Introduction: During the evolution of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, several drug candidates have been proposed for repositioning towards a quest for more effective treatments. Methodology: We reviewed recent literature (Pubmed, Google, Clinicaltrials.gov), as of the middle of May 2021, for evidence regarding the potential benefit from poly(ADP-ribose)-polymerase inhibitors and vascular endothelial growth factor blockade in severe SARS-CoV-2 infection. Results: poly(ADP-ribose)-polymerase inhibitors have been suggested as potential agents against coronavirus disease 2019 (COVID-19) by a variety of mechanisms. vascular endothelial growth factor-associated vascular permeability is implicated with increased vascular leakage and pulmonary oedema. Thus, anti-angiogenesis factors, such as bevacizumab are being investigated in critically ill COVID-19 patients. Conclusions: The synergistic potential of these two classes of inhibitors in severe COVID-19 management could be beneficial. Further research should be carried out in order to support this hypothesis.