Circulating neutrophil extracellular trap (NET)-forming 'rogue' neutrophil subset, immunotype [DEspR + CD11b +], mediate multi-organ failure in COVID-19- an observational study .
Autor: | Herrera VLM; Department of Medicine and Whitaker Cardiovascular Institute, Boston University Chobanian and Avedisian School of Medicine, Boston, Massachusetts USA., Bosch NA; Section of Pulmonary and Critical Care Medicine, Department of Medicine, Boston University Chobanian and Avedisian School of Medicine, Boston, Massachusetts USA., Lok JJ; Department of Mathematics and Statistics, Boston University, Boston, Massachusetts USA., Nguyen MQ; Department of Medicine and Whitaker Cardiovascular Institute, Boston University Chobanian and Avedisian School of Medicine, Boston, Massachusetts USA., Lenae KA; Department of Medicine and Whitaker Cardiovascular Institute, Boston University Chobanian and Avedisian School of Medicine, Boston, Massachusetts USA., deKay JT; Maine Health Institute for Research, Scarborough, Maine USA., Ryzhov SV; Maine Health Institute for Research, Scarborough, Maine USA., Seder DB; Maine Health Institute for Research, Scarborough, Maine USA.; Department of Critical Care Services, Maine Medical Center, Portland, Maine USA., Ruiz-Opazo N; Department of Medicine and Whitaker Cardiovascular Institute, Boston University Chobanian and Avedisian School of Medicine, Boston, Massachusetts USA., Walkey AJ; Section of Pulmonary and Critical Care Medicine, Department of Medicine, Boston University Chobanian and Avedisian School of Medicine, Boston, Massachusetts USA. |
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Jazyk: | angličtina |
Zdroj: | Translational medicine communications [Transl Med Commun] 2023; Vol. 8 (1), pp. 12. Date of Electronic Publication: 2023 Apr 18. |
DOI: | 10.1186/s41231-023-00143-x |
Abstrakt: | Background: Cumulative research show association of neutrophils and neutrophil extracellular traps (NETs) with poor outcomes in severe COVID-19. However, to date, there is no curative intent therapy able to block neutrophil/NETs-mediated progression of multi-organ dysfunction. Because of emerging neutrophil heterogeneity, the study of subsets of circulating NET-forming neutrophils [NET + Ns] as mediators of multi-organ failure progression among patients with COVID-19 is critical to identification of therapeutic targets. Methods: We conducted a prospective observational study of circulating levels of CD11b + [NET + N] immunotyped for dual endothelin-1/signal peptide receptor (DEspR ±) expression by quantitative immunofluorescence-cytology and causal mediation analysis. In 36 consented adults hospitalized with mod-severe COVID-19, May to September 2020, we measured acute multi-organ failure via SOFA-scores and respiratory failure via SaO2/FiO2 (SF)-ratio at time points t1 (average 5.5 days from ICU/hospital admission) and t2 (the day before ICU-discharge or death), and ICU-free days at day28 (ICUFD). Circulating absolute neutrophil counts (ANC) and [NET + N] subset-specific counts were measured at t1. Spearman correlation and causal mediation analyses were conducted. Results: Spearman correlation analyses showed correlations of t1-SOFA with t2-SOFA ( rho r Conclusions: Despite equivalent correlations, DEspR + [NET + Ns], but not ANC, mediated progression of multi-organ failure in acute COVID-19, and its hypothetical reduction is projected to improve ICUFD. These translational findings warrant further studies of DEspR + [NET + Ns] as potential patient-stratifier and actionable therapeutic target for multi-organ failure in COVID-19. Supplementary Information: The online version contains supplementary material available at 10.1186/s41231-023-00143-x. Competing Interests: Competing interestsBoston University holds awarded patents on DEspR as novel therapeutic approach for cancer, stroke, COVID-19, NETosis and activated neutrophils. VLMH and NRO are co-inventors in patents filed by Boston University. (© The Author(s) 2023.) |
Databáze: | MEDLINE |
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