Featured Publications
A multicenter evaluation of computable phenotyping approaches for SARS-CoV-2 infection and COVID-19 hospitalizations
Khera R, Mortazavi BJ, Sangha V, Warner F, Patrick Young H, Ross JS, Shah ND, Theel ES, Jenkinson WG, Knepper C, Wang K, Peaper D, Martinello RA, Brandt CA, Lin Z, Ko AI, Krumholz HM, Pollock BD, Schulz WL. A multicenter evaluation of computable phenotyping approaches for SARS-CoV-2 infection and COVID-19 hospitalizations. Npj Digital Medicine 2022, 5: 27. PMID: 35260762, PMCID: PMC8904579, DOI: 10.1038/s41746-022-00570-4.Peer-Reviewed Original ResearchCOVID-19 hospitalizationMayo ClinicDiagnosis codesCOVID-19 diagnosisPositive SARS-CoV-2 PCRYale New Haven Health SystemPositive SARS-CoV-2 testSARS-CoV-2 infectionSARS-CoV-2 PCRSARS-CoV-2 testCOVID-19Higher inhospital mortalitySARS-CoV2 infectionElectronic health record dataICD-10 diagnosisPositive laboratory testsHealth record dataInhospital mortalityAdditional patientsAntigen testSecondary diagnosisPrincipal diagnosisMulticenter evaluationPositive testComputable phenotype definitionsClinical characteristics and outcomes for 7,995 patients with SARS-CoV-2 infection
McPadden J, Warner F, Young HP, Hurley NC, Pulk RA, Singh A, Durant TJS, Gong G, Desai N, Haimovich A, Taylor RA, Gunel M, Dela Cruz CS, Farhadian SF, Siner J, Villanueva M, Churchwell K, Hsiao A, Torre CJ, Velazquez EJ, Herbst RS, Iwasaki A, Ko AI, Mortazavi BJ, Krumholz HM, Schulz WL. Clinical characteristics and outcomes for 7,995 patients with SARS-CoV-2 infection. PLOS ONE 2021, 16: e0243291. PMID: 33788846, PMCID: PMC8011821, DOI: 10.1371/journal.pone.0243291.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 infectionYale New Haven HealthSARS-CoV-2Hospital mortalityRisk of admissionMale sexRisk factorsSARS-CoV-2 testingInvasive mechanical ventilationSevere acute respiratory syndrome virusBurden of diseaseRT-PCR testingAcademic health systemDiverse patient populationsRespiratory syndrome virusEthnic groupsAdult patientsClinical characteristicsDischarge dispositionRespiratory supportPrimary outcomeTreatment guidelinesMechanical ventilationRetrospective studyPatient populationAssociation between primary or booster COVID-19 mRNA vaccination and Omicron lineage BA.1 SARS-CoV-2 infection in people with a prior SARS-CoV-2 infection: A test-negative case–control analysis
Lind M, Robertson A, Silva J, Warner F, Coppi A, Price N, Duckwall C, Sosensky P, Di Giuseppe E, Borg R, Fofana M, Ranzani O, Dean N, Andrews J, Croda J, Iwasaki A, Cummings D, Ko A, Hitchings M, Schulz W. Association between primary or booster COVID-19 mRNA vaccination and Omicron lineage BA.1 SARS-CoV-2 infection in people with a prior SARS-CoV-2 infection: A test-negative case–control analysis. PLOS Medicine 2022, 19: e1004136. PMID: 36454733, PMCID: PMC9714718, DOI: 10.1371/journal.pmed.1004136.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 infectionBooster vaccinationPrior infectionOmicron infectionPrimary vaccinationMRNA vaccinationOdds ratioAcute respiratory syndrome coronavirus 2 infectionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectionPrior SARS-CoV-2 infectionTest-negative case-control analysisYale New Haven Health SystemTest-negative case-control studyCOVID-19 mRNA vaccinationSyndrome coronavirus 2 infectionOmicron variant infectionPrior infection statusCoronavirus 2 infectionCase-control studyCase-control analysisOdds of infectionRisk of infectionRace/ethnicityBooster dosesDate of test
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
Evidence of leaky protection following COVID-19 vaccination and SARS-CoV-2 infection in an incarcerated population
Lind M, Dorion M, Houde A, Lansing M, Lapidus S, Thomas R, Yildirim I, Omer S, Schulz W, Andrews J, Hitchings M, Kennedy B, Richeson R, Cummings D, Ko A. Evidence of leaky protection following COVID-19 vaccination and SARS-CoV-2 infection in an incarcerated population. Nature Communications 2023, 14: 5055. PMID: 37598213, PMCID: PMC10439918, DOI: 10.1038/s41467-023-40750-8.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 infectionPrior infectionHybrid immunityInfection riskCOVID-19 vaccinationNon-pharmaceutical interventionsInfected residentsVaccinationInfectionDocumented exposureDelta periodCell exposureIncarcerated populationsExposureImmunityRiskAssociationPotential benefitsCorrectional facilitiesCrowded settingsResidentsPeriod
2022
MIF is a common genetic determinant of COVID-19 symptomatic infection and severity
Shin JJ, Fan W, Par-Young J, Piecychna M, Leng L, Israni-Winger K, Qing H, Gu J, Zhao H, Schulz WL, Unlu S, Kuster J, Young G, Liu J, Ko AI, Garcia A, Sauler M, Wisnewski AV, Young L, Orduña A, Wang A, Klementina O, Garcia AB, Hegyi P, Armstrong ME, Mitchell P, Ordiz DB, Garami A, Kang I, Bucala R. MIF is a common genetic determinant of COVID-19 symptomatic infection and severity. QJM 2022, 116: 205-212. PMID: 36222594, PMCID: PMC9620729, DOI: 10.1093/qjmed/hcac234.Peer-Reviewed Original ResearchConceptsMacrophage migration inhibitory factorLow-expression MIF alleleCOVID-19 infectionMIF allelesCATT7 alleleHealthy controlsCOVID-19Serum macrophage migration inhibitory factorSymptomatic SARS-CoV-2 infectionHigher serum MIF levelsHigh-expression MIF allelesRetrospective case-control studySARS-CoV-2 infectionFunctional polymorphismsAvailable clinical characteristicsMultinational retrospective studySerum MIF levelsUninfected healthy controlsSymptomatic COVID-19Tertiary medical centerHealthy control subjectsCase-control studyMigration inhibitory factorCoronavirus disease 2019Common functional polymorphismsChange in covid-19 risk over time following vaccination with CoronaVac: test negative case-control study
Hitchings MDT, Ranzani OT, Lind ML, Dorion M, D'Agostini TL, de Paula RC, de Paula OFP, de Moura Villela EF, Scaramuzzini Torres MS, de Oliveira SB, Schulz W, Almiron M, Said R, de Oliveira RD, Vieira da Silva P, de Araújo WN, Gorinchteyn JC, Dean NE, Andrews JR, Cummings DAT, Ko AI, Croda J. Change in covid-19 risk over time following vaccination with CoronaVac: test negative case-control study. The BMJ 2022, 377: e070102. PMID: 35697361, PMCID: PMC9189440, DOI: 10.1136/bmj-2022-070102.Peer-Reviewed Original ResearchConceptsSymptomatic COVID-19Negative case-control studyCase-control studyHospital admissionOdds ratioCOVID-19Series completionCovid-19 related hospital admissionReverse transcription polymerase chain reaction testingTranscription polymerase chain reaction testingSevere COVID-19 outcomesSARS-CoV-2 infectionPolymerase chain reaction testingInactivated whole virus vaccineDoses of CoronaVacAcute respiratory illnessTest-negative controlsWhole virus vaccineRelated hospital admissionsHealthcare worker statusConditional logistic regressionCOVID-19 outcomesCOVID-19 symptomsMunicipality of residenceSARS-CoV-2De novo emergence of a remdesivir resistance mutation during treatment of persistent SARS-CoV-2 infection in an immunocompromised patient: a case report
Gandhi S, Klein J, Robertson AJ, Peña-Hernández MA, Lin MJ, Roychoudhury P, Lu P, Fournier J, Ferguson D, Mohamed Bakhash SAK, Catherine Muenker M, Srivathsan A, Wunder EA, Kerantzas N, Wang W, Lindenbach B, Pyle A, Wilen CB, Ogbuagu O, Greninger AL, Iwasaki A, Schulz WL, Ko AI. De novo emergence of a remdesivir resistance mutation during treatment of persistent SARS-CoV-2 infection in an immunocompromised patient: a case report. Nature Communications 2022, 13: 1547. PMID: 35301314, PMCID: PMC8930970, DOI: 10.1038/s41467-022-29104-y.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 infectionVirologic responsePersistent SARS-CoV-2 infectionResistance mutationsPre-treatment specimensB-cell deficiencyRemdesivir resistanceRemdesivir therapyViral sheddingCase reportAntiviral agentsPatientsCombinatorial therapyInfectionTherapyWhole-genome sequencingTreatmentImportance of monitoringDe novo emergenceFold increaseRNA-dependent RNA polymeraseNovo emergencePotential benefitsMutationsIndolent
2021
Effectiveness of CoronaVac among healthcare workers in the setting of high SARS-CoV-2 Gamma variant transmission in Manaus, Brazil: A test-negative case-control study
Hitchings MDT, Ranzani OT, Torres MSS, de Oliveira SB, Almiron M, Said R, Borg R, Schulz WL, de Oliveira RD, da Silva PV, de Castro DB, de Souza Sampaio V, de Albuquerque BC, Ramos TCA, Fraxe SHH, da Costa CF, Naveca FG, Siqueira AM, de Araújo WN, Andrews JR, Cummings DAT, Ko AI, Croda J. Effectiveness of CoronaVac among healthcare workers in the setting of high SARS-CoV-2 Gamma variant transmission in Manaus, Brazil: A test-negative case-control study. The Lancet Regional Health - Americas 2021, 1: 100025. PMID: 34386791, PMCID: PMC8310555, DOI: 10.1016/j.lana.2021.100025.Peer-Reviewed Original ResearchSymptomatic SARS-CoV-2 infectionSARS-CoV-2 infectionTwo-dose scheduleTest-negative case-control studyEffectiveness of CoronaVacCase-control studyHealthcare workersVariant transmissionVaccine doseFirst doseSecond doseSample collection dateSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variantsDose of CoronaVacTest-negative studiesVaccine effectiveness estimatesEffectiveness of vaccinesRT-PCR testingCase-control pairsRT-PCR testMunicipal Health SecretarySARS-CoV-2 samplesNon-pharmaceutical interventionsPeriod 14 daysUnvaccinated individualsLongitudinal Assessment of SARS-CoV-2 Anti-Nucleocapsid and anti-Spike-1-RBD Antibody Testing Following PCR-Detected SARS-CoV-2 Infection
El-Khoury JM, Schulz WL, Durant TJS. Longitudinal Assessment of SARS-CoV-2 Anti-Nucleocapsid and anti-Spike-1-RBD Antibody Testing Following PCR-Detected SARS-CoV-2 Infection. The Journal Of Applied Laboratory Medicine 2021, 6: jfab030-. PMID: 33822964, PMCID: PMC8083453, DOI: 10.1093/jalm/jfab030.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 infectionDays post-PCR positivitySARS-CoV-2-positive cohortRBD antibodiesAnti-SARSSerologic assaysSARS-CoV-2 serologic assaysDiagnostic sensitivityElecsys Anti-SARSCoV-2 SResidual clinical samplesAntibody testingRemote historyCoV-2S1-RBDUS populationLongitudinal assessmentInfection statusInfectionDiagnostic aidCohortTime pointsDiscrepant resultsClinical samplesPositivityDiverse 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 prevalenceAutoantibodiesMaternal respiratory SARS-CoV-2 infection in pregnancy is associated with a robust inflammatory response at the maternal-fetal interface
Lu-Culligan A, Chavan AR, Vijayakumar P, Irshaid L, Courchaine EM, Milano KM, Tang Z, Pope SD, Song E, Vogels CBF, Lu-Culligan WJ, Campbell KH, Casanovas-Massana A, Bermejo S, Toothaker JM, Lee HJ, Liu F, Schulz W, Fournier J, Muenker MC, Moore AJ, Team Y, Konnikova L, Neugebauer KM, Ring A, Grubaugh ND, Ko AI, Morotti R, Guller S, Kliman HJ, Iwasaki A, Farhadian SF. Maternal respiratory SARS-CoV-2 infection in pregnancy is associated with a robust inflammatory response at the maternal-fetal interface. Med 2021, 2: 591-610.e10. PMID: 33969332, PMCID: PMC8084634, DOI: 10.1016/j.medj.2021.04.016.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 infectionMaternal-fetal interfaceACE2 expressionNatural killerPregnant womenPlacental cellsAcute respiratory syndrome coronavirus 2 infectionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectionSARS-CoV-2-infected womenTerm placentaSyndrome coronavirus 2 infectionCoronavirus 2 infectionPotential immune mechanismsRobust inflammatory responseRobust immune responseCoronavirus disease 2019Detectable viral RNAInterferon-related genesLower ACE2 expressionMajority of placentasPregnancy complicationsPlacental histologyHofbauer cellsEarly pregnancyImmune activation
2020
Sex 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 cytokines