Vascular normalization to improve treatment of COVID-19: Lessons from treatment of cancer.

Munn, Lance L; Stylianopoulos, Triantafyllos; Jain, Natalie K; Hardin, C Corey; Khandekar, Melin J; Jain, Rakesh K

The dramatic impact of the COVID-19 pandemic has resulted in an "all hands on deck" approach to finding new therapies to improve outcomes in this disease. In addition to causing significant respiratory pathology, infection with SARS-CoV-2 (like infection with other respiratory viruses) directly or indirectly results in abnormal vasculature which may contribute to hypoxemia. These vascular effects cause significant morbidity and may contribute to mortality from the disease. Given that abnormal vasculature and poor oxygenation are also hallmarks of solid tumors, lessons from the treatment of cancer may help identify drugs that can be repurposed to treat COVID-19. Although the mechanisms that result in vascular abnormalities in COVID-19 are not fully understood, it is possible that there is dysregulation of many of the same angiogenic and thrombotic pathways seen in cancer patients. Many anti-cancer therapeutics, including androgen deprivation therapy (ADT) and immune checkpoint blockade (ICB), result in vascular normalization in addition to their direct effects on tumor cells. Therefore, these therapies, which have been extensively explored in clinical trials of cancer patients, may have beneficial effects on the vasculature of COVID-19 patients. Furthermore, these drugs may have additional effects on the disease course, as some ADT may impact viral entry, and ICBs may accelerate T-cell mediated viral clearance. These insights from the treatment of cancer may be leveraged to abrogate the vascular pathologies found in COVID-19 and other forms of hypoxemic respiratory failure.