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
Longitudinal Immune Profiling of a Severe Acute Respiratory Syndrome Coronavirus 2 Reinfection in a Solid Organ Transplant Recipient
Klein J, Brito AF, Trubin P, Lu P, Wong P, Alpert T, Peña-Hernández MA, Haynes W, Kamath K, Liu F, Vogels CBF, Fauver JR, Lucas C, Oh J, Mao T, Silva J, Wyllie AL, Muenker MC, Casanovas-Massana A, Moore AJ, Petrone ME, Kalinich CC, Dela Cruz C, Farhadian S, Ring A, Shon J, Ko AI, Grubaugh ND, Israelow B, Iwasaki A, Azar MM, Team F. Longitudinal Immune Profiling of a Severe Acute Respiratory Syndrome Coronavirus 2 Reinfection in a Solid Organ Transplant Recipient. The Journal Of Infectious Diseases 2021, 225: 374-384. PMID: 34718647, PMCID: PMC8807168, DOI: 10.1093/infdis/jiab553.Peer-Reviewed Original ResearchConceptsSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfectionLongitudinal immune profilingTransplant recipientsImmune profilingPrimary SARS-CoV-2 infectionCD4 T cell poolMale renal transplant recipientSolid organ transplant recipientsSARS-CoV-2 reinfectionSARS-CoV-2 antibodiesSARS-CoV-2 infectionWhole viral genome sequencingRenal transplant recipientsImmune escape mutationsOrgan transplant recipientsT cell poolTime of reinfectionCoronavirus disease 2019Lower neutralization titersHumoral memory responsesViral genome sequencingInitial diagnosisImmunologic deficiencyHumoral responseImmunologic investigationsDiverse functional autoantibodies in patients with COVID-19
Wang EY, Mao T, Klein J, Dai Y, Huck JD, Jaycox JR, Liu F, Zhou T, Israelow B, Wong P, Coppi A, Lucas C, Silva J, Oh JE, Song E, Perotti ES, Zheng NS, Fischer S, Campbell M, Fournier JB, Wyllie AL, Vogels CBF, Ott IM, Kalinich CC, Petrone ME, Watkins AE, Dela Cruz C, Farhadian S, Schulz W, Ma S, Grubaugh N, Ko A, Iwasaki A, Ring A. Diverse functional autoantibodies in patients with COVID-19. Nature 2021, 595: 283-288. PMID: 34010947, DOI: 10.1038/s41586-021-03631-y.Peer-Reviewed Original ResearchConceptsPeripheral immune cell compositionSARS-CoV-2 infectionCOVID-19Effects of autoantibodiesTissue-associated antigensSpecific clinical characteristicsInnate immune activationImmune cell compositionCOVID-19 exhibitCOVID-19 manifestsAnalysis of autoantibodiesSARS-CoV-2Functional autoantibodiesMouse surrogateClinical characteristicsVirological controlClinical outcomesImmune activationMild diseaseAsymptomatic infectionAutoantibody reactivityDisease progressionHealthcare workersHigh prevalenceAutoantibodiesDelayed production of neutralizing antibodies correlates with fatal COVID-19
Lucas C, Klein J, Sundaram ME, Liu F, Wong P, Silva J, Mao T, Oh JE, Mohanty S, Huang J, Tokuyama M, Lu P, Venkataraman A, Park A, Israelow B, Vogels CBF, Muenker MC, Chang CH, Casanovas-Massana A, Moore AJ, Zell J, Fournier JB, Wyllie A, Campbell M, Lee A, Chun H, Grubaugh N, Schulz W, Farhadian S, Dela Cruz C, Ring A, Shaw A, Wisnewski A, Yildirim I, Ko A, Omer S, Iwasaki A. Delayed production of neutralizing antibodies correlates with fatal COVID-19. Nature Medicine 2021, 27: 1178-1186. PMID: 33953384, PMCID: PMC8785364, DOI: 10.1038/s41591-021-01355-0.Peer-Reviewed Original ResearchConceptsDeceased patientsAntibody levelsAntibody responseDisease severityAnti-S IgG levelsCOVID-19 disease outcomesFatal COVID-19Impaired viral controlWorse clinical progressionWorse disease severitySevere COVID-19Length of hospitalizationImmunoglobulin G levelsHumoral immune responseCoronavirus disease 2019COVID-19 mortalityCOVID-19Domain (RBD) IgGSeroconversion kineticsDisease courseIgG levelsClinical parametersClinical progressionHumoral responseDisease onsetTracking 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 individuals
2020
Sex differences in immune responses that underlie COVID-19 disease outcomes
Takahashi T, Ellingson MK, Wong P, Israelow B, Lucas C, Klein J, Silva J, Mao T, Oh JE, Tokuyama M, Lu P, Venkataraman A, Park A, Liu F, Meir A, Sun J, Wang EY, Casanovas-Massana A, Wyllie AL, Vogels CBF, Earnest R, Lapidus S, Ott IM, Moore AJ, Shaw A, Fournier J, Odio C, Farhadian S, Dela Cruz C, Grubaugh N, Schulz W, Ring A, Ko A, Omer S, Iwasaki A. Sex differences in immune responses that underlie COVID-19 disease outcomes. Nature 2020, 588: 315-320. PMID: 32846427, PMCID: PMC7725931, DOI: 10.1038/s41586-020-2700-3.Peer-Reviewed Original ResearchConceptsInnate immune cytokinesFemale patientsMale patientsImmune cytokinesDisease outcomeImmune responseCOVID-19COVID-19 disease outcomesPoor T cell responsesSARS-CoV-2 infectionSevere acute respiratory syndrome coronavirusAcute respiratory syndrome coronavirusSex-based approachModerate COVID-19Sex differencesRobust T cell activationT cell responsesWorse disease progressionWorse disease outcomesHigher plasma levelsNon-classical monocytesCoronavirus disease 2019T cell activationImmunomodulatory medicationsPlasma cytokinesLongitudinal analyses reveal immunological misfiring in severe COVID-19
Lucas C, Wong P, Klein J, Castro TBR, Silva J, Sundaram M, Ellingson MK, Mao T, Oh JE, Israelow B, Takahashi T, Tokuyama M, Lu P, Venkataraman A, Park A, Mohanty S, Wang H, Wyllie AL, Vogels CBF, Earnest R, Lapidus S, Ott IM, Moore AJ, Muenker MC, Fournier JB, Campbell M, Odio CD, Casanovas-Massana A, Herbst R, Shaw A, Medzhitov R, Schulz W, Grubaugh N, Dela Cruz C, Farhadian S, Ko A, Omer S, Iwasaki A. Longitudinal analyses reveal immunological misfiring in severe COVID-19. Nature 2020, 584: 463-469. PMID: 32717743, PMCID: PMC7477538, DOI: 10.1038/s41586-020-2588-y.Peer-Reviewed Original ResearchConceptsSevere COVID-19Moderate COVID-19Immune signaturesDisease outcomeCOVID-19Disease trajectoriesInterleukin-5Early immune signaturesInnate cell lineagesType 2 effectorsT cell numbersPoor clinical outcomeWorse disease outcomesImmune response profileCoronavirus disease 2019Distinct disease trajectoriesCytokine levelsImmunological correlatesImmune profileClinical outcomesEarly elevationImmune profilingIL-13Immunoglobulin EDisease 2019
2019
Joint sequencing of human and pathogen genomes reveals the genetics of pneumococcal meningitis
Lees JA, Ferwerda B, Kremer PHC, Wheeler NE, Serón MV, Croucher NJ, Gladstone RA, Bootsma HJ, Rots NY, Wijmega-Monsuur AJ, Sanders EAM, Trzciński K, Wyllie AL, Zwinderman AH, van den Berg LH, van Rheenen W, Veldink JH, Harboe ZB, Lundbo LF, de Groot LCPGM, van Schoor NM, van der Velde N, Ängquist LH, Sørensen TIA, Nohr EA, Mentzer AJ, Mills TC, Knight JC, du Plessis M, Nzenze S, Weiser JN, Parkhill J, Madhi S, Benfield T, von Gottberg A, van der Ende A, Brouwer MC, Barrett JC, Bentley SD, van de Beek D. Joint sequencing of human and pathogen genomes reveals the genetics of pneumococcal meningitis. Nature Communications 2019, 10: 2176. PMID: 31092817, PMCID: PMC6520353, DOI: 10.1038/s41467-019-09976-3.Peer-Reviewed Original ResearchConceptsGenetic variationGenome-wide association studiesCommon nasopharyngeal colonizerPathogen genomesHalf of variationPneumococcal factorsPneumococcal genesAssociation studiesJoint sequencingHuman variationInvasive potentialLife-threatening invasive diseasesGenesPathogensInteraction analysisInvasivenessGenomeZmpDGeneticsSequencingColonizersHumansVariationHostSusceptibility
2018
Exploring Immune Development in Infants With Moderate to Severe Atopic Dermatitis
Hulshof L, Overbeek SA, Wyllie AL, Chu MLJN, Bogaert D, de Jager W, Knippels LMJ, Sanders EAM, van Aalderen WMC, Garssen J, Land B, Sprikkelman AB, Group T, Blauw A, Dontje B, Duijvestein Y, de Boom W, Groot I, Boks M, van Kooyk Y, Fandri D, Hijnen D, Middelkamp-Hup M, Papi B, Roelofs M, Rijnierse A, Veening D, Support C, Prakken B, Tusscher G, Tupker R, Willemsen L. Exploring Immune Development in Infants With Moderate to Severe Atopic Dermatitis. Frontiers In Immunology 2018, 9: 630. PMID: 29966024, PMCID: PMC5884950, DOI: 10.3389/fimmu.2018.00630.Peer-Reviewed Original ResearchConceptsSevere atopic dermatitisAtopic dermatitisDietary interventionAD severityCommon chronic inflammatory skin diseaseT helper cell type 2Understanding of ADChronic inflammatory skin diseaseCC chemokine ligand 17CXC chemokine ligand 9Serum chemokine levelsSpecific IgE levelsInflammatory skin diseaseChemokine ligand 17Cell type 2Dietary intervention studyWhey-based formulaChemokine ligand 9Post-intervention samplesMonths of ageCCL22 chemokinesTh1 chemokinesTh2 chemokinesChemokine levelsM-16V
2016
Development of the Nasopharyngeal Microbiota in Infants with Cystic Fibrosis
Prevaes SM, de Winter-de Groot KM, Janssens HM, de Steenhuijsen Piters WA, Tramper-Stranders GA, Wyllie AL, Hasrat R, Tiddens HA, van Westreenen M, van der Ent CK, Sanders EA, Bogaert D. Development of the Nasopharyngeal Microbiota in Infants with Cystic Fibrosis. American Journal Of Respiratory And Critical Care Medicine 2016, 193: 504-515. PMID: 26492486, DOI: 10.1164/rccm.201509-1759oc.Peer-Reviewed Original ResearchMeSH KeywordsAnti-Bacterial AgentsBurkholderiaBurkholderia InfectionsCarrier StateCase-Control StudiesCohort StudiesCorynebacteriumCorynebacterium InfectionsCystic FibrosisDNA, BacterialEnterobacteriaceaeEnterobacteriaceae InfectionsFemaleHaemophilus InfectionsHaemophilus influenzaeHumansInfantInfant, NewbornMaleMicrobiotaMoraxellaMoraxellaceae InfectionsNasopharynxProspective StudiesReal-Time Polymerase Chain ReactionRNA, Ribosomal, 16SStaphylococcal InfectionsStaphylococcus aureusStreptococcal InfectionsStreptococcus mitisConceptsHealthy control subjectsControl subjectsMonths of lifeMonths of ageCystic fibrosisAntibiotic useMicrobiota profilesAge-matched healthy control subjectsEarly structural lung diseaseNasopharyngeal microbiota profilesNasopharynx of infantsProspective cohort studyStructural lung diseaseTime of diagnosisMoraxella sppPotential respiratory pathogensRespiratory symptomsAntibiotic therapyCohort studyPulmonary infectionLung diseaseNasopharyngeal microbiotaRespiratory pathogensHaemophilus influenzaeNasopharynx samples
2015
Dysbiosis of upper respiratory tract microbiota in elderly pneumonia patients
de Steenhuijsen Piters WA, Huijskens EG, Wyllie AL, Biesbroek G, van den Bergh MR, Veenhoven RH, Wang X, Trzciński K, Bonten MJ, Rossen JW, Sanders EA, Bogaert D. Dysbiosis of upper respiratory tract microbiota in elderly pneumonia patients. The ISME Journal: Multidisciplinary Journal Of Microbial Ecology 2015, 10: 97-108. PMID: 26151645, PMCID: PMC4681870, DOI: 10.1038/ismej.2015.99.Peer-Reviewed Original ResearchConceptsElderly pneumonia patientsAdult pneumonia patientsPneumonia patientsMicrobiota profilesUpper respiratory tract microbiomeUpper respiratory tract microbiotaRespiratory tract microbiomeDevelopment of pneumoniaRespiratory tract microbiotaYoung healthy adultsURT microbiomeBacterial overgrowthBacterial pneumoniaPathogen overgrowthHealthy controlsOropharyngeal microbiotaHealthy individualsPatientsHealthy adultsPneumoniaDisease statusPrevotella melaninogenicaMicrobiome changesURT microbiotaDysbiosisCarriage of Streptococcus pneumoniae in Aged Adults with Influenza-Like-Illness
Krone CL, Wyllie AL, van Beek J, Rots NY, Oja AE, Chu ML, Bruin JP, Bogaert D, Sanders EA, Trzciński K. Carriage of Streptococcus pneumoniae in Aged Adults with Influenza-Like-Illness. PLOS ONE 2015, 10: e0119875. PMID: 25789854, PMCID: PMC4366201, DOI: 10.1371/journal.pone.0119875.Peer-Reviewed Original ResearchConceptsS. pneumoniaeStreptococcus pneumoniaeCarriage detectionSaliva samplesPneumococcal conjugated vaccineStudy time pointsPCV13 serotypesPneumococcal diseaseCarriage prevalenceNasopharyngeal colonisationNasopharyngeal swabsConjugated vaccineNasopharyngealAged adultsPneumococciTime pointsPneumoniaeCarriageInfantsConventional cultureIllnessSalivaInfluenzaDiseaseSerotypes
2014
Streptococcus pneumoniae in Saliva of Dutch Primary School Children
Wyllie AL, Chu ML, Schellens MH, van Engelsdorp Gastelaars J, Jansen MD, van der Ende A, Bogaert D, Sanders EA, Trzciński K. Streptococcus pneumoniae in Saliva of Dutch Primary School Children. PLOS ONE 2014, 9: e102045. PMID: 25013895, PMCID: PMC4094488, DOI: 10.1371/journal.pone.0102045.Peer-Reviewed Original ResearchConceptsPneumoniae carriagePneumococcal carriagePneumococcal strainsMultiple pneumococcal strainsStreptococcus pneumoniae carriageS. pneumoniae carriageS. pneumoniae strainsNumber of serotypesDutch primary school childrenNasopharyngeal samplingSchool-aged childrenPneumococcal detectionSurveillance studyS. pneumoniaePneumoniae strainsStreptococcus pneumoniaeSerotype composition