High-sensitivity analysis of clonal hematopoiesis reveals increased clonal complexity of potential-driver mutations in severe COVID-19 patients.

Autor: Ronchini C; Clinical Genomics, European Institute of Oncology IRCCS, Milan, Italy., Caprioli C; Department of Experimental Oncology, European Institute of Oncology IRCCS, Milan, Italy., Tunzi G; Clinical Genomics, European Institute of Oncology IRCCS, Milan, Italy., D'Amico FF; Clinical Genomics, European Institute of Oncology IRCCS, Milan, Italy., Colombo E; Department of Experimental Oncology, European Institute of Oncology IRCCS, Milan, Italy.; Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy., Giani M; School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.; Department of Emergency and Intensive Care, Ospedale San Gerardo, Monza, Italy., Foti G; School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.; Department of Emergency and Intensive Care, Ospedale San Gerardo, Monza, Italy., Conconi D; School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy., Lavitrano M; School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy., Passerini R; Division of Laboratory Medicine, European Institute of Oncology IRCCS, Milan, Italy., Pase L; Occupational Medicine, European Institute of Oncology IRCCS, Milan, Italy., Capizzi S; Medical Administration, CMO, IEO, European Institute of Oncology, IRCCS, Milan, Italy., Mastrilli F; Medical Administration, CMO, IEO, European Institute of Oncology, IRCCS, Milan, Italy., Alcalay M; Department of Experimental Oncology, European Institute of Oncology IRCCS, Milan, Italy.; Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy., Orecchia R; Scientific Directorate, European Institute of Oncology IRCCS, Milan, Italy., Natoli G; Department of Experimental Oncology, European Institute of Oncology IRCCS, Milan, Italy., Pelicci PG; Department of Experimental Oncology, European Institute of Oncology IRCCS, Milan, Italy.; Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2024 Jan 10; Vol. 19 (1), pp. e0282546. Date of Electronic Publication: 2024 Jan 10 (Print Publication: 2024).
DOI: 10.1371/journal.pone.0282546
Abstrakt: Whether Clonal Hematopoiesis (CH) represents a risk factor for severity of the COVID-19 disease remains a controversial issue. We report the first high- sensitivity analysis of CH in COVID-19 patients (threshold of detection at 0.5% vs 1 or 2% in previous studies). We analyzed 24 patients admitted to ICU for COVID-19 (COV-ICU) and 19 controls, including healthy subjects and asymptomatic SARS-CoV2-positive individuals. Despite the significantly higher numbers of CH mutations identified (80% mutations with <2% variant allele frequency, VAF), we did not find significant differences between COV-ICU patients and controls in the prevalence of CH or in the numbers, VAF or functional categories of the mutated genes, suggesting that CH is not overrepresented in patients with COVID-19. However, when considering potential drivers CH mutations (CH-PD), COV-ICU patients showed higher clonal complexity, in terms of both mutation numbers and VAF, and enrichment of variants reported in myeloid neoplasms. However, we did not score an impact of increased CH-PD on patient survival or clinical parameters associated with inflammation. These data suggest that COVID-19 influence the clonal composition of the peripheral blood and call for further investigations addressing the potential long-term clinical impact of CH on people experiencing severe COVID-19. We acknowledge that it will indispensable to perform further studies on larger patient cohorts in order to validate and generalize our conclusions. Moreover, we performed CH analysis at a single time point. It will be necessary to consider longitudinal approaches with long periods of follow-up in order to assess if the COVID-19 disease could have an impact on the evolution of CH and long-term consequences in patients that experienced severe COVID-19.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Ronchini et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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