowledgments
Projectteam:StevenSchachter,WadeBolton,EricEvans,TaniaFernandez,Enrique Rabellino,D’lynnePlummer,AlexandraSmith,andMallakTaleb.
RADx®TechCollaborators
AaronBlack,AaronChockla,AbigailConte,AceEdwards,AdamHoffman,AdamSamuta, AdannayaAmadi,AdannayaPathology,AdrianaQuintana,AdrienneHoey,AghaMirza, AhmedBabiker,AhmedHassan,AinatKoren,AlbertLee,AlbineMartin,AlecBoudreau, AlemaJackson,AletheaWieland,AlexGreninger,AlexanderGreen,AlexisBeatty,Ali Haide,AliciaLoffler,AlisonCernich,AllenBreiner,AllenGraham,AllieSuessmith, AllisonBlodgett,AllisonCristman,AllisonEason,AllysonChabot,AlokKapoor, AlpdoganKantarci,AlyssaOwens,AmandaDion-Schultz,AmandaFoster,Amanda Grindle,AmandaGrindle,AmandaMacLeod,AmandaRiley,AmandaStrudwick, AmandaSutton,AmberShowers,AmberThomas,AminulJoelIslam,AmyBaker,Amy Bucher,AmyKrafft,AmyMiarecki,AndreaDepatie,AndreaSjostedt,AndrewAdelman, AndrewDiMeo,AndrewGlenn,AndrewHastings,AndrewNeish,AndrewPerez,Andrew Potter,AndrewWebster,AndrewWeitz,AndyPekosz,AndyWinffel,AngelaStallworth, AniketPatel,AnissaElayadi,AnnChahroudi,AnnGawalt,AnnMartin,AnnaHorney, AnnaLowe,AnnaWood,AnnabelleSt.Pierre,AnnePiantadosi,AnneWyllie,Annette Esper,AnnieMiller,AnnmarieWalsh,AnthonyCurro,AnthonyKirilusha,AnuradhaRao, AnyeloDiaz,ApurvSoni,ArthurBray-Simon,ArunanSkandarajah,ArynneWilburn,Asha Storm,AshleyBanks,AshleyCrawley,AsifRizwan,AtamDhawan,AustinTigerLu,Babar Akhter,BaibaBerzins,BarbaraThompson,BarbaraVanDerPol,BarceyLevy,Benedict Kalibala,BenjaminHelmericks,BernadetteShaw,BethanneGiehl,BethanyTrainor, BethanyWatson,BetsyPeters,BeverlyBricker,BeverlyRogers,BillHeetderks,Bill O’Sick,BillRiley,BobStorey,BonoloMathekga,BradleyHanberry,BrandiLimbago, BrandyMai,BraylonRumph,BrendanMurphy,BrentIngraham,BrettGiroir,Brian Mustanski,BrianWalsh,BrittanyGoldberg,BrookeBeckman,BrookeSeitter,Brooke Staples,BruceBarton,BruceGay,BruceGnade,BruceTromberg,BryanBuchholz,Bryan Du,CadeidreWashington,CaesarMelendez,CaitlinPretz,CandaceDufour,Candice Miller,CangyuanLi,CaraBarnes,CarlKumpf,CarlPark,CarlosAparicio,Carlos Moreno,CarlosPerez,CarolBova,CarolGovern,CarterUsowski,CassieBednarek, CathrynLapierre,CathyCambria,CecileDavis,ChadAchenbach,ChaoQi,Charles Anamelechi,CharlesDaitch,CharlesHart,CharlesHill,CharlesOyesile,Charlette Bronson,CharlotteGaydos,CherylBastian,CherylMaier,CherylShimer,CherylStone, ChiaraGhezzi,ChrisBocus,ChrisBunn,ChrisDesrosiers,ChrisElkins,ChristianFlanery, ChristieCanaria,ChristieJohnson,ChristinaMacauliffe,ChristinaRostad,Christine Cooper,ChristineFarrell,ChristineHanson,ChristineWalter,ChristopherBrooke, ChristopherHartshorn,ChristopherPorter,ChunHuaiLuo,Chung-JungChiu,Cindy Pryor,CindyTeixeira,ClairO’Donovan,ClaudiaHawkins,ClaudiaMorris,Colin Brenan,ColleenKraft,ColleenMatte,ColleenSico,CollinTimm,ColtonJoseph,Connie Arthur,ConnieRivers,ConnorSeabrook,ConradTucker,CorneliusMoore,CourtneyLias, CourtneySabino,CraigLilly,CrystalReinhart,CynthiaHilgren,CynthiaNicholson,Dale xvii
Gort,DanMarshak,DanWattendorf,DaneshThirukumaran,DanielKalman,Daniel Murphy,DanielleDiMezza,DanielleHoward,DanielleOliver,DarashDesai,Darci Edmonson,DarwinSalgado,DavetaBrown,DavidAlter,DavidD.McManus,David George,DavidGiarracco,DavidGoldstein,DavidGottfried,DavidHoaglin,DavidKu, DavidMudd,DavidSanford,DavidSmith,DeborahKelly,DeborahLee,DeniseEhlen, DeniseR.Dunlap,DeniseScholtens,DenizPeker,DennisRose,DevonCampbell,Devon Hartigan,DianaBianchi,DianeLawrence,DianeQuinn,DianeSpiliotis,DigvijaySingh, DilhariPeiris,DinaSimon,DipanwitaBasu,DonCroteau,DonnaMatson,Donna McGrath,DoreenTrotta,DorothyMaxwell,DougSheeley,DouglasBryant,EdithOtabil, EdwardBerger,EdwardEhrman,ElaineKim,ElaynByron,ElenaKoustova,EliasCaro, EliseoPerez-Stable,EliseoVelasquez,ElizabethBulger,ElizabethChristian,Elizabeth Heald,ElizabethOrvek,ElizabethWalsh,EllenClegg,EllieBrent,EmBeauchamp,Emily Cisney,EmilyMuth,EmilySousa,EmmaWojtowicz,EriOrtlund,EricCecco,EricLai,Eric Nehl,EricPadmore,EricStratton,EricaLandis,EricardoEdwards,ErikaTyburski,Erin Iturriaga,EsmerldaMeyer,EthanBerke,EtienneDembele,EugeneRogers,EunMiLee, EvanAnderson,EvanBradley,FajarNuriddin,FarazIlyas,FeliciaQashu,FilippViola, FrancisCollins,FrankCable,FranziskaMeockel,FrederickBalagadde,GabrielaVarela Heslin,GailRadclifee,GallyaGannot,GaryDisbrow,GaryPlace,GarySudusky,Gaurav Mehta,GavinHarris,GeneCivillico,Geoff Bonn,GeoffreySmith,GermánChiriboga, GlennNeuman,GokhanOzalp,GraceBendinger,GraceTran,GrahamThreadhil,Greg Gibson,GregMartin,GregoryMarcus,GretchenArmington,GulNowshad,GuyBenian, HangChen,HansVerkerke,HaroldSullivan,HeathNaquin,HeatherBowers,Heather Tessier,HebaMostafa,HeleneLangevin,HershPatel,HesamHafizi,HibaAbbas,Hilary Dupre,HimaniBisht,HollyAlvarez,HollySommers,HollyTaylor,HopeKrebell,Howard Golub,HurKoser,IanMisner,IlanaGoldberg,J.ChristopherFlaherty,JacobKhouri, JacquelineMartinez,JaiprasathSachithanandhamm,JamesAnderson,JamesPatzke,Jane Holl,JanetFigueroa,JanetHale,JaniceBell,JaniceLegace,JannetteGuarner,Jared Kimbrough,JaredO’Neal,JasmineChaitram,JasonFord,JasonOpdyke,JasonWheeler, JayButler,JeanWelsh,JeanetteDaly,JeanneKeruly,Jeff Evans,Jeff Shuren,Jeff Winner, JeffreyBrocious,JeffreyE.Olgin,JeffreyHolden,JeffreyOlgin,JeffreyWilliams,Jen Afamefuna,JenicaPatterson,JenniferBaker,JenniferBiemer,JenniferCampbell,Jennifer Fediani,JenniferHolme,JenniferJackson,JenniferK.Frediani,JenniferMcKenney,Jeremy Boutin,JeroanAllison,JesandSylve,JessaWaggoner,JessicaIngersoll,JessicaMeade, JessicaOrozco,JessicaScott,JianLou,JillHeemskerk,JillMorgan,JillianMcClain,Jo Hiatt,JoanDavis,JoannaNathan,JoanneAndreadis,JoanneLebrun,JoanneMatthew, JoanyJackman,JocelynMontgomery,JodiBlack,JodyCiolino,JoeDavenport,JohnBarnes, JohnBlackwood,JohnBroach,JohnClick,JohnDiggs,JohnHaran,JohnHealey,JohnLear, JohnLee,JohnMcQuiston,JohnNuckols,JohnP.Broach,JohnParrish,JohnRoback,Jon McGrath,JonathanPatton,JonggyuBaek,JosephBriggs,JosephHutter,JosephOdorisio, JosephValdesuso,JosephWalsh,JoshTolkoff,JoshuaJacob,JoshuaLevy,JoshuaRumbut, JoshuaWolfe,JueChen,JuliaAdams,JuliaTisheh,JuliaZakashansky,JulieFlahive,Julie Norton,JulieStephens,JulieSullivan,JulieWilkinson,JunGuo,JustinBurns,Justin Hardick,JustinMcAteer,JustinTiao,JustinYang,KalpanaRegarajan,KamilahRashid, KaraPalamountain,KaraPenny,KarenAnnLavallee,KarenDel’Olio,KarenGilliam, KarenGriffin,KarenOlsen,KarenWallace,KarlSimin,KateKlein,KateThoma, KaterinaPappas,KatharineEgan,KatherineImmergluck,KatherineLuzuriaga,Katherine Ramirez,KathrynLaneMusall,KathrynMarvel,KatieHambrick,KatieShapcott,Katrina
Bogan,KavitaBabu,KeivanZandi,KelliMalkin,KellyArmy,KellyGorman,KelseyWoods, KenBeall,KerryDemarco,KerryDiBenardo,KevinCoats,KevinLeite,KevinSeiki,Khawar Hamid,KimCaroline,KimNoble,KimPachura,Kim-JudyYou,KimberleeCantin, KimberlySciarretta,KiraMoresco,KiranVerma,K.J.Shaikh,KlemensWengert,Krishna Juluru,KristenHerzegh,KristenWeber,KristiCooper,KristianRoth,KristinLe,Kristina Lowe,KristopherBough,KyleRose,KyleSprow,KylieLanman,KyungMoon,LacyWilson, LaiaHussaini,LarryTabak,LauraBenedit,LauraFerrara,LauraGibson,LauraRose,Laura Sampath,LaurelO’Connor,LaurenBalmert,LaurenHowe,LeaE.Widdice,LedaBassit,Lee Payne,LeonaWells,LeonaWells,LeonardoAngelone,LeticiaRockenbach,LeylaKara,Leyla Rose,LiLi,LieslWarbel,LifangHou,LilliamMartinezBello,LindaSmith,LindseyGieger,Lisa Council,LisaHirchhorn,LisaPonce,LisaPortner,LisaR.Hirschhorn,LisaSmith,LisaWaples, LisaWei,LiuXu,LizDiNenno,LizMcCarty,LizRuark,LoriPbert,LoriRandall,LouisVuga, LucieLow,LuckyJain,LydiaGarciaJacinto,LydiaMcClure,LynnFurtaw,M.DidemAvciogluAyturk,MacArthurBenoit,MackSchermer,MadelineHobbs,MadelineMarx,MadisonConte, MaggieHassan,MaggieLi,MaheshVangala,MamoudouMaiga,MandiBlochberger,Mandy O’Reilly,ManuelKingley,MaraAspinall,MaraHeng,MarayanaiahCeedarla,MarcCharette, MarenDowning,MargaretMcManus,MargaretNeja,MargaretOchocinska,MargoKinneyPetrucha,MariaCordero,MariaDavilla,MariaGrainger,MarianneWeinell,MarissaFayer, MarkBobrow,MarkBonaficio,MarkBonifacio,MarkFisher,MarkGonzalez,MarkGriffiths, MarkGuitarini,MarkHuffman,MarkMarino,MarkPletcher,MarkSmith,MarkSnyder, MarshallR.Collins,MaryAnnPicard,MaryBethTull,MaryCo,MaryDubuque,Mary Fadden,MaryJanetMcCarthy,MaryAnnLambert,MarzanKhan,MassielMota,Matt Durgin,MattO’Connell,MatthewCaputo,MatthewGluckserg,MatthewHart,Matthew Humbard,MatthewMcMahon,MatthewRobinson,MatthewSanders,MaudMavigner, MaureenBeanan,MaureenGarner,MaureenRichardson,MeganSchmidt,MeganShaw, MelaniePeel,MelindaMathis,MelissaFrangie,MelissaHenson,MelissaRamos,Melissa Rotella,MelvaSteps,MiaCirrincione,MichaelBoyce-Jacino,MichaelBrady,Michael Cariseo,MichaelCentola,MichaelDempsey,MichaelHarsh,MichaelHirsh,Michael Huggins,MichaelIademarco,MichaelKochersperger,MichaelKoeris,MichaelLauer, MichaelMasterman-Smith,MichaelNewcomb,MichaelNorton,MichaelPalmer,Michael Wolfson,MicheleListon,MichelleBerny-Lang,MichelleMcConnell,MichellePopler,Mike Ryan,MilagrosRosal,MiriamVos,MonicaLowell,MonicaO’Brian,MorganGreenleaf, MukthaNatrajan,MylaLai-Goldman,NadiaHassan,NancyElder,NancyGagliano,Nancy Mortimer,NancySencabaugh,NaomiBraun,NatalieBruning,NatalieLee,NateWade, NathanielHafer,NatiaSaakadze,NealConnors,NealDickert,NeetaShenvi,NeilMucci, NicholasGallagher,NickD’Aimco,NicoleBenevento,NigistmariamYasin,NikkiPowell, NilsSchoof,NimiFifadara,NiraPollock,NishaFahey,NitikaGupta,NoahPeyser,Noni Byrnes,OladapoOlaitan,OlgaBrown,OlgaHartman,OliverBrand,PaigeEzernack,Pamela McGuinness,PamelaMiller,ParangKim,ParitoshChandwade,PatriciaHelbin,PatriciaWiley, PattiBrennan,PattiO’Neill,PaulBaker,PaulEder,PaulTessier,PaulYoo,PaulinaRebolledo, PekoHosoi,PennyFord-Carleton,PeterD’Entremont,PeterLazar,PeterRice,PeterTobin, PetrSulc,PhilWeilerstein,PunamMathur,QimingShi,QuierraWells,RachaelFleurence, RachelAgoglia,RachelFactor,RachelFink,RachelKrebs,RahulSalla,RanaSaber,Randall Morse,RaoDivi,RashadWood,RashidaFerebee, RayEbert,RaymondCariseo,RaymondFelix Schinazi,RaymondMacDougall,RebeccaCleeton,RebeccaGore,RebeccaKirby,Rebekah Neal,RenSalerno,RenateMyles,ReneeSimon,ReshikaMendia,RhondaGibson,Ribhi Shawar,RicardoRamos,RichardAnderson,RichardCreager,RichardGirards,Richard
Hodes,RichardRothman,RickBright,RickD’Augustine,RickGagliano,RickWoychik,Rik Madison,RishaNayee,RjsekharGuddneppanavar,RobertEisinger,RobertFineberg,Robert Jerris,RobertKircher,RobertL.Murphy,RobertMannino,RobertNobles,RobertScalese, RocioLuparello,RodneyKincaid,RodneyWallace,RonTedesco,RoryCarrillo,Rosemary Humes,RoslynSeitz,RoxaneBurkett,RubenSalinas,RuifengZhou,RussellKempker,Ryan Eckmeier,SadanandGite,SajaAsakrah,SalStrods,SallyMcFall,SamDolphin,Samantha Strickler,SandeepPatel,SandraMaher,SandraOtt,SaraBrenner,SaraCaudillo,SarahBank, SarahEisenberg,SarahFarmer,SarahFey,SarahHernandez,SarahHuban,SarahMcGee, SathmurthyGourisankar,SauntelleByfield,ScottEibel,ScottTanner,SeegarSwanson,Seila Selimovic,SerenaCarroll,ShahidRashid,ShaminyManoranjithan,ShannaBruflodt,Shanna Spencer,ShannonGriffin,ShannonMoore,SharinaPerson,ShaukatSoofi,ShawnMulvaney, ShawnPatel,SheilaBaker,ShirleyConey-Johnson,ShirleyRuiz-Lundgren,SiluHu,Skyler Ward,SofiaMartinez,SoniaGales,SonjaDavis,SonjaDill,SotiriosGeragonis,Sreeram Ramakrishnan,StaceyCarroll,StaceySpies,StacyHellman,StacyTurner,StephanieAdams, StephanieBehar,StephanieMeisner,StephenieLemon,SteveBlanc,StevenSantos,Stewart Ellis,SuminKoo,SunitaGopalani,SunitaPark,SunshineMoore,SusanGregurick,Susan Moreira,SyedNaeem,TamaraMcBrayer,TamaraMcKenzie,TamaraWesley,TamiHagberg, TamilaDover,TammyBeckman,TammyFalla,TaraKnox,TaraLoomis,TaraSchwetz,Tatia Hodges,TaylorGilliland,TempistEvenson,TeresaZembower,ThanujaRamachandra, TheodoreZainal,ThomasGrifa,ThomasJohnson,ThomasPribyl,ThomasVanderford, TiffaniLash,TiffanyWilson,TimStenzel,TimThurman,TimmyMoore-Simas,Timothy Moulton,TimothyVanderford,TobyLowe,ToddMerchak,ToddSherer,TonyBoiers,Tony Haney,TonyVoiers,ToyaMorrison,TraciLeong,TracyMcMahon,TracyWilloughby,Truc Le,UgurCelik,UyenLe,ViNguyen,VickiAnastasi,VictorSine,VictoriaStittleburg,Vidurshi Gupta,VijayDhaka,VijayVanguri,VincentAhonkhai,VintonGrant,VivianaClaveria, VyjayantiKasinathan,W.O’Neal,WaltCarney,WayneWang,WebbStone,WendiKuhnert, WilburA.Lam,WilliamClarke,WilliamDaunch,WilliamHaddad,WilliamPierce,Wolfgang Krull,XaiveraMartinez-Armenta,XavierPeralta,YasminHaider,YolandaZeringue,YuHsiangHsieh,YufeiYu,YukariC.Manabe,YurimaGuilarte-Walker,ZacharyBuono, ZacharyEllison,ZacharyFavakeh,ZihanYang,ZinaBrown,ZiyueWang.
OtherAcknowledgments
BillRodrigues,MarcelleAbell-Rosen,SergioCarmona,JimDensmore,EdwardTharp, BradleyWait,BenWalker,JustinValliere,LisaButler,BrandiTalkington;Huck StrategiesLLC.
Introduction
TaniaFernandez
Theendof2022markedthreeyearssincethe firstreportsappearedinthenewsof apotentiallynovelcoronavirusinaseafoodmarketinWuhan,China.Commencingin December2019,COVID-19 – causedbythesevereacuterespiratorydiseasecoronavirus2 (SARS-CoV-2) – spreadrapidlyacrosscontinents,withthe firstcaseofCOVID-19being reportedintheUnitedStatesasearlyasJanuary20,2020.Twomonthslater,withtheofficial announcementbeingmadebytheWorldHealthOrganization,therewasnodenyingthe realitythatwewereinthemidstofaragingpandemic.
Atitsinception,noonecouldhavepredictedthepowerofthevirus.Itsweptthrough humanity,infectingmorethan700millionpeople,killingmorethan6.9millionpeople across215countries,cuttingacrosscaste,creed,andcolor.
Thisbookisatributetothe “warriors” whoworkedinthetrenchesdayandnightto combatthevirusandwagethedeadlywaragainstthepandemic.Itismeanttoserveas asoberingreminderofthesacrificesmadebysomany.Wededicatethisbooktothemillions oflivesthatwerelosttoCOVID-19andtofrontlineworkersacrosstheglobewhosacrificed theirlivesinthelineofduty.
Thisisourstoryofhowhumanitycametogetherduringanincrediblychallengingtime touniteforcesand fightacommonenemy.Itisastoryofreflectionsandlessonslearned, arecordofwhatwedidrightandwhatwecouldhavedonebetter,but,aboveall,thisis astorythatiswritteningratitudetotheunconquerablespiritofhumankindandthe relentlesspursuitofscientificknowledgetoservehumanity.
Thisbookchroniclesthepowerofinnovation,theacceleratedcommercializationof diagnostics,thebirthofnewbusinessmodelsandcreative financingventures,theperseveranceandcommitmentofentrepreneurs,andtheagilityandresourcefulnessofgovernment institutionsastheyadaptedtomeettheimminentneedsofthepandemicandservethe community.
Coronavirusesarenotnewtohumankind.Humanityhaswitnessedthreedeadlypandemicsinthetwenty-firstcenturyalone,allofwhichwereassociatedwiththisgroupof viruses.In2002,theworldwitnessedthe firstlethalcoronavirus-induceddisease,whichwas namedsevereacuterespiratorysyndromecoronavirus(SARS-CoV).Adecadelater,in2012, adifferentcoronavirusoutbreakunraveledintheMiddleEast,earningthenameMiddle Eastrespiratorysyndromecoronavirus(MERS-CoV).Despiteourseemingfamiliaritywith thisgroupofviruses,theglobalcommunitywasunpreparedwhenanovelcoronavirus reareditsuglyheadandsweptthroughhumankindwithaferocitylastwitnessedonly duringtheSpanishinfluenzapandemicof1917causedbytheH1N1virusandoftenreferred toasthegreatestmedicalholocaustinhistory.
Despitepreviousappearances,thiscoronaviruswaslabeledasnovelbecause acomparisonoftheviralgenomerevealedthatithadonly79.5%homologywithSARSCoVand40%homologywithMERS-CoV.Thus,itwasbattletimeagain.Wehadno armamentariumto fightthevirusoranyspecializedknowledgeofwhatweweredealing with.OurunderstandingoftheevolutionofSARSCoV-2andhowitspreadwasparticularly unclearduringtheearlystagesoftheCOVID-19pandemic.Misconceptionsandmyths aboutitsoriginanditsmodeoftransmissionragedlikewildfiresacrosscontinents,fueling panicandchaos.
Thepandemichadmadeitswayintothelifeofthemasses,andthescientificcommunity wasforcedtomeetthedemandsofquestioningandangrycommunitiesdemanding answers.Whateversideofthefenceonewasonwithregardtothequalityofscientific rigoronsocialmedia,itcannotbedeniedthatthemediaservedtodisseminateknowledge andinformationatanunprecedentedspeed.
Intheworldthatweliveintoday,whereCOVID-19,socialdistancing,lockdowns, contacttracing,superspreaderevents,antigentests,andpolymerasechainreaction(PCR) testshaveallbecomecommonhouseholdparlance,letusnotforgetthat,inDecember2019, theworldwasadifferentplace.Awarenessofpandemicswasatanall-timelow,despitethe occasionalvisionarymessagesofcautionthatwerevoicedbyaselectfewbutlargely neglected.
Thedepthandbreadthofscientificknowledgethatwehaveamassedsincethatfatalday thatSARS-CoV-2interruptedhumanityservesasatributetoallthescientists,clinicians, andhealth-careworkerswhoworkedtirelesslyatanunprecedentedpacetoadvance coronavirusresearch.DuringitsearlyspreadinJanuary,thousandsofviralgenomeswere rapidlysequencedbyresearchlaboratoriesaroundtheworldandsharedinopen-access databasessuchastheEpiCoVdatabasefromtheGlobalInitiativeonSharingAllInfluenza Data(GISAID)andtheOurWorldinDataCOVID-19dataset.Withinamonthofthe releaseoftheSARSCoV-2genome,theCDChaddevelopedthe firstSARS-CoV-2diagnostictestkitwhichgotFDAEUAapprovalonFebruary4,2020.
Aglimmerofhopearosethatwidespreadtestingandearlydetectionmightserveto interveneindiseaseprogressionandthuscounteracttheincreasingmortalitythathumanity waswitnessing.Accordingly,manycountriesrushedtoimplementpopulation-basedtestingtomonitorspreadandimplementquarantiningtoreduceviraltransmission.This createdenormouspressureforhigh-quality,reliableteststobedevelopedandcommercializedatrecord-breakingpace.Theplanetmorphedintothelargestglobaltestinggroundfor humanity.Governmentsacrosstheworldrosetotheoccasion,astheyhavetraditionally done,tofundresearchandinnovation.FromsequencingtheSARS-CoV-2genomeand sharingitwiththeworldtocharacterizingmethodsofviralentryandspread,aswellas ongoingsurveillanceofanassaultofviralvariantsanddealingwiththeconfusionandutter despairofthosewhowereasymptomaticallyspreadingthevirus,thescientificcommunity workedtirelesslytopushtheboundariesofunderstandingthebiologyofthevirus.
Thechaptersinthisbookarewrittenbyawiderangeofauthorswithvaryingexperiencesandexpertise,whohaveworkedacrossthespectrumfromresearchanddevelopment tocommercializationofCOVID-19diagnostics.Giventhemultidisciplinarynatureofthis initiative,eachchapterhasbeenwrittenbyauthorswithrelevantexpertiseandprovidesan in-depthnarrativefromtheirownuniqueperspectives.Thechaptershavebeencompiledto takethereaderonajourneywithusaswechronicletheearlystagesofthepandemic,the historicalevents,andtheeffectivenessofthedecision-makingprocessesduringcrucial
phasesofthepandemic.Wedelvebrieflyintotheimmunologyofthevirusanditsrapid evolutionthroughmutagenesisandtouchuponthecontroversialtopicofimmunitytothe virus.
IntheUnitedStates,SARS-CoV-2spreadrapidly,andwithitgrewtheinabilitytokeep pacewiththeincreasingdemandsforCOVID-19diagnostictesting.InApril2020,as mortalitycontinuedtosoarandtheneedfortestingwithintheUnitedStatesbecame imminent,theNationalInstitutesofHealth(NIH)receiveda$1.5billionappropriation fromCongresstoexpandtestingcapacityintheUSA.Thus,itwasthat,whiletheworld continuedtooperateinachaoticfrenzy,anewinnovativeprogramwasbornwithin five daysafterthelegislationwassignedintolaw.
TheNIHlaunchedtheRapidAccelerationofDiagnostics(RADx®)program.TheRADx Techinitiativewascreatedtosupportthedevelopment,validation,production,andcommercializationofaccurate,point-of-care,andhometests,aswellastoimproveexistingclinical teststhatcoulddetectSARS-CoV-2.Thisbrainchildinitiativepusheddiagnostics,amuchneglectedsector,totheforefrontthroughafocusonthecompressionofadiagnosticprototype-to-productlaunchfromover fiveyearstounderayear.Manyofthechaptersinthisbook arewrittenbyauthorswhowerepartoftheRADxinitiativeandworkedinthetrenches.These chaptersgointointricatedetailoneachaspectofthejourney,fromdevelopmenttodeployment,andwhatittooktoacceleratediagnosticcapacityinatimeofcrisis.
Overall,theRADxTechinitiativewasanunprecedentedprogramthatinvestedahuge amountofcapitalintoCOVID-19diagnosticsacrossthespectrum,fromtestsperformedin referencelaboratoriestopoint-of-carediagnosticsandover-the-counterhometests.The programusedarigorous “deepdive” diligenceprocessanda “sharktank” modelrunby leadingindustryexpertstoselectcompaniesandprojectswithinnovativetechnologiesthat hadthepotentialtoscaleupandaddressthetestingneedsindifferentsegmentsofsociety. Beyondthecapitalinvestments,RADxTechprovedtobeafertilegroundfortheevolution ofapublic–privatepartnershipmodelsuchastheindustryhadnotwitnessedbefore. Combiningthebestofbothworlds,itsetoutonitsmissionnotjustto financeinnovation incompaniesandde-risktechnology,buttoprovidecompanieswithanecosystembuiltto maximizesuccessincommercialization.Itsfocusonexternalverificationandvalidation throughkeyinstitutions,data-drivengo/no-godecisions,stringenttimelines,andoutcomes wasresponsibleforthesuccessoftheprogram.
AnotheruniqueaspectoftheinitiativewastheleverageofthePoint-of-CareTechnology ResearchNetwork(POCTRN),runbytheNationalInstituteofBiomedicalImagingand Engineering(NIBIB),whichthroughthreecyclesofpriorNIHfundinghadpreviously identifiedacriticalgapindiagnosticdevicedevelopmentaroundtheclinicalusecase.Thus, ascompaniesdevelopedtheirtechnologiesforCOVID-19tests,theywereguidedbyexperts intheareasofinfectiousdiseaseandemergencymedicine;ambulatory,pediatric,andadult clinicians;medicaldirectorsofcertifiedlaboratories;diagnosticdevelopers;andmarketing expertswithreal-worldexperience.Atthetimeofwritingthisbook,hundredsofmillionsof COVID-19testshavebeendevelopedandmarketed.
Itwasinitiallythoughtthat,withSARS-CoV-2beingwelladaptedtohumans,therewas minimalneedforconcernaboutmutationsamongcirculatingviruses(becauseofthe historicallyslowmutationrateofcoronavirusesandtheirinherentself-editingmechanism). Thischangedduringthelatermonthsof2020,whenthe firstreportsappearedofemergent SARS-CoV-2variantsthatwereassociatedwithincreasedtransmissibilityanddisease severity.
Diagnostictests,whichwerebasedontheoriginalWuhansequenceofSARS-CoV-2, werefoundtobeaffectedbythesemutations.TherepeatedemergenceofnewSARS-CoV-2 variantspresentedchallengestothedevelopmentofhigh-performingdiagnostics.The RADxVariantTaskForce – aninterdisciplinarygroupcomposedofrepresentativesof federalagencies,diagnosticdevicemanufacturers,privateandpublicbioinformaticscompaniesandorganizations,largelaboratoryorganizations,andacademicinstitutions – was thuscreatedasaprogramwithinthelargerRADxinitiativethatfocusedonassessingRADx technologiesagainstvariants.
Theclinicalmanagementchapter(Chapter3)focusesonpatientcareduringatimeof absolutecrisisandthesignificantshiftinclinicalpracticefromusingevidence-based medicinetobeingforcedtouseexperimentalmethodsoftreatment.Ithighlightsthe innovationinhealth-caredeliverymodelsashospitalleaderssoughttoincorporatetelemedicinetowidenpatientreachwhilenotcompromisingonquality.
AquotefromGeorgeSantayana(TheLifeofReason,1905)comestomind: “Thosewho donotrememberthepastarecondemnedtorepeatit.” So,letusnotforget.Letusnever ceasetorememberthesacrificeofdoctors,health-careworkers,andfrontlineresponders acrosstheglobe.Humanitywillalwaysbegratefultothemfortheirsacrificeduringthese unprecedentedtimes.Thisbookcapturescasestudiesofhowstrongandselflessleaders madeittheirmissiontofocusonthecareofpatientsinatimewhentherewerenoruleson howtocombatthisenemy.
Canwepreventthenextpandemic?Aswecontinuetoreflectonthatquestion,welook backnotjustatthemistakesthatweremadeduringthepandemicbutalsoatwhatwedid rightandthekeycontributionsthatweremadeinthisperiod.Afewofthenoteworthy successesincludebutarenotlimitedtocontrollingsupply-chainbottlenecks,therapid commercializationofdiagnosticsinatimeofcrisis,theunprecedentedrolloutofCOVID19testing,vaccinedevelopment,acceleratedregulatoryapprovals,andensuringthataffordabletestsweremadeavailableasmuchaspossible.Akeydifferentiatorofthisbookisthe factthat,ineachchapter,readerswill findmeticulouslydetailedroadmapsthatarespecific tothechapter.Wehopethatthesewillserveasusefultoolsforthenextgenerationofhealthcareleaderstocreate,implement,andexecuteoperationalstrategiesinthefaceofchaosand uncertaintyduringsuccessivediseaseoutbreaks.
Wearecognizantofthefactthat,inthisbook,wehaveanalyzedthepandemicthrough whatcouldbeconsideredaveryUS-centriclens.Whilepartofthiswaschoice,alargepartof itwasnecessity.Tobeabletocommunicatewithourreaderswiththeexperienceand expertisethatisrequiredtotellthisstory,wehadtowriteitfromthebattlefieldweoperated from,whichwastheUnitedStates.Innowaydowemeantodiminishtheheroiceffortsof othernationsthatfoughtthisbattle,andtheyshouldbeapplauded.Wherepossible,wehave referencedglobaleffortsanddrawnattentiontotheminselectchapters.
Apandemicaffectsvariousaspectsofsociety.Theclosureofessentialandnonessential businesses,restrictionsontravel,requiringindividualstoisolatetocombatrisingratesof mortalityandmorbidityalltooktheirtoll,andsocietyfacedexistentialthreatsaseconomies begantoshutdown.Variednationalresponsestothethreatofthevirus,aswellaseconomic andracialdifferencesacrossnations,ledtosocietaldisparitiesandvastlydifferentpandemic impactsacrosstheglobe.Thishasnotbeenignoredandisalsoafocusofthisbook.
Thereisnodoubtinanyone’smindthattheeffectofthepandemichavebeensevere,and wearestillwitnessingandwillcontinuetowitnessitslong-termdamagetosociety worldwide.Thepowerofsharingscientificdata,thestrengthofpartnerships,thecreativity
ofcollaborations,andtherefusaltoadmitdefeatinthepresenceofacommonenemyshould neverbeforgotten.Thesememorieswillserveuswellforbuildingabetterandmore resilientworld.
Throughthisbook,wehopetoaddressthemaincomponentsofthepandemicasit evolvedandtoprovidestrategiesandguidelinesforthemanagementofoutbreaksbeyond COVID-19,thusservingasalegacyformanyfuturegenerations.
