Anti-VEGF agents: As appealing targets in the setting of COVID-19 treatment in critically ill patients

Abstract

Recently, the medications used for the severe form of the coronavirus disease-19 (COVID-19) therapy are of particular interest. In this sense, it has been supposed that anti-VEGF compounds would be good candidates in the face of “cytokine storm” and intussuscepted angiogenesis due to having an appreciable anti-inflammatory effect. Therefore, they can be subjected to therapeutic protocols to manage acute respiratory distress syndrome (ARDS). Since the compelling evidence emphasized that VEGFs contribute to the inflammatory process and play a mainstay role in disease pathogenesis, in this review, we aimed to highlight the VEGF's plausible participation in the cytokine storm exacerbation in COVID-19. Next, the recent clinical advances regarding the anti-VEGF medications, including humanized monoclonal antibody, immunosuppressant, a tyrosine kinase inhibitor, and a cytokine inhibitor, have been addressed in the setting of COVID-19 treatment in critically ill patients. Together, retrieving the increased level of VEGF subsets, as well as antagonizing VEGF related receptors, could be helpful for the treatment of COVID-19, especially in those suffering from ARDS.

SARS-CoV-2 infection- induced growth factors play differential roles in COVID-19 pathogenesis

“…VEGF has recently been implicated in the pathogenesis of severe COVID-19 [38] . Specifically, the dysregulated VEGF in COVID-19 patients is associated with an ARDS-related phenotype, characterized by pulmonary edema, thrombotic events, and translocation of the virus into the systemic circulation [39] .…”

Insights into potential mechanisms of asthma patients with COVID-19: A study based on the gene expression profiling of bronchoalveolar lavage fluid

“…Severe vascular endothelial dysfunction predisposes to cause endodermatitis, vascular leakage and thrombosis [ 100 , 101 ]. Besides, VEGF participates in the cytokine storm exacerbation and thus antianti -VEGF compounds are supposed to be helpful candidates for COVID-19 [ 102 ]. IL-1 is a potential therapeutic target in patients with neutrophilic asthma [ 103 ] and severe inflammatory ARDS complicated by COVID-19 [ 104 ].…”

Network pharmacology and molecular docking analysis on molecular targets and mechanism prediction of Huanglian Jiedu Decoction in the treatment of COVID-19

“…It mainly exerts its physiological function by binding with receptors VEGF Receptor 1 (VEGFR1), VEGF Receptor 2 (VEGFR2), etc. [ 42 ] . Under pathological conditions, their combination can inhibit the apoptosis of vascular endothelial cells, promote their proliferation, migration and differentiation, increase vascular permeability, and stimulate neovascularization in the body [ 43 ] .…”