TY - BOOK AU - Wortmann, Glenn W TI - Persistent Oxidative Stress and Inflammasome Activation in CD14highCD16- Monocytes From COVID-19 Patients PY - 2021/// KW - *COVID-19/me [Metabolism] KW - *Inflammasomes/me [Metabolism] KW - *Lipopolysaccharide Receptors/me [Metabolism] KW - *Monocytes/me [Metabolism] KW - *Oxidative Stress/ph [Physiology] KW - *Receptors, IgG/me [Metabolism] KW - Aged KW - Caspase 1/me [Metabolism] KW - COVID-19/pa [Pathology] KW - Female KW - GPI-Linked Proteins/me [Metabolism] KW - Humans KW - Interleukin-1beta/me [Metabolism] KW - Male KW - Middle Aged KW - Mitochondria/me [Metabolism] KW - Mitochondria/pa [Pathology] KW - Monocytes/pa [Pathology] KW - NLR Family, Pyrin Domain-Containing 3 Protein/me [Metabolism] KW - SARS-CoV-2/me [Metabolism] KW - Signal Transduction/ph [Physiology] KW - MedStar Washington Hospital Center KW - Medicine/Infectious Diseases KW - Journal Article KW - Research Support, N.I.H., Intramural N2 - The poor outcome of the coronavirus disease-2019 (COVID-19), caused by SARS-CoV-2, is associated with systemic hyperinflammatory response and immunopathology. Although inflammasome and oxidative stress have independently been implicated in COVID-19, it is poorly understood whether these two pathways cooperatively contribute to disease severity. Herein, we found an enrichment of CD14highCD16- monocytes displaying inflammasome activation evidenced by caspase-1/ASC-speck formation in severe COVID-19 patients when compared to mild ones and healthy controls, respectively. Those cells also showed aberrant levels of mitochondrial superoxide and lipid peroxidation, both hallmarks of the oxidative stress response, which strongly correlated with caspase-1 activity. In addition, we found that NLRP3 inflammasome-derived IL-1beta secretion by SARS-CoV-2-exposed monocytes in vitro was partially dependent on lipid peroxidation. Importantly, altered inflammasome and stress responses persisted after short-term patient recovery. Collectively, our findings suggest oxidative stress/NLRP3 signaling pathway as a potential target for host-directed therapy to mitigate early COVID-19 hyperinflammation and also its long-term outcomes. Copyright (c) 2022 Lage, Amaral, Hilligan, Laidlaw, Rupert, Namasivayan, Rocco, Galindo, Kellogg, Kumar, Poon, Wortmann, Shannon, Hickman, Lisco, Manion, Sher and Sereti UR - https://dx.doi.org/10.3389/fimmu.2021.799558 ER -