El sexo como factor de riesgo de la mortalidad por COVID-19. Caso Ecuador

• Adriana Pedreañez Santana Cátedra de Inmunología. Departamento de Microbiología. Escuela de Bioanálisis. Facultad de Medicina. Universidad del Zulia. http://orcid.org/0000-0002-3937-0469
• Jesús Alberto Mosquera Sulbarán, Universidad del Zulia. Facultad de Medicina. Instituto de Investigaciones Clínicas “Dr. Américo Negrette”. Maracaibo. Zulia.
• Nelson Enrique Muñoz Castelo Universidad Nacional del Chimborazo. Facultad de Ciencias de la Salud. Riobamba
• Diego Mauricio Tene Salcan Laboratorio Clínico del Hospital General IESS. Riobamba https://orcid.org/0000-0002-1588-2005
• Jorge Guillermo Robalino Congacha Instituto de Ginecología y Osteoporosis INGINOST. Riobamba https://orcid.org/0000-0002-1588-2005

DOI: https://doi.org/10.5281/zenodo.5175260

Palabras clave: COVID-19, hombres, mortalidad, mujeres, dimorfismo sexual

Resumen

La COVID-19 es una enfermedad caracterizada por un sesgo sexual. Varios estudios han descrito que los hombres tienen mayor tendencia hacia el desarrollo de enfermedad severa y mayor mortalidad. El objetivo de esta investigación fue evaluar si el sexo constituye un factor de riesgo de mortalidad por COVID-19 en Ecuador. Para ello, se analizaron los datos publicados por el Ministerio de Salud Pública de Ecuador tomando en cuenta las cifras totales de fallecidos por COVID-19 y las cifras de fallecidos de acuerdo con la edad, el sexo y la distribución geográfica, desde el 21 de febrero de 2020 hasta el 9 de julio de 2021. Se aplicó el test Chi cuadrado para evaluar la asociación entre las variables, y se calculó la razón de probabilidades (Odds Ratio). En el periodo de tiempo estudiado, el 64.78% de las defunciones correspondieron al sexo masculino mientras que el 35.22% al sexo femenino. Se obtuvo un valor de OR= 1.746; IC: 95% (1.697-1.797); p<0.0001. En conclusión, los resultados indican que en Ecuador el sexo masculino está asociado con una mayor probabilidad de mortalidad debido a la COVID-19

Citas

Guan W, Ni Z, Hu Y, Liang W, Ou C, He J, et al. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med [Internet]. 2020;382(18):1708-20. Disponible en: https://doi.org/10.1056/NEJMoa2002032 DOI: 10.1056/NEJMoa2002032 PMID 32109013 PMCID PMC7092819

Ghebreyesus TA. WHO Director-General’s opening remarks at the media briefing on COVID-19 - 11 March 2020 [Internet]. WHO Director General’s speeches. 2020 [citado 20 de marzo de 2020]. Disponible en: https://www.who.int/director-general/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19---11-march-2020

Wu Z, McGoogan JM. Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention. JAMA [Internet]. 2020;323(13):1239-42. Disponible en: https://doi.org/10.1001/jama.2020.2648 DOI: 10.1001/jama.2020.2648 PMID 32091533

Yang X, Yu Y, Xu J, Shu H, Xia J, Liu H, et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med [Internet]. 2020;8(5):475-81. Disponible en: https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(20)30079-5/fulltext DOI: 10.1016/S2213-2600(20)30079-5 PMID 32105632 PMCID PMC7102538

Ministerio de Salud de Ecuador. Base de datos CoVID-19. 2020 [citado 20 de marzo de 2020] Disponible en https://public.tableau.com/profile/direcci.n.nacional.de.vigilancia.epidemiol.gica.msp#!/vizhome/COVID19ecu_MSP_DNVE/COVID-19MSP

Global Health. The Sex, Gender and COVID-19 [Internet]. Marzo. 2021 [citado 20 de marzo de 2020]. Disponible en: https://globalhealth5050.org/the-sex-gender-and-covid-19-project/

Mo P, Xing Y, Xiao Y, Deng L, Zhao Q, Wang H, et al. Clinical Characteristics of Refractory Coronavirus Disease 2019 in Wuhan, China. Clin Infect Dis [Internet]. 2020; Disponible en: https://doi.org/10.1093/cid/ciaa270 DOI: 10.1093/cid/ciaa270 PMID 32173725 PMCID PMC7184444

Zhao S, Cao P, Chong MKC, Gao D, Lou Y, Ran J, et al. COVID-19 and gender-specific difference: Analysis of public surveillance data in Hong Kong and Shenzhen, China, from January 10 to February 15, 2020. Infect Control Hosp Epidemiol [Internet]. 2020/03/09. 2020;41(6):750-1. Disponible en: https://www.cambridge.org/core/article/covid19-and-genderspecific-difference-analysis-of-public-surveillance-data-in-hong-kong-and-shenzhen-china-from-january-10-to-february-15-2020/D99B2708BAD5983D223E356BA5213D7C DOI: 10.1017/ice.2020.64 PMID 32146921 PMCID PMC7113032

Gargaglioni LH, Marques DA. Let’s talk about sex in the context of COVID-19. J Appl Physiol [Internet]. 2020;128(6):1533-8. Disponible en: https://doi.org/10.1152/japplphysiol.00335.2020 DOI: 10.1152/japplphysiol.00335.2020 PMID 32437244 PMCID: PMC7303729

Conti P, Younes A. Coronavirus COV-19/SARS-CoV-2 affects women less than men: clinical response to viral infection. J Biol Regul Homeost Agents [Internet]. 2020;34(2):339-43. Disponible en: https://www.biolifesas.org/biolife/2020/04/07/coronavirus-cov-19-sars-cov-2-affects-women-less-than-men-clinical-response-to-viral-infection/ DOI: 10.23812/Editorial-Conti-3 PMID 32253888

Cai H. Sex difference and smoking predisposition in patients with COVID-19. Lancet Respir Med [Internet]. 2020;8(4):e20. Disponible en: https://doi.org/10.1016/S2213-2600(20)30117-X DOI: 10.1016/S2213-2600(20)30117-X PMID 32171067 PMCID PMC7103991

Bhopal R. Covid-19 worldwide: we need precise data by age group and sex urgently. BMJ [Internet]. 2020;369:m1366. Disponible en: http://www.bmj.com/content/369/bmj.m1366.abstract DOI: 10.1136/bmj.m1366 PMID 32245830

Wenham C, Smith J, Morgan R. COVID-19: the gendered impacts of the outbreak. Lancet [Internet]. 2020;395(10227):846-8. Disponible en: https://doi.org/10.1016/S0140-6736(20)30526-2 DOI: 10.1016/S0140-6736(20)30526-2 PMID 32151325 PMCID: PMC7124625

Instituto Nacional de Estadística y Censos. Proyecciones Poblacionales [Internet]. 2010 [citado 12 de marzo de 2021]. Disponible en: https://www.ecuadorencifras.gob.ec/proyecciones-poblacionales/

Klein SL, Flanagan KL. Sex differences in immune responses. Nat Rev Immunol [Internet]. 2016;16(10):626-38. Disponible en: https://doi.org/10.1038/nri.2016.90 DOI: 10.1038/nri.2016.90 PMID 27546235

Migeon BR. The Role of X Inactivation and Cellular Mosaicism in Women’s Health and Sex-Specific Diseases. JAMA [Internet]. 2006;295(12):1428-33. Disponible en: https://doi.org/10.1001/jama.295.12.1428 DOI: 10.1001/jama.295.12.1428 PMID 16551715

Bouman A, Heineman MJ, Faas MM. Sex hormones and the immune response in humans. Hum Reprod Update [Internet]. 2005;11(4):411-23. Disponible en: https://doi.org/10.1093/humupd/dmi008 DOI: 10.1093/humupd/dmi008 PMID 15817524

Jaillon S, Berthenet K, Garlanda C. Sexual Dimorphism in Innate Immunity. Clin Rev Allergy Immunol [Internet]. 2019;56(3):308-21. Disponible en: https://doi.org/10.1007/s12016-017-8648-x DOI: 10.1007/s12016-017-8648-x PMID 28963611

Schurz H, Salie M, Tromp G, Hoal EG, Kinnear CJ, Möller M. The X chromosome and sex-specific effects in infectious disease susceptibility. Hum Genomics [Internet]. 2019;13(1):2. Disponible en: https://doi.org/10.1186/s40246-018-0185-z DOI: 10.1186/s40246-018-0185-z PMID 30621780 PMCID PMC6325731

Karlberg J, Chong DSY, Lai WYY. Do Men Have a Higher Case Fatality Rate of Severe Acute Respiratory Syndrome than Women Do? Am J Epidemiol [Internet]. 2004;159(3):229-31. Disponible en: https://doi.org/10.1093/aje/kwh056 DOI: 10.1093/aje/kwh056 PMID 14742282 PMCID: PMC7110237

Leong H-N, Earnest A, Lim H-H, Chin C-F, Tan CSH, Puhaindran ME, et al. SARS in Singapore--predictors of disease severity. Ann Acad Med Singapore [Internet]. 2006;35(5):326-31. Disponible en: https://www.annals.edu.sg/pdf/35VolNo5200606/V35N5p326.pdf PMID 16829999

Alghamdi IG, Hussain II, Almalki SS, Alghamdi MS, Alghamdi MM, El-Sheemy MA. The pattern of Middle East respiratory syndrome coronavirus in Saudi Arabia: a descriptive epidemiological analysis of data from the Saudi Ministry of Health. Int J Gen Med [Internet]. 2014;7:417-23. Disponible en: https://www.dovepress.com/the-pattern-of-middle-east-respiratory-syndrome-coronavirus-in-saudi-a-peer-reviewed-fulltext-article-IJGM DOI: 10.2147/IJGM.S67061 PMID 25187734 PMCID PMC4149400

Abdullah M, Chai P-S, Chong M-Y, Tohit ERM, Ramasamy R, Pei CP, et al. Gender effect on in vitro lymphocyte subset levels of healthy individuals. Cell Immunol [Internet]. 2012;272(2):214-9. Disponible en: https://www.sciencedirect.com/science/article/pii/S000887491100270X DOI: 10.1016/j.cellimm.2011.10.009 PMID 22078320

Hewagama A, Patel D, Yarlagadda S, Strickland FM, Richardson BC. Stronger inflammatory/cytotoxic T-cell response in women identified by microarray analysis. Genes Immun [Internet]. 2009;10(5):509-16. Disponible en: https://doi.org/10.1038/gene.2009.12 DOI: 10.1038/gene.2009.12 PMID 19279650 PMCID: PMC2735332

Voigt EA, Ovsyannikova IG, Kennedy RB, Grill DE, Goergen KM, Schaid DJ, et al. Sex Differences in Older Adults’ Immune Responses to Seasonal Influenza Vaccination. Front Immunol [Internet]. 2019;10:180. Disponible en: https://www.frontiersin.org/article/10.3389/fimmu.2019.00180 DOI: 10.3389/fimmu.2019.00180 PMID 30873150 PMCID: PMC6400991

Terpos E, Trougakos IP, Apostolakou F, Charitaki I, Sklirou AD, Mavrianou N, et al. Age-dependent and gender-dependent antibody responses against SARS-CoV-2 in health workers and octogenarians after vaccination with the BNT162b2 mRNA vaccine. Am J Hematol [Internet]. 2021;96(7):E257-9. Disponible en: https://doi.org/10.1002/ajh.26185 DOI: 10.1002/ajh.26185 PMID 33837984 PMCID PMC8250071

Ziegler SM, Altfeld M. Human Immunodeficiency Virus 1 and Type I Interferons—Where Sex Makes a Difference. Front Immunol [Internet]. 2017;8:1224. Disponible en: https://www.frontiersin.org/article/10.3389/fimmu.2017.01224 DOI: 10.3389/fimmu.2017.01224 PMID 29033943 PMCID PMC5625005

Webb K, Peckham H, Radziszewska A, Menon M, Oliveri P, Simpson F, et al. Sex and Pubertal Differences in the Type 1 Interferon Pathway Associate With Both X Chromosome Number and Serum Sex Hormone Concentration. Front Immunol [Internet]. 2019;9:3167. Disponible en: https://www.frontiersin.org/article/10.3389/fimmu.2018.03167 DOI: 10.3389/fimmu.2018.03167 PMID 30705679 PMCID: PMC6345344

Trouillet-Assant S, Viel S, Gaymard A, Pons S, Richard J-C, Perret M, et al. Type I IFN immunoprofiling in COVID-19 patients. J Allergy Clin Immunol [Internet]. 2020;146(1):206-208. Disponible en: https://doi.org/10.1016/j.jaci.2020.04.029 DOI: 10.1016/j.jaci.2020.04.029 PMID 32360285 PMCID PMC7189845

Laffont S, Rouquié N, Azar P, Seillet C, Plumas J, Aspord C, et al. X-Chromosome Complement and Estrogen Receptor Signaling Independently Contribute to the Enhanced TLR7-Mediated IFN-α Production of Plasmacytoid Dendritic Cells from Women. J Immunol [Internet]. 2014;193(11):5444-52. Disponible en: http://www.jimmunol.org/content/193/11/5444.abstract DOI: 10.4049/jimmunol.1303400 PMID 25339659

Spolarics Z, Peña G, Qin Y, Donnelly RJ, Livingston DH. Inherent X-Linked Genetic Variability and Cellular Mosaicism Unique to Females Contribute to Sex-Related Differences in the Innate Immune Response. Front Immunol [Internet]. 2017;8:1455. Disponible en: https://www.frontiersin.org/article/10.3389/fimmu.2017.01455 DOI: 10.3389/fimmu.2017.01455 PMID 29180997 PMCID: PMC5694032

Bianchi I, Lleo A, Gershwin ME, Invernizzi P. The X chromosome and immune associated genes. J Autoimmun [Internet]. 2012;38(2):J187-92. Disponible en: https://www.sciencedirect.com/science/article/pii/S0896841111001259 DOI: 10.1016/j.jaut.2011.11.012 PMID 22178198

Wang J, Syrett CM, Kramer MC, Basu A, Atchison ML, Anguera MC. Unusual maintenance of X chromosome inactivation predisposes female lymphocytes for increased expression from the inactive X. Proc Natl Acad Sci [Internet]. 2016;113(14):E2029-38. Disponible en: http://www.pnas.org/content/113/14/E2029.abstract DOI: 10.1073/pnas.1520113113 PMID 27001848 PMCID: PMC4833277

Khan D, Ansar Ahmed S. The Immune System Is a Natural Target for Estrogen Action: Opposing Effects of Estrogen in Two Prototypical Autoimmune Diseases. Front Immunol [Internet]. 2016;6:635. Disponible en: https://www.frontiersin.org/article/10.3389/fimmu.2015.00635 DOI: 10.3389/fimmu.2015.00635 PMID 26779182 PMCID PMC4701921

Bernardi AI, Andersson A, Grahnemo L, Nurkkala-Karlsson M, Ohlsson C, Carlsten H, et al. Effects of lasofoxifene and bazedoxifene on B cell development and function. Immunity, Inflamm Dis [Internet]. 2014;2(4):214-25. Disponible en: https://doi.org/10.1002/iid3.37 DOI: 10.1002/iid3.37 PMID 25866629 PMCID: PMC4386916

Jilma B, Eichler HG, Breiteneder H, Wolzt M, Aringer M, Graninger W, et al. Effects of 17 beta-estradiol on circulating adhesion molecules. J Clin Endocrinol Metab [Internet]. 1994;79(6):1619-24. Disponible en: https://doi.org/10.1210/jcem.79.6.7527406 DOI: 10.1210/jcem.79.6.7527406 PMID 7527406

Hou J, Wu FZ. Effect of sex hormones on NK and ADDC activity of mice. Int J Immunopharmacol [Internet]. 1988;10(1):15-22. Disponible en: https://www.sciencedirect.com/science/article/pii/0192056188901452 DOI: 10.1016/0192-0561(88)90145-2 PMID 3366506

D’Agostino P, Milano S, Barbera C, Di Bella G, La Rosa M, Ferlazzo V, et al. Sex Hormones Modulate Inflammatory Mediators Produced by Macrophagesa. Ann N Y Acad Sci [Internet]. 1999;876(1):426-9. Disponible en: https://doi.org/10.1111/j.1749-6632.1999.tb07667.x DOI: 10.1111/j.1749-6632.1999.tb07667.x PMID 10415638

Liva SM, Voskuhl RR. Testosterone Acts Directly on CD4+ T Lymphocytes to Increase IL-10 Production. J Immunol [Internet]. 2001;167(4):2060-7. Disponible en: http://www.jimmunol.org/content/167/4/2060.abstract DOI: 10.4049/jimmunol.167.4.2060 PMID 11489988

Fulop T, Larbi A, Dupuis G, Le Page A, Frost EH, Cohen AA, et al. Immunosenescence and Inflamm-Aging As Two Sides of the Same Coin: Friends or Foes? Front Immunol [Internet]. 2018;8:1960. Disponible en: https://www.frontiersin.org/article/10.3389/fimmu.2017.01960 DOI: 10.3389/fimmu.2017.01960 PMID 29375577 PMCID PMC5767595

Pedreañez Santana AB, Mosquera Sulbarán JA, Muñoz Castelo NE. Envejecimiento inflamatorio e inmunosenescencia, la posible respuesta a la severidad de la COVID-19 en los adultos mayores. Kasmera [Internet]. 2020;48(2):e48233906. Disponible en: https://produccioncientificaluz.org/index.php/kasmera/article/view/33906 DOI: 10.5281/zenodo.4268664

Gubbels Bupp MR. Sex, the aging immune system, and chronic disease. Cell Immunol [Internet]. 2015;294(2):102-10. Disponible en: https://www.sciencedirect.com/science/article/pii/S0008874915000295 DOI: 10.1016/j.cellimm.2015.02.002 PMID: 25700766

Shi Y, Yu X, Zhao H, Wang H, Zhao R, Sheng J. Host susceptibility to severe COVID-19 and establishment of a host risk score: findings of 487 cases outside Wuhan. Crit Care [Internet]. 2020;24(1):108. Disponible en: https://doi.org/10.1186/s13054-020-2833-7 DOI: 10.1186/s13054-020-2833-7 PMID 32188484 PMCID PMC7081524

Wambier CG, Goren A, Vaño-Galván S, Ramos PM, Ossimetha A, Nau G, et al. Androgen sensitivity gateway to COVID-19 disease severity. Drug Dev Res [Internet]. 2020;81(7):771-6. Disponible en: https://doi.org/10.1002/ddr.21688 DOI: 10.1002/ddr.21688 PMID 32412125 PMCID PMC7273095

Hoffmann M, Kleine-Weber H, Schroeder S, Krüger 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 [Internet]. 2020;181(2):271-280. Disponible en: https://doi.org/10.1016/j.cell.2020.02.052 DOI: 10.1016/j.cell.2020.02.052 PMID 32142651 PMCID: PMC7102627

Lucas JM, Heinlein C, Kim T, Hernandez SA, Malik MS, True LD, et al. The Androgen-Regulated Protease TMPRSS2 Activates a Proteolytic Cascade Involving Components of the Tumor Microenvironment and Promotes Prostate Cancer Metastasis. Cancer Discov [Internet]. 2014;4(11):1310-1325. Disponible en: http://cancerdiscovery.aacrjournals.org/content/4/11/1310.abstract DOI: 10.1158/2159-8290.CD-13-1010 PMID 25122198 PMCID: PMC4409786

Morley JE, Kim MJ, Haren MT. Frailty and Hormones. Rev Endocr Metab Disord [Internet]. 2005;6(2):101-8. Disponible en: https://doi.org/10.1007/s11154-005-6722-9 DOI: 10.1007/s11154-005-6722-9 PMID 15843881

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 [Internet]. 2017;242(14):1412-23. Disponible en: https://doi.org/10.1177/1535370217718808 DOI: 10.1177/1535370217718808 PMID 28661206 PMCID: PMC5544171

Salazar M, Barochiner J, Espeche W, Ennis I. COVID-19, hipertensión y enfermedad cardiovascular. Hipertens y Riesgo Vasc [Internet]. 2020;37(4):176-80. Disponible en: https://www.sciencedirect.com/science/article/pii/S1889183720300659 DOI: 10.1016/j.hipert.2020.06.003 PMID 32591283 PMCID: PMC7301092