Abstract: ORIGINAL ARTICLE Androgen-deprivation therapies for prostate cancer and risk of infection by SARS-CoV-2: a population-based study (N [ 4532) M. Montopoli1,2, S. Zumerle2,3, R. Vettor3, M. Rugge3,4, M. Zorzi4, C. V. Catapano5, G. M. Carbone5, A. Cavalli6, F. Pagano2, E. Ragazzi1, T. Prayer-Galetti7 & A. Alimonti2,3,5,8* 1 Department of Pharmaceutical and Pharmacological Sciences, Università degli Studi di Padova, Padova; 2VIMM e Veneto Institute of Molecular Medicine, Fondazione per la Ricerca Biomedica Avanzata, Padova; 3Department of Medicine, Università degli Studi di Padova, Padova; 4Veneto Tumour Registry e Azienda Zero, Padova, Italy; 5Institute of Oncology Research, Oncology Institute of Southern Switzerland, Università della Svizzera Italiana, Bellinzona; 6Institute for Research in Biomedicine, Università della Svizzera Italiana, Bellinzona, Switzerland; 7Department of Oncological and Gastroenterological Sciences e Urology Unit, Azienda Ospedaliera di Padova, Padova, Italy; 8Department of Health Sciences and Technology, ETH Zürich, Zurich, Switzerland Available online 6 May 2020 Background: Cell entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) depends on binding of the viral spike (S) proteins to angiotensin-converting enzyme 2 and on S protein priming by TMPRSS2. Inhibition of TMPRSS2 may work to block or decrease the severity of SARS-CoV-2 infections. Intriguingly, TMPRSS2 is an androgen-regulated gene that is up-regulated in prostate cancer where it supports tumor progression and is involved in a frequent genetic translocation with the ERG gene. First- or second-generation androgen-deprivation therapies (ADTs) decrease the levels of TMPRSS2. Here we put forward the hypothesis that ADTs may protect patients affected by prostate cancer from SARS-CoV-2 infections. Materials and methods: We extracted data regarding 9280 patients (4532 males) with laboratory-confirmed SARS-CoV2 infection from 68 hospitals in Veneto, one of the Italian regions that was most affected by the coronavirus disease 2019 (COVID-19) pandemic. The parameters used for each COVID-19-positive patient were sex, hospitalization, admission to intensive care unit, death, tumor diagnosis, prostate cancer diagnosis, and ADT. Results: There were evaluable 9280 SARS-CoV-2-positive patients in Veneto on 1 April 2020. Overall, males developed more severe complications, were more frequently hospitalized, and had a worse clinical outcome than females. Considering only the Veneto male population (2.4 million men), 0.2% and 0.3% of non-cancer and cancer patients, respectively, tested positive for SARS-CoV-2. Comparing the total number of SARS-CoV-2-positive cases, prostate cancer patients receiving ADT had a significantly lower risk of SARS-CoV-2 infection compared with patients who did not receive ADT (OR 4.05; 95% CI 1.55e10.59). A greater difference was found comparing prostate cancer patients receiving ADT with patients with any other type of cancer (OR 4.86; 95% CI 1.88e12.56). Conclusion: Our data suggest that cancer patients have an increased risk of SARS-CoV-2 infections compared with noncancer patients. However, prostate cancer patients receiving ADT appear to be partially protected from SARS-CoV-2 infections. Key words: androgen-deprivation therapy, COVID-19, prostate cancer