cfpdБюллетень физиологии и патологии дыханияBulletin Physiology and Pathology of Respiration1998-5029Дальневосточный научный центр физиологии и патологии дыхания10.36604/1998-5029-2022-86-120-128cfpd-1063Research ArticleОБЗОРЫREVIEWSРоль эстрогенов в течении и исходах COVID-19 в зависимости от половой принадлежности больныхCOVID-19 and sex differences: role of estrogenhttps://orcid.org/0000-0001-8938-3594ДовжиковаИ. В.DovzhikovaI. V.

Инна Викторовна Довжикова, д-р биол. наук, ведущий научный со­трудник, лаборатория механизмов этиопатогенеза и восстановитель­ных процессов дыхательной системы при неспецифических заболеваниях легких

675000, г. Благовещенск, ул. Калинина, 22

Inna V. Dovzhikova, PhD, DSc (Biol.), Leading Staff Scientist, Labo­ratory of Mechanisms of Etiopathogenesis and Recovery Processes of the Respiratory System at Non-Specific Lung Diseases

22 Kalinina Str., Blagoveshchensk

dov_kova100@rambler.ruhttps://orcid.org/0000-0003-0212-0201АндриевскаяИ. А.AndrievskayaI. A.

Ирина Анатольевна Андриевская, д-р биол. наук, профессор РАН, зав. лабораторией механизмов этиопатогенеза и восстановительных процессов дыхательной системы при неспецифических заболеваниях легких

675000, г. Благовещенск, ул. Калинина, 22

Irina A. Andrievskaya, PhD, DSc (Biol.), Professor of RAS, Head of La­boratory of Mechanisms of Etiopathogenesis and Recovery Processes of the Respiratory System at Non-Specific Lung Diseases

22 Kalinina Str., Blagoveshchensk

irina-andrievskaja@rambler.ruhttps://orcid.org/0000-0002-8329-3237ЛязгиянК. С.LyazgiyanK. S.

Карен Саргисович Лязгиян, аспирант, лаборатория механизмов этиопатогенеза и восстановительных процессов дыхательной си­стемы при неспецифических заболеваниях легких

675000, г. Благовещенск, ул. Калинина, 22

Karen S. Lyazgiyan, Postgraduate Student, Laboratory of Mechanisms of Etiopathogenesis and Recovery Processes of the Respiratory System at Non-Specific Lung Diseases

22 Kalinina Str., Blagoveshchensk

aren@mail.ruФедеральное государственное бюджетное научное учреждение «Дальневосточный научный центр физиологии и патологии дыханияРоссияFar Eastern Scientific Center of Physiology and Pathology of RespirationRussian Federation202223122022086120128Copyright © Довжикова И.В., Андриевская И.А., Лязгиян К.С., 20222022Довжикова И.В., Андриевская И.А., Лязгиян К.С.Dovzhikova I.V., Andrievskaya I.A., Lyazgiyan K.S.This work is licensed under a Creative Commons Attribution 4.0 License.https://cfpd.elpub.ru/jour/article/view/1063Введение

Введение. Во время пандемии COVID-19 были обнаружены половые различия в клиническом тече­нии и исходах заболевания.

Цель

Цель. Обобщение сведений о механизмах, лежащих в основе половых различий при COVID-19 с акцентом на роль эстрогенов.

Материалы и методы

Материалы и методы. Проведено исследование с использованием раз­личных баз данных до сентября 2022 года по ключевым словам «эстрогены» и «COVID-19». Все статьи были опубликованы на английском языке.

Результаты

Результаты. В обзоре обсуждено участие эстрогенов в реализации иммунного ответа при вирусной инфекции. Отдельные разделы статьи посвящены влиянию женских половых гормонов на коагуляцию, воспалительные процессы и ренин-ангиотензиновую систему.

Заключение

Заключение. В конце работы делается вывод о большом потенциале будущих исследований по расшифровке влияния гормонов на физиологию человека для объяснения гетерогенности патогенных реакций человека и планирования стратегии лечения вирусных ин­фекций

Introduction

Introduction. Sex differences in the course and outcomes of the disease were found during the COVID- 19 pandemic.

Aim

Aim. To summarize the knowledge about the mechanisms underlying sex differences in COVID-19, with a focus on the role of estrogen.

Materials and methods

Materials and methods. We conducted a study using various databases until September 2022 for the keywords “estrogen” and “COVID-19”. All articles were published in English.

Results

Results. The review discusses the involvement of estrogen in the implementation of the immune response in viral infection. Individual paragraphs of the article are devoted to the effect of female sex hormones on coagulation, inflammation, and the renin-angiotensin system.

Conclusion

Conclusion. At the end of the paper, it is concluded that there is great potential for future work deciphering hormonal effects on human physiology to explain the heterogeneity in pathogenic responses and may facilitate the development of more effective and personalized interventions.

COVID-19эстрогеныполовые различияCOVID-19estrogenssex differencesReferencesFerretti V.V., Klersy C., Bruno R., Cutti S., Nappi R.E. Men with COVID-19 die. Women survive // Maturitas. 2022. Vol.158. Р.34-36. https://doi.org/10.1016/j.maturitas.2021.11.014Ferretti V.V., Klersy C., Bruno R., Cutti S., Nappi R.E. Men with COVID-19 die. Women survive. Maturitas 2022; 158:34-36. https://doi.org/10.1016/j.maturitas.2021.11.014Rossato M., Andrisani A., Zabeo E., Di Vincenzo A. Men with COVID-19 die. Women survive.. .at any age! // Maturitas. 2022. Vol.163. Р.88. https://doi.org/10.1016/j.maturitas.2022.05.004Rossato M., Andrisani A., Zabeo E., Di Vincenzo A. Men with COVID-19 die. Women survive. ..at any age! Maturitas 2022; 163:88. https://doi.org/10.1016/j.maturitas.2022.05.004The Sex, Gender and COVID-19 Project. Global Health 5050. URL: https://globalhealth5050.org/the-sex-gender-and-covid-19-project/The Sex, Gender and COVID-19 Project. Global Health 5050. Available at: https://globalhealth5050.org/the-sex-gender-and-covid-19-project/Tukiainen T., Villani A.C., Yen A., Rivas M.A., Marshall J.L., Satija R., Aguirre M., Gauthier L., Fleharty M., Kirby A., Cummings B.B., Castel S.E., Karczewski K.J., Aguet F., Byrnes A. et al. Landscape of X chromosome inactivation across human tissues // Nature. 2017. Vol.550, Iss.7675. Р.244-248. https://doi.org/10.1038/nature24265Tukiainen T., Villani A.C., Yen A., Rivas M.A., Marshall J.L., Satija R., Aguirre M., Gauthier L., Fleharty M., Kirby A., Cummings B.B., Castel S.E., Karczewski K.J., Aguet F., Byrnes A. et al.; GTEx Consortium; Laboratory, Data Analysis &Coordinating Center (LDACC)-Analysis Working Group; Statistical Methods groups-Analysis Working Group; Enhancing GTEx (eGTEx) groups; NIH Common Fund; NIH/NCI; NIH/NHGRI; NIH/NIMH; NIH/NIDA; Biospecimen Collection Source Site-NDRI; Biospecimen Collection Source Site-RPCI; Biospecimen Core Resource-VARI; Brain Bank Repository-University of Miami Brain Endowment Bank; Leidos Biomedical-Project Management; ELSI Study; Genome Browser Data Integration &Visualization-EBI; Genome Browser Data Integration &Visualization-UCSC Genomics Institute, University of California Santa Cruz, Lappalainen T., Regev A., Ardlie K.G., Hacohen N., MacArthur D.G. Landscape of X chromosome inactivation across human tissues. Nature 2017; 550(7675):244-248. https://doi.org/10.1038/nature24265Tipnis S.R., Hooper N.M., Hyde R., Karran E., Christie G., Turner A.J. A human homolog of angiotensin-converting enzyme. Cloning and functional expression as a captopril-insensitive carboxypeptidase // J. Biol. Chem. 2000. Vol. 275, Iss.43. Р. 33238-33243. https://doi.org/10.1074/jbc.M002615200Tipnis S.R., Hooper N.M., Hyde R., Karran E., Christie G., Turner A.J. А human homolog of angiotensin-converting enzyme. Cloning and functional expression as a captopril-insensitive carboxypeptidase. J. Biol. Chem. 2000; 275:3323833243. https://doi.org/10.1074/jbc.M002615200Klein S.L., Flanagan K.L. Sex differences in immune responses // Nat. Rev. Immunol. 2016. Vol.16, Iss.10. Р.626-638. https://doi.org/10.1038/nri.2016.90Klein S.L., Flanagan K.L. Sex differences in immune responses. Nat Rev. Immunol. 2016; 16(10):626-638. https://doi.org/10.1038/nri.2016.90Bouman A., Jan Heineman M., Faas M.M. Sex hormones and the immune response in humans // Hum. Reprod. Update. 2005. Vol.11, Iss.4. Р.411-423. https://doi.org/10.1093/humupd/dmi008.Bouman A., Jan Heineman M., Faas M.M. Sex hormones and the immune response in humans. Hum. Reprod. Update 2005; 11(4):411-423. https://doi.org/10.1093/humupd/dmi008Fish E.N. The X-files in immunity: sex-based differences predispose immune responses // Nat. Rev. Immunol. 2008. Vol.8, Iss.9. Р.737-744. https://doi.org/10.1038/nri2394Fish E.N. The X-files in immunity: sex-based differences predispose immune responses. Nat. Rev. Immunol. 2008; 8(9):737-744. https://doi.org/10.1038/nri2394Zhang Z. Genomic biomarker heterogeneities between SARS-CoV-2 and COVID-19 // Vaccines (Basel). 2022. Vol.10, Iss.10. Article number: 1657. https://doi.org/10.3390/vaccines10101657Zhang Z. Genomic biomarker heterogeneities between SARS-CoV-2 and COVID-19. Vaccines (Basel) 2022; 10(10):1657. https://doi.org/10.3390/vaccines10101657Colona V.L., Vasiliou V., Watt J., Novelli G., Reichardt J.K.V. Correction to: Update on human genetic susceptibility to COVID-19: susceptibility to virus and response // Hum. Genomics. 2021. Vol.15, Iss.1. Article number: 59. https://doi.org/10.1186/s40246-021-00360-1Colona V.L., Vasiliou V., Watt J., Novelli G., Reichardt J.K.V. Correction to: Update on human genetic susceptibility to COVID-19: susceptibility to virus and response. Hum. Genomics 2021; 15(1):59. https://doi.org/10.1186/s40246-021-00360-1Kousathanas A., Pairo-Castineira E., Rawlik K., Stuckey A., Odhams C.A., Walker S., Russell C.D., Malinauskas T., Wu Y., Millar J., Shen X., Elliott K.S., Griffiths F., Oosthuyzen W., Morrice K., Keating S., Wang B., Rhodes D., Klaric L. , Zechner M. et al. Whole-genome sequencing reveals host factors underlying critical COVID-19 // Nature. 2022. Vol.607, Iss.7917. Р.97-103. https://doi.org/10.1038/s41586-022-04576-6Kousathanas A., Pairo-Castineira E., Rawlik K., Stuckey A., Odhams C.A., Walker S., Russell C.D., Malinauskas T., Wu Y., Millar J., Shen X., Elliott K.S., Griffiths F., Oosthuyzen W., Morrice K., Keating S., Wang B., Rhodes D., Klaric L., Zechner M., Parkinson N., Siddiq A., Goddard P., Donovan S., Maslove D., Nichol A., Semple M.G., Zainy T., Ma- leady-Crowe F., Todd L., Salehi S., Knight J., Elgar G., Chan G., Arumugam P., Patch C., Rendon A., Bentley D., Kingsley C., Kosmicki J.A., Horowitz J.E., Baras A., Abecasis G.R., Ferreira M.A.R., Justice A., Mirshahi T., Oetjens M., Rader D.J., Ritchie M.D., Verma A., Fowler T.A., Shankar-Hari M., Summers C., Hinds C., Horby P., Ling L., McAuley D., Montgomery H., Openshaw P.J.M., Elliott P., Walsh T., Tenesa A. GenOMICC investigators, 23andMe investigators, COVID-19 Human Genetics Initiative, Fawkes A., Murphy L., Rowan K., Ponting C.P., Vitart V., Wilson J.F., Yang J., Bretherick A.D., Scott R.H., Hendry S.C., Moutsianas L., Law A., Caulfield M.J., Baillie J.K. Whole-genome sequencing reveals host factors underlying critical COVID-19. Nature 2022; 607(7917):97-103. https://doi.org/10.1038/s41586-022- 04576-6Довжикова И.В. Ферменты стероидогенеза (обзор литературы) // Бюллетень физиологии и патологии дыхания. 2010. Вып.37. С.60-64. EDN: MXHHDH.Dovzhikova I.V. [Steroidogenesis enzymes (review)]. Bulleten' fiziologii ipatologii dyhania = Bulletin Physiology and Pathology of Respiration 2010; (37):60-64 (in Russian).Довжикова И.В., Андриевская И.А. Рецепторы эстрогенов (обзор литературы). Часть 1 // Бюллетень физиологии и патологии дыхания. 2019. Вып.72. С.120-127. EDN: WDQNKP. https://doi.org/10.12737/article_5d0ad2e5d54867.15780111Dovzhikova I.V, Andrievskaya I.A. [Estrogen receptors (review)]. Part 1. Bulleten' fiziologii i patologii dyhania = Bulletin Physiology and Pathology of Respiration 2019; (72):120-127 (in Russian). https://doi.org/10.12737/article_5d0ad2e5d54867.15780111Cheskis B.J., Greger J.G., Nagpal S., Freedman L.P. Signaling by estrogens // J. Cell Physiol. 2007. Vol.213, Iss.3. Р.610-617. https://doi.org/10.1002/jcp.21253Cheskis B.J., Greger J.G., Nagpal S., Freedman L.P. Signaling by estrogens. J. Cell Physiol. 2007; 213(3):610-617. https://doi.org/10.1002/jcp.21253Ambhore N.S., Kalidhindi R.S.R., Sathish V. Sex-Steroid signaling in lung diseases and inflammation // Adv. Exp. Med. Biol. 2021. Vol.1303. Р.243-273. https://doi.org/10.1007/978-3-030-63046-1_14Ambhore N.S., Kalidhindi R.S.R., Sathish V. Sex-Steroid signaling in lung diseases and inflammation. Adv. Exp. Med. Biol. 2021; 1303:243-273. https://doi.org/10.1007/978-3-030-63046-1_14Reyes-Garda J., Montano L.M., Carbajal-Garda A., Wang Y.X. Sex hormones and lung inflammation // Adv. Exp. Med. Biol. 2021. Vol.1304. Р.259-321. https://doi.org/10.1007/978-3-030-68748-9_15Reyes-Garda J., Montano L.M., Carbajal-Garda A., Wang Y.X. Sex hormones and lung inflammation. Adv. Exp. Med. Biol. 2021; 1304:259-321. https://doi.org/10.1007/978-3-030-68748-9_15Viveiros A., Rasmuson J., Vu J., Mulvagh S.L., Yip C.Y.Y., Norris C.M., Oudit G.Y. Sex differences in COVID-19: candidate pathways, genetics of ACE2, and sex hormones // Am. J. Physiol. Heart Circ. Physiol. 2021. Vol.320, Iss.1. P.H296-H304. https://doi.org/10.1152/ajpheart.00755.2020Viveiros A., Rasmuson J., Vu J., Mulvagh S.L., Yip C.Y.Y., Norris C.M., Oudit G.Y. Sex differences in COVID-19: candidate pathways, genetics of ACE2, and sex hormones. Am. J. Physiol. Heart Circ. Physiol. 2021; 320(1):H296-H304. https://doi.org/10.1152/ajpheart.00755.2020Fuentes N., Silveyra P. Endocrine regulation of lung disease and inflammation // Exp. Biol. Med (Maywood). 2018. Vol.243, Iss.17-18. Р.1313-1322. https://doi.org/10.1177/1535370218816653Fuentes N., Silveyra P. Endocrine regulation of lung disease and inflammation. Exp. Biol. Med. (Maywood) 2018; 243(17-18):1313-1322. https://doi.org/10.1177/1535370218816653Ghosh S., Klein R.S. Sex drives dimorphic immune responses to viral infections // J. Immunol. 2017. Vol.198, Iss.5. Р.1782-1790. https://doi.org/10.4049/jimmunol.1601166Ghosh S., Klein R.S. Sex drives dimorphic immune responses to viral infections. J. Immunol. 2017; 198(5):1782-1790. https://doi.org/10.4049/jimmunol.1601166Newson L., Manyonda I., Lewis R., Preissner R., Preissner S., Seeland U. Sensitive to Infection but strong in defense-female sex and the power of oestradiol in the COVID-19 Pandemic // Front. Glob. Womens Health. 2021. Vol.2. Article number: 651752. https://doi.org/10.3389/fgwh.2021.651752Newson L., Manyonda I., Lewis R., Preissner R., Preissner S., Seeland U. Sensitive to infection but strong in defense-female sex and the power of oestradiol in the COVID-19 Pandemic. Front. Glob. Womens Health 2021; 2:651752. https://doi.org/10.3389/fgwh.2021.651752Hao S., Zhao J., Zhou J., Zhao S., Hu Y., Hou Y. Modulation of 17beta-estradiol on the number and cytotoxicity of NK cells in vivo related to MCM and activating receptors // Int. Immunopharmacol. 2007. Vol.7, Iss.13. Р.1765-1775. https://doi.org/10.1016/j.intimp.2007.09.017Hao S., Zhao J., Zhou J., Zhao S., Hu Y., Hou Y. Modulation of 17beta-estradiol on the number and cytotoxicity of NK cells in vivo related to MCM and activating receptors. Int. Immunopharmacol. 2007; 7(13):1765-17675. https://doi.org/10.1016/j.intimp.2007.09.017Harding A.T., Heaton N.S. The Impact of estrogens and their receptors on immunity and inflammation during infection // Cancers (Basel). 2022. Vol.14, Iss.4. Article number: 909. https://doi.org/10.3390/cancers14040909Harding A.T., Heaton N.S. The Impact of estrogens and their receptors on immunity and inflammation during Infection. Cancers (Basel) 2022; 14(4):909. https://doi.org/10.3390/cancers14040909Potluri T., Fink A.L., Sylvia K.E., Dhakal S., Vermillion M.S., Vom Steeg L., Deshpande S., Narasimhan H., Klein S.L. Age-associated changes in the impact of sex steroids on influenza vaccine responses in males and females // NPJ Vaccines. 2019. Vol.4. Article number: 29. https://doi.org/10.1038/s41541-019-0124-6Potluri T., Fink A.L., Sylvia K.E., Dhakal S., Vermillion M.S., Vom Steeg L., Deshpande S., Narasimhan H., Klein S.L. Age-associated changes in the impact of sex steroids on influenza vaccine responses in males and females. NPJ Vaccines 2019; 4:29. https://doi.org/10.1038/s41541-019-0124-6Phiel K.L., Henderson R.A., Adelman S.J., Elloso M.M. Differential estrogen receptor gene expression in human peripheral blood mononuclear cell populations // Immunol. Lett. 2005. Vol.97, Iss.1. Р.107-113. https://doi.org/10.1016/j.imlet.2004.10.007Phiel K.L., Henderson R.A., Adelman S.J., Elloso M.M. Differential estrogen receptor gene expression in human peripheral blood mononuclear cell populations. Immunol. Lett. 2005; 97(1):107-113. doi: 10.1016/j.imlet.2004.10.007Breithaupt-Faloppa A.C., Correia C.J., Prado C.M., Stilhano R.S., Ureshino R.P., Moreira L.F.P. 17e-Estradiol, a potential ally to alleviate SARS-CoV-2 infection // Clinics (Sao Paulo). 2020. Vol.75. Article number: e1980. https://doi.org/10.6061/clinics/2020/e1980Breithaupt-Faloppa A.C., Correia C.J., Prado C.M., Stilhano R.S., Ureshino R.P., Moreira L.F.P. 17e-Estradiol, a potential ally to alleviate SARS-CoV-2 infection. Clinics (Sao Paulo) 2020; 75:e1980. https://doi.org/10.6061/clinics/2020/e1980Lipsa A., Prabhu J.S. Gender disparity in COVID-19: Role of sex steroid hormones // Asian Pac. J. Trop. Med. 2021. Vol.14, Iss.1. Р.5-9. https://doi.org/10.4103/1995-7645.304293Lipsa A., Prabhu J.S. Gender disparity in COVID-19: Role of sex steroid hormones. Asian Pac. J. Trop. Med. 2021; 14(1):5-9. https://doi.org/10.4103/1995-7645.304293Takahashi T., Ellingson M.K., Wong P., Israelow B., Lucas C., Klein J., Silva J., Mao T., Oh J.E., Tokuyama M., Lu P., Venkataraman A., Park A., Liu F., Meir A., Sun J., Wang E.Y., Casanovas-Massana A., Wyllie A.L., Vogels C.B.F., Earnest R., Lapidus S., Ott I.M., Moore A.J., Yale IMPACT Research Team, Shaw A., Fournier J.B., Odio C.D., Farhadian S., Dela Cruz C., Grubaugh N.D., Schulz W.L., Ring A.M., Ko A.I., Omer S.B., Iwasaki A. Sex differences in immune responses that underlie COVID-19 disease outcome // Nature. 2020. Vol.588, Iss.7837. Р.315-320. https://doi.org/10.1038/s41586-020-2700-3Takahashi T., Ellingson M.K., Wong P., Israelow B., Lucas C., Klein J., Silva J., Mao T., Oh J.E., Tokuyama M., Lu P., Venkataraman A., Park A., Liu F., Meir A., Sun J., Wang E.Y., Casanovas-Massana A., Wyllie A.L., Vogels C.B.F., Earnest R., Lapidus S., Ott I.M., Moore A.J., Yale IMPACT Research Team, Shaw A., Fournier J.B., Odio C.D., Farhadian S., Dela Cruz C., Grubaugh N.D., Schulz W.L., Ring A.M., Ko A.I., Omer S.B., Iwasaki A. Sex differences in immune responses that underlie COVID-19 disease outcomes. Nature 2020; 588(7837):315-320. https://doi.org/10.1038/s41586- 020-2700-3Haitao T., Vermunt J.V., Abeykoon J., Ghamrawi R., Gunaratne M., Jayachandran M., Narang K., Parashuram S., Suvakov S., Garovic V.D. COVID-19 and sex differences: mechanisms and biomarkers // Mayo Clin. Proc. 2020. Vol.95, Iss.10. Р.2189-2203. https://doi.org/10.1016/j.mayocp.2020.07.024Haitao T., Vermunt J.V., Abeykoon J., Ghamrawi R., Gunaratne M., Jayachandran M., Narang K., Parashuram S., Suvakov S., Garovic V.D. COVID-19 and sex differences: mechanisms and biomarkers. Mayo Clin. Proc. 2020; 95(10): 2189-2203. https://doi.org/10.1016/j.mayocp.2020.07.024Brandi M.L. Are sex hormones promising candidates to explain sex disparities in the COVID-19 pandemic? // Rev. Endocr. Metab. Disord. 2022. Vol.23, Iss.2. Р.171-183. https://doi.org/10.1007/s11154-021-09692-8Brandi M.L. Are sex hormones promising candidates to explain sex disparities in the COVID-19 pandemic? Rev. Endocr. Metab. Disord. 2022; 23(2):171-183. doi: 10.1007/s11154-021-09692-8Al-Lami R.A., Urban R.J., Volpi E., Algburi A.M.A., Baillargeon J. Sex hormones and novel corona virus infectious disease (COVID-19) // Mayo Clin. Proc. 2020. Vol.95, Iss.8. Р.1710-1714. https://doi.org/10.1016/j.mayocp.2020.05.013Al-Lami R.A., Urban R.J., Volpi E., Algburi A.M.A., Baillargeon J. Sex Hormones and novel corona virus infectious disease (COVID-19). Mayo Clin. Proc. 2020; 95(8):1710-1714. https://doi.Org/10.1016/j.mayocp.2020.05.013Mauvais-Jarvis F., Klein S.L., Levin E.R. Estradiol, progesterone, immunomodulation, and COVID-19 outcomes // Endocrinology. 2020. Vol.161, Iss.9. Article number: bqaa127. https://doi.org/10.1210/endocr/bqaa127Mauvais-Jarvis F., Klein S.L., Levin E.R. Estradiol, progesterone, immunomodulation, and COVID-19 Outcomes. Endocrinology 2020; 161(9):bqaa127. https://doi.org/10.1210/endocr/bqaa127Pivonello R., Auriemma R.S., Pivonello C., Isidori A.M., Corona G., Colao A., Millar RP. Sex disparities in COVID- 19 severity and outcome: are men weaker or women stronger? // Neuroendocrinology. 2021. Vol.111, Iss.11. Р.1066-1085. https://doi.org/10.1159/000513346Pivonello R., Auriemma R.S., Pivonello C., Isidori A.M., Corona G., Colao A., Millar R.P. Sex disparities in COVID-19 severity and outcome: are men weaker or women stronger? Neuroendocrinology 2021; 111(11):1066-1085. https://doi.org/10.1159/000513346Connors J.M., Levy J.H. COVID-19 and its implications for thrombosis and anticoagulation // Blood. 2020. Vol.135, Iss.23. Р.2033-2040. https://doi.org/10.1182/blood.2020006000Connors J.M., Levy J.H. COVID-19 and its implications for thrombosis and anticoagulation. Blood 2020; 135(23):2033-2040. https://doi.org/10.1182/blood.2020006000Salzano A., Demelo-Rodriguez P., Marra A.M., Proietti M. A focused review of gender differences in antithrombotic therapy // Curr. Med. Chem. 2017. Vol.24, Iss.24. Р.2576-2588. https://doi.org/10.2174/0929867323666161029223512Salzano A., Demelo-Rodriguez P., Marra A.M., Proietti M. A focused review of gender differences in antithrombotic therapy. Curr. Med. Chem. 2017; 24(24):2576-2588. https://doi.org/10.2174/0929867323666161029223512Emms H., Lewis G.P. Sex and hormonal influences on platelet sensitivity and coagulation in the rat // Br. J. Pharmacol. 1985. Vol.86, Iss.3. Р.557-563. https://doi.org/10.1111/j.1476-5381.1985.tb08931.xEmms H., Lewis G.P. Sex and hormonal influences on platelet sensitivity and coagulation in the rat. Br. J. Pharmacol. 1985; 86(3):557-563. https://doi.org/10.1111/j.1476-5381.1985.tb08931.xNakano Y., Oshima T., Matsuura H., Kajiyama G., Kambe M. Effect of 17beta-estradiol on inhibition of platelet aggregation in vitro is mediated by an increase in NO synthesis // Arterioscler. Thromb. Vasc. Biol. 1998. Vol.18, Iss.6. Р. 961-967. https://doi.Org/10.1161/01.atv.18.6.961Nakano Y., Oshima T., Matsuura H., Kajiyama G., Kambe M. Effect of 17beta-estradiol on inhibition of platelet aggregation in vitro is mediated by an increase in NO synthesis. Arterioscler. Thromb. Vasc. Biol. 1998; 18(6):961-967. https://doi.org/10.1161/01.atv.18.6.961Hoffmann M., Kleine-Weber H., Schroeder S., Kruger N., Herrler T., Erichsen S., Schiergens T.S., Herrler G., Wu N.H., Nitsche A., Muller M.A., Drosten C., Pohlmann S. SARS-CoV-2 Cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor // Cell. 2020. Vol.181, Iss.2. P.271-280.e8. https://doi.org/10.1016/j.cell.2020.02.052Hoffmann M., Kleine-Weber H., Schroeder S., Kruger N., Herrler T., Erichsen S., Schiergens T.S., Herrler G., Wu N.H., Nitsche A., Muller M.A., Drosten C., Pohlmann S. 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. https://doi.org/10.1016/j.cell.2020.02.052Crackower M.A., Sarao R., Oudit G.Y., Yagil C., Kozieradzki I., Scanga S.E., Oliveira-dos-Santos A.J., da Costa J., Zhang L., Pei Y., Scholey J., Ferrario C.M., Manoukian A.S., Chappell M.C., Backx P.H., Yagil Y., Penninger J.M. Angiotensin-converting enzyme 2 is an essential regulator of heart function // Nature. 2002. Vol.417, Iss.6891. Р.822-828. https://doi.org/10.1038/nature00786Crackower M.A., Sarao R., Oudit G.Y., Yagil C., Kozieradzki I., Scanga S.E., Oliveira-dos-Santos A.J., da Costa J., Zhang L., Pei Y., Scholey J., Ferrario C.M., Manoukian A.S., Chappell M.C., Backx P.H., Yagil Y., Penninger J.M. Angiotensin-converting enzyme 2 is an essential regulator of heart function. Nature 2002; 417(6891):822-828. https://doi.org/10.1038/nature00786Mompeon A., Lazaro-Franco M., Bueno-Beti C., Perez-Cremades D., Vidal-Gomez X., Monsalve E., Gironacci M.M., Hermenegildo C., Novella S. Estradiol, acting through ERa, induces endothelial non-classic renin-angiotensin system increasing angiotensin 1-7 production // Mol. Cell. Endocrinol. 2016. Vol.422, P.1-8. https://doi.org/10.1016/j.mce.2015.11.004Mompeon A., Lazaro-Franco M., Bueno-Beti C., Perez-Cremades D., Vidal-Gomez X., Monsalve E., Gironacci M.M., Hermenegildo C., Novella S. Estradiol, acting through ERa, induces endothelial non-classic renin-angiotensin system increasing angiotensin 1-7 production. Mol. Cell. Endocrinol. 2016; 422:1-8. https://doi.org/10.1016/j.mce.2015.11.004La Vignera S., Cannarella R., Condorelli R.A., Torre F., Aversa A., Calogero A.E. Sex-Specific SARS-CoV-2 mortality: among hormone-modulated ACE2 Expression, risk of venous thromboembolism and hypovitaminosis D // Int. J. Mol. Sci. 2020. Vol.21, Iss.8. Article number: 2948. https://doi.org/10.3390/ijms21082948La Vignera S., Cannarella R., Condorelli R.A., Torre F., Aversa A., Calogero A.E. 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. https://doi.org/10.3390/ijms21082948Ohnishi T., Nakamura T., Shima K., Noguchi K., Chiba N., Matsuguchi T. Periodontitis promotes the expression of gingival transmembrane serine protease 2 (TMPRSS2), a priming protease for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) // J. Oral. Biosci. 2022. Vol.64, Iss.2. Р.229-236. https://doi.org/10.1016/j.job.2022.04.004Ohnishi T., Nakamura T., Shima K., Noguchi K., Chiba N., Matsuguchi T. Periodontitis promotes the expression of gingival transmembrane serine protease 2 (TMPRSS2), a priming protease for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). J. Oral Biosci. 2022; 64(2):229-236. https://doi.org/10.1016/j.job.2022.04.004Baristaite G., Gurwitz D. Estradiol reduces ACE2 and TMPRSS2 mRNA levels in A549 human lung epithelial cells. Drug. Dev. Res. 2022. Vol.83, Iss.4. Р.961-966. https://doi.org/10.1002/ddr.21923Baristaite G., Gurwitz D. Estradiol reduces ACE2 and TMPRSS2 mRNA levels in A549 human lung epithelial cells. Drug Dev. Res. 2022; 83(4):961-966. https://doi.org/10.1002/ddr.21923Healy E.F., Lilic M. A model for COVID-19-induced dysregulation of ACE2 shedding by ADAM17 // Biochem. Biophys. Res. Commun. 2021. Vol.573. Р.158-163. https://doi.org/10.1016/j.bbrc.2021.08.040Healy E.F., Lilic M. A model for COVID-19-induced dysregulation of ACE2 shedding by ADAM17. Biochem. Biophys. Res. Commun. 2021; 573:158-163. https://doi.org/10.1016/j.bbrc.2021.08.040

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