Reduced development of COVID-19 in children reveals molecular checkpoints gating pathogenesis illuminating potential therapeutics
Steinman JB, Lum FM, Ho PP, Kaminski N, Steinman L. Reduced development of COVID-19 in children reveals molecular checkpoints gating pathogenesis illuminating potential therapeutics. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 24620-24626. PMID: 32883878, PMCID: PMC7547272, DOI: 10.1073/pnas.2012358117.Peer-Reviewed Original ResearchConceptsSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptorT helper 2 (Th2) immune responsesCross-reactive humoral immunityCOVID-19T cell immunityT helper 2SARS-CoV-2Cell immunityCommon coronavirusesHelper 2Humoral immunityInflammatory cytokinesRespiratory tractImmune responseCommon coldPandemic virusPotential therapeuticsChildrenPathogenesisImmunityReduced developmentMolecular checkpointsCoronavirusLow levelsEosinophiliaTocilizumab Treatment for Cytokine Release Syndrome in Hospitalized Patients With Coronavirus Disease 2019 Survival and Clinical Outcomes
Price CC, Altice FL, Shyr Y, Koff A, Pischel L, Goshua G, Azar MM, Mcmanus D, Chen SC, Gleeson SE, Britto CJ, Azmy V, Kaman K, Gaston DC, Davis M, Burrello T, Harris Z, Villanueva MS, Aoun-Barakat L, Kang I, Seropian S, Chupp G, Bucala R, Kaminski N, Lee AI, LoRusso PM, Topal JE, Dela Cruz C, Malinis M. Tocilizumab Treatment for Cytokine Release Syndrome in Hospitalized Patients With Coronavirus Disease 2019 Survival and Clinical Outcomes. CHEST Journal 2020, 158: 1397-1408. PMID: 32553536, PMCID: PMC7831876, DOI: 10.1016/j.chest.2020.06.006.Peer-Reviewed Original ResearchConceptsCytokine release syndromeTocilizumab-treated patientsSevere diseaseRelease syndromeTocilizumab treatmentInflammatory biomarkersNonsevere diseaseSoluble IL-2 receptor levelsHigh-sensitivity C-reactive proteinIL-2 receptor levelsConsecutive COVID-19 patientsIL-6 receptor antagonistMechanical ventilation outcomesC-reactive proteinCOVID-19 patientsHigher admission levelsRace/ethnicityMV daysVentilation outcomesAdverse eventsChart reviewClinical responseMedian ageWhite patientsClinical outcomesExpression of SARS-CoV-2 receptor ACE2 and coincident host response signature varies by asthma inflammatory phenotype
Camiolo M, Gauthier M, Kaminski N, Ray A, Wenzel SE. Expression of SARS-CoV-2 receptor ACE2 and coincident host response signature varies by asthma inflammatory phenotype. Journal Of Allergy And Clinical Immunology 2020, 146: 315-324.e7. PMID: 32531372, PMCID: PMC7283064, DOI: 10.1016/j.jaci.2020.05.051.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAngiotensin-Converting Enzyme 2AsthmaBetacoronavirusBiomarkersBronchiBronchoalveolar Lavage FluidCohort StudiesCoronavirus InfectionsCOVID-19EosinophilsFemaleGene Expression ProfilingHumansInterferon Type IInterferon-gammaMaleMiddle AgedPandemicsPeptidyl-Dipeptidase APneumonia, ViralProtein Interaction MappingReceptors, VirusRisk FactorsSARS-CoV-2Severity of Illness IndexT-LymphocytesTranscriptomeUnited StatesConceptsCoronavirus disease 2019Severe coronavirus disease 2019Subset of patientsDisease 2019Risk factorsBronchial epitheliumAcute respiratory syndrome coronavirus 2 infectionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectionSevere acute respiratory syndrome coronavirus 2Syndrome coronavirus 2 infectionType 2 inflammatory biomarkersAcute respiratory syndrome coronavirus 2Receptor ACE2SARS-CoV-2 receptor ACE2Respiratory syndrome coronavirus 2Asthma inflammatory phenotypesLarge asthma cohortsLower peripheral bloodT cell-activating factorCoronavirus 2 infectionEnzyme 2 (ACE2) expressionHistory of hypertensionDiagnosis of asthmaBronchoalveolar lavage lymphocytesT cell recruitmentCOVID-19 vulnerability: the potential impact of genetic susceptibility and airborne transmission
Godri Pollitt KJ, Peccia J, Ko AI, Kaminski N, Dela Cruz CS, Nebert DW, Reichardt JKV, Thompson DC, Vasiliou V. COVID-19 vulnerability: the potential impact of genetic susceptibility and airborne transmission. Human Genomics 2020, 14: 17. PMID: 32398162, PMCID: PMC7214856, DOI: 10.1186/s40246-020-00267-3.Peer-Reviewed Original ResearchSARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues
Ziegler C, Allon S, Nyquist S, Mbano I, Miao V, Tzouanas C, Cao Y, Yousif A, Bals J, Hauser B, Feldman J, Muus C, Wadsworth M, Kazer S, Hughes T, Doran B, Gatter G, Vukovic M, Taliaferro F, Mead B, Guo Z, Wang J, Gras D, Plaisant M, Ansari M, Angelidis I, Adler H, Sucre J, Taylor C, Lin B, Waghray A, Mitsialis V, Dwyer D, Buchheit K, Boyce J, Barrett N, Laidlaw T, Carroll S, Colonna L, Tkachev V, Peterson C, Yu A, Zheng H, Gideon H, Winchell C, Lin P, Bingle C, Snapper S, Kropski J, Theis F, Schiller H, Zaragosi L, Barbry P, Leslie A, Kiem H, Flynn J, Fortune S, Berger B, Finberg R, Kean L, Garber M, Schmidt A, Lingwood D, Shalek A, Ordovas-Montanes J, Network H, Banovich N, Barbry P, Brazma A, Desai T, Duong T, Eickelberg O, Falk C, Farzan M, Glass I, Haniffa M, Horvath P, Hung D, Kaminski N, Krasnow M, Kropski J, Kuhnemund M, Lafyatis R, Lee H, Leroy S, Linnarson S, Lundeberg J, Meyer K, Misharin A, Nawijn M, Nikolic M, Ordovas-Montanes J, Pe’er D, Powell J, Quake S, Rajagopal J, Tata P, Rawlins E, Regev A, Reyfman P, Rojas M, Rosen O, Saeb-Parsy K, Samakovlis C, Schiller H, Schultze J, Seibold M, Shalek A, Shepherd D, Spence J, Spira A, Sun X, Teichmann S, Theis F, Tsankov A, van den Berge M, von Papen M, Whitsett J, Xavier R, Xu Y, Zaragosi L, Zhang K. SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues. Cell 2020, 181: 1016-1035.e19. PMID: 32413319, PMCID: PMC7252096, DOI: 10.1016/j.cell.2020.04.035.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAlveolar Epithelial CellsAngiotensin-Converting Enzyme 2AnimalsBetacoronavirusCell LineCells, CulturedChildCoronavirus InfectionsCOVID-19EnterocytesGoblet CellsHIV InfectionsHumansInfluenza, HumanInterferon Type ILungMacaca mulattaMiceMycobacterium tuberculosisNasal MucosaPandemicsPeptidyl-Dipeptidase APneumonia, ViralReceptors, VirusSARS-CoV-2Serine EndopeptidasesSingle-Cell AnalysisTuberculosisUp-RegulationConceptsSARS-CoV-2Interferon-stimulated genesAirway epithelial cellsCell subsetsSingle-cell RNA sequencing datasetsRNA sequencing datasetsSARS-CoV-2 receptor ACE2Human interferon-stimulated genesTransmembrane serine protease 2Human airway epithelial cellsEpithelial cellsSevere acute respiratory syndrome coronavirus clade 2SARS-CoV-2 spike proteinType II pneumocytesSerine protease 2Clade 2Putative targetsNon-human primatesSpecific cell subsetsCo-expressing cellsDisease COVID-19ACE2 expressionLung injuryLung type II pneumocytesAbsorptive enterocytes