Association between SARS-CoV-2 infection and disease severity among prostate cancer patients on androgen deprivation therapy: a systematic review and meta-analysis

Abstract

Purpose Androgen-regulated enzymes such as the angiotensin-converting enzyme 2 (ACE2) and the transmembrane serine protease 2 (TMPRSS2) are involved in the SARS-CoV-2 infection process. The expression of TMPRSS2 and its fusion gene, which are increased in the epithelium of the human prostate gland during prostate carcinogenesis, are regulated by androgens. Our goal was to assess the risk of the SARS-CoV-2 infection and the severity of the disease in PCa patients treated with androgen deprivation therapy (ADT). Methods We conducted a systematic review and meta-analysis according to PRISMA guidelines. We queried PubMed and Web of Science databases on 1 July 2021. We used random- and/or fixed-effects meta-analytic models in the presence or absence of heterogeneity according to Cochrane’s Q test and I2 statistic, respectively. Results Six retrospective studies (n = 50,220 patients) were selected after considering inclusion and exclusion criteria for qualitative evidence synthesis. Four retrospective studies were included to assess the SARS-CoV-2 infection risk in PCa patients under ADT vs. no ADT and the summarized risk ratio (RR) was 0.8 (95% confidence intervals (CI) 0.44–1.47). Five retrospective studies were included to assess the severity of coronavirus disease 2019 (COVID-19) in PCa patients under ADT versus no ADT and the summarized RR was 1.23 (95% CI 0.9–1.68). Conclusion We found a non-significant association between the risk of SARS-CoV-2 infection and COVID-19 severity in PCa patients treated with ADT. However, our results suggest that during the COVID-19 pandemic PCa patients can safely undergo ADT as a cancer therapy without worsening COVID-19 risk and trajectory.

Association of hypernatremia with outcomes of COVID-19 patients: A systematic review and meta-analysis

“…[40] Many systematic reviews and meta-analysis have delineated ACE2 and TMPRSS2 genes to increase the risk of susceptibility and severity of COVID-19. [41][42][43] This could lead to tubulopathy or even renal failure, which could explain the loss of free water or sodium retention for hypernatremia. However, ICU patients are at high risk of hypernatremia due to their inability to maintain free water balance due to sedation, intubation and fluid restrictions for various other reasons.…”

COVID-19 Severity and Androgen Receptor Polymorphism

“…The immunological imbalance complicated by the testosterone blockade could represent an additional significant risk factor for a severe-to-critical disease in these subjects since the treatment reduces the androgen signaling and, likely, its anti-inflammatory function. While the literature data show that androgen deprivation therapy does not modify the risk of the infection itself [ 31 ], data on its influence on the prognosis are controversial. In fact, a recent trial failed to detect significant differences between those subjects undergoing anti-androgenic treatment and the controls [ 32 ], and a metanalysis of the available data could only show a trend of risk reduction [ 33 ].…”

Implications and effects of COVID-19 on diagnosis and management of prostate cancer

“…There is a theoretical role for ADT in the prevention of serious complications from COVID-19 as the transmembrane serine protease 2 is said to facilitate Severe acute respiratory syndrome coronavirus 2 cellular entry and is regulated by androgens [39]. However, multiple systematic reviews have found no association between ADT and reduced COVID-19 infection or mortality [40][41][42], suggesting no protective role of ADT for PCa patients against COVID-19. The use of ADT, although, could be beneficial when postponement of curative treatment for localised PCa is anticipated.…”