Numerous studies have reported vascular endothelial growth factor A (VEGF-A) has a significant impact on the pathophysiology of COVID-19. The objective of this systematic review and meta-analysis is to determine the prognostic value of increased levels of VEGF-A in individuals with COVID-19. A systematic literature search was conducted across multiple electronic databases, including PubMed, Web of Science, Cochrane Library, Scopus, EMBASE, and Google Scholar, up to January 2024. Studies examining the levels of VEGF-A in the serum or plasma of COVID-19 patients were incorporated, with specific attention given to contrasting severe/critical cases against moderate cases. Standardized mean differences (SMD) with 95% confidence intervals (CIs) were calculated using a random-effects model to determine overall effect sizes. Meta-regressions and subgroup analyses were performed to explore potential sources of heterogeneity. The meta-analysis synthesized data from 11 studies involving a total of 1119 COVID-19 patients. Elevated levels of VEGF-A were significantly associated with disease severity, with a pooled SMD of 0.525 (95% CI 0.239-0.058
P = 0.028). Research has indicated that the nature of the relationship differs among various age groups, and there were minor discrepancies in the techniques employed to obtain VEGF-A measurements. Furthermore, meta-regression analysis indicated a potential correlation between VEGF-A levels and assay technique and body mass index (BMI). This meta-analysis provides compelling evidence for the prognostic potency of VEGF-A in COVID-19. Understanding the intricate interplay between VEGF-A and COVID-19 pathophysiology holds promise for the development of targeted therapeutic strategies and prognostic indicators in the management of COVID-19.