key: cord-1048139-3fl98b87 authors: Patel, Vaibhav G.; Zhong, Xiaobo; Liaw, Bobby; Tremblay, Douglas; Tsao, Che-Kai; Galsky, Matthew D.; Oh, William K. title: Does androgen deprivation therapy protect against severe complications from COVID-19? date: 2020-07-09 journal: Ann Oncol DOI: 10.1016/j.annonc.2020.06.023 sha: dda22c709e2e6791465eab8951834492778ad342 doc_id: 1048139 cord_uid: 3fl98b87 nan Currently, there is a paucity of effective treatments to address the remarkably high morbidity and mortality associated with SARS-CoV-2 coronavirus disease-19 . This letter highlights a potential therapeutic strategy based on known biology of SARS-CoV-2 cellular entry and replication. SARS-CoV-2 relies on surface expression of ACE2 and TMPRSS2 for cellular entry and replication in the respiratory epithelium. 1,2 In in vitro and mouse models, TMPRSS2 inhibition limits respiratory cell damage and reduces severity of infection. 1,3 TMPRSS2 is commonly expressed in prostate cancer cells and is known to be regulated by androgens. 4 Hence, androgen deprivation therapy (ADT) may theoretically reduce TMPRSS2 expression limiting SARS-CoV-2 cellular entry and preventing severe complications from COVID-19. In fact, a recent report from Alimonti and colleagues demonstrated a lower rate of infection in prostate cancer patients on ADT, compared to those not on ADT. 5 Herein, we report our observational study of all patients in a single New York City health system with COVID-19 and prostate cancer to determine the impact of ADT on COVID-19 clinical outcomes. To our best knowledge, this is the largest study to report severity of COVID-19 in patients receiving ADT. This study was approved by the Mount Sinai School of Medicine Institutional Review Board. We identified all Mount Sinai Health System (MSHS) patients with prostate cancer and SARS-CoV-2 viral detection by polymerase chain reaction (based on testing within and outside MSHS) from 3/1/2020-4/6/2020. We collected clinical information including demographics, medical history, and medications including ADT use. ADT use was defined as a GnRH analog or antagonist administered within 3 months and/or documented testosterone levels < 50 ng/dL within 6 months of COVID-19 diagnosis. We collected COVID-19-related outcomes including death, hospitalization, oxygen utilization, and intubation. We performed bivariable and multivariable logistic regression models, adjusting for age, cardiac, and pulmonary disease, to evaluate differences in COVID-19-related outcomes between ADT and non-ADT cohorts. All tests were two-sided at a 0.05 level. We identified 58 patients in our study, 22 and 36 in the ADT and non-ADT cohorts, respectively. Baseline characteristics were similar in both groups, with the exception of prostate cancer clinical disease state and baseline pulmonary disease. Specifically, those in the ADT group had higher incidence of metastatic disease (64% vs. 0%, P<0.001) and higher rates of pulmonary disease (27% vs. 6%, P<0.02), compared to the non-ADT group. Median follow up in the entire cohort was 23 days (range 1-48). The clinical outcomes between ADT and non-ADT cohorts are listed in Table 1 . ADT use, after controlling for age, cardiac disease, and pulmonary disease, was associated with lower rates of hospitalization (Odds Ratio [OR] 0.23, 95%CI 0.06-0.79, P<0.02) and supplemental oxygen requirements (OR 0.26, 95%CI 0.07-0.92, P=0.036). ADT use was also associated with a protective effect on need for intubation (OR 0.31, P=0.192 ) and mortality (OR 0.37, 95%CI 0.08-1.80, P=0.22); however, it did not reach statistical significance. Despite the limitations of a small sample size, our data supports the hypothesis that ADT may limit severe complications from COVID-19, based on lower rates of hospitalization and supplemental oxygen requirements for COVID-19, compared to those infected patients not on ADT. Intubation rates and overall survival demonstrated similar trends but did not reach statistical significance. One important question not addressed in our study is whether ADT earlier in the disease course is more beneficial than in more severe cases. 6 Another limitation of this study is ascertainment bias. Specifically, one-third of our cohort were comprised of patients who reported information regarding COVID-19 testing performed elsewhere, predominantly in the ADT cohort. This may largely reflect a population who contracted COVID-19 with minimalto-mild symptoms. Our data, in conjunction with the report from Alimonti and colleagues, 5 suggest that ADT may have a protective effect in decreasing the severity of COVID-19. Given our study limitations, we aim to develop a larger multi-institution dataset for validation. Additionally, a prospective clinical trial is warranted to answer this important clinical question. Currently, there is a paucity of effective treatments to address the remarkably high morbidity and mortality associated with SARS-CoV-2 coronavirus disease-19 . This letter highlights a potential therapeutic strategy based on known biology of SARS-CoV-2 cellular entry and replication. SARS-CoV-2 relies on surface expression of ACE2 and TMPRSS2 for cellular entry and replication in the respiratory epithelium. 1,2 In in vitro and mouse models, TMPRSS2 inhibition limits respiratory cell damage and reduces severity of infection. 1,3 TMPRSS2 is commonly expressed in prostate cancer cells and is known to be regulated by androgens. 4 Hence, androgen deprivation therapy (ADT) may theoretically reduce TMPRSS2 expression limiting SARS-CoV-2 cellular entry and preventing severe complications from COVID-19. In fact, a recent report from Alimonti and colleagues demonstrated a lower rate of infection in prostate cancer patients on ADT, compared to those not on ADT. 5 Herein, we report our observational study of all patients in a single New York City health system with COVID-19 and prostate cancer to determine the impact of ADT on COVID-19 clinical outcomes. To our best knowledge, this is the largest study to report severity of COVID-19 in patients receiving ADT. This study was approved by the Mount Sinai School of Medicine Institutional Review Board. We identified all Mount Sinai Health System (MSHS) patients with prostate cancer and SARS-CoV-2 viral detection by polymerase chain reaction (based on testing within and outside MSHS) from 3/1/2020-4/6/2020. We collected clinical information including demographics, medical history, and medications including ADT use. ADT use was defined as a GnRH analog or antagonist administered within 3 months and/or documented testosterone levels < 50 ng/dL within 6 months of COVID-19 diagnosis. We collected COVID-19-related outcomes including death, hospitalization, oxygen utilization, and intubation. We performed bivariable and multivariable logistic regression models, adjusting for age, cardiac, and pulmonary disease, to evaluate differences in COVID-19related outcomes between ADT and non-ADT cohorts. All tests were two-sided at a 0.05 level. We identified 58 patients in our study, 22 and 36 in the ADT and non-ADT cohorts, respectively. Baseline characteristics were similar in both groups, with the exception of prostate cancer clinical disease state and baseline pulmonary disease. Specifically, those in the ADT group had higher incidence of metastatic disease (64% vs. 0%, P<0.001) and higher rates of pulmonary disease (27% vs. 6%, P<0.02), compared to the non-ADT group. Median follow up in the entire cohort was 23 days (range 1-48). The clinical outcomes between ADT and non-ADT cohorts are listed in Table 1 Despite the limitations of a small sample size, our data supports the hypothesis that ADT may limit severe complications from COVID-19, based on lower rates of hospitalization and supplemental oxygen requirements for COVID-19, compared to those infected patients not on ADT. Intubation rates and overall survival demonstrated similar trends but did not reach statistical significance. One important question not addressed in our study is whether ADT earlier in the disease course is more beneficial than in more severe cases. 6 Another limitation of this study is ascertainment bias. Specifically, one-third of our cohort were comprised of patients who reported information regarding COVID-19 testing performed elsewhere, predominantly in the ADT cohort. This may largely reflect a population who contracted COVID-19 with minimal-to-mild symptoms. Our data, in conjunction with the report from Alimonti and colleagues, 5 suggest that ADT may have a protective effect in decreasing the severity of COVID-19. A pneumonia outbreak associated with a new coronavirus of probable bat origin