Loading...
dcyphr | Impact of anti-androgenic therapies on COVID-19: an observational study in male population from a COVID-19 regional centre of Lombardy (Italy)

Abstract

Men and women appear to have different susceptibilities to (COVID-19). The S protein found on the surface of coronaviruses allows the virus to attach to the target (host) cell. After the virus is attached to the host, it will signal for a protein that modifies the S protein and allows the coronavirus to enter the cell. With higher levels of androgens (testosterone), the gene that codes for this protein is expressed more. This could explain why men are more susceptible to COVID19. In order to test this, a study was performed on men already using certain androgenic (testosterone) reduction therapies. The two anti-adrenergic therapies were 5-Alpha reductase inhibitors (5ARIs) and androgen deprivation therapy (ADT). Both therapies contained patients of a higher age which correlates to a much higher chance of death. Therefore, it is difficult to infer specific conclusions from this study. However, the results of this study do suggest a protective effect of anti-adrengeric therapies for the male sex. A potential issue is that the sample size in this observational study may have been too low to be generalized to a larger population. 

Background

The Coronavirus disease 2019  (COVID19) pandemic has been slowly shifting westward since its initial discovery. Currently Italy has the highest rates of infection at 258 cases per 100,000 people. Italy also has the highest mortality rate at 12.7% vs the average value of 6.2% (as of April 13th 2020). Although men and women get infected in roughly equal amounts, there is a higher vulnerability to the disease in men than in women, regardless of age. Understanding the gender differences will both directly and indirectly help alleviate the strain COVID-19 outbreak has on the world. 


The (S) Spike protein on the outside of the coronavirus is what allows the virus to initially bind to the cell surface. The coronavirus uses a portion of the (S) protein known as S1 to bind to the cell surface receptor called angiotensin converting enzyme 2 or (ACE2). After the virus is bound to the receptor this stimulates an enzyme called a protease, which is a type of enzyme that will cut the protein in a specific site. This enzyme is a serine protease known as TMPRSS2. This enzyme will then cut a specific site between the S1/S2 protein units on the (S) spike protein. The cutting of the protein (S) makes S2 active and the virus can now enter the cell. Therefore, without the TMPRSS2 enzyme the virus lacks the ability to enter the cell and cause harm. It has been noted that the TMPRSS2 enzyme is sensitive to androgens (testosterone) and therefore this study explores anti-adrenergic therapies in relation to its effectiveness against SARS-CoV2. 


Methods

This study included patients who were referred to the researchers’ study centre from March 1st to 31st, 2020. In order to be considered the patients must be positive for SARS-CoV02 according to the WHO guidelines. Researchers were interested in patients undergoing some version of anti-adrenergic therapy. These patients of interest were those who received 5 alpha reductase inhibitors (5ARI’s) for the treatment of prostate diseases, patients who are currently under androgen deprivation therapy (ADT) for treatment of prostate cancer, or patients who failed ADT androgen deprivation therapy treatment for certain prostate cancer types. This study focused not on the severity of COVID19, but on the lethality of the virus in men who were under anti-adrenergic therapy vs men who were not under anti-adrenergic therapy.


Results

Data from 421 patients positive for SARS-CoV2 were analyzed. Of those 421 patients 137 were women (32.54%) and 284 were men (67.56%). Overall, 84 of the 421 patients died. Of the 84 deceased patients 28 were women (33.33%) and 56 were men (66.67%). There was a significant difference in the mean age of living 61.41 yrs +/- 13.5 versus dead 75.08 +/- 10.4 patients. The overall lethality rate for male patients taking anti-androgen therapies was 27.78%. The lethality rate of all male patients included in this study was 19.17%. This result can be explained by the higher age of males on anti-androgen therapies (mean age 75.66yrs +-11.46). 

Discussion

Hospitals and Intensive care units (ICU) have a limited capacity. In order to most successfully prevent the spread of the pandemic, institutions must understand the probable patient outcomes of various patient populations. This study does suggest that anti-adrenergic therapies are helpful as a protective measure, but it should be noted that this study has numerous limitations. This study observed a highly specialized group of individuals within a short time frame. The sample size was small, and patients with other illnesses accompanying the COVID-19 infection were not accounted for in the data. Similarly, this study suggests a correlation between anti-adrenergic therapies and the level of TMPRSS2 expression but does not investigate it directly. This study also does not test for a correlation between severity of disease, but instead focuses on lethality rate. Further studies should be conducted to address these limitations.