Human Reproduction Archives
Human Reproduction Archives
REVIEW ARTICLE Endometriosis

Could endometriosis increase the severity of COVID-19 infection symptoms?

Bhianca Lopes Teixeira, Camila Pereira Almeida, Helen Lima Del Puerto, Enio Ferreira

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Endometriosis is a chronic condition that affects women of reproductive age worldwide. Although the etiology is still uncertain, it has been characterized as endometrial stroma and glands outside the uterus cavity. Evidence suggests that women with this condition have implications like immunological alterations, the frequent presence of comorbidities, and chronic inflammation, which has been described to cause pain and contribute to the disease’s aggravation. Besides that, patients with endometriosis have not been considered a higher-risk group to severe cases of COVID-19. However, the real implications of the infection in patients with endometriosis are still unknown. Since hyper inflammation in endometriosis is related to severe disease cases and exacerbated inflammatory response in COVID-19 may worsen clinical symptoms. Even to patient’s death, the purpose of this review is to correlate inflammation in both conditions, drawing to a possible risk factor related to an exacerbation of inflammatory response in patients with endometriosis followed by COVID-19 infection


COVID-19; Endometriosis; IL-6; Inflammation; Inflammatory response; SARS -CoV-2.


1. World Health Organization. Endometriosis [Internet]. 2021 [cited 2021 May 5]. Available from: fact-sheets/detail/endometriosis

2. Eisenberg VH, Weil C, Chodick G, Shalev V. Epidemiology of endometriosis: a large population-based database study from a healthcare provider with 2 million members. BJOG. 2018;125(1):55-62. PMid:28444957.

3. Johnson NP, Hummelshoj L, Adamson GD, Keckstein J, Taylor HS, Abrao MS, et al. World Endometriosis Society consensus on the classification of endometriosis. Hum Reprod. 2017;32(2):315-24. PMid:27920089.

4. Chapron C, Chopin N, Borghese B, Foulot H, Dousset B, Vacher-Lavenu MC, et al. Deeply infiltrating endometriosis: pathogenetic implications of the anatomical distribution. Hum Reprod. 2006;21(7):1839-45. PMid:16543256.

5. Bobbio A, Canny E, Mansuet Lupo A, Lococo F, Legras A, Magdeleinat P,  et  al. Thoracic endometriosis syndrome other than pneumothorax: clinical and pathological findings. Ann Thorac Surg. 2017;104(6):1865-71. athoracsur.2017.06.049. PMid:29054304.

6. Agostinis C, Balduit A, Mangogna A, Zito G, Romano F, Ricci G, et al. Immunological basis of the endometriosis: the complement system as a potential therapeutic target. Front Immunol. 2021;11:599117. PMid:33505394.

7. Gruenwald P. Origin of endometriosis from the mesenchyme of the celomic walls. Am J Obstet Gynecol. 1942;44(3):470-4. http://

8. Sampson JA. Metastatic or embolic endometriosis, due to the menstrual dissemination of endometrial tissue into the venous circulation*. Am J Pathol. 1927;3(2):93. PMid:19969738.

9. Sampson JA. Peritoneal endometriosis due to the menstrual dissemination of endometrial tissue into the peritoneal cavity. Am J Obstet Gynecol. 1927;14(4):422-69.

10. Zhang P, Sun Y, Zhang C, Yang Y, Zhang L, Wang N, et al. Cesarean scar endometriosis: Presentation of 198 cases and literature review. BMC Womens Health. 2019;19(1):14. PMid:30658623.

11. Nnoaham KE, Hummelshoj L, Webster P, D’Hooghe T, De Cicco Nardone F, De Cicco Nardone C, et al. Impact of endometriosis on quality of life and work productivity: a multicenter study across ten countries. Fertil Steril. 2011;96(2):366-373.e8. http:// PMid:21718982.

12. DiVasta AD, Vitonis AF, Laufer MR, Missmer SA. Spectrum of symptoms in women diagnosed with endometriosis during adolescence vs adulthood. Am J Obstet Gynecol. 2018;218(3):324.e1-11. PMid:29247637.

13. Prescott J, Farland LV, Tobias DK, Gaskins AJ, Spiegelman D, Chavarro JE, et al. A prospective cohort study of endometriosis and subsequent risk of infertility. Hum Reprod. 2016;31(7):1475-82. PMid:27141041.

14. Bellelis P, Dias JA Jr, Podgaec S, Gonzales M, Baracat EC, Abrão MS. Epidemiological and clinical aspects of pelvic endometriosis: a case series. Rev Assoc Med Bras. 2010;56(4):467-71. PMid:20835646.

15. Mu F, Harris HR, Rich-Edwards JW, Hankinson SE, Rimm EB, Spiegelman D, et al. A Prospective Study of Inflammatory Markers and Risk of Endometriosis. Am J Epidemiol. 2018;187(3):515-22. PMid:28992341.

16. Marí-Alexandre J, Barceló-Molina M, Belmonte-López E, García-Oms J, Estellés A, Braza-Boïls A, et al. Micro-RNA profile and proteins in peritoneal fluid from women with endometriosis: their relationship with sterility. Fertil Steril. 2018;109(4):675-684. e2. PMid:29605406.

17. Wang XM, Ma ZY, Song N. Inflammatory cytokines IL-6, IL-10, IL-13, TNF-α and peritoneal fluid flora were associated with infertility in patients with endometriosis. Eur Rev Med Pharmacol Sci. 2018;22(9):2513-8. PMid:29771400.

18. Lin SC, Li YH, Wu MH, Chang YF, Lee DK, Tsai SY, et al. Suppression of COUP-TFII by proinflammatory cytokines contributes to the pathogenesis of endometriosis. J Clin Endocrinol Metab. 2014;99(3):E427-37. PMid:24423359.

19. Tseng JF, Ryan IP, Milam TD, Murai JT, Schriock ED, Landers DV, et al. Interleukin-6 secretion in vitro is up-regulated in ectopic and eutopic endometrial stromal cells from women with endometriosis. J Clin Endocrinol Metab. 1996;81(3):1118-22. PMid:8772585.

20. Králíčková M, Vetvicka V. Immunological aspects of endometriosis: a review. Ann Transl Med. 2015;3(11):153. PMid:26244140.

21. Jaeger-Lansky A, Schmidthaler K, Kuessel L, Gstöttner M, Waidhofer-Söllner P, Zlabinger GJ, et al. Local and systemic levels of cytokines and danger signals in endometriosis-affected women. J Reprod Immunol. 2018;130(June):7-10. jri.2018.07.006. PMid:30099220.

22. Porpora MG, Scaramuzzino S, Sangiuliano C, Piacenti I, Bonanni V, Piccioni MG, et al. High prevalence of autoimmune diseases in women with endometriosis: a case-control study. Gynecol Endocrinol. 2020;36(4):356-9. 0.2019.1655727. PMid:31476950.

23. Sinaii N, Cleary SD, Ballweg ML, Nieman LK, Stratton P. High rates of autoimmune and endocrine disorders, fibromyalgia, chronic fatigue syndrome and atopic diseases among women with endometriosis: a survey analysis. Hum Reprod. 2002;17(10):2715-24. PMid:12351553.

24. Yuk JS, Park EJ, Seo YS, Kim HJ, Kwon SY, Park WI. Graves disease is associated with endometriosis: a 3-year population-based cross-sectional study. Medicine. 2016;95(10):e2975. PMid:26962803.

25. Peng YH, Su SY, Liao WC, Huang CW, Hsu CY, Chen HJ, et al. Asthma is associated with endometriosis: a retrospective populationbased cohort study. Respir Med. 2017;132:112-6. PMid:29229082.

26. Ashkenazi MS, Huseby OL, Kroken G, Soto-Mota A, Pents M, Loschiavo A, et al. COVID-19 pandemic and the consequential effect on patients with endometriosis. Human Reproduction Open. 2022;2022(2):c013. PMid:35386120.

27. Centers for Disease Control and Prevention – CDC. Underlying medical conditions associated with higher risk for severe COVID-19: information for healthcare providers [Internet]. 2021 [cited 2021 Oct 26]. Available from: ncov/hcp/clinical-care/underlyingconditions.html

28. Kompaniyets L, Pennington AF, Goodman AB, Rosenblum HG, Belay B, Ko JY, et al. Underlying medical conditions and severe illness among 540,667 adults hospitalized with COVID-19, march 2020-march 2021. Prev Chronic Dis. 2021;18:E66. http://dx.doi. org/10.5888/pcd18.210123. PMid:34197283.

29. Moazzami B, Chaichian S, Samie S, Zolbin MM, Jesmi F, Akhlaghdoust M, et al. Does endometriosis increase susceptibility to COVID-19 infections? A case-control study in women of reproductive age. BMC Womens Health. 2021;21(1):119. http://dx.doi. org/10.1186/s12905-021-01270-z. PMid:33752656.

30. Gorbalenya AE, Baker SC, Baric RS, de Groot RJ, Drosten C, Gulyaeva AA, et al. The species severe acute respiratory syndromerelated coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nat Microbiol. 2020;5(4):536-44. s41564-020-0695-z. PMid:32123347.

31. Yang P, Ding Y, Xu Z, Pu R, Li P, Yan J, et al. Epidemiological and clinical features of COVID-19 patients with and without pneumonia in Beijing, China. medRxiv. 2020.

32. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497-506. PMid:31986264.

33. Zhang H, Wang CY, Zhou P, Yue H, Du R. Histopathologic changes and SARS-CoV-2 immunostaining in the lung of a patient with COVID-19. Ann Intern Med. 2020;173(4):324. PMid:32805177.

34. Madewell ZJ, Yang Y, Jr IML, Halloran ME, Dean NE. Characteristics of lymphocyte subsets and cytokines in peripheral blood of 123 hospitalized patients with 2019 novel coronavirus pneumonia (NCP). medRxiv. 2020;6(165):1-13.

35. Yoshikawa T, Hill T, Li K, Peters CJ, Tseng C-TK. Severe Acute Respiratory Syndrome (SARS) coronavirus-induced lung epithelial cytokines exacerbate SARS pathogenesis by modulating intrinsic functions of monocyte-derived macrophages and dendritic cells. J Virol. 2009;83(7):3039-48. PMid:19004938.

36. Zhang S, Li L, Shen A, Chen Y, Qi Z. Rational use of tocilizumab in the treatment of novel coronavirus pneumonia. Vol. 40. Clin Drug Investig. 2020;40(6):511-8. PMid:32337664.

37. Atal S, Fatima Z. IL-6 inhibitors in the treatment of serious COVID-19: a promising therapy? Pharmaceut Med. 2020;34(4):223-31. PMid:32535732.

38. Copaescu A, Smibert O, Gibson A, Phillips EJ, Trubiano JA. The role of IL-6 and other mediators in the cytokine storm associated with SARS-CoV-2 infection. J Allergy Clin Immunol. 2020;146(3):518-534.e1. PMid:32896310.

39. Liu F, Li L, Xu M, Wu J, Luo D, Zhu Y, et al. Prognostic value of interleukin-6, C-reactive protein, and procalcitonin in patients with COVID-19. J Clin Virol. 2020;127:104370. PMid:32344321.

40. Galván-Román JM, Rodríguez-García SC, Roy-Vallejo E, Marcos-Jiménez A, Sánchez-Alonso S, Fernández-Díaz C, et al. IL-6 serum levels predict severity and response to tocilizumab in COVID-19: an observational study. J Allergy Clin Immunol. 2021;147(1):72-80. e8. PMid:33010257.

41. Zegeye MM, Lindkvist M, Fälker K, Kumawat AK, Paramel G, Grenegård M, et al. activation of the JAK/STAT3 and PI3K/AKT pathways are crucial for IL-6 trans- response in human vascular endothelial cells. Cell Commun Signal. 2018;16(1):55. http:// PMid:30185178.

42. Villarino AV, Kanno Y, O’Shea JJ. Mechanisms and consequences of Jak-STAT signaling in the immune system. Nat Immunol. 2017;18(4):374-84. PMid:28323260.

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