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 infectionSARS-CoV-2-related bat viruses evade human intrinsic immunity but lack efficient transmission capacity
Peña-Hernández M, Alfajaro M, Filler R, Moriyama M, Keeler E, Ranglin Z, Kong Y, Mao T, Menasche B, Mankowski M, Zhao Z, Vogels C, Hahn A, Kalinich C, Zhang S, Huston N, Wan H, Araujo-Tavares R, Lindenbach B, Homer R, Pyle A, Martinez D, Grubaugh N, Israelow B, Iwasaki A, Wilen C. SARS-CoV-2-related bat viruses evade human intrinsic immunity but lack efficient transmission capacity. Nature Microbiology 2024, 9: 2038-2050. PMID: 39075235, DOI: 10.1038/s41564-024-01765-z.Peer-Reviewed Original ResearchBat coronavirusesRelatives of SARS-CoV-2Upper airwayUpper airways of miceEpithelial cellsHuman nasal epithelial cellsAirways of miceMajor histocompatibility complex class I.SARS-CoV-2Nasal epithelial cellsHistocompatibility complex class I.Human bronchial epithelial cellsGenetic similarityBronchial epithelial cellsInnate immune restrictionCoronavirus replicationFunctional characterizationMolecular cloningReduced pathogenesisImpaired replicationBat virusCoronavirus pathogenesisPandemic potentialHigh-risk familiesImmune restrictionLow 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 testPersistent SARS-CoV-2 infection: significance and implications
Machkovech H, Hahn A, Garonzik Wang J, Grubaugh N, Halfmann P, Johnson M, Lemieux J, O'Connor D, Piantadosi A, Wei W, Friedrich T. Persistent SARS-CoV-2 infection: significance and implications. The Lancet Infectious Diseases 2024, 24: e453-e462. PMID: 38340735, DOI: 10.1016/s1473-3099(23)00815-0.Peer-Reviewed Original ResearchPersistent SARS-CoV-2 infectionSARS-CoV-2 infectionSuboptimal immune responsesPre-existing immunityPersistent virus replicationMonitoring viral evolutionPublic health problemTissue reservoirsImmunocompromised individualsTreatment strategiesPersistent infectionPublic health priorityImmune responseSARS-CoV-2 replicationSARS-CoV-2Virus replicationInfectionVirus variantsViral evolutionHealth priorityHealth problemsTreatmentPathophysiologyPatientsDiagnosis
2023
Enhanced inhibition of MHC-I expression by SARS-CoV-2 Omicron subvariants
Moriyama M, Lucas C, Monteiro V, Initiative Y, Iwasaki A, Chen N, Breban M, Hahn A, Pham K, Koch T, Chaguza C, Tikhonova I, Castaldi C, Mane S, De Kumar B, Ferguson D, Kerantzas N, Peaper D, Landry M, Schulz W, Vogels C, Grubaugh N. Enhanced inhibition of MHC-I expression by SARS-CoV-2 Omicron subvariants. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2221652120. PMID: 37036977, PMCID: PMC10120007, DOI: 10.1073/pnas.2221652120.Peer-Reviewed Original ResearchConceptsMHC-I expressionBreakthrough infectionsSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variantsMajor histocompatibility complex class I expressionCell-mediated immunityInfluenza virus infectionSARS-CoV-2 VOCsMHC-I upregulationClass I expressionSARS-CoV-2T cell recognitionVirus infectionMHC II expressionSpike proteinEnhanced inhibitionInfectionCell recognitionCommon mutationsReinfectionE proteinAntibodiesViral genesSubvariantsExpressionRoutine saliva testing for SARS-CoV-2 in children: Methods for partnering with community childcare centers
Rayack E, Askari H, Zirinsky E, Lapidus S, Sheikha H, Peno C, Kazemi Y, Yolda-Carr D, Liu C, Grubaugh N, Ko A, Wyllie A, Spatz E, Oliveira C, Bei A. Routine saliva testing for SARS-CoV-2 in children: Methods for partnering with community childcare centers. Frontiers In Public Health 2023, 11: 1003158. PMID: 36817891, PMCID: PMC9936085, DOI: 10.3389/fpubh.2023.1003158.Peer-Reviewed Original ResearchConceptsParents/guardiansOnline patient portalYounger age groupsSARS-CoV-2Age groupsSurveillance programSaliva collectionSARS-CoV-2 testingSARS-CoV-2 screeningWeekly saliva samplesRT-PCR testingChildcare centre staffCritical age groupRoutine surveillance toolRoutine testing programsChildcare centersCOVID-19 transmissionAsymptomatic screeningSaliva collection methodNasal swabsPatient portalsSymptomatic testingPublic health dataSaliva samplesChildcare facilitiesNasal host response-based screening for undiagnosed respiratory viruses: a pathogen surveillance and detection study
Cheemarla N, Hanron A, Fauver J, Bishai J, Watkins T, Brito A, Zhao D, Alpert T, Vogels C, Ko A, Schulz W, Landry M, Grubaugh N, van Dijk D, Foxman E. Nasal host response-based screening for undiagnosed respiratory viruses: a pathogen surveillance and detection study. The Lancet Microbe 2023, 4: e38-e46. PMID: 36586415, PMCID: PMC9835789, DOI: 10.1016/s2666-5247(22)00296-8.Peer-Reviewed Original ResearchConceptsRespiratory virus panelPg/mLCXCL10 concentrationsSARS-CoV-2Bacterial pathobiontsRespiratory virusesSARS-CoV-2 negative samplesViral respiratory infectionsSARS-CoV-2 positive samplesClinical virology laboratoryHealth care systemVirus-positive samplesQuantitative RT-PCRInfluenza C virusSymptomatic patientsRespiratory infectionsSeasonal coronavirusesNasopharyngeal swabsVirus panelC virusCommon virusesCXCL10Host responseInterferon responseVirology laboratory
2022
Global disparities in SARS-CoV-2 genomic surveillance
Brito A, Semenova E, Dudas G, Hassler G, Kalinich C, Kraemer M, Ho J, Tegally H, Githinji G, Agoti C, Matkin L, Whittaker C, Howden B, Sintchenko V, Zuckerman N, Mor O, Blankenship H, de Oliveira T, Lin R, Siqueira M, Resende P, Vasconcelos A, Spilki F, Aguiar R, Alexiev I, Ivanov I, Philipova I, Carrington C, Sahadeo N, Branda B, Gurry C, Maurer-Stroh S, Naidoo D, von Eije K, Perkins M, van Kerkhove M, Hill S, Sabino E, Pybus O, Dye C, Bhatt S, Flaxman S, Suchard M, Grubaugh N, Baele G, Faria N. Global disparities in SARS-CoV-2 genomic surveillance. Nature Communications 2022, 13: 7003. PMID: 36385137, PMCID: PMC9667854, DOI: 10.1038/s41467-022-33713-y.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 genomic surveillanceMiddle-income countriesHigh-income countriesGenomic surveillanceSARS-CoV-2Global pandemic preparednessPublic health responseCOVID-19 casesPandemic preparednessHealth responseMolecular testsSocioeconomic inequalitiesTurnaround timeIncome countriesSurveillanceGlobal disparitiesDaysGenomic sequencingVaccineLineage abundance estimation for SARS-CoV-2 in wastewater using transcriptome quantification techniques
Baaijens J, Zulli A, Ott I, Nika I, van der Lugt M, Petrone M, Alpert T, Fauver J, Kalinich C, Vogels C, Breban M, Duvallet C, McElroy K, Ghaeli N, Imakaev M, Mckenzie-Bennett M, Robison K, Plocik A, Schilling R, Pierson M, Littlefield R, Spencer M, Simen B, Hanage W, Grubaugh N, Peccia J, Baym M. Lineage abundance estimation for SARS-CoV-2 in wastewater using transcriptome quantification techniques. Genome Biology 2022, 23: 236. PMID: 36348471, PMCID: PMC9643916, DOI: 10.1186/s13059-022-02805-9.Peer-Reviewed Original ResearchOmicron-specific mRNA vaccination alone and as a heterologous booster against SARS-CoV-2
Fang Z, Peng L, Filler R, Suzuki K, McNamara A, Lin Q, Renauer PA, Yang L, Menasche B, Sanchez A, Ren P, Xiong Q, Strine M, Clark P, Lin C, Ko AI, Grubaugh ND, Wilen CB, Chen S. Omicron-specific mRNA vaccination alone and as a heterologous booster against SARS-CoV-2. Nature Communications 2022, 13: 3250. PMID: 35668119, PMCID: PMC9169595, DOI: 10.1038/s41467-022-30878-4.Peer-Reviewed Original ResearchConceptsHeterologous boosterSARS-CoV-2Antibody responseMRNA vaccinesMRNA vaccinationDelta variantOmicron variantType of vaccinationStrong antibody responseMRNA vaccine candidatesVaccine candidatesNeutralization potencyImmune evasionSARS-CoV.Two weeksComparable titersVaccinationVaccineTiters 10MiceOmicronWeeksWA-1LNP-mRNABoosterPartial ORF1ab Gene Target Failure with Omicron BA.2.12.1
Rodino KG, Peaper DR, Kelly BJ, Bushman F, Marques A, Adhikari H, Tu ZJ, Rolon R, Westblade LF, Green DA, Berry GJ, Wu F, Annavajhala MK, Uhlemann AC, Parikh BA, McMillen T, Jani K, Babady NE, Hahn AM, Koch RT, Grubaugh ND, Initiative Y, Rhoads DD. Partial ORF1ab Gene Target Failure with Omicron BA.2.12.1. Journal Of Clinical Microbiology 2022, 60: e00600-22. PMID: 35582905, PMCID: PMC9199403, DOI: 10.1128/jcm.00600-22.Peer-Reviewed Original ResearchRapid emergence of SARS-CoV-2 Omicron variant is associated with an infection advantage over Delta in vaccinated persons
Chaguza C, Coppi A, Earnest R, Ferguson D, Kerantzas N, Warner F, Young HP, Breban MI, Billig K, Koch RT, Pham K, Kalinich CC, Ott IM, Fauver JR, Hahn AM, Tikhonova IR, Castaldi C, De Kumar B, Pettker CM, Warren JL, Weinberger DM, Landry ML, Peaper DR, Schulz W, Vogels CBF, Grubaugh ND. Rapid emergence of SARS-CoV-2 Omicron variant is associated with an infection advantage over Delta in vaccinated persons. Med 2022, 3: 325-334.e4. PMID: 35399324, PMCID: PMC8983481, DOI: 10.1016/j.medj.2022.03.010.Peer-Reviewed Original ResearchConceptsSpike gene target failureSARS-CoV-2 Omicron variantPositivity rateOmicron variantOmicron infectionVaccine dosesVaccine-induced immunityNumber of dosesTest positivity rateOdds of infectionSARS-CoV-2Significant reductionDominant Delta variantUnvaccinated personsVaccination statusHigher oddsDelta variantInfectionVaccine manufacturersDisease controlVirus copiesDosesPCR testOddsTarget failureAssessment 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 resultsAn outbreak of SARS‐CoV‐2 on a transplant unit in the early vaccination era
Roberts SC, Palacios C, Grubaugh ND, Alpert T, Ott IM, Breban MI, Initiative Y, Martinello RA, Smith C, Davis MW, Mcmanus D, Tirmizi S, Topal JE, Azar MM, Malinis M. An outbreak of SARS‐CoV‐2 on a transplant unit in the early vaccination era. Transplant Infectious Disease 2022, 24: e13782. PMID: 34969164, DOI: 10.1111/tid.13782.Peer-Reviewed Original ResearchConceptsSARS-CoV-2Infection prevention practicesSARS-CoV-2 outbreakTransplant unitCOVID-19-associated morbiditySolid organ transplant recipientsSARS-CoV-2 vaccinationPrevention practicesHospital day 18Potential index casesOrgan transplant recipientsInfection prevention behaviorsMonoclonal antibody therapyCOVID-19SARS-CoV-2 clustersHospital staff membersWhole-genome sequencingAsymptomatic patientsTransplant recipientsPositive patientsAtypical presentationImmunocompromised patientsAntibody therapyVaccination eraDisease progressionSequencing SARS-CoV-2 genomes from saliva
Alpert T, Vogels CBF, Breban MI, Petrone ME, Wyllie A, Grubaugh N, Fauver J. Sequencing SARS-CoV-2 genomes from saliva. Virus Evolution 2022, 8: veab098. PMID: 35542310, PMCID: PMC9074962, DOI: 10.1093/ve/veab098.Peer-Reviewed Original Research
2021
COVID-19 Outcomes and Genomic Characterization of SARS-CoV-2 Isolated From Veterans in New England States: Retrospective Analysis
Lee M, Sallah YH, Petrone M, Ringer M, Cosentino D, Vogels CBF, Fauver JR, Alpert TD, Grubaugh ND, Gupta S. COVID-19 Outcomes and Genomic Characterization of SARS-CoV-2 Isolated From Veterans in New England States: Retrospective Analysis. JMIRx Med 2021, 2: e31503. PMID: 35014989, PMCID: PMC8722526, DOI: 10.2196/31503.Peer-Reviewed Original ResearchSARS-CoV-2 infectionPeak disease severityCOVID-19 outcomesChart reviewMean ageDisease severityHigher comorbidity burdenRetrospective chart reviewSARS-CoV-2 RNACohort of veteransGeneral US populationNon-white raceCOVID-19 infectionManual chart reviewSARS-CoV-2Multivariate regression analysisO2 requirementsNon-white veteransSARS-CoV-2 lineagesComorbidity burdenVirologic factorsD614G substitutionMultiple SARS-CoV-2 lineagesVirologic characteristicsClinical outcomes362. Saliva as a Reliable Sample Type for Mass SARS-CoV-2 Testing Strategies
Wyllie A, Vogels C, Allicock O, Watkins A, Petrone M, Yolda-Carr D, Harden C, Brackney D, Kalinich C, Breban M, Ott I, Sikka R, Kadiri L, Grubaugh N. 362. Saliva as a Reliable Sample Type for Mass SARS-CoV-2 Testing Strategies. Open Forum Infectious Diseases 2021, 8: 284-284. PMCID: PMC8644416, DOI: 10.1093/ofid/ofab466.563.Peer-Reviewed Original ResearchSARS-CoV-2A stem-loop RNA RIG-I agonist protects against acute and chronic SARS-CoV-2 infection in mice
Mao T, Israelow B, Lucas C, Vogels CBF, Gomez-Calvo ML, Fedorova O, Breban MI, Menasche BL, Dong H, Linehan M, Alpert T, Anderson F, Earnest R, Fauver J, Kalinich C, Munyenyembe K, Ott I, Petrone M, Rothman J, Watkins A, Wilen C, Landry M, Grubaugh N, Pyle A, Iwasaki A. A stem-loop RNA RIG-I agonist protects against acute and chronic SARS-CoV-2 infection in mice. Journal Of Experimental Medicine 2021, 219: e20211818. PMID: 34757384, PMCID: PMC8590200, DOI: 10.1084/jem.20211818.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 infectionChronic SARS-CoV-2 infectionVariants of concernLethal SARS-CoV-2 infectionPost-infection therapyLower respiratory tractPost-exposure treatmentType I interferonSARS-CoV-2Effective medical countermeasuresAdaptive immune systemBroad-spectrum antiviralsContext of infectionSingle doseRespiratory tractViral controlImmunodeficient miceSevere diseaseMouse modelI interferonViral infectionImmune systemInnate immunityDisease preventionConsiderable efficacyImpact 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 reductionEvidence for SARS-CoV-2 Spike Protein in the Urine of COVID-19 Patients
George S, Pal AC, Gagnon J, Timalsina S, Singh P, Vydyam P, Munshi M, Chiu JE, Renard I, Harden CA, Ott IM, Watkins AE, Vogels CBF, Lu P, Tokuyama M, Venkataraman A, Casanovas-Massana A, Wyllie AL, Rao V, Campbell M, Farhadian SF, Grubaugh ND, Dela Cruz CS, Ko AI, Perez A, Akaho EH, Moledina DG, Testani J, John AR, Ledizet M, Mamoun CB, Team A. Evidence for SARS-CoV-2 Spike Protein in the Urine of COVID-19 Patients. Kidney360 2021, 2: 924-936. PMID: 35373072, PMCID: PMC8791366, DOI: 10.34067/kid.0002172021.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 spike proteinSARS-CoV-2Spike proteinUrine samplesSARS-CoV-2 infectionYale-New Haven HospitalCOVID-19 patientsAntigen capture assayDetectable viral RNANew Haven HospitalPositive PCR resultsPossible long-term consequencesSpike S1 proteinNP PCRChildren's HospitalNasopharyngeal swabsSARS-CoV-2 spike S1 proteinRenal abnormalitiesLong-term effectsCystatin CLong-term consequencesHospitalUrineViral RNAAlbuminuria