2023
An 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 biomarkersEnhanced 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 genesSubvariantsExpression
2022
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
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 testDe 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
Reply 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 ResearchAuthor Correction: Delayed 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. Author Correction: Delayed production of neutralizing antibodies correlates with fatal COVID-19. Nature Medicine 2021, 27: 1309-1309. PMID: 34145437, PMCID: PMC8212078, DOI: 10.1038/s41591-021-01416-4.Peer-Reviewed Original ResearchDiverse 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 onsetMaternal 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 activationClinical 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 population
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 2019