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 definitions
2024
SOFA score performs worse than age for predicting mortality in patients with COVID-19
Sherak R, Sajjadi H, Khimani N, Tolchin B, Jubanyik K, Taylor R, Schulz W, Mortazavi B, Haimovich A. SOFA score performs worse than age for predicting mortality in patients with COVID-19. PLOS ONE 2024, 19: e0301013. PMID: 38758942, PMCID: PMC11101117, DOI: 10.1371/journal.pone.0301013.Peer-Reviewed Original ResearchConceptsCrisis standards of careIn-hospital mortalityIntensive care unitAcademic health systemSequential Organ Failure Assessment scoreCohort of intensive care unitSequential Organ Failure AssessmentStandard of careLogistic regression modelsMortality predictionPredicting in-hospital mortalityHealth systemUnivariate logistic regression modelCrisis standardsDisease morbidityCOVID-19
2023
Microfluidic Immuno‐Serolomic Assay Reveals Systems Level Association with COVID‐19 Pathology and Vaccine Protection (Small Methods 10/2023)
Kim D, Biancon G, Bai Z, VanOudenhove J, Liu Y, Kothari S, Gowda L, Kwan J, Buitrago‐Pocasangre N, Lele N, Asashima H, Racke M, Wilson J, Givens T, Tomayko M, Schulz W, Longbrake E, Hafler D, Halene S, Fan R. Microfluidic Immuno‐Serolomic Assay Reveals Systems Level Association with COVID‐19 Pathology and Vaccine Protection (Small Methods 10/2023). Small Methods 2023, 7 DOI: 10.1002/smtd.202370057.Peer-Reviewed Original ResearchAn AI-powered patient triage platform for future viral outbreaks using COVID-19 as a disease model
Charkoftaki G, Aalizadeh R, Santos-Neto A, Tan W, Davidson E, Nikolopoulou V, Wang Y, Thompson B, Furnary T, Chen Y, Wunder E, Coppi A, Schulz W, Iwasaki A, Pierce R, Cruz C, Desir G, Kaminski N, Farhadian S, Veselkov K, Datta R, Campbell M, Thomaidis N, Ko A, Thompson D, Vasiliou V. An AI-powered patient triage platform for future viral outbreaks using COVID-19 as a disease model. Human Genomics 2023, 17: 80. PMID: 37641126, PMCID: PMC10463861, DOI: 10.1186/s40246-023-00521-4.Peer-Reviewed Original ResearchConceptsCOVID-19 patientsDisease severityViral outbreaksFuture viral outbreaksLength of hospitalizationIntensive care unitWorse disease prognosisLife-threatening illnessEffective medical interventionsCOVID-19Clinical decision treeGlucuronic acid metabolitesNew potential biomarkersHospitalization lengthCare unitComorbidity dataSerotonin levelsDisease progressionHealthy controlsPatient outcomesDisease prognosisPatient transferPatientsHealthcare resourcesPotential biomarkers
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-2
2021
Effectiveness of ChAdOx1 vaccine in older adults during SARS-CoV-2 Gamma variant circulation in São Paulo
Hitchings MDT, Ranzani OT, Dorion M, D’Agostini T, de Paula RC, de Paula OFP, de Moura Villela EF, Torres MSS, de Oliveira SB, Schulz W, Almiron M, Said R, de Oliveira RD, Silva PV, de Araújo WN, Gorinchteyn JC, Andrews JR, Cummings DAT, Ko AI, Croda J. Effectiveness of ChAdOx1 vaccine in older adults during SARS-CoV-2 Gamma variant circulation in São Paulo. Nature Communications 2021, 12: 6220. PMID: 34711813, PMCID: PMC8553924, DOI: 10.1038/s41467-021-26459-6.Peer-Reviewed Original ResearchConceptsSingle doseOxford-AstraZeneca COVID-19 vaccineTest-negative case-control studySevere COVID-19 outcomesCOVID-19COVID-19-related deathsTwo-dose scheduleTwo-dose regimenCase-control studyCOVID-19 outcomesInter-dose intervalCOVID-19 hospitalizationCOVID-19 vaccineSARS-CoV-2ChAdOx1 vaccinePrimary endpointSecondary endpointsFirst doseSecond doseHigh prevalenceElderly individualsElderly populationVariant prevalenceVaccine supplyHospitalizationEffectiveness of the CoronaVac vaccine in older adults during a gamma variant associated epidemic of covid-19 in Brazil: test negative case-control study
Ranzani OT, Hitchings MDT, Dorion M, D'Agostini TL, de Paula RC, de Paula OFP, Villela EFM, Torres MSS, de Oliveira SB, Schulz W, Almiron M, Said R, de Oliveira RD, Vieira da Silva P, de Araújo WN, Gorinchteyn JC, Andrews JR, Cummings DAT, Ko AI, Croda J. Effectiveness of the CoronaVac vaccine in older adults during a gamma variant associated epidemic of covid-19 in Brazil: test negative case-control study. The BMJ 2021, 374: n2015. PMID: 34417194, PMCID: PMC8377801, DOI: 10.1136/bmj.n2015.Peer-Reviewed Original ResearchConceptsSymptomatic COVID-19Negative case-control studyCase-control studyHospital admissionVaccine effectivenessSecond doseDose regimenElderly populationCOVID-19Reverse transcription polymerase chain reaction testingTranscription polymerase chain reaction testingPolymerase chain reaction testingGamma variantInactivated whole virus vaccineAdjusted vaccine effectivenessTest-negative controlsWhole virus vaccineCOVID-19 statusCOVID-19 symptomsYounger age groupsMunicipality of residenceSARS-CoV-2RT-PCR testSelf-reported raceCoronaVac vaccineDiverse 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 onsetThe Association of COVID-19 With Acute Kidney Injury Independent of Severity of Illness: A Multicenter Cohort Study
Moledina DG, Simonov M, Yamamoto Y, Alausa J, Arora T, Biswas A, Cantley LG, Ghazi L, Greenberg JH, Hinchcliff M, Huang C, Mansour SG, Martin M, Peixoto A, Schulz W, Subair L, Testani JM, Ugwuowo U, Young P, Wilson FP. The Association of COVID-19 With Acute Kidney Injury Independent of Severity of Illness: A Multicenter Cohort Study. American Journal Of Kidney Diseases 2021, 77: 490-499.e1. PMID: 33422598, PMCID: PMC7791318, DOI: 10.1053/j.ajkd.2020.12.007.Peer-Reviewed Original ResearchMeSH KeywordsAcute Kidney InjuryAgedCohort StudiesCOVID-19C-Reactive ProteinCreatinineDiureticsFemaleHospital MortalityHumansIntensive Care UnitsLength of StayMaleMiddle AgedProportional Hazards ModelsRenal DialysisRenal Insufficiency, ChronicRespiration, ArtificialRisk FactorsSARS-CoV-2Severity of Illness IndexUnited StatesVasoconstrictor AgentsConceptsAcute kidney injurySARS-CoV-2Cohort studyRisk factorsCOVID-19Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testingTime-updated Cox proportional hazards modelsDialysis-requiring acute kidney injuryYale New Haven Health SystemHigher inflammatory marker levelsMore acute kidney injuryCox proportional hazards modelMulticenter cohort studyHigh rateInflammatory marker levelsTraditional risk factorsProportional hazards modelCoronavirus disease 2019KDIGO criteriaNephrotoxin exposureKidney injuryInjury independentUnivariable analysisNasopharyngeal samplesMarker levels
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 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 2019Impact of COVID-19 Pandemic on Laboratory Utilization
Durant TJS, Peaper DR, Ferguson D, Schulz WL. Impact of COVID-19 Pandemic on Laboratory Utilization. The Journal Of Applied Laboratory Medicine 2020, 5: 1194-1205. PMID: 32663258, PMCID: PMC7454564, DOI: 10.1093/jalm/jfaa121.Peer-Reviewed Original ResearchMeSH KeywordsBetacoronavirusClinical Laboratory ServicesClinical Laboratory TechniquesCoronavirus InfectionsCOVID-19COVID-19 TestingFacilities and Services UtilizationHumansIncidencePandemicsPneumonia, ViralPolymerase Chain ReactionReagent Kits, DiagnosticRetrospective StudiesSARS-CoV-2Specimen HandlingPatient factors associated with SARS‐CoV‐2 in an admitted emergency department population
Haimovich A, Warner F, Young HP, Ravindra NG, Sehanobish A, Gong G, Wilson FP, van Dijk D, Schulz W, Taylor R. Patient factors associated with SARS‐CoV‐2 in an admitted emergency department population. Journal Of The American College Of Emergency Physicians Open 2020, 1: 569-577. PMID: 32838371, PMCID: PMC7280703, DOI: 10.1002/emp2.12145.Peer-Reviewed Original ResearchCOVID-19 positive patientsPatient characteristicsPatient factorsCOVID-19Positive COVID-19 testMultivariable logistic regression modelLow pulse oximetryChronic lung diseaseRetrospective observational studyCOVID-19 test resultsEmergency department patientsPrimary outcome measureEmergency department populationLower leukocyte countsPositive COVID-19 resultHistory of alcoholPositive test resultsSARS-CoV-2 virusSARS-CoV-2COVID-19 testingLogistic regression modelsCOVID-19 testCOVID-19 resultsED cohortNegative patients