2023
The potential of saliva as an accessible and sensitive sample type for the detection of respiratory pathogens and host immunity
Laxton C, Peno C, Hahn A, Allicock O, Perniciaro S, Wyllie A. The potential of saliva as an accessible and sensitive sample type for the detection of respiratory pathogens and host immunity. The Lancet Microbe 2023, 4: e837-e850. PMID: 37516121, DOI: 10.1016/s2666-5247(23)00135-0.Peer-Reviewed Original ResearchConceptsSARS-CoV-2Respiratory pathogensPotential of salivaUsefulness of salivaUse of salivaRespiratory specimenRespiratory secretionsDisease burdenImmunological componentsImmunity surveillanceClinical utilityHost immunityClinical useDiagnostic testsNon-invasive natureSalivaCOVID-19 pandemicSample typesMethodological factorsPathogensImmunitySecretionPersistence of Pneumococcal Carriage among Older Adults in the Community despite COVID-19 Mitigation Measures
Wyllie A, Mbodj S, Thammavongsa D, Hislop M, Yolda-Carr D, Waghela P, Nakahata M, Stahlfeld A, Vega N, York A, Allicock O, Wilkins G, Ouyang A, Siqueiros L, Strong Y, Anastasio K, Alexander-Parrish R, Arguedas A, Gessner B, Weinberger D. Persistence of Pneumococcal Carriage among Older Adults in the Community despite COVID-19 Mitigation Measures. Microbiology Spectrum 2023, 11: e04879-22. PMID: 37036377, PMCID: PMC10269788, DOI: 10.1128/spectrum.04879-22.Peer-Reviewed Original ResearchConceptsInvasive pneumococcal diseasePneumococcal diseaseSchool-aged childrenOlder adultsPneumococcal carriageSaliva samplesCOVID-19 pandemicRate of carriageCOVID-19-related disruptionsUpper respiratory tractRegular contactNew Haven areaFirst yearCarriage prevalencePre-pandemic levelsMedical historyRespiratory tractHigh prevalenceStreptococcus pneumoniaeCOVID-19 mitigation measuresStudy participantsPneumococciPrevalenceDiseaseCarriageRoutine 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 facilities
2022
Saliva as a sample type for SARS-CoV-2 detection: implementation successes and opportunities around the globe
Tobik ER, Kitfield-Vernon LB, Thomas RJ, Steel SA, Tan SH, Allicock OM, Choate BL, Akbarzada S, Wyllie AL. Saliva as a sample type for SARS-CoV-2 detection: implementation successes and opportunities around the globe. Expert Review Of Molecular Diagnostics 2022, 22: 519-535. PMID: 35763281, DOI: 10.1080/14737159.2022.2094250.Peer-Reviewed Original ResearchEvaluation of saliva self-collection devices for SARS-CoV-2 diagnostics
Allicock OM, Petrone ME, Yolda-Carr D, Breban M, Walsh H, Watkins AE, Rothman JE, Farhadian SF, Grubaugh ND, Wyllie AL. Evaluation of saliva self-collection devices for SARS-CoV-2 diagnostics. BMC Infectious Diseases 2022, 22: 284. PMID: 35337266, PMCID: PMC8953967, DOI: 10.1186/s12879-022-07285-7.Peer-Reviewed Original ResearchEvaluation of the Liberty16 Mobile Real Time PCR Device for Use With the SalivaDirect Assay for SARS-CoV-2 Testing
Yolda-Carr D, Thammavongsa DA, Vega N, Turner SJ, Pickering PJ, Wyllie AL. Evaluation of the Liberty16 Mobile Real Time PCR Device for Use With the SalivaDirect Assay for SARS-CoV-2 Testing. Frontiers In Cellular And Infection Microbiology 2022, 11: 808773. PMID: 35118013, PMCID: PMC8804088, DOI: 10.3389/fcimb.2021.808773.Peer-Reviewed Original ResearchConceptsLimit of detectionReal-time PCR deviceSARS-CoV-2 testingSmall portable devicesPCR devicePortable devicesSARS-CoV-2 detectionHigh sensitivitySARS-CoV-2 RNADevicesInfectious respiratory diseaseSARS-CoV-2Low-resource settingsRespiratory diseaseImplementation of testingFurther optimizationSaliva samplesProtocolGold standardRT-qPCRTimely accessCOVID-19 pandemicDetectionLOD rangeSensitivity
2021
Loop-Mediated Isothermal Amplification Detection of SARS-CoV-2 and Myriad Other Applications.
Moore KJM, Cahill J, Aidelberg G, Aronoff R, Bektaş A, Bezdan D, Butler DJ, Chittur SV, Codyre M, Federici F, Tanner NA, Tighe SW, True R, Ware SB, Wyllie AL, Afshin EE, Bendesky A, Chang CB, Dela Rosa R, Elhaik E, Erickson D, Goldsborough AS, Grills G, Hadasch K, Hayden A, Her SY, Karl JA, Kim CH, Kriegel AJ, Kunstman T, Landau Z, Land K, Langhorst BW, Lindner AB, Mayer BE, McLaughlin LA, McLaughlin MT, Molloy J, Mozsary C, Nadler JL, D'Silva M, Ng D, O'Connor DH, Ongerth JE, Osuolale O, Pinharanda A, Plenker D, Ranjan R, Rosbash M, Rotem A, Segarra J, Schürer S, Sherrill-Mix S, Solo-Gabriele H, To S, Vogt MC, Yu AD, Mason CE. Loop-Mediated Isothermal Amplification Detection of SARS-CoV-2 and Myriad Other Applications. Journal Of Biomolecular Techniques 2021, 32: 228-275. PMID: 35136384, PMCID: PMC8802757, DOI: 10.7171/jbt.21-3203-017.Peer-Reviewed Original ResearchEvidence 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
2020
Detection of SARS-CoV-2 RNA by multiplex RT-qPCR
Kudo E, Israelow B, Vogels CBF, Lu P, Wyllie AL, Tokuyama M, Venkataraman A, Brackney DE, Ott IM, Petrone ME, Earnest R, Lapidus S, Muenker MC, Moore AJ, Casanovas-Massana A, Team Y, Omer SB, Dela Cruz CS, Farhadian SF, Ko AI, Grubaugh ND, Iwasaki A. Detection of SARS-CoV-2 RNA by multiplex RT-qPCR. PLOS Biology 2020, 18: e3000867. PMID: 33027248, PMCID: PMC7571696, DOI: 10.1371/journal.pbio.3000867.Peer-Reviewed Original ResearchMeSH KeywordsBetacoronavirusCase-Control StudiesClinical Laboratory TechniquesCoronavirus InfectionsCOVID-19COVID-19 TestingDNA PrimersHEK293 CellsHumansLimit of DetectionMultiplex Polymerase Chain ReactionNasopharynxPandemicsPneumonia, ViralReagent Kits, DiagnosticReverse Transcriptase Polymerase Chain ReactionRNA, ViralSARS-CoV-2United StatesConceptsSARS-CoV-2 RNAMultiplex RT-qPCRRT-qPCRSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testingSARS-CoV-2Quantitative reverse transcription PCRCycle threshold valuesReverse transcription-PCRRT-qPCR assaysDisease controlMultiplex RT-qPCR assayTranscription-PCRAssaysSingle assayLow copy numberSaliva or Nasopharyngeal Swab Specimens for Detection of SARS-CoV-2
Wyllie AL, Fournier J, Casanovas-Massana A, Campbell M, Tokuyama M, Vijayakumar P, Warren JL, Geng B, Muenker MC, Moore AJ, Vogels CBF, Petrone ME, Ott IM, Lu P, Venkataraman A, Lu-Culligan A, Klein J, Earnest R, Simonov M, Datta R, Handoko R, Naushad N, Sewanan LR, Valdez J, White EB, Lapidus S, Kalinich CC, Jiang X, Kim DJ, Kudo E, Linehan M, Mao T, Moriyama M, Oh JE, Park A, Silva J, Song E, Takahashi T, Taura M, Weizman OE, Wong P, Yang Y, Bermejo S, Odio CD, Omer SB, Dela Cruz CS, Farhadian S, Martinello RA, Iwasaki A, Grubaugh ND, Ko AI. Saliva or Nasopharyngeal Swab Specimens for Detection of SARS-CoV-2. New England Journal Of Medicine 2020, 383: 1283-1286. PMID: 32857487, PMCID: PMC7484747, DOI: 10.1056/nejmc2016359.Peer-Reviewed Original ResearchReal-time public health communication of local SARS-CoV-2 genomic epidemiology
Kalinich CC, Jensen CG, Neugebauer P, Petrone ME, Peña-Hernández M, Ott IM, Wyllie AL, Alpert T, Vogels CBF, Fauver JR, Grubaugh ND, Brito AF. Real-time public health communication of local SARS-CoV-2 genomic epidemiology. PLOS Biology 2020, 18: e3000869. PMID: 32822393, PMCID: PMC7467297, DOI: 10.1371/journal.pbio.3000869.Peer-Reviewed Original ResearchThe COVID-19 XPRIZE and the need for scalable, fast, and widespread testing
MacKay MJ, Hooker AC, Afshinnekoo E, Salit M, Kelly J, Feldstein JV, Haft N, Schenkel D, Nambi S, Cai Y, Zhang F, Church G, Dai J, Wang CL, Levy S, Huber J, Ji HP, Kriegel A, Wyllie AL, Mason CE. The COVID-19 XPRIZE and the need for scalable, fast, and widespread testing. Nature Biotechnology 2020, 38: 1021-1024. PMID: 32820257, PMCID: PMC7543743, DOI: 10.1038/s41587-020-0655-4.Peer-Reviewed Original ResearchSARS-CoV-2 infection of the placenta
Hosier H, Farhadian SF, Morotti RA, Deshmukh U, Lu-Culligan A, Campbell KH, Yasumoto Y, Vogels C, Casanovas-Massana A, Vijayakumar P, Geng B, Odio CD, Fournier J, Brito AF, Fauver JR, Liu F, Alpert T, Tal R, Szigeti-Buck K, Perincheri S, Larsen C, Gariepy AM, Aguilar G, Fardelmann KL, Harigopal M, Taylor HS, Pettker CM, Wyllie AL, Dela Cruz CS, Ring AM, Grubaugh ND, Ko AI, Horvath TL, Iwasaki A, Reddy UM, Lipkind HS. SARS-CoV-2 infection of the placenta. Journal Of Clinical Investigation 2020, 130: 4947-4953. PMID: 32573498, PMCID: PMC7456249, DOI: 10.1172/jci139569.Peer-Reviewed Case Reports and Technical NotesMeSH KeywordsAbortion, TherapeuticAbruptio PlacentaeAdultBetacoronavirusCoronavirus InfectionsCOVID-19FemaleHumansMicroscopy, Electron, TransmissionPandemicsPhylogenyPlacentaPneumonia, ViralPre-EclampsiaPregnancyPregnancy Complications, InfectiousPregnancy Trimester, SecondRNA, ViralSARS-CoV-2Viral LoadConceptsSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2SARS-CoV-2 infectionRespiratory syndrome coronavirus 2SARS-CoV-2 invasionMaternal antibody responseSymptomatic COVID-19Second trimester pregnancySyndrome coronavirus 2Coronavirus disease 2019Materno-fetal interfaceDense macrophage infiltratesPlacental abruptionSevere preeclampsiaMacrophage infiltratesSevere morbidityTrimester pregnancyPregnant womenCoronavirus 2Antibody responseBackgroundThe effectsDisease 2019Histological examinationImmunohistochemical assaysPlacentaLongitudinal 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 2019Analytical sensitivity and efficiency comparisons of SARS-CoV-2 RT–qPCR primer–probe sets
Vogels CBF, Brito AF, Wyllie AL, Fauver JR, Ott IM, Kalinich CC, Petrone ME, Casanovas-Massana A, Catherine Muenker M, Moore AJ, Klein J, Lu P, Lu-Culligan A, Jiang X, Kim DJ, Kudo E, Mao T, Moriyama M, Oh JE, Park A, Silva J, Song E, Takahashi T, Taura M, Tokuyama M, Venkataraman A, Weizman OE, Wong P, Yang Y, Cheemarla NR, White EB, Lapidus S, Earnest R, Geng B, Vijayakumar P, Odio C, Fournier J, Bermejo S, Farhadian S, Dela Cruz CS, Iwasaki A, Ko AI, Landry ML, Foxman EF, Grubaugh ND. Analytical sensitivity and efficiency comparisons of SARS-CoV-2 RT–qPCR primer–probe sets. Nature Microbiology 2020, 5: 1299-1305. PMID: 32651556, PMCID: PMC9241364, DOI: 10.1038/s41564-020-0761-6.Peer-Reviewed Original ResearchConceptsSARS-CoV-2SARS-CoV-2 RTSevere acute respiratory syndrome coronavirusAcute respiratory syndrome coronavirusViral RNA copiesPublic health laboratoriesPublic health interventionsReverse transcription-PCR assaySARS-CoV-2 diagnostic testingDiagnostic assaysTranscription-PCR assaySARS-CoV-2 evolutionQuantitative reverse transcription-PCR assaysRapid diagnostic assaysHealth laboratoriesHealth interventionsDiagnostic testingRNA copiesPrimer-probe setsAssaysLow sensitivityCritical needAnalytical sensitivityAcute 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 findingsInflammationCoast-to-Coast Spread of SARS-CoV-2 during the Early Epidemic in the United States
Fauver JR, Petrone ME, Hodcroft EB, Shioda K, Ehrlich HY, Watts AG, Vogels CBF, Brito AF, Alpert T, Muyombwe A, Razeq J, Downing R, Cheemarla NR, Wyllie AL, Kalinich CC, Ott IM, Quick J, Loman NJ, Neugebauer KM, Greninger AL, Jerome KR, Roychoudhury P, Xie H, Shrestha L, Huang ML, Pitzer VE, Iwasaki A, Omer SB, Khan K, Bogoch II, Martinello RA, Foxman EF, Landry ML, Neher RA, Ko AI, Grubaugh ND. Coast-to-Coast Spread of SARS-CoV-2 during the Early Epidemic in the United States. Cell 2020, 181: 990-996.e5. PMID: 32386545, PMCID: PMC7204677, DOI: 10.1016/j.cell.2020.04.021.Peer-Reviewed Original ResearchConceptsSARS-CoV-2Federal travel restrictionsSARS-CoV-2 transmissionCOVID-19 patientsCoronavirus SARS-CoV-2SARS-CoV-2 introductionsEarly SARS-CoV-2 transmissionPattern of spreadSustained transmissionLocal surveillanceEarly epidemicInternational importationCOVID-19 outbreakUnited StatesViral genomeInternational travel patternsPatientsCritical needTravel restrictions