2023
COVID-19 bacteremic co-infection is a major risk factor for mortality, ICU admission, and mechanical ventilation
Patton M, Orihuela C, Harrod K, Bhuiyan M, Dominic P, Kevil C, Fort D, Liu V, Farhat M, Koff J, Lal C, Gaggar A, Richter R, Erdmann N, Might M, Gaggar A. COVID-19 bacteremic co-infection is a major risk factor for mortality, ICU admission, and mechanical ventilation. Critical Care 2023, 27: 34. PMID: 36691080, PMCID: PMC9868503, DOI: 10.1186/s13054-023-04312-0.Peer-Reviewed Original ResearchConceptsBacterial co-infectionNeutrophil-to-lymphocyte ratioIn-hospital mortalityMechanical ventilationICU admissionCo-infectionRisk factorsSARS-CoV-2 variantsCohort studyIncreased riskPrimary outcomeIncreased risk of in-hospital mortalityRisk of in-hospital mortalityCommunity-acquired bacteremiaCulture-positive resultsRetrospective cohort studySingle-center reportsInpatient encountersMultivariate logistic regressionBlood culturesPrognostic indicatorOmicron SARS-CoV-2 variantComparison cohortOdds ratioSevere disease
2022
I-SPY COVID adaptive platform trial for COVID-19 acute respiratory failure: rationale, design and operations
Files DC, Matthay MA, Calfee CS, Aggarwal NR, Asare AL, Beitler JR, Berger PA, Burnham EL, Cimino G, Coleman MH, Crippa A, Discacciati A, Gandotra S, Gibbs KW, Henderson PT, Ittner CAG, Jauregui A, Khan KT, Koff JL, Lang J, LaRose M, Levitt J, Lu R, McKeehan JD, Meyer NJ, Russell DW, Thomas KW, Eklund M, Esserman LJ, Liu KD, Esserman L, Calfee C, Liu K, Coleman M, Matthay M, Beitler J, Mittel A, Asare A, Yen A, Jauregui A, Crippa A, Suarez A, Serra A, Amin A, Rosen A, Dzierba A, Discacciati A, Haczku A, Barker A, Weisman A, Daniel B, Morrissey B, Ittner C, Jones C, Creel-Bulos C, Angelucci C, Files D, Russell D, Ng D, Burnham E, Youssef F, Chaparro-Rojas F, Harris G, Barot H, Su H, Garcia I, Sutter J, Dodin J, McKeehan J, Lee J, Kazianis J, Reilly J, Koff J, Detelich J, Lang J, Muir J, Thomas K, Khan K, Gosek K, Nugent K, Gibbs K, Yee K, Rodrigues L, Macias L, Orr L, Boerger L, Rosario-Remigio L, Kufa L, Huerta L, Tanios M, Reyes M, Eklund M, LaRose M, Adelman M, Juarez M, Jung M, Meyers M, Sternlieb M, Cobb N, Aggarwal N, Mangalmurti N, Meyer N, Jones P, Berger P, Henderson P, Saban P, Marshall P, Robinson P, Yang P, Madahar P, Nair R, Sonti R, Lee R, Wunderink R, Wahab R, Lupu R, Lu R, Kumar S, Auld S, Fields S, Wong F, Gandotra S, Pearson S, Whealon S, Albertson T, Obermiller T, Oliver T, Darmanian A, Schicchi J, Martinez E, Sarafian F, Nguyen J, Weiler-Lisowski B, Wyatt J, Blevins D, Melendrez M, Lopez B, Tzehaie H, Amosu O, Simonson A, Patel C, Levitt J, Hardy E, Lindgren B, Peterfreund G, Landreth L, Parks L, Aggarwal N. I-SPY COVID adaptive platform trial for COVID-19 acute respiratory failure: rationale, design and operations. BMJ Open 2022, 12: e060664. PMID: 35667714, PMCID: PMC9170797, DOI: 10.1136/bmjopen-2021-060664.Peer-Reviewed Original ResearchConceptsSevere COVID-19COVID-19 trialsInvestigational agentsPlatform trialsCOVID-19 acute respiratory failureDefinitive efficacy trialAcute respiratory failureAdaptive platform trialPeer-reviewed medical journalsCOVID-19Novel effective therapeuticsCentral institutional review boardInstitutional review boardRespiratory failureIneffective therapyTherapeutic responseCommunity hospitalEfficacy trialsSerial studiesTrial designWake Forest SchoolEffective therapeuticsTrials NetworkPromising agentPatientsClinical trial design during and beyond the pandemic: the I-SPY COVID trial
Calfee C, Liu K, Asare A, Beitler J, Berger P, Coleman M, Crippa A, Discacciati A, Eklund M, Files D, Gandotra S, Gibbs K, Henderson P, Levitt J, Lu R, Matthay M, Meyer N, Russell D, Thomas K, Esserman L, Mittel A, Dzierba A, Madahar P, Serra A, Rosen A, Garcia I, Muir J, Schicchi J, Darmanian A, Wahab R, Gosek K, Auld S, Adelman M, Nugent K, Harris G, Creel-Bulos C, Yang P, Detelich J, Spainhour C, Cobb N, Sonti R, Orr L, Robinson P, Sarafian F, Martinez E, Jones P, Nguyen J, Obermiller T, Weiler-Lisowski B, Kufa L, Saba P, Wyatt J, Youssef F, Tanios M, Blevins D, Macias L, Suarez A, Reyes M, Jung M, Melendrez M, Rosario-Remigio L, Su H, Friedman E, Angelucci C, Chaparro-Rojas F, Sternlieb M, Sutter J, Whealon S, Nair R, Lopez B, Amosu O, Tzehaie H, Wunderink R, Patel C, Simonson A, Dodin J, Oliver T, Lupu R, Meyers M, Albertson T, Haczku A, Hardy E, Morrissey B, Juarez M, Pearson S, Lee R, Amin A, Jauregui A, Fields S, Ng D, Daniel B, Yee K, Jones C, Burnham E, McKeehan J, Ittner C, Reilly J, Mangalmurti N, Rodrigues L, Weisman A, Khan K, Wong S, Yen A, Peterfreund G, Kumar S, Marshall P, Huerta L, Lindgren B, Lee J, Barker A, Lang J, LaRose M, Landreth L, Parks L, Barot H, Koff J, Kazianis J, Boerger L. Clinical trial design during and beyond the pandemic: the I-SPY COVID trial. Nature Medicine 2022, 28: 9-11. PMID: 35058620, PMCID: PMC8922451, DOI: 10.1038/s41591-021-01617-x.Peer-Reviewed Original Research
2020
“Small” Intestinal Immunopathology Plays a “Big” Role in Lethal Cytokine Release Syndrome, and Its Modulation by Interferon-γ, IL-17A, and a Janus Kinase Inhibitor
Kale SD, Mehrkens BN, Stegman MM, Kastelberg B, Carnes H, McNeill RJ, Rizzo A, Karyala SV, Coutermarsh-Ott S, Fretz JA, Sun Y, Koff JL, Rajagopalan G. “Small” Intestinal Immunopathology Plays a “Big” Role in Lethal Cytokine Release Syndrome, and Its Modulation by Interferon-γ, IL-17A, and a Janus Kinase Inhibitor. Frontiers In Immunology 2020, 11: 1311. PMID: 32676080, PMCID: PMC7333770, DOI: 10.3389/fimmu.2020.01311.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCells, CulturedCoronavirus InfectionsCOVID-19Cytokine Release SyndromeCytokinesHLA-DR3 AntigenInterferon-gammaInterleukin-17Intestine, SmallJanus Kinase InhibitorsLymphocyte ActivationMiceMice, KnockoutNitrilesPandemicsPneumonia, ViralPyrazolesPyrimidinesT-Lymphocytes, Helper-InducerConceptsSmall bowel pathologyMultiple organ dysfunctionIL-17A deficiencySmall intestinal immunopathologyCytokine release syndromeToxic shock syndromeBowel pathologyIntestinal immunopathologyRelease syndromeChimeric antigen receptor T-cell therapySevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2Immune check point inhibitorsHLA-DR3 transgenic miceRespiratory syndrome coronavirus 2HLA-DR3 miceIFN-γ deficiencyCheck point inhibitorsSyndrome coronavirus 2T-cell therapyJAK 1/2 inhibitorJanus kinase inhibitorSmall intestinal tissueCoronavirus disease 2019T cell activation