Abstract / Summary
Abstract Background Post-COVID-19 syndrome (PCS) has previously been associated with structural and functional alterations of the retinal microvasculature, assessed cross-sectionally by retinal vessel analysis (RVA). Whether these alterations persist, resolve, or progress over time is unknown. Methods In this prospective single-center study, 102 PCS patients underwent static and dynamic RVA, patient-reported outcome measures (PROMs), and blood sampling at baseline; 82 (80.4%) completed six-month follow-up. Recovered controls were not reassessed longitudinally; follow-up between-group comparisons therefore used recovered baseline values, via matched and covariate-adjusted analyses. Longitudinal change, associations with PROMs and circulating biomarkers, and differences by ME/CFS status were examined. Results Within the PCS cohort, central retinal arteriolar equivalent (CRAE) increased from 178.2 ± 16.0 to 184.1 ± 17.6 µm and the arteriolar-to-venular ratio (AVR) increased from 0.83 ± 0.06 to 0.86 ± 0.06 (both p < 0.001). Venular flicker-induced dilation (vFID) remained stable within the PCS cohort over six months (3.66 ± 2.25% to 3.80 ± 2.70%, p = 0.821) but stayed significantly lower than in recovered controls at follow-up (adjusted β = -1.31 percentage points, 95% CI -2.58 to -0.04, p = 0.045), consistently across matched, unmatched, and 1:1-matching sensitivity analyses. Neither CRAE nor AVR differed from recovered controls at follow-up. RVA parameters showed little association with symptom burden. VCAM-1 correlated inversely with CRAE at follow-up (ρ = -0.38). vFID trajectories did not differ significantly by ME/CFS status. Conclusions Structural and functional retinal microvascular parameters followed divergent six-month trajectories in PCS. Reduced venular flicker-induced dilation persisted independently of symptom burden, supporting separate longitudinal assessment of structural and functional retinal domains in post-infectious illness. Trial registration: ClinicalTrials.gov, NCT05635552. Registered 30 November 2022 - Retrospectively registered, https://clinicaltrials.gov/study/NCT05635552