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Long-term immune and epigenetic dysregulation following COVID-19.

Clinical immunology (Orlando, Fla.)

Authors: Chrysanthi Sidiropoulou, Garyphallia Poulakou, Evdoxia Kyriazopoulou, Elisavet Tasouli, Efthymia Giannitsioti, Anna Strikou, Maria Tsilika, Eirini Christaki, Vassiliki Rapti, Vassiliki Evangelopoulou, Nikoletta Rovina, Nathalie Iannotti, Emanuele Nicastri, Eleonora Taddei, Helena Florou, Andrea Angheben, Matteo Bassetti, Lorenzo Dagna, Antonio Torres, Spyros Foutadakis, George Adamis, Emmanouil Stylianakis, Giannis Vatsellas, Georgia Damoraki, Leda Efstratiou, Christina Damoulari, Konstantinos Leventogiannis, Achilleas Laskaratos, Panagiotis Koufargyris, Nikoletta Charalampaki, Paraskevi Chra, Aglaia Galanopoulou, Dimitris Thanos, Periklis Panagopoulos, Konstantinos Syrigos, Athanasios Ziogas, Rob Ter Horst, Jos W M van der Meer, Konstantina Iliopoulou, Francesco Saverio Serino, Maria Pavlaki, Pierluigi Del Vecchio, Laura Scorzolini, Alessandra Bandera, Agamemnon Bakakos, Styliani Sympardi, Haralampos Milionis, Mihai G Netea, Evangelos J Giamarellos-Bourboulis

Post-Acute COVID-19 syndrome (PACS) is heterogeneous in phenotype and functional state. This prospective, observational study studied adults six months after acute COVID-19. We defined clinical phenotypes and profiled plasma mediators grouped into functional pathways (IL-1, IL-17, IFNγ/IFNγ-related cytokines, pro-/anti-inflammatory clusters). A subset underwent RNA-seq and ChIP-seq experiments. Three cohorts were analyzed (Exploratory n = 46; Discovery n = 591; Validation Cohort n = 289). PACS compatible symptoms were identified in 69.6 %; 59.2 % and 54.7 % respectively. Five phenotypes emerged. IL-1 cytokines (OR: 3.17, 95 % CIs: 1.94-5.19, p: 4.5 × 10), IL-17 cytokines (OR: 2.45, 95 % CIs: 1.47-4.07 p: 5.88 × 10) and the anti-inflammatory biomarkers (OR: 2.15, 95 % CIs: 1.34-3.45, p: 1.5 × 10) were upregulated in PACS patients. Respiratory phenotype was correlated with IL-1 upregulation (OR 4.23; 95 % CIs, 1.69-10.8, p = 0.0025). Transcriptomic and epigenomic changes were observed. Distinct phenotypes of PACS are driven by different immunological mechanisms at the DNA, transcriptomic, and protein levels.

Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.

PMID: 41391701

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