We read the article with great interest, and appreciate the authors’ efforts to analyze the mechanistic differences of expression and activity of angiotensin-converting enzyme 2 (ACE2) in male[1].
However, we would like to point out 1 concern.

First, it was recently demonstrated that both ACE2 and the transmembrane protease, serine 2 (TMPRSS2) are crucial for the sever acute respiratory coronavirus 2 (SARS-CoV-2) entry into host cells[2, 3]. The SARS-CoV-2 binds to ACE2 for cell entry, followed by proteolytic cleavage of the S protein by TMPRSS2 allowing the fusion of viral and cellular membranes. In vitro and in vivo results indicates that androgen administration induces TMPRSS2 expression in human lung epithelial cells and androgen deprivation reduces TMPRSS2 transcription in murine lung[4]. The patients with prostate cancer receiving androgen deprivation therapy (ADT) had a significantly lower risk of SARS-CoV-2 infection compared with patients who did not receive ADT. This report implicates that ADT is beneficial for the treatment of SARS-CoV-2[5]. In addition to this, in vitro evidence indicates that TMPRSS2 inhibition may be beneficial to prevent the infection of SARS-CoV-2[6].
Additionally some group reports that use of testosterone may be considered to reduce the associated pulmonary syndrome, thus preventing progression to severe COVID-19 disease[7].
Hence, it is important to consider TMPRSS2 and testosterone in addition to ACE2 when we consider the influence of the difference of biological sex.

References:
1 . Klein SL, Dhakal S, Ursin RL, Deshpande S, Sandberg K, Mauvais-Jarvis F: Biological sex impacts COVID-19 outcomes. PROS Pathogens 2020;16(6):e1008570.
2. Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler Y, Erichsen S, Schiergens TS, Herrler G, Wu NH, Nitsche A, et al: SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell 2020;181(2):271-280.e8.
3. Matsuyama S, Nao N, Shirato K, Kawase M, Saito S, Takayama I, Nagata N, Sekizuka T, Katoh H, Kato F, et al. Enhanced isolation of SARS-CoV-2 by TMPRSS2-expressing cells. PNAS 2020;117(13):7001-7003.
4. Mikkonen L, Pihlajamaa P, Sahu B, Zhang FP, Jänne OA. Androgen receptor and androgen-dependent gene expression in lung. Molecular and Cellular Endocrinology 2010;317(1-2):14-24.
5. Montopoli M, Zumerle S, Vettor R, Rugge M, Zorzi M, Catapano CV, Carbone GM, Cavalli A, Pagano F, Ragazzi E, Prayer-Galetti T, Alimonti A. Androgen-deprivation therapies for prostate cancer and risk of infection by SARS-CoV-2: a population-based study (N = 4532). Annals of Ooncology 2020; S0923-7534(20)39797-0.
6. Hoffmann M, Schroeder S, Kleine-Weber H, Müller MA, Drosten C, Pöhlmann S. Nafamostat mesylate blocks activation of SARS-CoV-2: new treatment option for COVID- 19. Antimicrob Agents Chemother 2020;64(6):e00754- 20.
7. Pozzillia P, Lenzib A. Commentary: Testosterone, a key hormone in the context of COVID-19 pandemic. Metabolism Clinical and Experimental 2020;108:154252.