Susceptibility to SARS‐Cov‐2 infection and risk for severe COVID‐19 in patients with prostate cancer on androgen deprivation therapy

Abstract

Androgen deprivation therapy (ADT) has been hypothesized to protect against COVID‐19, but previous observational studies of men with prostate cancer on ADT have been inconsistent regarding mortality risk from coronavirus disease 2019 (COVID‐19). Using data from the Prostate Cancer data Base Sweden (PCBaSe), we identified a cohort of 114 547 men with prevalent prostate cancer on the start of follow‐up in February 2020, and followed them until 16 December 2020 to evaluate the association between ADT and time to test positive for COVID‐19. Among men testing positive for COVID‐19, we used regression analyses to estimate the association between ADT and risk of COVID‐19‐related hospital admission/death from any cause within 30 days of the positive test. In total, 1695 men with prostate cancer tested positive for COVID‐19. In crude analyses, exposure to ADT was associated with a 3‐fold increased risk of both testing positive for COVID‐19 infection and subsequent hospital admission/death. Adjustment for age, comorbidity and prostate cancer risk category substantially attenuated the associations: HR 1.3 (95% CI: 1.1‐1.5) for testing positive for COVID‐19, and OR 1.4 (95% CI: 1.0‐1.9) for risk of subsequent hospital admission/death. In conclusion, although these results suggest increased risks of a positive COVID‐19 test, and COVID‐19‐related hospital admission/death in men on ADT, these findings are likely explained by confounding by old age, cancer‐associated morbidity and other comorbidities being more prevalent in men on ADT, rather than a direct effect of the therapy.

Antiandrogens as Therapies for COVID-19: A Systematic Review

“…Considering the risk of subsequent hospital admission or death, these results were even higher (OR, 1.4; 95% CI: 1.0-1.9). Again, these data seem to disprove the protective role of ADT in preventing SARS-CoV-2 infection and its sequelae, enforcing data from another smaller Swedish case-control analysis [58,86].…”

“…Similarly, abiraterone acetate, a selective inhibitor of the enzyme 17αhydroxylase/C17,20-lyase (CYP17) and a partial antagonist of AR, has been evaluated as an anti-SARS-CoV-2 therapy: in vitro results suggested that abiraterone might reduce the size of viral plaques and decrease N and S viral protein production [56]. Subsequent in vivo studies later disproved these results and abiraterone has consequently not been employed as an anti-viral treatment [57][58][59]. The effect of apalutamide, an oral competitive signaling inhibitor of the ligand-binding domain of the androgen receptor, on SARS-CoV-2 infection has also been tested by in vitro studies with Calu-3 lung adenocarcinoma cells and primary human nasal epithelial cells, finding a reduction in SARS-CoV-2 entry [6].…”

Apalutamide Prevents SARS-CoV-2 Infection in Lung Epithelial Cells and in Human Nasal Epithelial Cells

“…Thus, ADT may have a protective effect, decreasing the severity of COVID-19 in PCa patients [ 40 ]. However, other clinical studies obtained discordant results and the role of ADT in reducing COVID-19 infection severity in men is still a matter of debate [ 41 , 42 , 43 , 44 , 45 , 46 ]. Particularly, recent studies have shown that PCa patients under ADT treatment presented a higher risk of contracting COVID-19 and hospital admission [ 44 , 47 ].…”

“…However, other clinical studies obtained discordant results and the role of ADT in reducing COVID-19 infection severity in men is still a matter of debate [ 41 , 42 , 43 , 44 , 45 , 46 ]. Particularly, recent studies have shown that PCa patients under ADT treatment presented a higher risk of contracting COVID-19 and hospital admission [ 44 , 47 ]. Still, Schmidt et al noted no association between ADT treatment and 30-day mortality among patients with PCa and COVID-19 [ 43 ].…”