2024
Genome-wide association study between SARS-CoV-2 single nucleotide polymorphisms and virus copies during infections
Li K, Chaguza C, Stamp J, Chew Y, Chen N, Ferguson D, Pandya S, Kerantzas N, Schulz W, Initiative Y, Hahn A, Ogbunugafor C, Pitzer V, Crawford L, Weinberger D, Grubaugh N. Genome-wide association study between SARS-CoV-2 single nucleotide polymorphisms and virus copies during infections. PLOS Computational Biology 2024, 20: e1012469. PMID: 39288189, PMCID: PMC11432881, DOI: 10.1371/journal.pcbi.1012469.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesSingle-nucleotide polymorphismsAssociation studiesWhole-genome sequencingAmino acid changesSingle nucleotide polymorphismsPairs of substitutionsViral copiesEpistasis testsGenome sequenceGenetic variationSpike geneAcid changesViral genomeNucleotide polymorphismsSARS-CoV-2Detect interactionsHost factorsVirus copiesCopyInfection dynamicsRT-qPCRPolymorphismOmicron BASARS-CoV-2 infection
2023
Age-dependent impairment in antibody responses elicited by a homologous CoronaVac booster dose
Filardi B, Monteiro V, Schwartzmann P, do Prado Martins V, Zucca L, Baiocchi G, Malik A, Silva J, Hahn A, Chen N, Pham K, Pérez-Then E, Miric M, Brache V, Cochon L, Larocca R, Della Rosa Mendez R, Silveira D, Pinto A, Croda J, Yildirim I, Omer S, Ko A, Vermund S, Grubaugh N, Iwasaki A, Lucas C, Initiative Y, Vogels C, Breban M, Koch T, Chaguza C, Tikhonova I, Castaldi C, Mane S, De Kumar B, Ferguson D, Kerantzas N, Peaper D, Landry M, Schulz W. Age-dependent impairment in antibody responses elicited by a homologous CoronaVac booster dose. Science Translational Medicine 2023, 15: eade6023. PMID: 36791210, DOI: 10.1126/scitranslmed.ade6023.Peer-Reviewed Original ResearchConceptsBooster doseAntibody responseNeutralization titersVirus-specific IgG titersOlder adultsAntiviral humoral immunityPlasma antibody responsesHigh-risk populationSARS-CoV-2 spikeYears of ageAge-dependent impairmentHeterologous regimensBooster dosesBooster vaccineCoronaVac vaccineIgG titersProtective immunityHumoral immunityHumoral responseCoronaVacOmicron waveBooster strategyAge groupsEarly controlVaccine
2022
Quantifying the impact of immune history and variant on SARS-CoV-2 viral kinetics and infection rebound: A retrospective cohort study
Hay J, Kissler S, Fauver J, Mack C, Tai C, Samant R, Connolly S, Anderson D, Khullar G, MacKay M, Patel M, Kelly S, Manhertz A, Eiter I, Salgado D, Baker T, Howard B, Dudley J, Mason C, Nair M, Huang Y, DiFiori J, Ho D, Grubaugh N, Grad Y. Quantifying the impact of immune history and variant on SARS-CoV-2 viral kinetics and infection rebound: A retrospective cohort study. ELife 2022, 11: e81849. PMID: 36383192, PMCID: PMC9711520, DOI: 10.7554/elife.81849.Peer-Reviewed Original ResearchConceptsViral kineticsSARS-CoV-2 strainsAntibody titersViral reboundVaccination statusLonger clearance timeLower peak viral loadRetrospective cohort studyClearance timePeak viral loadSARS-CoV-2 variantsHigh antibody titersEffective immune responseRT-qPCR testingBooster vaccinationCohort studyEffect of ageViral loadHealth cohortSymptom statusImmune historyImmune responseInfection historyClearance rateInfectionSingle-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 investigationsImpact of circulating SARS-CoV-2 variants on mRNA vaccine-induced immunity
Lucas C, Vogels CBF, Yildirim I, Rothman JE, Lu P, Monteiro V, Gehlhausen JR, Campbell M, Silva J, Tabachnikova A, Peña-Hernandez MA, Muenker MC, Breban MI, Fauver JR, Mohanty S, Huang J, Shaw A, Ko A, Omer S, Grubaugh N, Iwasaki A. Impact of circulating SARS-CoV-2 variants on mRNA vaccine-induced immunity. Nature 2021, 600: 523-529. PMID: 34634791, PMCID: PMC9348899, DOI: 10.1038/s41586-021-04085-y.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 variantsMRNA vaccine-induced immunityT-cell activation markersSARS-CoV-2 antibodiesSecond vaccine doseVaccine-induced immunityCell activation markersT cell responsesHigh antibody titresSARS-CoV-2Vaccine boosterVaccine doseActivation markersVaccine dosesHumoral immunityAntibody titresMRNA vaccinesVitro stimulationNeutralization capacityNeutralization responseCell responsesE484KNucleocapsid peptideAntibody-binding sitesGreater reductionLying in wait: the resurgence of dengue virus after the Zika epidemic in Brazil
Brito AF, Machado LC, Oidtman RJ, Siconelli MJL, Tran QM, Fauver JR, Carvalho RDO, Dezordi FZ, Pereira MR, de Castro-Jorge LA, Minto ECM, Passos LMR, Kalinich CC, Petrone ME, Allen E, España GC, Huang AT, Cummings DAT, Baele G, Franca RFO, da Fonseca BAL, Perkins TA, Wallau GL, Grubaugh ND. Lying in wait: the resurgence of dengue virus after the Zika epidemic in Brazil. Nature Communications 2021, 12: 2619. PMID: 33976183, PMCID: PMC8113494, DOI: 10.1038/s41467-021-22921-7.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAged, 80 and overAntibodies, ViralBrazilChildChild, PreschoolDengueDengue VirusDisease SusceptibilityEpidemicsEpidemiological MonitoringFemaleGenome, ViralHumansImmunity, HeterologousIncidenceInfantInfant, NewbornMaleMiddle AgedMolecular TypingMosquito VectorsPhylogeographySerotypingYoung AdultZika VirusZika Virus InfectionConceptsDengue virus serotype 1Zika epidemicZika virus epidemicDENV lineagesVirus serotype 1DENV infectionProtective immunityDENV transmissionDengue susceptibilityDengue virusViral spreadLow transmission levelsSerotype 1Virus epidemicMajor outbreaksModel mosquitoEpidemicInfectionDengueTransmission suitabilityDengue incidenceYearsDengue dynamicsOutbreakIncidenceDelayed 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 onset
2020
Longitudinal 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 2019Acute encephalopathy with elevated CSF inflammatory markers as the initial presentation of COVID-19
Farhadian S, Glick LR, Vogels CBF, Thomas J, Chiarella J, Casanovas-Massana A, Zhou J, Odio C, Vijayakumar P, Geng B, Fournier J, Bermejo S, Fauver JR, Alpert T, Wyllie AL, Turcotte C, Steinle M, Paczkowski P, Dela Cruz C, Wilen C, Ko AI, MacKay S, Grubaugh ND, Spudich S, Barakat LA. Acute encephalopathy with elevated CSF inflammatory markers as the initial presentation of COVID-19. BMC Neurology 2020, 20: 248. PMID: 32552792, PMCID: PMC7301053, DOI: 10.1186/s12883-020-01812-2.Peer-Reviewed Original ResearchConceptsInitial presentationCentral nervous system inflammationSARS-CoV-2 infectionCSF inflammatory markersNervous system inflammationCerebrospinal fluid (CSF) cytokinesSeizure-like activityCOVID-19 infectionVirus SARS-CoV-2COVID-19SARS-CoV-2BackgroundCOVID-19Inflammatory markersNeurologic complicationsSystem inflammationImmunocompromised womanNeurologic manifestationsNeurologic symptomsViral neuroinvasionCase presentationWeInfected patientsMental statusRespiratory pathogensConclusionOur findingsInflammation