2024
SARS-CoV-2-related bat viruses evade human intrinsic immunity but lack efficient transmission capacity
Peña-Hernández M, Alfajaro M, Filler R, Moriyama M, Keeler E, Ranglin Z, Kong Y, Mao T, Menasche B, Mankowski M, Zhao Z, Vogels C, Hahn A, Kalinich C, Zhang S, Huston N, Wan H, Araujo-Tavares R, Lindenbach B, Homer R, Pyle A, Martinez D, Grubaugh N, Israelow B, Iwasaki A, Wilen C. SARS-CoV-2-related bat viruses evade human intrinsic immunity but lack efficient transmission capacity. Nature Microbiology 2024, 1-13. PMID: 39075235, DOI: 10.1038/s41564-024-01765-z.Peer-Reviewed Original ResearchBat coronavirusesRelatives of SARS-CoV-2Upper airwayUpper airways of miceEpithelial cellsHuman nasal epithelial cellsAirways of miceMajor histocompatibility complex class I.SARS-CoV-2Nasal epithelial cellsHistocompatibility complex class I.Human bronchial epithelial cellsGenetic similarityBronchial epithelial cellsInnate immune restrictionCoronavirus replicationFunctional characterizationMolecular cloningReduced pathogenesisImpaired replicationBat virusCoronavirus pathogenesisPandemic potentialHigh-risk familiesImmune restrictionInternal tremors and vibrations in long COVID: a cross-sectional study
Zhou T, Sawano M, Arun A, Caraballo C, Michelsen T, McAlpine L, Bhattacharjee B, Lu Y, Khera R, Huang C, Warner F, Herrin J, Iwasaki A, Krumholz H. Internal tremors and vibrations in long COVID: a cross-sectional study. The American Journal Of Medicine 2024 PMID: 39069199, DOI: 10.1016/j.amjmed.2024.07.008.Peer-Reviewed Original ResearchNew-onset conditionsInternal tremorLong COVID symptomsCOVID symptomsNon-Hispanic whitesCross-sectional studyQuality of lifeVisual analogue scaleWorse healthHealth statusStudy participantsDemographic characteristicsAnalogue scaleOutcome variablesNeurological conditionsLong COVIDMast cell disordersTreatment experienceHealthComorbiditiesSymptomsMedian agePeopleCell disordersInflammatory Response and Defects on Myelin Integrity in the Olfactory System of K18hACE2 Mice Infected with SARS-CoV-2
Martin-Lopez E, Brennan B, Mao T, Spence N, Meller S, Han K, Yahiaoui N, Wang C, Iwasaki A, Greer C. Inflammatory Response and Defects on Myelin Integrity in the Olfactory System of K18hACE2 Mice Infected with SARS-CoV-2. ENeuro 2024, 11: eneuro.0106-24.2024. PMID: 38834299, PMCID: PMC11185043, DOI: 10.1523/eneuro.0106-24.2024.Peer-Reviewed Original ResearchOlfactory bulbOlfactory epitheliumPiriform cortexOlfactory tractOlfactory systemSARS-CoV-2Projection neuronsMyelination defectsOlfactory sensory neuronsLateral olfactory tractLoss of olfactionRespiratory epithelial cellsLamina propria macrophagesSARS-CoV-2 infectionInfected SCDays of infectionIntegrity of myelinOlfactory dysfunctionInfected microgliaSensitive to infectionOlfactory deficitsSensory neuronsSustentacular cellsNasal cavityNeuronal conductionThe PAX LC Trial: A Decentralized, Phase 2, Randomized, Double-blind Study of Nirmatrelvir/Ritonavir Compared with Placebo/Ritonavir for Long COVID
Krumholz H, Sawano M, Bhattacharjee B, Caraballo C, Khera R, Li S, Herrin J, Coppi A, Holub J, Henriquez Y, Johnson M, Goddard T, Rocco E, Hummel A, Al Mouslmani M, Putrino D, Carr K, Carvajal-Gonzalez S, Charnas L, De Jesus M, Ziegler F, Iwasaki A. The PAX LC Trial: A Decentralized, Phase 2, Randomized, Double-blind Study of Nirmatrelvir/Ritonavir Compared with Placebo/Ritonavir for Long COVID. The American Journal Of Medicine 2024 PMID: 38735354, DOI: 10.1016/j.amjmed.2024.04.030.Peer-Reviewed Original ResearchLC trialPROMIS-29Participants' homesTargeting viral persistencePlacebo-controlled trialDouble-blind studyElectronic health recordsCore Outcome MeasuresLong COVIDEQ-5D-5LRepeated measures analysisEvidence-based treatmentsPhase 2Double-blindParticipant-centred approachStudy drugPrimary endpointSecondary endpointsCommunity-dwellingHealth recordsHealthcare utilizationContiguous US statesViral persistencePatient groupDrug treatmentLong COVID Characteristics and Experience: A Descriptive Study from the Yale LISTEN Research Cohort
Sawano M, Wu Y, Shah R, Zhou T, Arun A, Khosla P, Kaleem S, Vashist A, Bhattacharjee B, Ding Q, Lu Y, Caraballo C, Warner F, Huang C, Herrin J, Putrino D, Michelsen T, Fisher L, Adinig C, Iwasaki A, Krumholz H. Long COVID Characteristics and Experience: A Descriptive Study from the Yale LISTEN Research Cohort. The American Journal Of Medicine 2024 PMID: 38663793, DOI: 10.1016/j.amjmed.2024.04.015.Peer-Reviewed Original ResearchExperiences of peopleHealth statusLong COVIDLower health statusNew-onset conditionsCommunity support servicesNon-Hispanic whitesArray of healthQuality of lifeVisual analogue scaleMental healthPsychological distressPsychological statusDescriptive studyHealthcare systemMedian scoreSupport servicesResearch cohortSocial isolationDemographic characteristicsAnalogue scaleImpact of long COVIDHealthFinancial stressParticipantsIntranasal neomycin evokes broad-spectrum antiviral immunity in the upper respiratory tract
Mao T, Kim J, Peña-Hernández M, Valle G, Moriyama M, Luyten S, Ott I, Gomez-Calvo M, Gehlhausen J, Baker E, Israelow B, Slade M, Sharma L, Liu W, Ryu C, Korde A, Lee C, Monteiro V, Lucas C, Dong H, Yang Y, Initiative Y, Gopinath S, Wilen C, Palm N, Dela Cruz C, Iwasaki A, Vogels C, Hahn A, Chen N, Breban M, Koch T, Chaguza C, Tikhonova I, Castaldi C, Mane S, De Kumar B, Ferguson D, Kerantzas N, Peaper D, Landry M, Schulz W, Grubaugh N. Intranasal neomycin evokes broad-spectrum antiviral immunity in the upper respiratory tract. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2319566121. PMID: 38648490, PMCID: PMC11067057, DOI: 10.1073/pnas.2319566121.Peer-Reviewed Original ResearchConceptsInterferon-stimulated genesRespiratory infectionsStrains of influenza A virusTreatment of respiratory viral infectionsRespiratory virus infectionsInfluenza A virusMouse model of COVID-19Respiratory viral infectionsNeomycin treatmentExpression of interferon-stimulated genesUpper respiratory infectionInterferon-stimulated gene expressionLower respiratory infectionsBroad spectrum of diseasesAdministration of neomycinRespiratory viral diseasesDisease to patientsUpper respiratory tractIntranasal deliveryCongenic miceIntranasal applicationNasal mucosaSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2A virusFactors Associated with Long COVID Recovery among US Adults
Shah K, Shah R, Sawano M, Wu Y, Bishop P, Iwasaki A, Krumholz H. Factors Associated with Long COVID Recovery among US Adults. The American Journal Of Medicine 2024 PMID: 38649004, DOI: 10.1016/j.amjmed.2024.04.017.Peer-Reviewed Original ResearchUS adultsNational Health Interview SurveyNon-institutionalized US adultsLong COVIDFactors associated with Long COVIDReport recoveryHealth Interview SurveyNationally representative estimatesMultivariate logistic regression modelHigh school degreeLogistic regression modelsCOVID-19 symptomsCross-sectional sampleMultivariate logistic regression analysisNational survey dataHispanic adultsLogistic regression analysisInterview SurveyWhite adultsRepresentative estimatesAmerican adultsStudy sampleSchool degreeNonresponse biasRegression modelsBeyond antiviral: role of IFN-I in brain development
Baker C, Iwasaki A. Beyond antiviral: role of IFN-I in brain development. Trends In Immunology 2024, 45: 322-324. PMID: 38644134, DOI: 10.1016/j.it.2024.04.004.Commentaries, Editorials and LettersRandomized Phase II Trial of Imiquimod with or without 9-Valent HPV Vaccine versus Observation in Patients with High-grade Pre-neoplastic Cervical Lesions (NCT02864147)
Sheth S, Oh J, Bellone S, Siegel E, Greenman M, Mutlu L, McNamara B, Pathy S, Clark M, Azodi M, Altwerger G, Andikyan V, Huang G, Ratner E, Kim D, Iwasaki A, Levi A, Buza N, Hui P, Flaherty S, Schwartz P, Santin A. Randomized Phase II Trial of Imiquimod with or without 9-Valent HPV Vaccine versus Observation in Patients with High-grade Pre-neoplastic Cervical Lesions (NCT02864147). Clinical Cancer Research 2024, 30: of1-of10. PMID: 38592381, DOI: 10.1158/1078-0432.ccr-23-3639.Peer-Reviewed Original ResearchConceptsRandomized phase II trialCD4/CD8 T cellsT cellsHPV clearanceArm BNo significant differenceClinical surveillanceRate of HPV clearanceSecondary outcomesPre-neoplastic cervical lesionsCervical intraepithelial neoplasiaT cell infiltrationT cell responsesSignificant differenceCIN3 patientsIntraepithelial neoplasiaArm ACervical lesionsImiquimod groupSurveillance armVaginal suppositoriesProspective trialsArm CHPV vaccinationImiquimodExploring new perspectives in immunology
Medzhitov R, Iwasaki A. Exploring new perspectives in immunology. Cell 2024, 187: 2079-2094. PMID: 38670066, DOI: 10.1016/j.cell.2024.03.038.Peer-Reviewed Original ResearchFactors Associated with Long COVID: Insights from Two Nationwide Surveys
Wu Y, Sawano M, Wu Y, Shah R, Bishop P, Iwasaki A, Krumholz H. Factors Associated with Long COVID: Insights from Two Nationwide Surveys. The American Journal Of Medicine 2024, 137: 515-519. PMID: 38490304, DOI: 10.1016/j.amjmed.2024.02.032.Peer-Reviewed Original ResearchBehavioral Risk Factor Surveillance SystemNational Health Interview SurveyAssociated with long COVIDNational Health Interview Survey cohortRisk Factor Surveillance SystemNon-Hispanic White individualsLong COVIDFactors associated with Long COVIDHealth Interview SurveyCross-sectional studyPositive COVID-19 testNon-HispanicInterview SurveyDoctor's diagnosisWhite individualsCOVID-19 testingCollege degreeCOVID-19 infectionFemale sexSurveillance systemBlack AmericansNationwide surveySeverity of acute COVID-19 infectionAcute COVID-19 infectionCohortCompartmentalized ocular lymphatic system mediates eye–brain immunity
Yin X, Zhang S, Lee J, Dong H, Mourgkos G, Terwilliger G, Kraus A, Geraldo L, Poulet M, Fischer S, Zhou T, Mohammed F, Zhou J, Wang Y, Malloy S, Rohner N, Sharma L, Salinas I, Eichmann A, Thomas J, Saltzman W, Huttner A, Zeiss C, Ring A, Iwasaki A, Song E. Compartmentalized ocular lymphatic system mediates eye–brain immunity. Nature 2024, 628: 204-211. PMID: 38418880, PMCID: PMC10990932, DOI: 10.1038/s41586-024-07130-8.Peer-Reviewed Original ResearchResponse to herpes simplex virusCentral nervous systemImmune response to herpes simplex virusPosterior eyeImmune responseTherapeutic immune responsesOptic nerve sheathCervical lymph nodesAdeno-associated virusCNS diseaseDeep cervical lymph nodesHerpes simplex virusImmune protected miceCentral nervous system tissueLymphatic drainage systemImmunological featuresAnatomical extensionNerve sheathOptic nerveGene therapyLymph nodesMultiple dosesSimplex virusLymphatic circuitLymphatic signal
2023
Cancer Relevance of Circulating Antibodies Against LINE-1 Antigens in Humans
Vylegzhanina A, Bespalov I, Novototskaya-Vlasova K, Hall B, Gleiberman A, Yu H, Leontieva O, Leonova K, Kurnasov O, Osterman A, Dy G, Komissarov A, Vasilieva E, Gehlhausen J, Iwasaki A, Ambrosone C, Tsuji T, Matsuzaki J, Odunsi K, Andrianova E, Gudkov A. Cancer Relevance of Circulating Antibodies Against LINE-1 Antigens in Humans. Cancer Research Communications 2023, 3: 2256-2267. PMID: 37870410, PMCID: PMC10631453, DOI: 10.1158/2767-9764.crc-23-0289.Peer-Reviewed Original ResearchConceptsL1 antigenCancer typesDisease stage 1Discovery of autoantibodiesHigh IgG titersTumor-associated antigensDetermination of immunoreactivityTumor immunoreactivityCirculating AntibodiesIgG titersAntibody responseImmune responseLiver cancerReactive IgGHealthy individualsCurable cancer typesImmune systemAntigenNormal tissuesPatientsCancerEarly detectionElevated levelsCarcinogenic processAutoantibodies1025 Tumor-specific CD8+ T cells epigenetically licensed by IL-7R are critical for anti-tumor immunity in melanoma
Micevic G, Daniels A, Flem-Karlsen K, Park K, Talty R, McGeary M, Mirza H, Blackburn H, Sefik E, Cheung J, Hornick N, Aizenbud L, Joshi N, Kluger H, Iwasaki A, Bosenberg M, Flavell R. 1025 Tumor-specific CD8+ T cells epigenetically licensed by IL-7R are critical for anti-tumor immunity in melanoma. 2023, a1133-a1133. DOI: 10.1136/jitc-2023-sitc2023.1025.Peer-Reviewed Original ResearchDeveloping synthetic tools to decipher the tumor–immune interactome
Weizman O, Luyten S, Lu P, Song E, Qin K, Mostaghimi D, Ring A, Iwasaki A. Developing synthetic tools to decipher the tumor–immune interactome. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2306632120. PMID: 37871202, PMCID: PMC10622925, DOI: 10.1073/pnas.2306632120.Peer-Reviewed Original ResearchConceptsImmune cellsImmune-based therapiesTumor-immune cell interactionsDifferent immunotherapiesRetroviral reportersSensitive tumorsImmune surveillanceTumor subtypesTumor microenvironmentSynthetic Notch receptorCell interactionsCell contactTissue functionTissue locationNotch receptorsVivoOptimal tissue functionCellsComprehensive landscapeImmunotherapyTherapyTumorsImmunogenicitySubtypesDistinguishing features of long COVID identified through immune profiling
Klein J, Wood J, Jaycox J, Dhodapkar R, Lu P, Gehlhausen J, Tabachnikova A, Greene K, Tabacof L, Malik A, Silva Monteiro V, Silva J, Kamath K, Zhang M, Dhal A, Ott I, Valle G, Peña-Hernández M, Mao T, Bhattacharjee B, Takahashi T, Lucas C, Song E, McCarthy D, Breyman E, Tosto-Mancuso J, Dai Y, Perotti E, Akduman K, Tzeng T, Xu L, Geraghty A, Monje M, Yildirim I, Shon J, Medzhitov R, Lutchmansingh D, Possick J, Kaminski N, Omer S, Krumholz H, Guan L, Dela Cruz C, van Dijk D, Ring A, Putrino D, Iwasaki A. Distinguishing features of long COVID identified through immune profiling. Nature 2023, 623: 139-148. PMID: 37748514, PMCID: PMC10620090, DOI: 10.1038/s41586-023-06651-y.Peer-Reviewed Original ResearchConceptsLong COVIDSARS-CoV-2Infection syndromeExaggerated humoral responseSoluble immune mediatorsEpstein-Barr virusPost-exertional malaiseCross-sectional studyHigher antibody responseImmune mediatorsImmune phenotypingImmune profilingHumoral responseAntibody responseLymphocyte populationsCOVID statusUnbiased machineCortisol levelsLC statusRelevant biomarkersViral pathogensSyndromeCOVIDFuture studiesBiological featuresAuthor Correction: SARS-CoV-2 reservoir in post-acute sequelae of COVID-19 (PASC)
Proal A, VanElzakker M, Aleman S, Bach K, Boribong B, Buggert M, Cherry S, Chertow D, Davies H, Dupont C, Deeks S, Eimer W, Ely E, Fasano A, Freire M, Geng L, Griffin D, Henrich T, Iwasaki A, Izquierdo-Garcia D, Locci M, Mehandru S, Painter M, Peluso M, Pretorius E, Price D, Putrino D, Scheuermann R, Tan G, Tanzi R, VanBrocklin H, Yonker L, Wherry E. Author Correction: SARS-CoV-2 reservoir in post-acute sequelae of COVID-19 (PASC). Nature Immunology 2023, 24: 1778-1778. PMID: 37723351, DOI: 10.1038/s41590-023-01646-3.Peer-Reviewed Original ResearchSARS-CoV-2 reservoir in post-acute sequelae of COVID-19 (PASC)
Proal A, VanElzakker M, Aleman S, Bach K, Boribong B, Buggert M, Cherry S, Chertow D, Davies H, Dupont C, Deeks S, Eimer W, Ely E, Fasano A, Freire M, Geng L, Griffin D, Henrich T, Iwasaki A, Izquierdo-Garcia D, Locci M, Mehandru S, Painter M, Peluso M, Pretorius E, Price D, Putrino D, Scheuermann R, Tan G, Tanzi R, VanBrocklin H, Yonker L, Wherry E. SARS-CoV-2 reservoir in post-acute sequelae of COVID-19 (PASC). Nature Immunology 2023, 24: 1616-1627. PMID: 37667052, DOI: 10.1038/s41590-023-01601-2.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 reservoirPost-acute sequelaeImmune responseHost immune responseCoronavirus SARS-CoV-2COVID-19SARS-CoV-2Neuroimmune abnormalitiesAcute infectionLong COVIDClinical trialsViral RNAMillions of peopleSequelaeFurther studiesViral proteinsPathologyResearch prioritiesRNA/proteinBiological factorsPASCAntiviralsInfectionAbnormalitiesTrialsAn AI-powered patient triage platform for future viral outbreaks using COVID-19 as a disease model
Charkoftaki G, Aalizadeh R, Santos-Neto A, Tan W, Davidson E, Nikolopoulou V, Wang Y, Thompson B, Furnary T, Chen Y, Wunder E, Coppi A, Schulz W, Iwasaki A, Pierce R, Cruz C, Desir G, Kaminski N, Farhadian S, Veselkov K, Datta R, Campbell M, Thomaidis N, Ko A, Thompson D, Vasiliou V. An AI-powered patient triage platform for future viral outbreaks using COVID-19 as a disease model. Human Genomics 2023, 17: 80. PMID: 37641126, PMCID: PMC10463861, DOI: 10.1186/s40246-023-00521-4.Peer-Reviewed Original ResearchConceptsCOVID-19 patientsDisease severityViral outbreaksFuture viral outbreaksLength of hospitalizationIntensive care unitWorse disease prognosisLife-threatening illnessEffective medical interventionsCOVID-19Clinical decision treeGlucuronic acid metabolitesNew potential biomarkersHospitalization lengthCare unitComorbidity dataSerotonin levelsDisease progressionHealthy controlsPatient outcomesDisease prognosisPatient transferPatientsHealthcare resourcesPotential biomarkersPolymer nanoparticles deliver mRNA to the lung for mucosal vaccination
Suberi A, Grun M, Mao T, Israelow B, Reschke M, Grundler J, Akhtar L, Lee T, Shin K, Piotrowski-Daspit A, Homer R, Iwasaki A, Suh H, Saltzman W. Polymer nanoparticles deliver mRNA to the lung for mucosal vaccination. Science Translational Medicine 2023, 15: eabq0603. PMID: 37585505, PMCID: PMC11137749, DOI: 10.1126/scitranslmed.abq0603.Peer-Reviewed Original ResearchConceptsSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2Respiratory syndrome coronavirus 2Lethal viral challengeAntigen-presenting cellsSyndrome coronavirus 2Humoral adaptive immunityLung-targeting deliveryIntranasal vaccinationMucosal vaccinationPulmonary diseaseMucosal vaccinesSusceptible miceCoronavirus 2Viral challengeAdaptive immunityLungTranslational potentialMessenger RNA (mRNA) therapeuticsVaccinationMRNADeliveryTherapeuticsRNA therapeuticsTherapeutic delivery