Variability in Arterial Stiffness and Vascular Endothelial Function After COVID-19 During 1.5 Years of Follow-Up-Systematic Review and Meta-Analysis.

Increasing long-term observations suggest that coronavirus disease 2019 (COVID-19) vasculopathy may persist even 1.5 years after the acute phase, potentially accelerating the development of atherosclerotic cardiovascular diseases. This study systematically reviewed the variability of brachial flow-mediated dilation (FMD) and carotid-femoral pulse wave velocity (cfPWV) from the acute phase of COVID-19 through 16 months of follow-up (F/U). Databases including PubMed, Web of Science, MEDLINE, and Embase were screened for a meta-analysis without language or date restrictions (PROSPERO reference CRD42025642888, last search conducted on 1 February 2025). The quality of the included studies was assessed using the Newcastle-Ottawa Quality Scale. We considered all studies (interventional pre-post studies, prospective observational studies, prospective randomized, and non-randomized trials) that assessed FMD or cfPWV in adults (aged ≥ 18 years) with or after laboratory-confirmed COVID-19 compared with non-COVID-19 controls or that assessed changes in these parameters during the F/U. Twenty-one studies reported differences in FMD, and 18 studies examined cfPWV between COVID-19 patients and control groups during various stages: acute/subacute COVID-19 (≤30 days from disease onset), early (>30-90 days), mid-term (>90-180 days), late (>180-270 days), and very late (>270 days) post-COVID-19 recovery. Six studies assessed variability in FMD, while nine did so for cfPWV during the F/U. Data from 14 FMD studies (627 cases and 694 controls) and 15 cfPWV studies (578 cases and 703 controls) were included in our meta-analysis. FMD showed a significant decrease compared to controls during the acute/subacute phase (standardized mean difference [SMD]= -2.02, < 0.001), with partial improvements noted from the acute/subacute phase to early recovery (SMD = 0.95, < 0.001) and from early to mid-term recovery (SMD = 0.92, = 0.006). Normalization compared to controls was observed in late recovery (SMD = 0.12, = 0.69). In contrast, cfPWV values, which were higher than controls in the acute/subacute phase (SMD = 1.27, < 0.001), remained elevated throughout the F/U, with no significant changes except for a decrease from mid-term to very late recovery (SMD= -0.39, < 0.001). In the very late recovery, cfPWV values remained higher than those of controls (SMD = 0.45, = 0.010). In the manuscript, we discuss how various factors, including the severity of acute COVID-19, the persistence of long-term COVID-19 syndrome, and the patient's initial vascular age, depending on metrics age and cardiovascular risk factors, influenced the time and degree of FMD and cfPWV improvement.