2022
Inflammasome activation in infected macrophages drives COVID-19 pathology
Sefik E, Qu R, Junqueira C, Kaffe E, Mirza H, Zhao J, Brewer JR, Han A, Steach HR, Israelow B, Blackburn HN, Velazquez SE, Chen YG, Halene S, Iwasaki A, Meffre E, Nussenzweig M, Lieberman J, Wilen CB, Kluger Y, Flavell RA. Inflammasome activation in infected macrophages drives COVID-19 pathology. Nature 2022, 606: 585-593. PMID: 35483404, PMCID: PMC9288243, DOI: 10.1038/s41586-022-04802-1.Peer-Reviewed Original ResearchConceptsInflammasome activationLung inflammationInflammatory responseInfected macrophagesSARS-CoV-2 infectionHuman macrophagesChronic lung pathologyPersistent lung inflammationSevere COVID-19Immune inflammatory responseInflammatory cytokine productionHumanized mouse modelNLRP3 inflammasome pathwayCOVID-19 pathologyCOVID-19SARS-CoV-2Productive viral cycleHyperinflammatory stateChronic stageIL-18Cytokine productionInflammatory cytokinesLung pathologyInflammasome pathwayInterleukin-1
2021
A neutrophil activation signature predicts critical illness and mortality in COVID-19
Meizlish ML, Pine AB, Bishai JD, Goshua G, Nadelmann ER, Simonov M, Chang CH, Zhang H, Shallow M, Bahel P, Owusu K, Yamamoto Y, Arora T, Atri DS, Patel A, Gbyli R, Kwan J, Won CH, Dela Cruz C, Price C, Koff J, King BA, Rinder HM, Wilson FP, Hwa J, Halene S, Damsky W, van Dijk D, Lee AI, Chun HJ. A neutrophil activation signature predicts critical illness and mortality in COVID-19. Blood Advances 2021, 5: 1164-1177. PMID: 33635335, PMCID: PMC7908851, DOI: 10.1182/bloodadvances.2020003568.Peer-Reviewed Original ResearchConceptsCritical illnessHealth system databaseNeutrophil activationCOVID-19Neutrophil activation signatureSevere COVID-19Intensive care unitGranulocyte colony-stimulating factorHigh mortality rateColony-stimulating factorSystem databaseHepatocyte growth factorClinical decompensationNeutrophil countImmune hyperactivationCare unitEarly elevationLipocalin-2Interleukin-8Longitudinal cohortClinical dataMortality ratePatientsIllnessActivation signature
2020
Thrombocytopathy and endotheliopathy: crucial contributors to COVID-19 thromboinflammation
Gu SX, Tyagi T, Jain K, Gu VW, Lee SH, Hwa JM, Kwan JM, Krause DS, Lee AI, Halene S, Martin KA, Chun HJ, Hwa J. Thrombocytopathy and endotheliopathy: crucial contributors to COVID-19 thromboinflammation. Nature Reviews Cardiology 2020, 18: 194-209. PMID: 33214651, PMCID: PMC7675396, DOI: 10.1038/s41569-020-00469-1.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsAdministration, InhalationAnticoagulantsBlood Coagulation DisordersBlood Platelet DisordersCOVID-19COVID-19 Drug TreatmentEndothelium, VascularEndothelium-Dependent Relaxing FactorsEpoprostenolHeart Disease Risk FactorsHumansIloprostInflammationNitric OxidePlatelet Aggregation InhibitorsSARS-CoV-2Systemic Inflammatory Response SyndromeThrombosisThrombotic MicroangiopathiesVascular DiseasesVasodilator AgentsVenous ThromboembolismConceptsCardiovascular risk factorsRisk factorsCOVID-19Severe acute respiratory syndrome coronavirus 2Pre-existing cardiovascular diseaseAcute respiratory syndrome coronavirus 2Traditional cardiovascular risk factorsAcute respiratory distress syndromeRespiratory syndrome coronavirus 2Respiratory distress syndromeManagement of patientsSyndrome coronavirus 2COVID-19 pathologyCoronavirus disease 2019Potential therapeutic strategyCytokine stormEndothelial dysfunctionThrombotic complicationsDistress syndromeExcessive inflammationCoronavirus 2Severe outcomesAdvanced ageCardiovascular diseaseDisease 2019Endotheliopathy in COVID-19-associated coagulopathy: evidence from a single-centre, cross-sectional study
Goshua G, Pine AB, Meizlish ML, Chang CH, Zhang H, Bahel P, Baluha A, Bar N, Bona RD, Burns AJ, Dela Cruz CS, Dumont A, Halene S, Hwa J, Koff J, Menninger H, Neparidze N, Price C, Siner JM, Tormey C, Rinder HM, Chun HJ, Lee AI. Endotheliopathy in COVID-19-associated coagulopathy: evidence from a single-centre, cross-sectional study. The Lancet Haematology 2020, 7: e575-e582. PMID: 32619411, PMCID: PMC7326446, DOI: 10.1016/s2352-3026(20)30216-7.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overBetacoronavirusBiomarkersBlood Coagulation DisordersCoronavirus InfectionsCOVID-19Critical IllnessCross-Sectional StudiesEndothelium, VascularFemaleFollow-Up StudiesHumansIntensive Care UnitsMaleMiddle AgedPandemicsPneumonia, ViralPrognosisSARS-CoV-2Vascular DiseasesYoung AdultConceptsCOVID-19-associated coagulopathyNon-ICU patientsIntensive care unitKaplan-Meier analysisSoluble P-selectinCross-sectional studyPlatelet activationHospital dischargeICU patientsSoluble thrombomodulinEndothelial cellsVWF antigenCOVID-19P-selectinSingle-center cross-sectional studyLaboratory-confirmed COVID-19Medical intensive care unitSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogenesisVon Willebrand factor antigenSoluble thrombomodulin concentrationsVWF antigen concentrationEndothelial cell injurySoluble CD40 ligandMicrovascular complicationsAdult patients