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| Item Type: | Preprint |
|---|---|
| Title: | Microvascular remodeling and endothelial dysfunction across Post-COVID-19 and ME/CFS: insights from the All Eyes on PCS Study |
| Creators Name: | Wallraven, Timon, Günthner, Roman, Lethen, Isabelle, Ribeiro, Andrea, Lech, Maciej, Oertel, Frederike Cosima, Reeß, Lukas G., Haller, Bernhard, Streese, Lukas, Hanssen, Henner, Wunderle, Michael and Schmaderer, Christoph |
| Abstract: | BACKGROUND: Post-viral diseases, including post-COVID-19 syndrome (PCS) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), cause substantial long-term morbidity. Persistent cardiovascular (CV) risk after acute infection highlights the need for accessible tools to quantify microvascular health. METHODS: All Eyes on PCS is a prospective, observational study investigating the retinal microcirculation using retinal vessel analysis (RVA). We compared RVA parameters in 102 PCS patients with 204 age- and sex-matched healthy controls (HC, matched from n = 303). Secondary matched analyses included never infected controls (NI, n = 96), recovered individuals (n = 102), PCS patients, and ME/CFS patients (n = 62). Laboratory variables, circulating markers of endothelial dysfunction (ED) and inflammation were compared between cohorts and their associations with RVA parameters were examined. RESULTS: Compared with HC, PCS patients showed reduced venular flicker-induced dilation (3.7 ± 2.2% vs. 4.5 ± 2.7%, p = 0.005), narrow retinal arterioles (CRAE, 178.3 ± 15.5 µm vs. 183.3 ± 15.9 µm, p = 0.009), and lower arteriolar-to-venular ratio (0.83 ± 0.06 vs. 0.86 ± 0.07, p = 0.004). Findings persisted after adjustment for CV factors and remained evident in an extended secondary matched analysis across NI, recovered, and PCS patients. ME/CFS patients showed the most pronounced alterations. PCS severity correlated with lower AVR (r = -0.21, p = 0.037) and reduced arteriolar FID (r = -0.21, p = 0.039), particularly for neurocognitive symptoms. IL-6, ICAM-1 and VCAM1 were elevated in PCS and ME/CFS and lower AVR correlated with inflammatory and iron-related markers (all adjusted p < 0.01). A combined model discriminated ME/CFS patients with good accuracy (AUC = 0.80). CONCLUSIONS: PCS is associated with persistent ED, most pronounced in ME/CFS patients and linked to symptom severity and ongoing inflammation. RVA may provide a noninvasive, readout of ED in post-viral syndromes. |
| Keywords: | Post-COVID-19 Syndrome, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, Endothelial Dysfunction, Retinal Microcirculation, Retinal Vessel Analysis |
| Source: | medRxiv |
| Publisher: | Cold Spring Harbor Laboratory Press |
| Article Number: | 2026.01.22.26344661 |
| Date: | 25 January 2026 |
| Official Publication: | https://doi.org/10.64898/2026.01.22.26344661 |
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