Publication date: Dec 12, 2025
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 cD7 10), IL-17 cytokines (OR: 2. 45, 95 % CIs: 1. 47-4. 07 p: 5. 88 cD7 10) and the anti-inflammatory biomarkers (OR: 2. 15, 95 % CIs: 1. 34-3. 45, p: 1. 5 cD7 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.
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| Concepts | Keywords |
|---|---|
| Adults | Cytokines |
| Covid | IL-1 |
| Dna | Immune dysregulation |
| Immunological | Lung function tests |
| Months | Phenotypes |
Semantics
| Type | Source | Name |
|---|---|---|
| disease | MESH | COVID-19 |
| disease | MESH | Post-Acute COVID-19 syndrome |