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

• DOI: 10.1371/journal.pone.0282546
• Publication Date: 2024-01-10T18:25:22Z
• Authors: Chiara Ronchini; Chiara Caprioli; Gianleo Tunzi; Francesco Furio D...; Emanuela Colombo; Marco Giani; Giuseppe Foti; Donatella Conconi; Marialuisa Lavitrano; Rita Passerini; Luca Pase; Silvio Capizzi; Fabrizio Mastrilli; Myriam Alcalay; Roberto Orecchia; Gioacchino Natoli; Pier Giuseppe Pel...
• Keywords: Science; Q; R; Medicine; Clonal Hematopoiesis; COVID-19; Humans; Mutation; RNA, Viral; SARS-CoV-2; Research Article

Whether Clonal Hematopoiesis (CH) represents a risk factor for severity of the COVID-19 disease remains controversial issue. We report first high- sensitivity analysis CH in patients (threshold detection at 0.5% vs 1 or 2% previous studies). analyzed 24 admitted to ICU (COV-ICU) and 19 controls, including healthy subjects asymptomatic SARS-CoV2-positive individuals. Despite significantly higher numbers mutations identified (80% with <2% variant allele frequency, VAF), we did not find significant differences between COV-ICU controls prevalence numbers, VAF functional categories mutated genes, suggesting that is overrepresented COVID-19. However, when considering potential drivers (CH-PD), showed clonal complexity, terms both mutation VAF, enrichment variants reported myeloid neoplasms. score an impact increased CH-PD on patient survival clinical parameters associated inflammation. These data suggest influence composition peripheral blood call further investigations addressing long-term people experiencing severe acknowledge it will indispensable perform studies larger cohorts order validate generalize our conclusions. Moreover, performed single time point. It be necessary consider longitudinal approaches long periods follow-up assess if could have evolution consequences experienced