Comparing two groups of women with and without endometriosis showed no difference in the frequency of COVID–19 infection. The prevalence of the disease depends on the interaction between the virus and the individual’s immune system. Our studies’ findings represent that women with endometriosis do not have a higher risk of COVID–19 and the risk of COVID–19 infection in these patients are similar to women without endometriosis who referred to the same center for routine Pap smear test. The recent COVID–19 pandemic has forced researchers to focus on the different aspects of this disease, and studying factors that can predispose the individual to disease (20). Studies have investigated the effect of nutrition (21), serum parameters, such as blood group (22) and elevated plasmin(ogen) (23), as well as underlying autoimmune diseases, such as tuberculosis (24) and lupus erythematosus (25), on COVID–19 susceptibility. However, as far as the authors are concerned, the risk of COVID–19 infection in women with endometriosis has not been clinically evaluated, to date.
The endometrial susceptibility to COVID–19 is still under investigation. In a molecular genetic study by Henarejos–Castillo et al., analyzing data of 112 women with normal endometrial cells demonstrated that the lower expression of host proteases, related to SARS–CoV-2 infection, such as ACE2 and TMPRSS2 may result in a lower risk of endometrial susceptibility to COVID–19 infection, but the expression varies in different phases of the menstrual cycle and increases during implantation and in older women (11). It is also assumed that COVID–19 can induce changes in endometrial tissue and affect the female reproductive potential (26). However, the susceptibility of endometrial tissue to COVID–19 has not been confirmed in the clinical setting (14). Studying large databases has shown that the uterine corpus endometrial carcinoma tissue is more susceptible to SARS–CoV-2 infection, which also affected the tumor prognosis after COVID–19 infection (27). Other cancer types, including gastrointestinal and urinary tract tumors have also shown higher susceptibility to COVID–19 infection, attributed to the expression of ACE2 and TMPRSS2 in cancer tissues (22, 28). However, the published articles are expert opinion or molecular based and further clinical studies are required in this regard. It has been previously demonstrated that despite the indefinite pathophysiology of endometriosis, the immune system is considered as a cause of development of endometriosis and several immunologic and inflammatory changes are observed during endometriosis (29). The main immunologic changes during endometriosis include reduction of T cell reactivity, natural killer (NK) cell’s cytotoxicity, increased antibody production, macrophages polarization and inflammatory mediators release (30). The increased infiltration level of immune cells, including B cell, CD4+T cell, neutrophil, and dendritic cells as well as increased expression of ACE2 has been correlated with SARS–CoV-2 susceptibility in endometrial cancer (22). However, such association has not been found in endometriosis and the results of our study showed no difference in susceptibility to COVID–19 infection in endometriosis women, which maybe due to the fact that the inflammatory and immunologic pathways in endometriosis is chronic (31), while that of COVID–19 is acute.
In the current study, it was found that the frequency of COVID–19 symptoms differed between women with and without endometriosis; endometriotic women had a lower frequency of asymptomatic and febrile infection, but higher frequency of other symptoms, including gastrointestinal, dermatologic, hematologic, and neuronal disorders. These results indicated that more attention should be paid to women with endometriosis for diagnosis of COVID–19 infection, as they mainly do not present common symptoms. Of note, many of the asymptomatic cases with COVID–19 infection may be in the development period and present the symptoms in the next few days or present with uncommon symptoms that make diagnosis difficult (32). COVID–19 infection interferes with the antigen-presenting cells in the immune system and creates bilayer vesicles, which can block the expression of Pattern Recognition Receptor (PRR) and, as a result, the patient’s innate immune system does not recognize them and continue to proliferate within the vesicle, they also, disable the production of Type I interferons as one of the most important antiviral factors so it will develop as an asymptomatic disease in some cases (33). Asymptomatic COVID–19 is considered the Achilles’ heel for disease control, due to the strong infectivity and transmission during this period, and the major role of asymptomatic carriers in the person–to–person disease transmission (34). As the clinical signs and computed tomography (CT), imaging do not help much in diagnosing asymptomatic carriers, the best approach to diagnose these people are rt-PCR; however, information on asymptomatic carriers is limited and the mechanism of its occurrence needs further investigation (35). We supposed that the different frequency of asymptomatic COVID–19, lower frequency of fever, and higher frequency of uncommon symptoms in women with endometriosis in the present study can be attributed to the immune interactions during endometriosis (15). It has been previously suggested that patients with immune-mediated inflammatory diseases, such as rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, psoriasis, and inflammatory bowel disease have different disease characteristics of COVID–19 (36). The immune system should fight against SARS–CoV-2 by activation of cellular and innate inflammatory responses (37), which may be altered by the underlying immune dysfunction in the patient (38) and hence cause the different response of women with endometriosis to COVID–19, as shown in the present study. Further molecular studies are required to understand the exact mechanism of this finding. Another important factor affecting COVID–19 disease course is the underlying disease in the patient (39). In our study, the majority of women with endometriosis had no concomitant disease and the frequency of underlying diseases, such as cardiovascular diseases, hypertension, and lupus erythematosus were higher in the control group, which can be another cause for the different symptoms of the two study groups.
We also analyzed factors associated with COVID–19 infection and the results revealed that close contact with a patient infected with COVID–19 was the only risk factor in both groups that resulted in a slightly increased chance (.3– and .2–folds higher odds in the case and control groups, respectively), while other variables such as social distancing, traveling, underlying diseases, thyroid disorders, and endometriosis stage were not associated with COVID–19 infection. As far as no vaccination and definite treatment are available for COVID–19, preventive measures should be considered by everyone to reduce the transmission rate and the prevalence of this epidemic (40). Accordingly, several guidelines have been devised for flattening the curve of COVID–19 (41). As the results of our study showed, close contact with an infected patient was the most important factor for both groups, which indicate the need for increasing the knowledge and awareness of the general population about the necessary precautions to be taken during the current outbreak (42).
The limitations of the present study include the cross-sectional nature of the study and lack of follow–up. Therefore, we could only suggest associations, rather than the causal relationship between the study variables. Furthermore, we matched the control group in terms of age with the case group and selected women were from the same medical center; however, differences in other characteristics between the groups may affect the results. Also, we recruited participants by census method and the nonrandomized patient selection increases the chance of confounders on the results.