Featured Publications
Multi-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 signatures
2024
Integrated longitudinal multiomics study identifies immune programs associated with acute COVID-19 severity and mortality
Gygi J, Maguire C, Patel R, Shinde P, Konstorum A, Shannon C, Xu L, Hoch A, Jayavelu N, Haddad E, Network I, Reed E, Kraft M, McComsey G, Metcalf J, Ozonoff A, Esserman D, Cairns C, Rouphael N, Bosinger S, Kim-Schulze S, Krammer F, Rosen L, van Bakel H, Wilson M, Eckalbar W, Maecker H, Langelier C, Steen H, Altman M, Montgomery R, Levy O, Melamed E, Pulendran B, Diray-Arce J, Smolen K, Fragiadakis G, Becker P, Sekaly R, Ehrlich L, Fourati S, Peters B, Kleinstein S, Guan L. Integrated longitudinal multiomics study identifies immune programs associated with acute COVID-19 severity and mortality. Journal Of Clinical Investigation 2024, 134: e176640. PMID: 38690733, PMCID: PMC11060740, DOI: 10.1172/jci176640.Peer-Reviewed Original ResearchConceptsClinical outcomesImmune cascadeElevated levels of inflammatory cytokinesDisease severityLevels of inflammatory cytokinesFormation of neutrophil extracellular trapsAcute COVID-19 severityCritically ill patientsNeutrophil extracellular trapsDevelopment of therapiesCOVID-19 cohortCOVID-19 severityViral clearanceImmunosuppressive metabolitesDeep immunophenotypingMultiomic modelIFN-stimulated genesImmunophenotypic assessmentB cellsDisease courseEarly upregulationInflammatory cytokinesDisease progressionIFN inhibitorsExtracellular trapsIgM N-glycosylation correlates with COVID-19 severity and rate of complement deposition
Ozonoff A, Ehrlich L, Melamed E, Sesma A, Simon V, Pulendran B, Nadeau K, Davis M, McCoey G, Sekaly R, Baden L, Levy O, Schaenman J, Reed E, Shaw A, Hafler D, Montgomery R, Kleinstein S, Becker P, Augustine A, Calfee C, Erle D, DeBakey M, Corry D, Kheradmand F, Atkinson M, Brakenridge S, Higuita N, Metcalf J, Hough C, Messer W, Kraft M, Bime C, Peters B, Milliren C, Syphurs C, McEnaney K, Barton B, Lentucci C, Saluvan M, Chang A, Hoch A, Albert M, Shaheen T, Kho A, Liu S, Thomas S, Chen J, Murphy M, Cooney M, Hayati A, Bryant R, Abraham J, Jayavelu N, Presnell S, Jancsyk T, Maguire C, Qi J, Lee B, Fourati S, Esserman D, Guan L, Gygi J, Pawar S, Brito A, Fragiadakis G, Patel R, Overton J, Vita R, Westendorf K, Shannon C, Tebbutt S, Thyagarajan R, Rousseau J, Wylie D, Triplett T, Kojic E, Chinthrajah S, Ahuja N, Rogers A, Artandi M, Geng L, Yendewa G, Powell D, Kim J, Simmons B, Goonewardene I, Smith C, Martens M, Sherman A, Walsh S, Issa N, Salehi-Rad R, Dela Cruz C, Farhadian S, Iwasaki A, Ko A, Anderson E, Mehta A, Sevransky J, Seyfert-Margolis V, Leligdowicz A, Matthay M, Singer J, Kangelaris K, Hendrickson C, Krummel M, Langelier C, Woodruff P, Corry D, Kheradmand F, Anderson M, Guirgis F, Drevets D, Brown B, Siegel S, Lu Z, Mosier J, Kimura H, Khor B, van Bakel H, Rahman A, Stadlbauer D, Dutta J, Xie H, Kim-Schulze S, Gonzalez-Reiche A, van de Guchte A, Carreño J, Singh G, Raskin A, Tcheou J, Bielak D, Kawabata H, Kelly G, Patel M, Nie K, Yellin T, Fried M, Sullivan L, Morris S, Sieg S, Steen H, van Zalm P, Fatou B, Mendez K, Lasky-Su J, Hutton S, Michelotti G, Wong K, Jha M, Viode A, Kanarek N, Petrova B, Zhao Y, Bosinger S, Boddapati A, Tharp G, Pellegrini K, Beagle E, Cowan D, Hamilton S, Ribeiro S, Hodder T, Rosen L, Lee S, Wilson M, Dandekar R, Alvarenga B, Rajan J, Eckalbar W, Schroeder A, Tsitsiklis A, Mick E, Guerrero Y, Love C, Maliskova L, Adkisson M, Siles N, Geltman J, Hurley K, Saksena M, Altman D, Srivastava K, Eaker L, Bermúdez-González M, Beach K, Sominsky L, Azad A, Mulder L, Kleiner G, Lee A, Do E, Fernandes A, Manohar M, Hagan T, Blish C, Din H, Roque J, Yang S, Sigal N, Chang I, Tribout H, Harris P, Consolo M, Edwards C, Lee E, Lin E, Croen B, Semenza N, Rogowski B, Melnyk N, Bell M, Furukawa S, McLin R, Schearer P, Sheidy J, Tegos G, Nagle C, 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, Rooks R, Elashoff D, Brook J, Ramires-Sanchez E, Llamas M, Rivera A, Perdomo C, Ward D, Magyar C, Fulcher J, Pickering H, Sen S, Chaudhary O, Coppi A, Fournier J, Mohanty S, Muenker C, Nelson A, Raddassi K, Rainone M, Ruff W, Salahuddin S, Schulz W, Vijayakumar P, Wang H, Wunder E, Young H, Rothman J, Konstorum A, Chen E, Cotsapas C, Grubaugh N, Wang X, Xu L, Asashima H, Bristow L, Hussaini L, Hellmeister K, Samaha H, Wimalasena S, Cheng A, Spainhour C, Scherer E, Johnson B, Bechnak A, Ciric C, Hewitt L, Carter E, Mcnair N, Panganiban B, Huerta C, Usher J, Vaysman T, Holland S, Abe-Jones Y, Asthana S, Beagle A, Bhide S, Carrillo S, Chak S, 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, Thakur N, Vasquez J, Santhosh L, Song L, Nelson E, Moldawer L, Borresen B, Roth-Manning B, Ungaro R, Oberhaus J, Booth J, Sinko L, Brunton A, Sullivan P, Strnad M, Lyski Z, Coulter F, Micheleti C, Conway M, Francisco D, Molzahn A, Erickson H, Wilson C, Schunk R, Sierra B, Hughes T. IgM N-glycosylation correlates with COVID-19 severity and rate of complement deposition. Nature Communications 2024, 15: 404. PMID: 38195739, PMCID: PMC10776791, DOI: 10.1038/s41467-023-44211-0.Peer-Reviewed Original Research
2023
Prior cycles of anti-CD20 antibodies affect antibody responses after repeated SARS-CoV-2 mRNA vaccination
Asashima H, Kim D, Wang K, Lele N, Buitrago-Pocasangre N, Lutz R, Cruz I, Raddassi K, Ruff W, Racke M, Wilson J, Givens T, Grifoni A, Weiskopf D, Sette A, Kleinstein S, Montgomery R, Shaw A, Li F, Fan R, Hafler D, Tomayko M, Longbrake E. Prior cycles of anti-CD20 antibodies affect antibody responses after repeated SARS-CoV-2 mRNA vaccination. JCI Insight 2023, 8: e168102. PMID: 37606046, PMCID: PMC10543713, DOI: 10.1172/jci.insight.168102.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 mRNA vaccinationB-cell-depleted patientsB-cell depletionAntibody responseMRNA vaccinationThird doseCell depletionT cellsClaude D. Pepper Older Americans Independence CenterB cellsNational Multiple Sclerosis SocietyAnti-CD20 antibodySpike-specific antibodiesMultiple Sclerosis SocietyLow cumulative exposureLogistic regression modelsImportant clinical needCD20 therapyCD20 treatmentMost patientsThird vaccineSerologic responseVaccine dosesMRNA vaccinesVaccination strategiesA pipeline for the retrieval and extraction of domain-specific information with application to COVID-19 immune signatures
Newton A, Chartash D, Kleinstein S, McDougal R. A pipeline for the retrieval and extraction of domain-specific information with application to COVID-19 immune signatures. BMC Bioinformatics 2023, 24: 292. PMID: 37474900, PMCID: PMC10357743, DOI: 10.1186/s12859-023-05397-8.Peer-Reviewed Original ResearchConceptsDomain-specific informationDocument embeddingsSVM classifierSemi-structured representationsTraining setWeb-based formKnowledge repositoryInformation modelAutomatic analysisClassifier predictionsClassifierSignature informationAutomated systemBiomedical publicationsPaper authorsEmbeddingIncomplete information modelLiterature miningIterative processSpecific informationSuch informationInformationLimited setSetQueriesTracking B cell responses to the SARS-CoV-2 mRNA-1273 vaccine
de Assis F, Hoehn K, Zhang X, Kardava L, Smith C, Merhebi O, Buckner C, Trihemasava K, Wang W, Seamon C, Chen V, Schaughency P, Cheung F, Martins A, Chiang C, Li Y, Tsang J, Chun T, Kleinstein S, Moir S. Tracking B cell responses to the SARS-CoV-2 mRNA-1273 vaccine. Cell Reports 2023, 42: 112780. PMID: 37440409, PMCID: PMC10529190, DOI: 10.1016/j.celrep.2023.112780.Peer-Reviewed Original ResearchConceptsMemory B cellsB cell receptorB cellsAtypical memory B cellsInfection-naïve individualsTwo-dose SARSSARS-CoV-2 mRNAB cell responsesAntibody-secreting cellsMonth 6Protective immunityCell responsesCell receptorClonal expansionImmunoglobulin GEarly timepointsLater timepointsPlasmablastsVaccinationCD71TimepointsSurface proteinsCellsMultimodal single-cell analysisMRNA
2022
Adaptive immune responses to SARS-CoV-2 persist in the pharyngeal lymphoid tissue of children
Xu Q, Milanez-Almeida P, Martins A, Radtke A, Hoehn K, Oguz C, Chen J, Liu C, Tang J, Grubbs G, Stein S, Ramelli S, Kabat J, Behzadpour H, Karkanitsa M, Spathies J, Kalish H, Kardava L, Kirby M, Cheung F, Preite S, Duncker P, Kitakule M, Romero N, Preciado D, Gitman L, Koroleva G, Smith G, Shaffer A, McBain I, McGuire P, Pittaluga S, Germain R, Apps R, Schwartz D, Sadtler K, Moir S, Chertow D, Kleinstein S, Khurana S, Tsang J, Mudd P, Schwartzberg P, Manthiram K. Adaptive immune responses to SARS-CoV-2 persist in the pharyngeal lymphoid tissue of children. Nature Immunology 2022, 24: 186-199. PMID: 36536106, PMCID: PMC10777159, DOI: 10.1038/s41590-022-01367-z.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityAntibodies, ViralChildCOVID-19HumansPalatine TonsilPandemicsSARS-CoV-2ConceptsT cell receptorImmune responseGerminal centersPrevious SARS-CoV-2 infectionSARS-CoV-2 infectionB-cell receptor sequencingTissue-specific immunityCell receptor sequencingAdaptive immune responsesUpper respiratory tractMemory B cellsT cell clonotypesSite of infectionSARS-CoV-2Pharyngeal lymphoid tissuePeripheral bloodLymphocyte populationsLymphoid tissueRespiratory tractCell clonotypesAdaptive immunityB cellsCDR3 sequencesAdenoidsCell receptorMulti-objective optimization identifies a specific and interpretable COVID-19 host response signature
Cappuccio A, Chawla D, Chen X, Rubenstein A, Cheng W, Mao W, Burke T, Tsalik E, Petzold E, Henao R, McClain M, Woods C, Chikina M, Troyanskaya O, Sealfon S, Kleinstein S, Zaslavsky E. Multi-objective optimization identifies a specific and interpretable COVID-19 host response signature. Cell Systems 2022, 13: 989-1001.e8. PMID: 36549275, DOI: 10.1016/j.cels.2022.11.008.Peer-Reviewed Original ResearchPhenotypes 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 hospitalizationSingle-cell multi-omics reveals dyssynchrony of the innate and adaptive immune system in progressive COVID-19
Unterman A, Sumida TS, Nouri N, Yan X, Zhao AY, Gasque V, Schupp JC, Asashima H, Liu Y, Cosme C, Deng W, Chen M, Raredon MSB, Hoehn KB, Wang G, Wang Z, DeIuliis G, Ravindra NG, Li N, Castaldi C, Wong P, Fournier J, Bermejo S, Sharma L, Casanovas-Massana A, Vogels CBF, Wyllie AL, Grubaugh ND, Melillo A, Meng H, Stein Y, Minasyan M, Mohanty S, Ruff WE, Cohen I, Raddassi K, Niklason L, Ko A, Montgomery R, Farhadian S, Iwasaki A, Shaw A, van Dijk D, Zhao H, Kleinstein S, Hafler D, Kaminski N, Dela Cruz C. Single-cell multi-omics reveals dyssynchrony of the innate and adaptive immune system in progressive COVID-19. Nature Communications 2022, 13: 440. PMID: 35064122, PMCID: PMC8782894, DOI: 10.1038/s41467-021-27716-4.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityAgedAntibodies, Monoclonal, HumanizedCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCells, CulturedCOVID-19COVID-19 Drug TreatmentFemaleGene Expression ProfilingGene Expression RegulationHumansImmunity, InnateMaleReceptors, Antigen, B-CellReceptors, Antigen, T-CellRNA-SeqSARS-CoV-2Single-Cell AnalysisConceptsProgressive COVID-19B cell clonesSingle-cell analysisT cellsImmune responseMulti-omics single-cell analysisCOVID-19Cell clonesAdaptive immune interactionsSevere COVID-19Dynamic immune responsesGene expressionSARS-CoV-2 virusAdaptive immune systemSomatic hypermutation frequenciesCellular effectsProtein markersEffector CD8Immune signaturesProgressive diseaseHypermutation frequencyProgressive courseClassical monocytesClonesImmune interactions
2021
Immunophenotyping assessment in a COVID-19 cohort (IMPACC): A prospective longitudinal study
, , Rouphael N, Maecker H, Montgomery R, Diray-Arce J, Kleinstein S, Altman M, Bosinger S, Eckalbar W, Guan L, Hough C, Krammer F, Langelier C, Levy O, McEnaney K, Peters B, Rahman A, Rajan J, Sigelman S, Steen H, van Bakel H, Ward A, Wilson M, Woodruff P, Zamecnik C, Augustine A, Ozonoff A, Reed E, Becker P, Higuita N, Altman M, Atkinson M, Baden L, Becker P, Bime C, Brakenridge S, Calfee C, Cairns C, Corry D, Davis M, Augustine A, Ehrlich L, Haddad E, Erle D, Fernandez-Sesma A, Hafler D, Hough C, Kheradmand F, Kleinstein S, Kraft M, Levy O, McComsey G, Melamed E, Messer W, Metcalf J, Montgomery R, Nadeau K, Ozonoff A, Peters B, Pulendran B, Reed E, Rouphael N, Sarwal M, Schaenman J, Sekaly R, Shaw A, Simon V. Immunophenotyping assessment in a COVID-19 cohort (IMPACC): A prospective longitudinal study. Science Immunology 2021, 6: eabf3733. PMID: 34376480, PMCID: PMC8713959, DOI: 10.1126/sciimmunol.abf3733.Peer-Reviewed Original ResearchConceptsCOVID-19 cohortProspective longitudinal studyHost immune responseLongitudinal studyCOVID-19Identification of biomarkersHospitalized patientsRespiratory secretionsClinical criteriaDisease progressionImmune responseRadiographic dataImmunologic assaysEffective therapeuticsOptimal timingStudy designBiologic samplingSuch interventionsCohortSeveritySample collectionAssay protocolsPatientsMind the gap from research laboratory to clinic: Challenges and opportunities for next-generation assays in human diseases
D'Souza MP, Palin AC, Calder T, Golding H, Kleinstein SH, Milliken EL, O'Connor D, Tomaras G, Warren J, Boggiano C. Mind the gap from research laboratory to clinic: Challenges and opportunities for next-generation assays in human diseases. Vaccine 2021, 39: 5233-5239. PMID: 34366145, PMCID: PMC8343370, DOI: 10.1016/j.vaccine.2021.07.071.Peer-Reviewed Original ResearchConceptsNext-generation assaysSevere acute respiratory syndrome coronavirus type 2Human immunodeficiency virusCoronavirus type 2National InstituteVaccine delivery methodNovel animal modelProtective immunityImmunodeficiency virusLicensed vaccineEffective vaccineModern vaccinologyPowerful adjuvantAnimal modelsImproved vaccinesType 2Immune systemImmunogen designVaccine developmentInfectious diseasesVaccineGeneration assaysTuberculosisDiseaseCritical pathogensCutting Edge: Distinct B Cell Repertoires Characterize Patients with Mild and Severe COVID-19
Hoehn KB, Ramanathan P, Unterman A, Sumida TS, Asashima H, Hafler DA, Kaminski N, Dela Cruz CS, Sealfon SC, Bukreyev A, Kleinstein SH. Cutting Edge: Distinct B Cell Repertoires Characterize Patients with Mild and Severe COVID-19. The Journal Of Immunology 2021, 206: 2785-2790. PMID: 34049971, PMCID: PMC8627528, DOI: 10.4049/jimmunol.2100135.Peer-Reviewed Original ResearchConceptsSevere COVID-19Mild COVID-19B cell responsesMemory B cellsB cell repertoireB cellsCell repertoireCOVID-19Cell responsesExtrafollicular B cell responsesLong-term immunitySymptomatic COVID-19Onset of symptomsB cell populationsGerminal center reactionProtective immunityPlasma cellsSingle-cell RNA sequencingCenter reactionPatientsCell populationsImmunityRNA sequencingCellsPostvaccinationImmune dysregulation and autoreactivity correlate with disease severity in SARS-CoV-2-associated multisystem inflammatory syndrome in children
Ramaswamy A, Brodsky NN, Sumida TS, Comi M, Asashima H, Hoehn KB, Li N, Liu Y, Shah A, Ravindra NG, Bishai J, Khan A, Lau W, Sellers B, Bansal N, Guerrerio P, Unterman A, Habet V, Rice AJ, Catanzaro J, Chandnani H, Lopez M, Kaminski N, Dela Cruz CS, Tsang JS, Wang Z, Yan X, Kleinstein SH, van Dijk D, Pierce RW, Hafler DA, Lucas CL. Immune dysregulation and autoreactivity correlate with disease severity in SARS-CoV-2-associated multisystem inflammatory syndrome in children. Immunity 2021, 54: 1083-1095.e7. PMID: 33891889, PMCID: PMC8043654, DOI: 10.1016/j.immuni.2021.04.003.Peer-Reviewed Original ResearchConceptsMIS-C patientsDisease severityInflammatory syndromeTCR repertoireSARS-CoV-2-associated multisystem inflammatory syndromeAsymptomatic SARS-CoV-2 infectionSARS-CoV-2 infectionAdult COVID-19Post-infectious complicationsMultisystem inflammatory syndromeCytotoxicity genesHealthy pediatricImmune dysregulationMemory TActive infectionMyeloid dysfunctionPatientsSingle-cell RNA sequencingFlow cytometrySerum proteomicsRepertoire analysisElevated expressionSeverityAlarminsCOVID-19
2020
A Potently Neutralizing Antibody Protects Mice against SARS-CoV-2 Infection
Alsoussi WB, Turner JS, Case JB, Zhao H, Schmitz AJ, Zhou JQ, Chen RE, Lei T, Rizk AA, McIntire KM, Winkler ES, Fox JM, Kafai NM, Thackray LB, Hassan AO, Amanat F, Krammer F, Watson CT, Kleinstein SH, Fremont DH, Diamond MS, Ellebedy AH. A Potently Neutralizing Antibody Protects Mice against SARS-CoV-2 Infection. The Journal Of Immunology 2020, 205: ji2000583. PMID: 32591393, PMCID: PMC7566074, DOI: 10.4049/jimmunol.2000583.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin-Converting Enzyme 2AnimalsAntibodies, MonoclonalAntibodies, NeutralizingAntibodies, ViralBetacoronavirusChlorocebus aethiopsCoronavirus InfectionsCOVID-19Disease Models, AnimalEpitope MappingFemaleHEK293 CellsHumansImmunodominant EpitopesMiceMice, Inbred C57BLPandemicsPeptidyl-Dipeptidase APneumonia, ViralProtein Interaction Domains and MotifsSARS-CoV-2Spike Glycoprotein, CoronavirusTransfectionVero CellsConceptsSARS-CoV-2 infectionSARS-CoV-2Receptor-binding domainSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2Respiratory syndrome coronavirus 2Angiotensin-converting enzyme 2Human angiotensin-converting enzyme 2Wild-type SARS-CoV-2Lung viral loadsSyndrome coronavirus 2Millions of infectionsTrimeric spike glycoproteinLicensed therapeuticsViral loadCoronavirus 2Systemic disseminationEffective antiviralsEnzyme 2Murine modelMurine mAbsEffective interventionsInfectionWeight lossSpike glycoprotein