Androgen-deprivation therapies for prostate cancer and risk of infection by SARS-CoV-2: a population-based study (N = 4532)

Abstract

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-CoV-2 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.

TMPRSS2, a SARS-CoV-2 Internalization Protease is Downregulated in Head and Neck Cancer Patients.

“…Unlike other members of the Coronaviridae that circulate in the human population and cause only mild respiratory disease, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel betacoronavirus which is transmitted from animals to humans and severely affects pulmonary respiration [1][2][3][4][5]. SARS-CoV-2 enters host cells through the binding of Spike protein to ACE2 receptor and subsequent S protein priming performed by host proteases including TPMRSS2 [6][7][8].…”

In silico dynamics of COVID-19 phenotypes for optimizing clinical management

“…These results suggest that reduced viral entry into cells due to lower TMPRSS2 level can explain the improved outcomes in females-even if the adaptive immune response is not as vigorous 38 .…”

“…An outstanding question is why males tend to have more severe COVID-19 disease compared with females 38 .…”

Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blockers and The Risk of SARS-CoV-2 Infection: A Systematic Review and Meta-analysis 

“…Thus, factors regulating TMRSS2 expression or its enzymatic activity would modulate SARS-CoV-2 infectivity. For example, TMPRSS2 expression is regulated by androgens and has been reported in a recent study that men treated with antiandrogenic therapy were less susceptible to CoV-2 infection 35 . Accordingly, population differences in testosterone levels, androgen receptor function and it's downstream signaling pathway could affect TMPRSS2 levels and hence susceptibility to SARS-CoV-2 infection.…”