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 infectionLow antibody levels associated with significantly increased rate of SARS‐CoV‐2 infection in a highly vaccinated population from the US National Basketball Association
Tai C, Haviland M, Kissler S, Lucia R, Merson M, Maragakis L, Ho D, Anderson D, DiFiori J, Grubaugh N, Grad Y, Mack C. Low antibody levels associated with significantly increased rate of SARS‐CoV‐2 infection in a highly vaccinated population from the US National Basketball Association. Journal Of Medical Virology 2024, 96: e29505. PMID: 38465748, DOI: 10.1002/jmv.29505.Peer-Reviewed Original ResearchConceptsAntibody levelsSARS-CoV-2 infectionSARS-CoV-2 antibody levelsPfizer-BioNTech mRNA vaccineHistory of SARS-CoV-2 infectionCox proportional hazards modelsLow antibody levelsProportional hazards modelRisk of infectionMRNA vaccinesRates of SARS-CoV-2 infectionAnalytic cohortPrimary seriesPfizer-BioNTechVaccine doseIncreased rate of SARS-CoV-2 infectionInterquartile rangeBooster schedulesHazards modelSerological testsInfectionSARS-CoV-2Vaccinated individualsAntibodiesAntibody test
2022
Assessment of Clinical Effectiveness of BNT162b2 COVID-19 Vaccine in US Adolescents
Oliveira CR, Niccolai LM, Sheikha H, Elmansy L, Kalinich CC, Grubaugh ND, Shapiro ED, Billig K, Breban M, Brito A, Earnest R, Fauver J, Koch T, Ott I, Petrone M, Vogels C, Pham K, Tikhonova I, Castaldi C, Mane S, Bilguvar K, De Kumar B, Ferguson D, Kerantzas N, Landry M, Peaper D, Schulz W. Assessment of Clinical Effectiveness of BNT162b2 COVID-19 Vaccine in US Adolescents. JAMA Network Open 2022, 5: e220935. PMID: 35238933, PMCID: PMC8895259, DOI: 10.1001/jamanetworkopen.2022.0935.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 infectionCase-control studyVaccine effectivenessBNT162b2 vaccineSARS-CoV-2Medical recordsAsymptomatic SARS-CoV-2 infectionBNT162b2 COVID-19 vaccineRetrospective case-control studyRT-PCR test resultsSARS-CoV-2 testUS adolescentsReverse transcription polymerase chain reaction testConditional logistic regression modelsTranscription polymerase chain reaction testDoses of vaccineControl participantsClinical trial populationsRelevant clinical dataCase participantsCOVID-19 vaccinePositive test resultsChain reaction testCounty of residenceNegative test resultsSingle-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 reductionViral dynamics of acute SARS-CoV-2 infection and applications to diagnostic and public health strategies
Kissler SM, Fauver JR, Mack C, Olesen SW, Tai C, Shiue KY, Kalinich CC, Jednak S, Ott IM, Vogels CBF, Wohlgemuth J, Weisberger J, DiFiori J, Anderson DJ, Mancell J, Ho DD, Grubaugh ND, Grad YH. Viral dynamics of acute SARS-CoV-2 infection and applications to diagnostic and public health strategies. PLOS Biology 2021, 19: e3001333. PMID: 34252080, PMCID: PMC8297933, DOI: 10.1371/journal.pbio.3001333.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 infectionViral RNA concentrationClearance phaseAcute SARS-CoV-2 infectionReverse transcription-PCR testingPeak viral concentrationPersistent viral RNAPositive PCR testTranscription-PCR testingViral proliferationPublic health strategiesRNA concentrationViral concentrationInfection stagesCycle threshold valuesAcute infectionAsymptomatic individualsTest turnaround timeSymptomatic individualsClinical measuresHealth strategiesPatient progressPCR testingInfectionViral dynamicsDiverse 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 prevalenceAutoantibodiesLying 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 onsetEarly introductions and transmission of SARS-CoV-2 variant B.1.1.7 in the United States
Alpert T, Brito AF, Lasek-Nesselquist E, Rothman J, Valesano AL, MacKay MJ, Petrone ME, Breban MI, Watkins AE, Vogels CBF, Kalinich CC, Dellicour S, Russell A, Kelly JP, Shudt M, Plitnick J, Schneider E, Fitzsimmons WJ, Khullar G, Metti J, Dudley JT, Nash M, Beaubier N, Wang J, Liu C, Hui P, Muyombwe A, Downing R, Razeq J, Bart SM, Grills A, Morrison SM, Murphy S, Neal C, Laszlo E, Rennert H, Cushing M, Westblade L, Velu P, Craney A, Cong L, Peaper DR, Landry ML, Cook PW, Fauver JR, Mason CE, Lauring AS, St George K, MacCannell DR, Grubaugh ND. Early introductions and transmission of SARS-CoV-2 variant B.1.1.7 in the United States. Cell 2021, 184: 2595-2604.e13. PMID: 33891875, PMCID: PMC8018830, DOI: 10.1016/j.cell.2021.03.061.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 lineage B.1.1.7SARS-CoV-2 variant B.1.1.7Global public health concernPublic health concernPublic health responseCOVID-19 casesLineage B.1.1.7Variant B.1.1.7Health responseHealth concernB.1.1.7Increased transmissibilityEarly introductionGenomic surveillanceUnited StatesDiagnostic dataDominant lineageTracking 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 individualsAsynchronicity of endemic and emerging mosquito-borne disease outbreaks in the Dominican Republic
Petrone ME, Earnest R, Lourenço J, Kraemer MUG, Paulino-Ramirez R, Grubaugh ND, Tapia L. Asynchronicity of endemic and emerging mosquito-borne disease outbreaks in the Dominican Republic. Nature Communications 2021, 12: 151. PMID: 33420058, PMCID: PMC7794562, DOI: 10.1038/s41467-020-20391-x.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAedesAnimalsChikungunya FeverChikungunya virusChildChild, PreschoolCommunicable Diseases, EmergingDengueDengue VirusDisease OutbreaksDominican RepublicEndemic DiseasesEpidemiological MonitoringFemaleHumansInfantInfant, NewbornMaleMosquito ControlMosquito VectorsSpatio-Temporal AnalysisYoung AdultZika VirusZika Virus InfectionConceptsDengue outbreakDisease outbreaksDengue fever casesOutbreak of chikungunyaMosquito-Borne VirusesFever casesFuture health crisesMosquito-borne disease outbreaksFuture outbreaksVirus transmissionAedes mosquitoesSustainable disease control measuresHealth crisisVirusDisease control measuresOutbreakChikungunyaConstant surveillanceZikaControl measuresDominican Republic
2020
Two Sides of a Coin: a Zika Virus Mutation Selected in Pregnant Rhesus Macaques Promotes Fetal Infection in Mice but at a Cost of Reduced Fitness in Nonpregnant Macaques and Diminished Transmissibility by Vectors
Lemos D, Stuart JB, Louie W, Singapuri A, Ramírez AL, Watanabe J, Usachenko J, Keesler RI, Martin CS, Li T, Martyn C, Oliveira G, Saraf S, Grubaugh ND, Andersen KG, Thissen J, Allen J, Borucki M, Tsetsarkin KA, Pletnev AG, Chiu CY, Van Rompay KKA, Coffey LL. Two Sides of a Coin: a Zika Virus Mutation Selected in Pregnant Rhesus Macaques Promotes Fetal Infection in Mice but at a Cost of Reduced Fitness in Nonpregnant Macaques and Diminished Transmissibility by Vectors. Journal Of Virology 2020, 94: 10.1128/jvi.01605-20. PMID: 32999034, PMCID: PMC7925200, DOI: 10.1128/jvi.01605-20.Peer-Reviewed Original ResearchConceptsCongenital Zika syndromeZika virusFetal infectionFetal deathZika syndromePregnant micePregnant wild-type miceRhesus macaque fetusesPregnant rhesus macaquesZika virus infectionWild-type miceNonpregnant hostsPlacental infectionLow viremiaMajority of animalsPregnant womenPregnant macaquesSevere outcomesMacaque fetusesVirus infectionFetusesInfectionZIKV polyproteinMouse fetusesRhesus macaquesSex 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
2016
Isolation of a Novel Insect-Specific Flavivirus from Culiseta melanura in the Northeastern United States
Misencik MJ, Grubaugh ND, Andreadis TG, Ebel GD, Armstrong PM. Isolation of a Novel Insect-Specific Flavivirus from Culiseta melanura in the Northeastern United States. Vector-Borne And Zoonotic Diseases 2016, 16: 181-190. PMID: 26807512, PMCID: PMC4779966, DOI: 10.1089/vbz.2015.1889.Peer-Reviewed Original ResearchConceptsInsect-specific flavivirusesOpen reading framePhylogenetic analysisDistinct evolutionary lineagesAmino acid sequence identityObvious geographic structureLimited genetic variationNovel insect-specific flavivirusEvolutionary lineagesHost associationsGeographic structureComplete genomeGenetic variationField-collected mosquitoesReading frameMelanura larvaeNucleotide sequenceSequence identityLarval stagesSampled populationsNortheastern United StatesGenus FlavivirusCalbertado virusNS5 geneViral sequences