in-depth modelling with narrower age categories. Sex was selfreported and no effort was made to query patients regarding transsexualism. Given rates of transsexualism nationwide ranging from 0.39–0.56%, discordance between reported sex and biologic sex is unlikely to impact our results.32
CONCLUSION
In the NYC population, men have higher rates of COVID-19
and higher rates of hospitalization and death due to COVID-19.
Numerous theories have been postulated to explain these
underlying differences, and while studies considering the role
of androgens and other sex hormones offer the most robust
evidence to date, this relationship is complex and warrants
further study.
DISCLOSURES
Authors have no relevant conflicts to report.
Funding: NP is supported by the Frederick J. and Theresa Dow Wallace Fund of the New York Community Trust and Urology Care Foundation Research Scholars Award.
Funding: NP is supported by the Frederick J. and Theresa Dow Wallace Fund of the New York Community Trust and Urology Care Foundation Research Scholars Award.
ACKNOWLEDGMENT
We are indebted to the Surveillance and Epidemiology Branch
and Bureau of Vital Statistics at the New York City Department
of Health and Mental Hygeine, most notably Sara Archie and
Molly Kratz.
REFERENCES
1. Singh A, Shaikh A, Singh R, Singh AK. COVID-19: From bench to bed side. Diabetes Metab Syndr. 2020;14:277-81.
2. Medicine JHUo. Coronavirus Resource Center. 2020.
3. Zheng Z, Peng F, Xu B, Zhao J, Liu H, Peng J, et al. Risk factors of critical & mortal COVID-19 cases: A systematic literature review and meta-analysis. J Infect. 2020.
4. Bhala N, Curry G, Martineau AR, Agyemang C, Bhopal R. Sharpening the global focus on ethnicity and race in the time of COVID-19. Lancet. 2020;395:1673-6.
5. Serge R, Vandromme J, Charlotte M. Are we equal in adversity? Does Covid-19 affect women and men differently? Maturitas. 2020.
6. Health NYC. COVID-19: Data. New York, NY2020.
7. Reporter C. Census Reporter - New York, NY. 2018.
8. Chen J, Lu H, Melino G, Boccia S, Piacentini M, Ricciardi W, et al. COVID-19 infection: the China and Italy perspectives. Cell Death Dis. 2020;11:438.
9. Hoffmann M, Kleine-Weber H, Schroeder S, Kruger N, Herrler T, Erichsen S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020;181:271-80 e8.
10. Sungnak W, Huang N, Becavin C, Berg M, Queen R, Litvinukova M, et al. SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes. Nat Med. 2020;26:681-7.
11. Gemmati D, Bramanti B, Serino ML, Secchiero P, Zauli G, Tisato V. COVID-19 and individual genetic susceptibility/receptivity: role of ACE1/ACE2 Genes, immunity, inflammation and coagulation. might the double x-chromosome in females be protective against SARS-CoV-2 Compared to the single X-chromosome in males? Int J Mol Sci. 2020;21.
12. Lin B, Ferguson C, White JT, Wang S, Vessella R, True LD, et al. Prostatelocalized and androgen-regulated expression of the membrane-bound serine protease TMPRSS2. Cancer Res. 1999;59:4180-4.
13. Pan F, Xiao X, Guo J, Song Y, Li H, Patel DP, et al. No evidence of severe acute respiratory syndrome-coronavirus 2 in semen of males recovering from coronavirus disease 2019. Fertil Steril. 2020;113:1135-9.
14. Xu J, Qi L, Chi X, Yang J, Wei X, Gong E, et al. Orchitis: a complication of severe acute respiratory syndrome (SARS). Biol Reprod. 2006;74:410-6.
15. Quan W, Chen J, Liu Z, Tian J, Chen X, Wu T, et al. No SARS-CoV-2 in expressed prostatic secretion of patients with coronavirus disease 2019: a descriptive multicentre study in China. medrxiv. 2020.
16. Yang M, Chen S, Huang B, Zhong JM, Su H, Chen YJ, et al. Pathological findings in the testes of COVID-19 Patients: clinical implications. Eur Urol Focus. 2020.
17. Wambier CG, Goren A. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is likely to be androgen mediated. J Am Acad Dermatol. 2020;83:308-9.
18. Goren A, Vano-Galvan S, Wambier CG, McCoy J, Gomez-Zubiaur A, Moreno- Arrones OM, et al. A preliminary observation: Male pattern hair loss among hospitalized COVID-19 patients in Spain - a potential clue to the role of androgens in COVID-19 severity. J Cosmet Dermatol. 2020;19:1545-7.
19. McCoy J, Wambier CG, Vano-Galvan S, Shapiro J, Sinclair R, Ramos PM, et al. Racial variations in COVID-19 deaths may be due to androgen receptor genetic variants associated with prostate cancer and androgenetic alopecia. Are anti-androgens a potential treatment for COVID-19? J Cosmet Dermatol. 2020;19:1542-3.
20. Montopoli M, Zumerle S, Vettor R, Rugge M, Zorzi M, Catapano CV, et al. Androgen-deprivation therapies for prostate cancer and risk of infection by SARS-CoV-2: a population-based study (N = 4532). Ann Oncol. 2020.
21. Ghazizadeh Z, Majd H, Richter M, Samuel R, Zekavat SM, Asgharian H, et al. Androgen regulates SARS-CoV-2 receptor levels and is associated with severe COVID-19 symptoms in men. bioRxiv. 2020.
22. Cadegiani FA, Wambier CG, Goren A. Spironolactone: an anti-androgenic and anti-hypertensive drug that may provide protection against the novel coronavirus (SARS-CoV-2) induced acute respiratory distress syndrome (ARDS) in COVID-19. Frontiers in Medicine. 2020.
23. Kaufman JM, Vermeulen A. The decline of androgen levels in elderly men and its clinical and therapeutic implications. Endocr Rev. 2005;26:833-76.
24. Mohamad NV, Wong SK, Wan Hasan WN, Jolly JJ, Nur-Farhana MF, Ima- Nirwana S, et al. The relationship between circulating testosterone and inflammatory cytokines in men. Aging Male. 2019;22:129-40.
25. Schett G, Sticherling M, Neurath MF. COVID-19: risk for cytokine targeting in chronic inflammatory diseases? Nat Rev Immunol. 2020;20:271-2.
26. Ghosh S, Klein RS. Sex Drives Dimorphic Immune Responses to Viral Infections. J Immunol. 2017;198:1782-90.
27. Ghosh M, Rodriguez-Garcia M, Wira CR. The immune system in menopause: pros and cons of hormone therapy. J Steroid Biochem Mol Biol. 2014;142:171-5.
28. Bukowska A, Spiller L, Wolke C, Lendeckel U, Weinert S, Hoffmann J, et al. Protective regulation of the ACE2/ACE gene expression by estrogen in human atrial tissue from elderly men. Exp Biol Med (Maywood). 2017;242:1412-23.
29. Lee HK, Lee JK, Cho B. The role of androgen in the adipose tissue of males. World J Mens Health. 2013;31:136-40.
30. Prevention CfDCa. Coronavirus disease 2019 (COVID-19) - who is at increased risk for severe illness? 2020.
31. Punjani N, Flannigan R, Oliffe JL, McCreary DR, Black N, Goldenberg SL. Unhealthy behaviors among Canadian men are predictors of comorbidities: implications for clinical practice. Am J Mens Health. 2018;12:2183-93.
32. Nolan IT, Kuhner CJ, Dy GW. Demographic and temporal trends in transgender identities and gender confirming surgery. Transl Androl Urol. 2019;8:184-90.
2. Medicine JHUo. Coronavirus Resource Center. 2020.
3. Zheng Z, Peng F, Xu B, Zhao J, Liu H, Peng J, et al. Risk factors of critical & mortal COVID-19 cases: A systematic literature review and meta-analysis. J Infect. 2020.
4. Bhala N, Curry G, Martineau AR, Agyemang C, Bhopal R. Sharpening the global focus on ethnicity and race in the time of COVID-19. Lancet. 2020;395:1673-6.
5. Serge R, Vandromme J, Charlotte M. Are we equal in adversity? Does Covid-19 affect women and men differently? Maturitas. 2020.
6. Health NYC. COVID-19: Data. New York, NY2020.
7. Reporter C. Census Reporter - New York, NY. 2018.
8. Chen J, Lu H, Melino G, Boccia S, Piacentini M, Ricciardi W, et al. COVID-19 infection: the China and Italy perspectives. Cell Death Dis. 2020;11:438.
9. Hoffmann M, Kleine-Weber H, Schroeder S, Kruger N, Herrler T, Erichsen S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020;181:271-80 e8.
10. Sungnak W, Huang N, Becavin C, Berg M, Queen R, Litvinukova M, et al. SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes. Nat Med. 2020;26:681-7.
11. Gemmati D, Bramanti B, Serino ML, Secchiero P, Zauli G, Tisato V. COVID-19 and individual genetic susceptibility/receptivity: role of ACE1/ACE2 Genes, immunity, inflammation and coagulation. might the double x-chromosome in females be protective against SARS-CoV-2 Compared to the single X-chromosome in males? Int J Mol Sci. 2020;21.
12. Lin B, Ferguson C, White JT, Wang S, Vessella R, True LD, et al. Prostatelocalized and androgen-regulated expression of the membrane-bound serine protease TMPRSS2. Cancer Res. 1999;59:4180-4.
13. Pan F, Xiao X, Guo J, Song Y, Li H, Patel DP, et al. No evidence of severe acute respiratory syndrome-coronavirus 2 in semen of males recovering from coronavirus disease 2019. Fertil Steril. 2020;113:1135-9.
14. Xu J, Qi L, Chi X, Yang J, Wei X, Gong E, et al. Orchitis: a complication of severe acute respiratory syndrome (SARS). Biol Reprod. 2006;74:410-6.
15. Quan W, Chen J, Liu Z, Tian J, Chen X, Wu T, et al. No SARS-CoV-2 in expressed prostatic secretion of patients with coronavirus disease 2019: a descriptive multicentre study in China. medrxiv. 2020.
16. Yang M, Chen S, Huang B, Zhong JM, Su H, Chen YJ, et al. Pathological findings in the testes of COVID-19 Patients: clinical implications. Eur Urol Focus. 2020.
17. Wambier CG, Goren A. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is likely to be androgen mediated. J Am Acad Dermatol. 2020;83:308-9.
18. Goren A, Vano-Galvan S, Wambier CG, McCoy J, Gomez-Zubiaur A, Moreno- Arrones OM, et al. A preliminary observation: Male pattern hair loss among hospitalized COVID-19 patients in Spain - a potential clue to the role of androgens in COVID-19 severity. J Cosmet Dermatol. 2020;19:1545-7.
19. McCoy J, Wambier CG, Vano-Galvan S, Shapiro J, Sinclair R, Ramos PM, et al. Racial variations in COVID-19 deaths may be due to androgen receptor genetic variants associated with prostate cancer and androgenetic alopecia. Are anti-androgens a potential treatment for COVID-19? J Cosmet Dermatol. 2020;19:1542-3.
20. Montopoli M, Zumerle S, Vettor R, Rugge M, Zorzi M, Catapano CV, et al. Androgen-deprivation therapies for prostate cancer and risk of infection by SARS-CoV-2: a population-based study (N = 4532). Ann Oncol. 2020.
21. Ghazizadeh Z, Majd H, Richter M, Samuel R, Zekavat SM, Asgharian H, et al. Androgen regulates SARS-CoV-2 receptor levels and is associated with severe COVID-19 symptoms in men. bioRxiv. 2020.
22. Cadegiani FA, Wambier CG, Goren A. Spironolactone: an anti-androgenic and anti-hypertensive drug that may provide protection against the novel coronavirus (SARS-CoV-2) induced acute respiratory distress syndrome (ARDS) in COVID-19. Frontiers in Medicine. 2020.
23. Kaufman JM, Vermeulen A. The decline of androgen levels in elderly men and its clinical and therapeutic implications. Endocr Rev. 2005;26:833-76.
24. Mohamad NV, Wong SK, Wan Hasan WN, Jolly JJ, Nur-Farhana MF, Ima- Nirwana S, et al. The relationship between circulating testosterone and inflammatory cytokines in men. Aging Male. 2019;22:129-40.
25. Schett G, Sticherling M, Neurath MF. COVID-19: risk for cytokine targeting in chronic inflammatory diseases? Nat Rev Immunol. 2020;20:271-2.
26. Ghosh S, Klein RS. Sex Drives Dimorphic Immune Responses to Viral Infections. J Immunol. 2017;198:1782-90.
27. Ghosh M, Rodriguez-Garcia M, Wira CR. The immune system in menopause: pros and cons of hormone therapy. J Steroid Biochem Mol Biol. 2014;142:171-5.
28. Bukowska A, Spiller L, Wolke C, Lendeckel U, Weinert S, Hoffmann J, et al. Protective regulation of the ACE2/ACE gene expression by estrogen in human atrial tissue from elderly men. Exp Biol Med (Maywood). 2017;242:1412-23.
29. Lee HK, Lee JK, Cho B. The role of androgen in the adipose tissue of males. World J Mens Health. 2013;31:136-40.
30. Prevention CfDCa. Coronavirus disease 2019 (COVID-19) - who is at increased risk for severe illness? 2020.
31. Punjani N, Flannigan R, Oliffe JL, McCreary DR, Black N, Goldenberg SL. Unhealthy behaviors among Canadian men are predictors of comorbidities: implications for clinical practice. Am J Mens Health. 2018;12:2183-93.
32. Nolan IT, Kuhner CJ, Dy GW. Demographic and temporal trends in transgender identities and gender confirming surgery. Transl Androl Urol. 2019;8:184-90.
AUTHOR CORRESPONDENCE
Joseph P. Alukal MD jpa2148@cumc.columbia.edu
