Table 1.

The Characteristic of Medications Used for VEGF Regulation.

Anti- VEGF Agent	Targets	Relevant Functions	Anti-VEGF effects	Anticipated effect in the COVID-19
Bevacizumab (mAb)	VEGF	Circulating VEGF inhibition	Primary	In severe cases of COVID-19, adding bevacizumab to standard of care improves oxygenation (PaO2/FiO2 ratios) and reduced ventilation support.
Siltuximab (mAb)	IL-6/VEGF	Preventing the binding of IL-6 to its soluble or membrane receptors	Secondary	Siltuximab improves clinical status in patients with ARDS secondary to COVID-19.
Tocilizumab (mAb)	IL-6 receptor/VEGF	Antagonizing the IL-6	Secondary	In severe cases of COVID-19, adding tocilizumab to standard of care decreases the need for mechanical ventilation and is associated with better survival.
Sunitinib Sorafenib (Multi-TKIs)	TK Receptor	Blockage of VEGF and PDGF	Secondary	In patients with rapidly progressing COVID-19 respiratory failure on ventilatory support, siltuximab may improve survival and cytokine hyperinflammation
Apatinib/Rivoceranib (TKI)	TK Receptor	Selectively VEGFR-2 inhibition	Primary	Although TKIs have not been studied in COVID-19 yet, given the selective inhibitory effects of these drugs on VEGFR-2, they may be useful in patients with severe COVID-19 in a cytokine hyperinflammation phase.
Cyclosporine	Cytokines	Modulates the T-cell activation and down-regulates VEGF production through cAMP-mediated signaling pathway	Secondary	Adding cyclosporine to the low-dose steroids appears to be beneficial in hospitalized patients with COVID-19 induced pneumonia.

Abbreviations: Interleukin-6, IL-6; mAb, Monoclonal antibody; PDGF, Platelet Endothelial Growth Factor; TKI, tyrosine kinases receptor inhibitors; VEGF, Vascular Endothelial Growth Factor, PaO₂/FiO₂, ratio of arterial oxygen partial pressure to fractional inspired oxygen; ARDS, Acute respiratory distress syndrome.