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 biomarkersMulti-omic longitudinal study reveals immune correlates of clinical course among hospitalized COVID-19 patients
Diray-Arce J, Fourati S, Jayavelu N, Patel R, Maguire C, Chang A, Dandekar R, Qi J, Lee B, van Zalm P, Schroeder A, Chen E, Konstorum A, Brito A, Gygi J, Kho A, Chen J, Pawar S, Gonzalez-Reiche A, Hoch A, Milliren C, Overton J, Westendorf K, Network I, Abraham J, Adkisson M, Albert M, Torres L, Alvarenga B, Anderson M, Anderson E, Arnett A, Asashima H, Atkinson M, Baden L, Barton B, Beach K, Beagle E, Becker P, Bell M, Bernui M, Bime C, Kumar A, Booth L, Borresen B, Brakenridge S, Bristow L, Bryant R, Calfee C, Manuel J, Carrillo S, Chak S, Chang I, Connors J, Conway M, Corry D, Cowan D, Croen B, Dela Cruz C, Cusimano G, Eaker L, Edwards C, Ehrlich L, Elashoff D, Erickson H, Erle D, Farhadian S, Farrugia K, Fatou B, Fernandes A, Fernandez-Sesma A, Fragiadakis G, Furukawa S, Geltman J, Ghale R, Bermúdez M, Goonewardene M, Sanchez E, Guirgis F, Hafler D, Hamilton S, Harris P, Nemati A, Hendrickson C, Agudelo N, Hodder T, Holland S, Hough C, Huerta C, Hurley K, Hutton S, Iwasaki A, Jauregui A, Jha M, Johnson B, Joyner D, Kangelaris K, Kelly G, Khalil Z, Khan Z, Kheradmand F, Kim J, Kimura H, Ko A, Kohr B, Kraft M, Krummel M, Kutzler M, Lasky-Su J, Lee S, Lee D, Leipold M, Lentucci C, Leroux C, Lin E, Liu S, Love C, Lu Z, Maliskova L, Roth B, Manohar M, Martens M, McComsey G, McEnaney K, McLin R, Melamed E, Melnyk N, Mendez K, Messer W, Metcalf J, Michelotti G, Mick E, Mohanty S, Mosier J, Mulder L, Murphy M, Nadeau K, Nelson E, Nelson A, Nguyen V, Oberhaus J, Panganiban B, Pellegrini K, Pickering H, Powell D, Presnell S, Pulendran B, Rahman A, Sadeed A, Raskin A, Reed E, Pereira S, Rivera A, Rogers J, Rogers A, Rogowski B, Rooks R, Rosenberg-Hasson Y, Rothman J, Rousseau J, Salehi-Rad R, Saluvan M, Samaha H, Schaenman J, Schunk R, Semenza N, Sen S, Sevransky J, Seyfert-Margolis V, Shaheen T, Shaw A, Sieg S, Siegel S, Sigal N, Siles N, Simmons B, Simon V, Singh G, Sinko L, Smith C, Smolen K, Song L, Srivastava K, Sullivan P, Syphurs C, Tcheou J, Tegos G, Tharp G, Ally A, Tsitsiklis A, Ungaro R, Vaysman T, Viode A, Vita R, Wang X, Ward A, Ward D, Willmore A, Woloszczuk K, Wong K, Woodruff P, Xu L, van Haren S, van de Guchte A, Zhao Y, Cairns C, Rouphael N, Bosinger S, Kim-Schulze S, Krammer F, Rosen L, Grubaugh N, van Bakel H, Wilson M, Rajan J, Steen H, Eckalbar W, Cotsapas C, Langelier C, Levy O, Altman M, Maecker H, Montgomery R, Haddad E, Sekaly R, Esserman D, Ozonoff A, Becker P, Augustine A, Guan L, Peters B, Kleinstein S. Multi-omic longitudinal study reveals immune correlates of clinical course among hospitalized COVID-19 patients. Cell Reports Medicine 2023, 4: 101079. PMID: 37327781, PMCID: PMC10203880, DOI: 10.1016/j.xcrm.2023.101079.Peer-Reviewed Original ResearchConceptsDisease courseFatal COVID-19 diseaseHospitalized COVID-19 patientsSevere disease courseCOVID-19 participantsCOVID-19 patientsTrajectory groupsHost immune responseCOVID-19 diseaseImmune correlatesAcute infectionClinical courseHospital admissionClinical outcomesFatal outcomeClinical prognosisImmune responseSevere diseaseLongitudinal bloodNasal samplesBiologic stateLongitudinal studyDistinct assaysCohortMolecular signaturesSARS-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 microbiomePatientsPhenotypes of disease severity in a cohort of hospitalized COVID-19 patients: Results from the IMPACC study
Ozonoff A, Schaenman J, Jayavelu ND, Milliren CE, Calfee CS, Cairns CB, Kraft M, Baden LR, Shaw AC, Krammer F, van Bakel H, Esserman DA, Liu S, Sesma AF, Simon V, Hafler DA, Montgomery RR, Kleinstein SH, Levy O, Bime C, Haddad EK, Erle DJ, Pulendran B, Nadeau KC, Davis MM, Hough CL, Messer WB, Higuita NIA, Metcalf JP, Atkinson MA, Brakenridge SC, Corry D, Kheradmand F, Ehrlich LIR, Melamed E, McComsey GA, Sekaly R, Diray-Arce J, Peters B, Augustine AD, Reed EF, Altman MC, Becker PM, Rouphael N, Ozonoff A, Schaenman J, Jayavelu N, Milliren C, Calfee C, Cairns C, Kraft M, Baden L, Shaw A, Krammer F, van Bakel H, Esserman D, Liu S, Sesma A, Simon V, Hafler D, Montgomery R, Kleinstein S, Levy O, Bime C, Haddad E, Erle D, Pulendran B, Nadeau K, Davis M, Hough C, Messer W, Higuita N, Metcalf J, Atkinson M, Brakenridge S, Corry D, Kheradmand F, Ehrlich L, Melamed E, McComsey G, Sekaly R, Diray-Arce J, Peters B, Augustine A, Reed E, McEnaney K, Barton B, Lentucci C, Saluvan M, Chang A, Hoch A, Albert M, Shaheen T, Kho A, Thomas S, Chen J, Murphy M, Cooney M, Presnell S, Fragiadakis G, Patel R, Guan L, Gygi J, Pawar S, Brito A, Khalil Z, Maguire C, Fourati S, Overton J, Vita R, Westendorf K, Salehi-Rad R, Leligdowicz A, Matthay M, Singer J, Kangelaris K, Hendrickson C, Krummel M, Langelier C, Woodruff P, Powell D, Kim J, Simmons B, Goonewardene I, Smith C, Martens M, Mosier J, Kimura H, Sherman A, Walsh S, Issa N, Dela Cruz C, Farhadian S, Iwasaki A, Ko A, Chinthrajah S, Ahuja N, Rogers A, Artandi M, Siegel S, Lu Z, Drevets D, Brown B, Anderson M, Guirgis F, Thyagarajan R, Rousseau J, Wylie D, Busch J, Gandhi S, Triplett T, Yendewa G, Giddings O, Anderson E, Mehta A, Sevransky J, Khor B, Rahman A, Stadlbauer D, Dutta J, Xie H, Kim-Schulze S, Gonzalez-Reiche A, van de Guchte A, Farrugia K, Khan Z, Maecker H, Elashoff D, Brook J, Ramires-Sanchez E, Llamas M, Rivera A, Perdomo C, Ward D, Magyar C, Fulcher J, Abe-Jones Y, Asthana S, Beagle A, Bhide S, Carrillo S, Chak S, Fragiadakis G, Ghale R, Gonzalez A, Jauregui A, Jones N, Lea T, Lee D, Lota R, Milush J, Nguyen V, Pierce L, Prasad P, Rao A, Samad B, Shaw C, Sigman A, Sinha P, Ward A, Willmore A, Zhan J, Rashid S, Rodriguez N, Tang K, Altamirano L, Betancourt L, Curiel C, Sutter N, Paz M, Tietje-Ulrich G, Leroux C, Connors J, Bernui M, Kutzler M, Edwards C, Lee E, Lin E, Croen B, Semenza N, Rogowski B, Melnyk N, Woloszczuk K, Cusimano G, Bell M, Furukawa S, McLin R, Marrero P, Sheidy J, Tegos G, Nagle C, Mege N, Ulring K, Seyfert-Margolis V, Conway M, Francisco D, Molzahn A, Erickson H, Wilson C, Schunk R, Sierra B, Hughes T, Smolen K, Desjardins M, van Haren S, Mitre X, Cauley J, Li X, Tong A, Evans B, Montesano C, Licona J, Krauss J, Chang J, Izaguirre N, Chaudhary O, Coppi A, Fournier J, Mohanty S, Muenker M, Nelson A, Raddassi K, Rainone M, Ruff W, Salahuddin S, Schulz W, Vijayakumar P, Wang H, Wunder E, Young H, Zhao Y, Saksena M, Altman D, Kojic E, Srivastava K, Eaker L, Bermúdez-González M, Beach K, Sominsky L, Azad A, Carreño J, Singh G, Raskin A, Tcheou J, Bielak D, Kawabata H, Mulder L, Kleiner G, Lee A, Do Do E, Fernandes A, Manohar M, Hagan T, Blish C, Din H, Roque J, Yang S, Brunton A, Sullivan P, Strnad M, Lyski Z, Coulter F, Booth J, Sinko L, Moldawer L, Borresen B, Roth-Manning B, Song L, Nelson E, Lewis-Smith M, Smith J, Tipan P, Siles N, Bazzi S, Geltman J, Hurley K, Gabriele G, Sieg S, Vaysman T, Bristow L, Hussaini L, Hellmeister K, Samaha H, Cheng A, Spainhour C, Scherer E, Johnson B, Bechnak A, Ciric C, Hewitt L, Carter E, Mcnair N, Panganiban B, Huerta C, Usher J, Ribeiro S, Altman M, Becker P, Rouphael N. Phenotypes of disease severity in a cohort of hospitalized COVID-19 patients: Results from the IMPACC study. EBioMedicine 2022, 83: 104208. PMID: 35952496, PMCID: PMC9359694, DOI: 10.1016/j.ebiom.2022.104208.Peer-Reviewed Original ResearchConceptsRisk factorsRadiographic findingsFemale sexDisease severityHospitalized COVID-19 patientsSARS-CoV-2 antibodiesSARS-CoV-2 PCRLong COVID-19Presence of infiltratesInvasive mechanical ventilationCharacteristics of patientsOnly female sexViral load levelsClinical laboratory valuesCOVID-19 cohortMultivariable logistic regressionCOVID-19 patientsCoronavirus disease 2019PCR cycle thresholdCOVID-19Baseline creatinineBaseline lymphopeniaMedian ageOverall mortalityProlonged hospitalizationAssociation of renalase with clinical outcomes in hospitalized patients with COVID-19
Safdar B, Wang M, Guo X, Cha C, Chun HJ, Deng Y, Dziura J, El-Khoury JM, Gorelick F, Ko AI, Lee AI, Safirstein R, Simonov M, Zhou B, Desir GV. Association of renalase with clinical outcomes in hospitalized patients with COVID-19. PLOS ONE 2022, 17: e0264178. PMID: 35259186, PMCID: PMC8903289, DOI: 10.1371/journal.pone.0264178.Peer-Reviewed Original ResearchConceptsCOVID-19 patientsRenalase levelsIntensive care unit admissionHospitalized COVID-19 patientsMean age 64 yearsCOVID-19Cox proportional hazards modelCare unit admissionPrimary composite outcomeRetrospective cohort studyUse of vasopressorsSevere COVID-19IL-6 levelsAge 64 yearsRisk of deathCOVID-19 subjectsInitial disease severityProportional hazards modelCOVID-19 diseasePlasma renalaseUnit admissionICU admissionCohort studyComposite outcomeCytokine levels
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 malePatientsMalesOutcomesResponseMetabolitesEvidence for SARS-CoV-2 Spike Protein in the Urine of COVID-19 Patients
George S, Pal AC, Gagnon J, Timalsina S, Singh P, Vydyam P, Munshi M, Chiu JE, Renard I, Harden CA, Ott IM, Watkins AE, Vogels CBF, Lu P, Tokuyama M, Venkataraman A, Casanovas-Massana A, Wyllie AL, Rao V, Campbell M, Farhadian SF, Grubaugh ND, Dela Cruz CS, Ko AI, Perez A, Akaho EH, Moledina DG, Testani J, John AR, Ledizet M, Mamoun CB, Team A. Evidence for SARS-CoV-2 Spike Protein in the Urine of COVID-19 Patients. Kidney360 2021, 2: 924-936. PMID: 35373072, PMCID: PMC8791366, DOI: 10.34067/kid.0002172021.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 spike proteinSARS-CoV-2Spike proteinUrine samplesSARS-CoV-2 infectionYale-New Haven HospitalCOVID-19 patientsAntigen capture assayDetectable viral RNANew Haven HospitalPositive PCR resultsPossible long-term consequencesSpike S1 proteinNP PCRChildren's HospitalNasopharyngeal swabsSARS-CoV-2 spike S1 proteinRenal abnormalitiesLong-term effectsCystatin CLong-term consequencesHospitalUrineViral RNAAlbuminuriaDivergent 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 individualsCutting Edge: Severe SARS-CoV-2 Infection in Humans Is Defined by a Shift in the Serum Lipidome, Resulting in Dysregulation of Eicosanoid Immune Mediators
Schwarz B, Sharma L, Roberts L, Peng X, Bermejo S, Leighton I, Casanovas-Massana A, Minasyan M, Farhadian S, Ko AI, Team Y, Dela Cruz CS, Bosio CM. Cutting Edge: Severe SARS-CoV-2 Infection in Humans Is Defined by a Shift in the Serum Lipidome, Resulting in Dysregulation of Eicosanoid Immune Mediators. The Journal Of Immunology 2021, 206: ji2001025. PMID: 33277388, PMCID: PMC7962598, DOI: 10.4049/jimmunol.2001025.Peer-Reviewed Original ResearchConceptsLipid mediatorsRisk factorsSevere diseaseSevere SARS-CoV-2 infectionHospitalized COVID-19 patientsSARS-CoV-2 infectionImportant immune regulatory roleSevere COVID-19COVID-19 patientsImmune regulatory roleProinflammatory lipid mediatorsCOVID-19Immunomodulatory eicosanoidsImmune mediatorsSerum lipidomeAdvanced agePatientsCOVID-19 pandemicCytochrome P450MortalityDiseaseDysregulationMediatorsLMS productsLipidome
2020
Coast-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