COVID-19 y salud reproductiva

El comportamiento de las enfermedades microbianas, ya sea por virus, bacterias o protozoos, y su respuesta inflamatoria son diferentes entre hombres y mujeres. Esta diferencia se hace notoria en la pandemia derivada por la enfermedad por coronavirus (COVID-19). Desde el reporte del primer caso de neumonía en diciembre de 2019, en Wuhan, China, la COVID-19 se ha diseminado a 212 países y territorios y, a la fecha, se ha confirmado más de 3,5 millones de casos, con una mortalidad mundial del 7%, lo que la convierte en una emergencia sanitaria internacional (1). Hasta ahora, en Colombia, hay más de 7000 casos confirmados, con más de 300 defunciones, de los cuales, más del 60% pertenecen al sexo masculino. Hasta el momento, la literatura científica disponible relacionada con la COVID-19 solo abarca ciertos aspectos de la salud reproductiva, tanto femenina como masculina, mientras se continúa recopilando más información que nos permita conocer y realizar un análisis más detallado de su impacto real en humanos durante el proceso infeccioso y las secuelas derivadas de este. Está confirmado que las condiciones médicas relacionadas con el síndrome metabólico y los estados de insulinorresistencia en hombres y mujeres agravan la presentación clínica y el pronóstico (2). La presente revisión pretende ilustrar los mecanismos relacionados con la respuesta inmunitaria diversa frente a las infecciones virales según el sexo del individuo, su compromiso gonadal y los efectos relacionados con la salud reproductiva masculina y femenina, que incluye la maternofetal y la posible transmisión vertical.

1. Worldometer. COVID-19 Coronavirus Pandemic [Internet]. Disponible en: https://www.worldometers.info/coronavirus/.
2. Suba Z. Prevention and Therapy of COVID-19 via Exogenous Estrogen Treatment for Both Male and Female Patients. J Pharm Pharm Sci. 2020;23(1):75-85. doi:10.18433/jpps31069.
3. Coronaviridae Study Group of the International Committee on Taxonomy of Viruses. The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nat Microbiol. 2020;5(4):536-44. doi: 10.1038/s41564-020-0695-z.
4. Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, et al. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med. 2020;382(8):727- 33. doi:10.1056/NEJMoa2001017.
5. Lu R, Zhao X, Li J, Niu P, Yang B, Wu H, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 2020;395(10224):565-74. doi: 10.1016/S0140- 6736(20)30251-8.
6. Li Q, Guan X, Wu P, Wang X, Zhou L, Tong L, et al. Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia. N Engl J Med. 2020;382(13):1199-207. doi: 10.1056/NEJMoa2001316.
7. Paraskevis D, Kostaki EG, Magiorkinis G, Panayiotakopoulos G, Sourvinos G, Tsiodras S. Full-genome evolutionary analysis of the novel corona virus (2019-nCoV) rejects the hypothesis of emergence as a result of a recent recombination event. Infect Genet Evol. 2020;79:104212. doi: 10.1016/j. meegid.2020.104212.
8. Tang X, Wu C, Li X, Song Y, Yao X, Wu X, et al. On the origin and continuing evolution of SARS-CoV-2. Nat Sci Rev. 2020;0:1-2. doi: 10.1093/nsr/ nwaa036.
9. Epidemiology Working Group for NCIP Epidemic Response; Chinese Center for Disease Control and Prevention. [The epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (COVID-19) in China]. Zhonghua Liu Xing Bing Xue Za Zhi. 2020;41(2):145-51. doi: 10.3760/cma. j.issn.0254-6450.2020.02.003.
10. Grasselli G, Zangrillo A, Zanella A, Antonelli M, Cabrini L, Castelli A, et al. Baseline characteristics and outcomes of 1591 patients infected with SARS-CoV-2 admitted to ICUs of the Lombardy Region, Italy. JAMA. 2020;323(16):1574-81. doi: https://doi.org/10.1001/jama.2020.5394.
11. Gov.co. Datos Abiertos. Estado de Casos de Coronavirus COVID-19 en Colombia [Internet]. Disponible en: https://bit.ly/36JqVrZ.
12. The Novel Coronavirus Pneumonia Emergency Response Epidemiology Team. Vital Surveillances: The Epidemiological Characteristics of an Outbreak of 2019 Novel Coronavirus Diseases (COVID-19). China, 2020. China CDC Weekly. 2020;2(8):113-22.
13. Kadel S, Kovats S. Sex Hormones Regulate Innate Immune Cells and Promote Sex Differences in Respiratory Virus Infection. Front Immunol. 2018;9:1653. doi:10.3389/fimmu.2018.01653.
14. Chan JF, Yuan S, Kok KH, To KKW, Chu H, Yang J, et al. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. Lancet. 2020;395(10223):514-23. doi: 10.1016/S0140-6736(20)30154-9.
15. Zhang W, Du RH, Li B, Zheng XS, Yang XL, Hu B, et al. Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes. Emerg Microbes Infect. 2020;9(1):386-9. doi: 10.1080/22221751.2020.1729071.
16. To KK, Tsang OT, Chik-Yan Yip C, Chan KH, Wu TC, et al. Consistent detection of 2019 novel coronavirus in saliva. Clin Infect Dis. 2020;ciaa149. doi:10.1093/cid/ciaa149.
17. Xia J, Tong J, Liu M, Shen Y, Guo D. Evaluation of coronavirus in tears and conjunctival secretions of patients with SARS-CoV-2 infection. J Med Virol. 2020;10.1002/jmv.25725. doi: 10.1002/jmv.25725.
18. Young K. COVID-19: Virus in Semen/DVT Findings on Autopsy/Anakinra [Internet]. NEJM Journal Watch. 2020. Disponible en: https://bit.ly/2UfFxdx.
19. Li D, Jin M, Bao, P, Zhao W, Zhang S. Clinical Characteristics and Results of Semen Tests Among Men With Coronavirus Disease 2019. JAMA Netw Open. 2020;3(5):e208292. doi: 10.1001/jamanetworkopen.2020.8292.
20. Lauer SA, Grantz KH, Bi Q, Jones FK, Zheng Q, Meredith HR, et al. The incubation period of coronavirus disease 2019 (COVID-19) from publicly reported confirmed cases: estimation and application. Ann Intern Med. 2020;172(9):577- 82. doi: 10.7326/M20-0504.
21. Jiang X, Niu Y, Li X, Li L, Cai W, Chen Y, et al. Is a 14-day quarantine period optimal for effectively controlling coronavirus disease 2019 (COVID-19)? medRxiv. 2020. doi: https://doi.org/10.1101/2020.03.15.20036533.
22. Yu P, Zhu J, Zhang Z, Han Y. A familial cluster of infection associated with the 2019 novel coronavirus indicating potential person-to-person transmission during the incubation period. J Infect Dis. 2020;221(11):1757-61. doi: 10.1093/ infdis/jiaa077.
23. Du Z, Xu X, Wu Y, Wang L, Cowling BJ, Meyers LA, et al. Serial interval of COVID-19 among publicly reported confirmed cases. Emerg Infect Dis. 2020;26(6)1341-3. doi: 10.3201/eid2606.200357.
24. Chen H, Guo J, Wang C, Luo F, Yu X, Zhang W, et al. Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records. Lancet. 2020;395(10226):809-15. doi: 10.1016/S0140-6736(20)30360-3.
25. Schwartz DA, Graham AL. Potential maternal and infant outcomes from (Wuhan) Coronavirus 2019-nCoV infecting pregnant women: Lessons from SARS, MERS, and other human coronavirus infections. Viruses. 2020;12(2):194. doi: 10.3390/v12020194.
26. Karimi-Zarchi M, Neamatzadeh H, Dastgheib SA, Abbasi H, Mirjalili SR, Behforouz A, et al. Vertical transmission of coronavirus disease 19 (COVID-19) from infected pregnant mothers to neonates: a review. Fetal Pediatr Pathol. 2020;1-5. doi: 10.1080/15513815.2020.1747120.
27. Schwartz DA. An analysis of 38 pregnant women with COVID-19, their newborn infants, and maternal- fetal transmission of SARS-CoV-2: maternal coronavirus infections and pregnancy outcomes. Arch Pathol Lab Med. 2020. doi: 10.5858/arpa.2020-0901-SA.
28. Wang S, Guo L, Chen L, Liu W, Cao Y, Zhang J, et al. A case report of neonatal COVID-19 infection in China. Clin Infect Dis. 2020;ciaa225. doi: 10.1093/cid/ ciaa225.
29. Zhu H, Wang L, Fang C, Peng S, Zhang L, Chang G, et al. Clinical analysis of 10 neonates born to mothers with 2019-nCoV pneumonia. Transl Pediatr. 2020;9(1):51-60. doi: 10.21037/tp.2020.02.06.
30. Zeng H, Xu C, Fan J, Tang Y, Deng Q, Zhang W, et al. Antibodies in infants born to mothers with COVID-19 pneumonia. JAMA. 2020;323(18):1848-9. doi:10.1001/jama.2020.4861.
31. Dong L, Tian J, He S, Zhu C, Wanh J, Liu C, et al. Possible vertical transmission of SARS-CoV-2 from an infected mother to her newborn. JAMA. 2020;323(18):1846-8. doi: 10.1001/jama.2020.4621.
32. Favre G, Pomar L, Musso D, Baud D. Epidemia 2019-nCoV: ¿qué pasa con los embarazos? Lancet. 2020;395(10224):e40. doi: 10.1016/S0140-6736.
33. Wong SF, Chow KM, Leung TN, Ng WF, Ng Tk, Sjek CC, et al. Pregnancy and Perinatal Outcomes of Women With Severe Acute Respiratory Syndrome. Am J Obstet Gynecol. 2004;191(1):292-7. doi: 10.1016/j.ajog.2003.11.019.
34. Vivanti A, Vauloup-Fellous C, Prevot S, Zupan V, Suffee C, Do-Cao J, et al. Transplacental transmission of SARS-CoV-2 infection [Internet]. Nature Research. 2020. doi:10.21203/rs.3.rs-28884/v1.
35. Chen L, Li Q, Zheng D, Jiang H, Wei Y, Zou L, et al. Clinical Characteristics of Pregnant Women with Covid-19 in Wuhan, China. N Engl J Med. 202;NEJMc2009226. doi:10.1056/NEJMc2009226.
36. Guan W, Ni Z, Hu Y, Liang WH, Ou CQ, He JX, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020;382(18):1708-20. doi:10.1056/NEJMoa2002032.
37. Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395(10223):507-13. doi: 10.1016/S0140-6736(20)30211-7.
38. Sutton D, Fuchs K, D’Alton M, Goffman D. Universal Screening for SARSCoV-2 in Women Admitted for Delivery. N Engl J Med. 2020;382(22):2163- 4. doi:10.1056/NEJMc2009316.
39. Pen?a-Lo?pez BO, Rinco?n-Orozco B. Generalidades de la pandemia por COVID-19 y su asociacio?n gene?tica con el virus del SARS. Salud UIS. 2020;52(2):83-6. doi: http://dx.doi.org/10.18273/revsal.v52n2-2020001.
40. 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(2):271-280.e8. doi: 10.1016/j.cell.2020.02.052.
41. Ferna?ndez-Serra A, Rubio-Briones B, Garci?a-Casado Z, Solsona E, Lo?pezGuerrero JA. Ca?ncer de pro?stata: la revolucio?n de los genes de fusio?n. Actas Urol Esp. 2011;35(7):420-8.
42. Wambier CA, Goren A. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is likely to be androgen mediated. J Am Acad Dermatol. 2020;S0190-9622(20)30608-3. doi: https://doi.org/10.1016/j.jaad.2020.04.032.
43. Sharifi N, Ryan CJ. Androgen hazards with COVID-19. Endocr Relat Cancer. 2020;27(6):E1-E3. doi: 10.1530/ERC-20-0133.
44. Wang Z, Xu X. scRNA-seq Profiling of Human Testes Reveals the Presence of the ACE2 Receptor, A Target for SARS-CoV-2 Infection in Spermatogonia, Leydig and Sertoli Cells. Cells. 2020;9(4):920. doi:10.3390/cells9040920.
45. Gheblawi M, Wang K, Viveiros A, Nguyen Q, Zhong J, Turner AJ, et al. Angiotensin-Converting Enzyme 2: SARS-CoV-2 Receptor and Regulator of the Renin-Angiotensin System. Circ Res. 2020;126(10):1457-75. doi: 10.1161/CIRCRESAHA.120.317015.
46. Douglas GC, O’Bryan MK, Hedger MP, Lee DK, Yarski MA, Smith AI, et al. The novel angiotensin-converting enzyme (ACE) homolog, ACE2, is selectively expressed by adult Leydig cells of the testis. Endocrinology. 2004;145(10):4703-11. doi: 10.1210/en.2004-0443.
47. Shaw AC, Goldstein DR, Montgomery RR. Age-dependent dysregulation of innate immunity. Nat Rev Immunol. 2013;13(12):875-87. doi: 10.1038/nri3547.
48. Mesa-Villanueva M, Patiño PJ. Receptores tipo Toll: entre el reconocimiento de lo no propio infeccioso y las sen?ales endo?genas de peligro. Inmunología. 2006;25(2):115-30.
49. Kovats S. Estrogen receptors regulate innate immune cells and signaling pathways. Cell Immunol. 2015;294(2):63-9. doi: 10.1016/j.cellimm.2015.01.018.
50. Channappanavar R, Fett C, Mack M, Ten Eyck PP, Meyerholz DK, Perlman S. Sex-based differences in susceptibility to severe acute respiratory syndrome coronavirus infection. J Immunol. 2017;198(10):4046-53. doi: 10.4049/jimmunol.1601896.
51. 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(2):410-6. doi:10.1095/biolreprod.105.044776.
52. Song C, Wang Y, Li W, Hu B, Chen G, Xia P, et al. Absence of 2019 novel coronavirus in semen and testes of COVID-19 patients. Biol Reprod. 2020;ioaa050. doi:10.1093/biolre/ioaa050.
53. Ma L, Xie W, Li D, Shi L, Mao Y, Xiong Y, et al. Effect of SARS-CoV-2 infection upon male gonadal function: A single center-based study. medRxiv. 2020. doi: https://doi.org/10.1101/2020.03.21.20037267.
54. Walker RF, Zakai NA, MacLehose RF, Cowan LT, Adam TJ, Alonso A, et al. Association of testosterone therapy with risk of venous thromboembolism among men with and without hypogonadism. JAMA Intern Med. 2019;180(2):190-7. doi: 10.1001/jamainternmed.2019.5135.
55. La Vignera S, Cannarella R, Condorelli RA , Torre F, Aversa A, Calogero A. Sex-Specific SARS-CoV-2 Mortality: Among Hormone-Modulated ACE2 Expression, Risk of Venous Thromboembolism and Hypovitaminosis D. Int J Mol Sci. 2020;21(8):2948. doi:10.3390/ijms21082948.
56. Goren A, Vaño-Galván S, Wambier CG, McCoy J, Gomez-Zubiaur A, MorenoArrones 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. doi: 10.1111/ jocd.13443.

Covid-19
gónadas
función gonadal masculina
hormonas sexuales
sistema reproductivo