Publication date: Dec 12, 2025
Long COVID (LC) involves a spectrum of chronic symptoms after acute severe acute respiratory syndrome coronavirus 2 infection. Current hypotheses for the pathogenesis of LC include persistent virus, tissue damage, autoimmunity, endocrine insufficiency, immune dysfunction and complement activation. We performed immunological, virological, transcriptomic and proteomic analyses from a cohort of 142 individuals between 2020 and 2021, including uninfected controls (n = 35), acutely infected individuals (n = 54), convalescent controls (n = 24) and patients with LC (n = 28). The LC group was characterized by persistent immune activation and proinflammatory responses for more than 180 days after initial infection compared with convalescent controls, including upregulation of JAK-STAT, interleukin-6, complement, metabolism and T cell exhaustion pathways. Similar findings were observed in a second cohort enrolled between 2023 and 2024, including convalescent controls (n = 20) and patients with LC (n = 18). These data suggest that LC is characterized by persistent activation of chronic inflammatory pathways, suggesting new therapeutic targets and potential biomarkers of disease.
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| Concepts | Keywords |
|---|---|
| Biomarkers | Activation |
| Coronavirus | Acute |
| Covid | Chronic |
| Exhaustion | Controls |
| Convalescent | |
| Covid | |
| Exhaustion | |
| Immune | |
| Including | |
| Infection | |
| Involves | |
| Long | |
| Pathways | |
| Persistent | |
| Proinflammatory |
Semantics
| Type | Source | Name |
|---|---|---|
| disease | MESH | Long COVID |
| disease | MESH | severe acute respiratory syndrome coronavirus 2 infection |
| disease | MESH | infection |
| pathway | REACTOME | Metabolism |
| disease | MESH | severe acute respiratory syndrome |
| disease | MESH | coronavirus infection |
| drug | DRUGBANK | Factor IX Complex (Human) |
| disease | MESH | PCC |
| disease | MESH | fatigue |
| disease | MESH | brain fog |
| drug | DRUGBANK | Hydrocortisone |
| drug | DRUGBANK | Ritonavir |
| drug | DRUGBANK | Coenzyme M |
| disease | MESH | varicella |
| disease | MESH | zoster |
| disease | MESH | Western equine encephalitis |
| disease | MESH | herpes simplex |
| disease | MESH | influenza |
| pathway | KEGG | Nitrogen metabolism |
| disease | MESH | death |
| drug | DRUGBANK | Amino acids |
| disease | MESH | inflammation |
| disease | MESH | included |
| disease | MESH | pain |
| disease | MESH | cough |