2021
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. 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 onsetClinical 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
Longitudinal 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
2017
Aging impairs both primary and secondary RIG-I signaling for interferon induction in human monocytes
Molony RD, Nguyen JT, Kong Y, Montgomery RR, Shaw AC, Iwasaki A. Aging impairs both primary and secondary RIG-I signaling for interferon induction in human monocytes. Science Signaling 2017, 10 PMID: 29233916, PMCID: PMC6429941, DOI: 10.1126/scisignal.aan2392.Peer-Reviewed Original ResearchConceptsType I IFNsI IFNsI interferonOlder adultsIFN inductionRetinoic acid-inducible gene IAcid-inducible gene IHealthy human donorsType I interferonRespiratory influenzaProinflammatory cytokinesVirus infectionType I IFN genesAdult monocytesAntiviral resistanceTranscription factor IRF8IFN responseHuman donorsMonocytesIncreased proteasomal degradationHuman monocytesYoung adultsIRF8 expressionIAV RNAInfected cells
2016
Mx1 reveals innate pathways to antiviral resistance and lethal influenza disease
Pillai PS, Molony RD, Martinod K, Dong H, Pang IK, Tal MC, Solis AG, Bielecki P, Mohanty S, Trentalange M, Homer RJ, Flavell RA, Wagner DD, Montgomery RR, Shaw AC, Staeheli P, Iwasaki A. Mx1 reveals innate pathways to antiviral resistance and lethal influenza disease. Science 2016, 352: 463-466. PMID: 27102485, PMCID: PMC5465864, DOI: 10.1126/science.aaf3926.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAdultAgedAged, 80 and overAnimalsBacterial InfectionsCaspase 1CaspasesCaspases, InitiatorFemaleHumansImmunity, InnateInfluenza A virusInfluenza, HumanInterferon-betaMaleMembrane GlycoproteinsMiceMonocytesMyxovirus Resistance ProteinsNeutrophilsOrthomyxoviridae InfectionsRespiratory Tract InfectionsToll-Like Receptor 7Viral LoadYoung AdultConceptsBacterial burdenAntiviral resistanceNeutrophil-dependent tissue damageMyD88-dependent signalingAntiviral interferon productionCaspase-1/11IAV diseaseViral loadInfluenza diseaseOlder humansTissue damageInterferon productionInflammasome responseOlder adultsTLR7Vivo consequencesDiseaseMiceIAVBurdenMx geneHumansMonocytesMortalityInfluenza