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 factorsPathogensImmunitySecretionMethod versatility in RNA extraction-free PCR detection of SARS-CoV-2 in saliva samples
Allicock O, Yolda-Carr D, Earnest R, Breban M, Vega N, Ott I, Kalinich C, Alpert T, Petrone M, Wyllie A. Method versatility in RNA extraction-free PCR detection of SARS-CoV-2 in saliva samples. Progress In Biophysics And Molecular Biology 2023, 182: 103-108. PMID: 37369293, PMCID: PMC10290768, DOI: 10.1016/j.pbiomolbio.2023.06.004.Peer-Reviewed Original ResearchPooled RNA-extraction-free testing of saliva for the detection of SARS-CoV-2
Allicock O, Yolda-Carr D, Todd J, Wyllie A. Pooled RNA-extraction-free testing of saliva for the detection of SARS-CoV-2. Scientific Reports 2023, 13: 7426. PMID: 37156888, PMCID: PMC10165292, DOI: 10.1038/s41598-023-34662-2.Peer-Reviewed Original ResearchConceptsSARS-CoV-2RT-qPCR assaysSARS-CoV-2 testingVirus-infected individualsAged care facilitiesSelf-collected salivaSARS-CoV-2 spreadActionable time frameAsymptomatic individualsTest turnaround timeHealthcare workersGeneral populationCare facilitiesTest availabilityWeekly testingFree testingClinical salivaPositive agreementClinical laboratoriesSalivaCT valuesSuch testingTesting workflowIndividual testingTesting protocolPersistence 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-based methods for SARS-CoV-2 testing in low- and middle-income countries
Tan S, Allicock O, Katamba A, Carrington C, Wyllie A, Armstrong-Hough M. Saliva-based methods for SARS-CoV-2 testing in low- and middle-income countries. Bulletin Of The World Health Organization 2022, 100: 808-814. PMID: 36466209, PMCID: PMC9706358, DOI: 10.2471/blt.22.288526.Peer-Reviewed Original ResearchAssociation of Upper Respiratory Streptococcus pneumoniae Colonization With Severe Acute Respiratory Syndrome Coronavirus 2 Infection Among Adults
Parker A, Jackson N, Awasthi S, Kim H, Alwan T, Wyllie A, Baldwin A, Brennick N, Moehle E, Giannikopoulos P, Kogut K, Holland N, Mora-Wyrobek A, Eskenazi B, Riley L, Lewnard J. Association of Upper Respiratory Streptococcus pneumoniae Colonization With Severe Acute Respiratory Syndrome Coronavirus 2 Infection Among Adults. Clinical Infectious Diseases 2022, 76: 1209-1217. PMID: 36401872, DOI: 10.1093/cid/ciac907.Peer-Reviewed Original ResearchMeSH KeywordsAdultCOVID-19HumansNasopharynxPneumococcal InfectionsSARS-CoV-2Streptococcus pneumoniaeConceptsSARS-CoV-2 infectionSARS-CoV-2Upper airwayAcute respiratory syndrome coronavirus 2 infectionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectionSevere acute respiratory syndrome coronavirus 2Syndrome coronavirus 2 infectionAcute respiratory syndrome coronavirus 2Respiratory syndrome coronavirus 2SARS-CoV-2 molecular testingCoronavirus 2 infectionStreptococcus pneumoniae colonizationViral respiratory pathogensSyndrome coronavirus 2Conditional logistic regressionWorking-age adultsQuantitative polymerase chain reactionPneumococcal carriersPneumococcal carriagePneumoniae colonizationOutpatient clinicCoronavirus 2Polymerase chain reactionRespiratory pathogensSaliva specimensSaliva 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 ResearchSingle-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 interactionsEvaluation 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 rangeSensitivitySaliva RT-PCR Sensitivity Over the Course of SARS-CoV-2 Infection
Wyllie AL, Premsrirut PK. Saliva RT-PCR Sensitivity Over the Course of SARS-CoV-2 Infection. JAMA 2022, 327: 182-183. PMID: 35015044, DOI: 10.1001/jama.2021.21703.Peer-Reviewed Original Research
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 investigationsReply to: A finding of sex similarities rather than differences in COVID-19 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 JB, Odio CD, Farhadian S, Dela Cruz C, Grubaugh ND, Schulz WL, Ring AM, Ko AI, Omer SB, Iwasaki A. Reply to: A finding of sex similarities rather than differences in COVID-19 outcomes. Nature 2021, 597: e10-e11. PMID: 34552250, DOI: 10.1038/s41586-021-03645-6.Peer-Reviewed Original ResearchLoop-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 ResearchUnderstanding the Barriers to Pooled SARS-CoV-2 Testing in the United States
Fenichel EP, Koch RT, Gilbert A, Gonsalves G, Wyllie AL. Understanding the Barriers to Pooled SARS-CoV-2 Testing in the United States. Microbiology Spectrum 2021, 9: e00312-21. PMID: 34378949, PMCID: PMC8552767, DOI: 10.1128/spectrum.00312-21.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 testingSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detectionPooled testingPooled testing strategyClinical Laboratory Improvement AmendmentsTraditional diagnostic testingEmergence of variantsTesting strategiesDiagnostic testingVirus resurgenceEarly detectionClear protocolsTest capacityTesting capacityUnited StatesTest priceSurveillance measuresTest reportingMajor barrierUptakeAdequate resourcesResponseTestingTesting programU.S. laboratoriesEvidence 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 RNAAlbuminuriaDiverse 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 onsetSaliva as a gold-standard sample for SARS-CoV-2 detection
Tan SH, Allicock O, Armstrong-Hough M, Wyllie AL. Saliva as a gold-standard sample for SARS-CoV-2 detection. The Lancet Respiratory Medicine 2021, 9: 562-564. PMID: 33887248, PMCID: PMC8055204, DOI: 10.1016/s2213-2600(21)00178-8.Peer-Reviewed Original Research