2023
An 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 biomarkersSARS-CoV-2 mRNA vaccines decouple anti-viral immunity from humoral autoimmunity
Jaycox J, Lucas C, Yildirim I, Dai Y, Wang E, Monteiro V, Lord S, Carlin J, Kita M, Buckner J, Ma S, Campbell M, Ko A, Omer S, Lucas C, Speake C, Iwasaki A, Ring A. SARS-CoV-2 mRNA vaccines decouple anti-viral immunity from humoral autoimmunity. Nature Communications 2023, 14: 1299. PMID: 36894554, PMCID: PMC9996559, DOI: 10.1038/s41467-023-36686-8.Peer-Reviewed Original ResearchConceptsVaccine-associated myocarditisAutoimmune patientsAutoantibody reactivitySARS-CoV-2 mRNA vaccinationVaccine-related adverse effectsSARS-CoV-2 immunitySARS-CoV-2 infectionAcute COVID-19Development of autoantibodiesCOVID-19 patientsAnti-viral immunityVirus-specific antibodiesCOVID-19 vaccineCOVID-19Humoral autoimmunityMRNA vaccinationAutoantibody responsePost vaccinationAutoantibody developmentAutoimmune diseasesHumoral responseHealthy individualsPatientsAntigen profilingAdverse effects
2022
Gut microbiome dysbiosis in antibiotic-treated COVID-19 patients is associated with microbial translocation and bacteremia
Bernard-Raichon L, Venzon M, Klein J, Axelrad J, Zhang C, Sullivan A, Hussey G, Casanovas-Massana A, Noval M, Valero-Jimenez A, Gago J, Putzel G, Pironti A, Wilder E, Thorpe L, Littman D, Dittmann M, Stapleford K, Shopsin B, Torres V, Ko A, Iwasaki A, Cadwell K, Schluter J. Gut microbiome dysbiosis in antibiotic-treated COVID-19 patients is associated with microbial translocation and bacteremia. Nature Communications 2022, 13: 5926. PMID: 36319618, PMCID: PMC9626559, DOI: 10.1038/s41467-022-33395-6.Peer-Reviewed Original ResearchConceptsGut microbiome dysbiosisCOVID-19 patientsMicrobiome dysbiosisSecondary infectionSARS-CoV-2 infection inducesLife-threatening secondary infectionsTranslocation of bacteriaBlood culture resultsCOVID-19 severityAntimicrobial-resistant speciesCOVID-19Different clinical sitesMicrobial translocationBloodstream infectionsInfection inducesBarrier permeabilitySystemic circulationDysbiosisGoblet cellsPaneth cellsClinical sitesCulture resultsPatient healthGut microbiomePatientsDevelopment and utilization of a surrogate SARS-CoV-2 viral neutralization assay to assess mRNA vaccine responses
Wisnewski AV, Liu J, Lucas C, Klein J, Iwasaki A, Cantley L, Fazen L, Luna J, Slade M, Redlich CA. Development and utilization of a surrogate SARS-CoV-2 viral neutralization assay to assess mRNA vaccine responses. PLOS ONE 2022, 17: e0262657. PMID: 35041700, PMCID: PMC8765639, DOI: 10.1371/journal.pone.0262657.Peer-Reviewed Original ResearchConceptsPlaque reduction neutralization testCOVID-19 patientsVaccine responsesRecovered COVID-19 patientsSARS-CoV-2 immunityBooster vaccine dosesMRNA vaccine responsePost-vaccine seraCompetitive ELISAEnzyme 2 (ACE2) receptorReduction neutralization testType of vaccineSARS-CoV-2 spike protein receptorSpike protein receptorVaccine seraVaccine recipientsPost vaccinationVaccinated individualsVaccine dosesViral culturePrior historyViral neutralizationNeutralization testBooster shotsPost vaccine
2021
Kynurenic acid may underlie sex-specific immune responses to COVID-19
Cai Y, Kim DJ, Takahashi T, Broadhurst DI, Yan H, Ma S, Rattray NJW, Casanovas-Massana A, Israelow B, Klein J, Lucas C, Mao T, Moore AJ, Muenker MC, Oh JE, Silva J, Wong P, team Y, Ko AI, Khan SA, Iwasaki A, Johnson CH. Kynurenic acid may underlie sex-specific immune responses to COVID-19. Science Signaling 2021, 14: eabf8483. PMID: 34230210, PMCID: PMC8432948, DOI: 10.1126/scisignal.abf8483.Peer-Reviewed Original ResearchConceptsKynurenic acidImmune responseClinical outcomesSex-specific immune responsesT cell responsesPoor clinical outcomeCOVID-19 patientsCoronavirus disease 2019COVID-19Sex-related differencesMale patientsCytokine abundanceInflammatory cytokinesKynurenine ratioSerum metabolomeDisease 2019Sex-specific linkKynurenine aminotransferaseCell responsesOld malePatientsMalesOutcomesResponseMetabolitesDivergent and self-reactive immune responses in the CNS of COVID-19 patients with neurological symptoms
Song E, Bartley CM, Chow RD, Ngo TT, Jiang R, Zamecnik CR, Dandekar R, Loudermilk RP, Dai Y, Liu F, Sunshine S, Liu J, Wu W, Hawes IA, Alvarenga BD, Huynh T, McAlpine L, Rahman NT, Geng B, Chiarella J, Goldman-Israelow B, Vogels CBF, Grubaugh ND, Casanovas-Massana A, Phinney BS, Salemi M, Alexander JR, Gallego JA, Lencz T, Walsh H, Wapniarski AE, Mohanty S, Lucas C, Klein J, Mao T, Oh J, Ring A, Spudich S, Ko AI, Kleinstein SH, Pak J, DeRisi JL, Iwasaki A, Pleasure SJ, Wilson MR, Farhadian SF. Divergent and self-reactive immune responses in the CNS of COVID-19 patients with neurological symptoms. Cell Reports Medicine 2021, 2: 100288. PMID: 33969321, PMCID: PMC8091032, DOI: 10.1016/j.xcrm.2021.100288.Peer-Reviewed Original ResearchNeurological symptomsImmune responseCerebrospinal fluidAnti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodiesCOVID-19Self-reactive immune responsesSARS-CoV-2 antibodiesCompartmentalized immune responseCSF immunoglobulin GRole of autoimmunityCOVID-19 patientsB cell responsesCoronavirus disease 2019Immune surveyNeurologic sequelaePulmonary infectionBrain infectionSerum antibodiesDisease 2019Monoclonal antibody targetsAnimal modelsTarget epitopesCell activationCell responsesSingle-cell RNA sequencingTracking smell loss to identify healthcare workers with SARS-CoV-2 infection
Weiss JJ, Attuquayefio TN, White EB, Li F, Herz RS, White TL, Campbell M, Geng B, Datta R, Wyllie AL, Grubaugh ND, Casanovas-Massana A, Muenker MC, Moore AJ, Handoko R, Iwasaki A, Martinello RA, Ko AI, Small DM, Farhadian SF, Team T. Tracking smell loss to identify healthcare workers with SARS-CoV-2 infection. PLOS ONE 2021, 16: e0248025. PMID: 33657167, PMCID: PMC7928484, DOI: 10.1371/journal.pone.0248025.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 infectionSARS-CoV-2 positive healthcare workersSmell lossHealthcare workersHome assessmentNeurological symptomsPositive SARS-CoV-2 testSARS-CoV-2 test positivitySARS-CoV-2 testPolymerase chain reaction testingReal-time quantitative polymerase chain reaction testingQuantitative polymerase chain reaction testingCOVID-19 patientsHigh-risk groupHigh-risk individualsSARS-CoV-2Self-reported changesProspective studyTest positivityAsymptomatic infectionSymptom SurveyVulnerable patientsHigh riskPositive testRisk individualsNeuroinvasion of SARS-CoV-2 in human and mouse brain
Song E, Zhang C, Israelow B, Lu-Culligan A, Prado AV, Skriabine S, Lu P, Weizman OE, Liu F, Dai Y, Szigeti-Buck K, Yasumoto Y, Wang G, Castaldi C, Heltke J, Ng E, Wheeler J, Alfajaro MM, Levavasseur E, Fontes B, Ravindra NG, Van Dijk D, Mane S, Gunel M, Ring A, Kazmi SAJ, Zhang K, Wilen CB, Horvath TL, Plu I, Haik S, Thomas JL, Louvi A, Farhadian SF, Huttner A, Seilhean D, Renier N, Bilguvar K, Iwasaki A. Neuroinvasion of SARS-CoV-2 in human and mouse brain. Journal Of Experimental Medicine 2021, 218: e20202135. PMID: 33433624, PMCID: PMC7808299, DOI: 10.1084/jem.20202135.Peer-Reviewed Original ResearchConceptsSARS-CoV-2Central nervous systemSARS-CoV-2 neuroinvasionImmune cell infiltratesCOVID-19 patientsType I interferon responseMultiple organ systemsCOVID-19I interferon responseHuman brain organoidsNeuroinvasive capacityCNS infectionsCell infiltrateNeuronal infectionPathological featuresCortical neuronsRespiratory diseaseDirect infectionCerebrospinal fluidNervous systemMouse brainInterferon responseOrgan systemsHuman ACE2Infection
2020
Mouse model of SARS-CoV-2 reveals inflammatory role of type I interferon signaling
Israelow B, Song E, Mao T, Lu P, Meir A, Liu F, Alfajaro MM, Wei J, Dong H, Homer RJ, Ring A, Wilen CB, Iwasaki A. Mouse model of SARS-CoV-2 reveals inflammatory role of type I interferon signaling. Journal Of Experimental Medicine 2020, 217: e20201241. PMID: 32750141, PMCID: PMC7401025, DOI: 10.1084/jem.20201241.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin-Converting Enzyme 2AnimalsBetacoronavirusCell Line, TumorCoronavirus InfectionsCOVID-19DependovirusDisease Models, AnimalFemaleHumansInflammationInterferon Type ILungMaleMiceMice, Inbred C57BLMice, TransgenicPandemicsParvoviridae InfectionsPeptidyl-Dipeptidase APneumonia, ViralSARS-CoV-2Signal TransductionVirus ReplicationConceptsSARS-CoV-2Type I interferonMouse modelI interferonRobust SARS-CoV-2 infectionSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2SARS-CoV-2 infectionRespiratory syndrome coronavirus 2SARS-CoV-2 replicationCOVID-19 patientsSyndrome coronavirus 2Patient-derived virusesSignificant fatality ratePathological findingsInflammatory rolePathological responseEnzyme 2Receptor angiotensinFatality rateVaccine developmentGenetic backgroundViral replicationCoronavirus diseaseMiceCoast-to-Coast Spread of SARS-CoV-2 during the Early Epidemic in the United States
Fauver JR, Petrone ME, Hodcroft EB, Shioda K, Ehrlich HY, Watts AG, Vogels CBF, Brito AF, Alpert T, Muyombwe A, Razeq J, Downing R, Cheemarla NR, Wyllie AL, Kalinich CC, Ott IM, Quick J, Loman NJ, Neugebauer KM, Greninger AL, Jerome KR, Roychoudhury P, Xie H, Shrestha L, Huang ML, Pitzer VE, Iwasaki A, Omer SB, Khan K, Bogoch II, Martinello RA, Foxman EF, Landry ML, Neher RA, Ko AI, Grubaugh ND. Coast-to-Coast Spread of SARS-CoV-2 during the Early Epidemic in the United States. Cell 2020, 181: 990-996.e5. PMID: 32386545, PMCID: PMC7204677, DOI: 10.1016/j.cell.2020.04.021.Peer-Reviewed Original ResearchConceptsSARS-CoV-2Federal travel restrictionsSARS-CoV-2 transmissionCOVID-19 patientsCoronavirus SARS-CoV-2SARS-CoV-2 introductionsEarly SARS-CoV-2 transmissionPattern of spreadSustained transmissionLocal surveillanceEarly epidemicInternational importationCOVID-19 outbreakUnited StatesViral genomeInternational travel patternsPatientsCritical needTravel restrictions