2022
Single-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
Gaining Insight into SARS-CoV-2 Infection and COVID-19 Severity Using Self-supervised Edge Features and Graph Neural Networks
Sehanobish A, Ravindra N, Van Dijk D. Gaining Insight into SARS-CoV-2 Infection and COVID-19 Severity Using Self-supervised Edge Features and Graph Neural Networks. Proceedings Of The AAAI Conference On Artificial Intelligence 2021, 35: 4864-4873. DOI: 10.1609/aaai.v35i6.16619.Peer-Reviewed Original ResearchSARS-CoV-2 infectionSingle-cell omics dataCOVID-19 severitySingle-cell RNA sequencing datasetsCell typesRNA sequencing datasetsSARS-CoV-2Transcriptomic patternsSequencing datasetsOmics dataCellular determinantsCellular understandingIndividual cellsBronchoalveolar lavage fluid samplesInfected cellsSevere COVID-19Lavage fluid samplesCOVID-19Lung organoidsDisease statesInfectionTranscriptomeCellsSeverityFluid samplesImmune 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-19A neutrophil activation signature predicts critical illness and mortality in COVID-19
Meizlish ML, Pine AB, Bishai JD, Goshua G, Nadelmann ER, Simonov M, Chang CH, Zhang H, Shallow M, Bahel P, Owusu K, Yamamoto Y, Arora T, Atri DS, Patel A, Gbyli R, Kwan J, Won CH, Dela Cruz C, Price C, Koff J, King BA, Rinder HM, Wilson FP, Hwa J, Halene S, Damsky W, van Dijk D, Lee AI, Chun HJ. A neutrophil activation signature predicts critical illness and mortality in COVID-19. Blood Advances 2021, 5: 1164-1177. PMID: 33635335, PMCID: PMC7908851, DOI: 10.1182/bloodadvances.2020003568.Peer-Reviewed Original ResearchConceptsCritical illnessHealth system databaseNeutrophil activationCOVID-19Neutrophil activation signatureSevere COVID-19Intensive care unitGranulocyte colony-stimulating factorHigh mortality rateColony-stimulating factorSystem databaseHepatocyte growth factorClinical decompensationNeutrophil countImmune hyperactivationCare unitEarly elevationLipocalin-2Interleukin-8Longitudinal cohortClinical dataMortality ratePatientsIllnessActivation signatureNeuroinvasion 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
Circulating markers of angiogenesis and endotheliopathy in COVID‐19
Pine AB, Meizlish ML, Goshua G, Chang C, Zhang H, Bishai J, Bahel P, Patel A, Gbyli R, Kwan JM, Won CH, Price C, Dela Cruz CS, Halene S, van Dijk D, Hwa J, Lee AI, Chun HJ. Circulating markers of angiogenesis and endotheliopathy in COVID‐19. Pulmonary Circulation 2020, 10: 1-4. PMID: 33282193, PMCID: PMC7691906, DOI: 10.1177/2045894020966547.Peer-Reviewed Original ResearchCOVID-19 infectionMarkers of angiogenesisEndothelial injuryDisease severityCOVID-19-associated coagulopathyCritical COVID-19 infectionCOVID-19 pathogenesisCOVID-19COVID-19 diseaseEndothelial cell functionHospital mortalityMicrovascular complicationsCritical illnessElevated markersHospitalized patientsPatient populationFuture therapiesPlasma profilingSurvival analysisPatientsInfectionCell functionPotential targetInjuryMarkersPatient factors associated with SARS‐CoV‐2 in an admitted emergency department population
Haimovich A, Warner F, Young HP, Ravindra NG, Sehanobish A, Gong G, Wilson FP, van Dijk D, Schulz W, Taylor R. Patient factors associated with SARS‐CoV‐2 in an admitted emergency department population. Journal Of The American College Of Emergency Physicians Open 2020, 1: 569-577. PMID: 32838371, PMCID: PMC7280703, DOI: 10.1002/emp2.12145.Peer-Reviewed Original ResearchCOVID-19 positive patientsPatient characteristicsPatient factorsCOVID-19Positive COVID-19 testMultivariable logistic regression modelLow pulse oximetryChronic lung diseaseRetrospective observational studyCOVID-19 test resultsEmergency department patientsPrimary outcome measureEmergency department populationLower leukocyte countsPositive COVID-19 resultHistory of alcoholPositive test resultsSARS-CoV-2 virusSARS-CoV-2COVID-19 testingLogistic regression modelsCOVID-19 testCOVID-19 resultsED cohortNegative patients