Abstract
Abstract Long-COVID-19 manifests as a multisystemic condition with varied symptoms lingering beyond three weeks of acute SARS-CoV-2 infection, though its underlying mechanisms remain elusive. Aiming to decipher the long-term molecular impacts of COVID-19, we conducted a transcriptomic analysis on PBMCs from 1-year post-covid patients, including individuals without pneumonia (NP, n=10), those with severe pneumonia (SP, n=11), and healthy controls (C, n=13). Our extensive RNA sequencing revealed 4843 differentially expressed genes (DEGs) and 1056 differentially expressed long non-coding RNAs (DElncRNAs) in “C vs NP,” 1651 DEGs and 577 DElncRNAs in “C vs SP,” 954 DEGs and 148 DElncRNAs in “NP vs SP,” with 291 DEGs and 70 DElncRNAs shared across all groups. We identified 14 hub genes from 291 DEGs, with functional enrichment analysis showing upregulated DEGs mainly linked to inflammation and osteoclast differentiation, and downregulated DEGs to viral infections and immune responses. These hub genes play central roles in inflammatory and immune processes and are significantly associated with pneumonitis and diverse lung diseases. Investigations revealed unique immune cell signatures across DEG categories, associating upregulated DEGs with neutrophils and monocytes, and downregulated DEGs with CD4 memory effector T cells. Analysis of 14 hub genes showed notable upregulation in the no pneumonia group versus healthy controls, displaying complex patterns in the severe pneumonia group. Our study uncovered potential idiopathic pulmonary fibrosis signals in Long-COVID-19 patients’ PBMC transcriptome, highlighting the urgency for thorough monitoring and extended research to understand COVID-19’s lasting effects. This study sheds light on COVID-19’s transcriptomic changes and potential lasting effects, guiding future research and therapeutic approaches for Long-COVID-19.