Does Endometriosis Increase Susceptibility to COVID–19 Infections? A case-control study in Women of Reproductive Age

Does Endometriosis Increase Susceptibility to COVID–19 Infections? 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A case-control study in Women of Reproductive Age Bahram Moazzami, Shahla Chaichian, Saeed Samie, Masoumeh Majidi Zolbin, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-53422/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 22 Mar, 2021 Read the published version in BMC Women's Health → Version 1 posted 9 You are reading this latest preprint version Abstract Background In today’s world, coronavirus disease 2019 (COVID–19) is the most critical health problem and research is continued on studying the associated factors. But it is not clear whether endometriosis increases the risk of COVID–19. Methods Women who referred to the gynecology clinic were evaluated and 507 women with endometriosis (case group) were compared with 520 women without endometriosis (control group). COVID–19 infection, symptoms, exposure, hospitalization, isolation, H1N1 infection and vaccination, and past medical history of the participants were recorded and compared between the groups using IBM SPSS Statistics for Windows version 21. Results Comparison between the groups represent COVID–19 infection in 3.2% of the case group and 3% of the control group (P = .942). The control group had a higher frequency of asymptomatic infection (95.7% vs. 94.5%; P < .001) and fever (1.6% vs. 0%; P = .004), while the frequency of rare symptoms was more common in the case group (P < .001). The average disease period was 14 days in both groups (P = .694). COVID–19 infection was correlated with close contact (r = .331; P < .001 in the case group and r = .244; P .05). Conclusion Endometriosis does not increase the susceptibility to COVID–19 infections, but alters the manifestation of the disease. The prevalence of the disease may depend on the interaction between the virus and the individual’s immune system but further studies are required in this regard. Internal Medicine Preventive Medicine Endometriosis Coronavirus Covid-19 Infections Risk Factors PCR Plain English Summary Coronavirus disease 2019 (COVID–19 infection) is today the most critical health issue, infecting more and more people each day without vaccination or definite treatment. It is thus important to determine the risk factors of COVID–19 infection. Several diseases are considered risk factor for susceptibility to infection or higher severity of COVID–19. Endometriosis is a common benign gynecologic disease and it has been suggested that it may increases the risk of COVID–19 infections, because in both diseases immunologic pathways are involved. In the present study, 507 women with endometriosis (case group) were compared with 520 women without endometriosis (control group) showed that endometriosis is not a risk factor for COVID–19 infection. Background Coronavirus disease 2019 (COVID–19 infection), is one of the most critical pandemics ever, resulting in about a 15% mortality rate in hospitalized patients ( 1 ). As a newly emerging disease, ongoing researches are running on different aspects of the disease; yet, no vaccination or definite treatment has been found ( 2 ). The virus mainly affects the respiratory system, presenting with cough, difficult breathing, pneumonia, and in severe cases, acute respiratory distress syndrome (ARDS), need for intensive care unit (ICU) admission and mechanical ventilation ( 3 ). Some cases of COVID–19 may be complicated by multiple organ failure (MOF) which results in death ( 4 ). Susceptibility of specific organs to COVID–19 has provoked research towards the disease mechanisms ( 5 ), which resulted in identification that the spike glycoprotein (S protein), one of the main structural components of SARS–CoV-2, facilitates binding of envelope viruses to host cells by forming homotrimers protruding on the viral surface, which attracts angiotensin-converting enzyme 2 (ACE 2 ) ( 6 ). Therefore, SARS–CoV-2 can directly damage organs which express ACE 2 , including lungs, heart, kidneys and intestines ( 7 ) and the virus entry through this receptor depends on the cleavage of the S protein, which varies in different virus strains and cell types ( 8 ). ACE 2 protein is also effective in the physiology and pathology of the reproductive system, including the testicles and ovaries, and fertility processes ( 9 ). COVID–19 may also affect the quality and quantity of sperm production, as well as the production of sex hormones, leading to decreased libido ( 10 ). Considering endometrial infection by SARS–CoV, it has been suggested that endometrium has a low risk of COVID–19 infection, due to the low expression of ACE 2 and transmembrane protease serine protease–2 (TMPRSS2), but the expression of these host receptors increase at specific stages of the menstrual cycle and varies based on the woman’s age ( 11 ). Previous studies on the endometrial disease have also determined the presence of ACE 2 in the glandular epithelium, stroma, perivascular space, and endothelium, and its significant increase in endometrial cancer tissue ( 12 , 13 ). Therefore, clinical studies are required to determine the risk of COVID–19 infection in the endometrial tissue ( 14 ). Endometriosis is a common benign gynecologic disease, in which the endometrial tissue is implanted anywhere in the female’s body outside the uterus, most commonly in the abdominal and pelvic cavities ( 15 ). The association of immune system disturbances with the incidence of endometriosis has been discovered previously ( 16 ). It has been suggested that intratracheal endometriosis may induce and/or worsen pulmonary symptoms of COVID–19 infection ( 17 ). An expert opinion has suggested specific treatment guidelines, in order to reduce the susceptibility of endometriosis patients to COVID–19 infection ( 18 ). However, to date, there is no evidence about the risk of COVID–19 infections in patients with endometriosis. Accordingly, the present study aimed to compare the risk of COVID–19 among women with or without endometriosis. Methods Study design The included participants were asked to complete a researcher–designated checklist via email or social networks or cell phone for evaluation of Real-Time polymerase chain reaction (rt-PCR) screening test and symptoms of COVID–19, the recent history of traveling to the high-risk areas, social distancing, relationship with a patient infected with COVID–19, positive COVID–19 rt-PCR Test, isolation due to COVID–19 infection, and hospitalization due to COVID–19. History of H1N1 infection and vaccination during last year, and a positive history of medical diseases. The symptoms included fever, sore throat, nasal congestion, cough, shortness of breath, headache, weakness and muscle pain, reduced sense of smell and/or taste, ocular problems, and other (including gastrointestinal, skin, hematologic, and neuronal) complications. Patients, younger than 18 or older than 45 were excluded from the study. This study was designed as a case-control study and conducted at Pars general hospital from May 21st to July 3rd, 2020. The study the population consisted of women with histologic confirmation of endometriosis (extracted sample during laparoscopy), compared with an age-matched control group, selected from women without endometriosis who referred to the gynecologic clinic for screening Pap smear test and had no complaints of any symptom related to endometriosis. The sample size of the study was considered at a minimum of 500 in each group, considering the estimated period prevalence of COVID–19 of 13% in the population, based on the study by Signorelli and colleagues ( 19 ), the power of the study was 80% and an alpha error of .05. The researcher selected the eligible participants according to the inclusion criteria, explained the study design and objectives to the eligible participants, and asked them to read and sign the written informed consent, and included the eligible participants (who gave consent) into the study by census method. The protocol of the present study was approved by the Ethics Committee of Pars Advanced and Minimally Invasive Medical Manners research center, Pars Hospital, Tehran, Iran. (code: 99G5018). Statistical analysis For describing the categorical variables, frequency (percentage) was reported. For numeric variables, first, Kolmogorov–Smirnov test was used to assess the normal distribution of data and according to the results of this test, the numeric variables were described by mean ± standard deviation (SD) or median and compared between the groups using independent t-test or Mann–Whitney U test, whenever the data did not appear to have normal distribution or when the assumption of equal variances was violated across the study groups. Categorical variables were, on the other hand, compared using chi-square or Fisher’s exact test. The association of variables was tested by Spearman’s correlation coefficient. For the statistical analysis, the statistical software IBM SPSS Statistics for Windows version 21.0 (IBM Corp. 2012. Armonk, NY: IBM Corp.) was used. P values of .05 or less were considered statistically significant. Results A total of 507 women were evaluated in the case group and 520 women in the control group. The mean ± SD of the women’s age was 29.08 ± 14.29 in the case group and 33.00 ± 7.06 in the control group (P = .379). The majority of the case group had stage IV endometriosis (N = 110, 63.2%), 17.2% had stage III (N = 30), 8% had stage II (N = 14), 11.4% had stage I endometriosis (N = 20). In the case group, 18.3% (N = 93) had a positive history of infertility. The results of comparing the COVID–19 characteristics between the case and control groups, as shown in Table 1 , showed no difference between the groups in terms of COVID–19 infection (P = .942), frequency of H1N1 vaccination, recent traveling to high-risk provinces, social distancing, close contact with an infected patient, as well as the frequency of performing screening test, admission and isolation due to COVID–19 (P > .05); but, the frequency of symptoms (P < .05) and H1N1 infection were significantly different between the groups (P < .001). As shown in Table 1 , the frequency of asymptomatic cases and the frequency of fever was higher in the control group (P < .001 and .004, respectively), and the frequency of other symptoms was higher in the case group (P < .001). The average disease period was 14 days in both groups (P = .694). Table 1 The results of comparing the coronavirus disease characteristics between the case and control groups Case group (N = 507) Control group (N = 520) p–value Variable Categories Number Percent Number Percent H1N1 infection No 462 91.1 490 2.0 < .001 * Yes 44 8.7 10 2.0 H1N1 vaccine No 488 96.3 495 97.4 .212 * Yes 18 3.6 13 2.6 Travel No 470 92.7 370 69.7 .059 * Yes 36 7.1 24 4.5 Social distancing No 397 78.3 267 67.8 .256 * Yes 109 21.5 127 32.2 Close contact No 475 93.7 358 91.8 .979 * Yes 31 6.1 32 8.2 COVID–19 infection No 490 96.6 515 97 .942 * Yes 16 3.2 16 3 symptoms None 479 94.5 508 95.7 < .001 * Fever 0 0 8 1.6 .004 † Sore throat 7 1.4 6 1.2 .745 * Nasal congestion 8 1.6 2 .4 .050 * Cough 7 1.4 6 1.2 .747 * Shortness of breath 8 1.6 6 1.2 .558 * Headache 4 .8 3 .6 .486 * Weakness and muscle pain 5 1.0 13 2.6 .094 * Reduced sense of smell and/or taste 9 1.8 7 1.4 .622 * Ocular problems 4 .8 1 .2 .179 † Other 11 2.2 0 0 < .001 † Screening No 477 94.1 476 89.6 .137 * Yes 29 5.7 42 7.9 Admission No 505 99.6 520 100 .494 † Yes 1 .2 0 0 Isolation No 493 97.2 420 97.2 .790 * Yes 13 2.6 12 2.8 Results of: * Chi square test, †: Fisher’s exact test The frequency of underlying diseases is shown in Table 2 . As demonstrated in this table, 80.5% in the case group and 72.3% in the control had no underlying disease (P = .002) and the frequency of diabetes mellitus (P = .038), cardiovascular disease, hypertension, and lupus erythematosus were higher in the control (all P < .001; Table 2 ). Table 2 The results of comparing the frequency of underlying diseases between the study groups Case group (N = 507) Control group (N = 520) P–value Frequency Percent Frequency Percent None 408 80.5 376 72.3 .002 * Thyroid disease 5 .98 3 .57 .501 † Diabetes mellitus 11 2.2 23 4.6 .038 * Cardiovascular disease 2 .4 36 7.2 < .001 * Hypertension 13 2.6 42 8.4 < .001 * Asthma 1 .2 6 1.2 .124† Allergy 13 2.6 23 4.6 .057 * Cancer 5 1.0 11 2.2 .097 * Sinusitis 6 1.2 2 .4 .173† Lupus erythematosus 2 .4 6 1.2 .156† Rheumatoid arthritis 4 .8 26 5.2 < .001† Other 18 3.6 24 4.8 .314 * Results of: * Chi-square test, †Fisher’s exact test Studying the association of the study variables with COVID–19 infection identified close contact with a patient infected with COVID–19 as a significant risk factor, both in the case (r = .331, P < .001) and the control group (r = .244, P .05; Table 3 ). Table 3 The association of COVID–19 infections with the study variables in each study group COVID–19–positive cases in the case group (N = 16) COVID–19–positive cases in the control group (N = 16) N (%) Pearson’s coefficient p-value N (%) Pearson’s coefficient p-value Underlying diseases Diabetes mellitus – .108 .611 1 (6.2%) .202 .533 Cardiovascular disease – 1 (6.2%) Hypertension – 2 (12.5%) Asthma – 1 (6.2%) Allergy – 1 (6.2%) Rheumatoid arthritis 2 (12.5%) 1 (6.2%) Thyroid disease 5 (31%) .032 .471 3 (18.6%) .026 .588 Admission due to COVID–19 1 (6.2%) .246 < .001 0 – – H1N1 vaccination 1 (6.2%) .026 .445 13 (81.2%) .026 .554 Travel 1 (6.2%) .006 1.000 4 (25%) .803 .465 Social distancing 5 (31%) .043 .355 4 (25%) .089 .510 Close contact 8 (50%) .331 < .001 6 (37.5%) .244 < .001 Discussion 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 ACE 2 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 ACE 2 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 ACE 2 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. Conclusions The results of the present study showed that endometriosis does not increase the susceptibility to COVID–19 infection, but changes the presenting symptoms. Therefore, more attention should be paid for accurate diagnosis of COVID–19 in women with endometriosis. The lower rate of fever and higher rate of uncommon symptoms in women with endometriosis may be due to the immune interactions of these two diseases. Since the exact mechanism of infection with this virus is not fully understood and no specific drug or vaccine has been designed for it so far, the most important task at present is to eliminate the transmission cycle. Identifying the predisposing factors can help diagnose the high-risk patients and achieve this aim. Abbreviations COVID–19 infection: Coronavirus disease 2019 ARDS: acute respiratory distress syndrome ICU: intensive care unit MOF: multiple organ failure ACE 2 : angiotensin-converting enzyme 2 TMPRSS2: transmembrane protease serine protease–2 rt-PCR: Real-Time polymerase chain reaction SD: standard deviation NK: natural killer PRR: Pattern Recognition Receptor CT: computed tomography Declarations Ethics approval and consent to participate: Written informed was obtained from the participants. Consent for publication: All participants gave consent for anonymous publication of their results. Availability of data and materials: Available upon request. Competing interests: The authors of the present study declare that they have no competing interests. Funding: This study is supported by, Pars General hospital, Tehran, Iran. The funder had role in data collection, but had no role in decision to publish, or preparation of the manuscript. 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Cite Share Download PDF Status: Published Journal Publication published 22 Mar, 2021 Read the published version in BMC Women's Health → Version 1 posted Editorial decision: Major revision 22 Nov, 2020 Review # 2 received at journal 21 Nov, 2020 Review # 1 received at journal 15 Nov, 2020 Reviewer # 2 agreed at journal 01 Nov, 2020 Reviewer # 1 agreed at journal 25 Oct, 2020 Reviewers invited by journal 02 Oct, 2020 Editor assigned by journal 01 Oct, 2020 Submission checks completed at journal 28 Sep, 2020 Editor invited by journal 24 Sep, 2020 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-53422","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research article","associatedPublications":[],"authors":[{"id":2851569,"identity":"f51a69af-cdc6-4305-a498-938d90fbcdf9","order_by":0,"name":"Bahram Moazzami","email":"","orcid":"","institution":"Iran University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Bahram","middleName":"","lastName":"Moazzami","suffix":""},{"id":2851570,"identity":"a469f00b-baa0-4747-8c75-f29c12e3f2f2","order_by":1,"name":"Shahla Chaichian","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA6klEQVRIiWNgGAWjYDACCQY2BgYDhgQgyfgAyOfhI0ULswFICxtxWhgYEoCYTQLEIqhFfnbzswc/Cuzy+NjPHqv8mmMnw8bA/PDRDTxaDO4cMzfsMUguZuPJS7stuy0Z6DA2Y+McfFokctgkeAwOJLYx5JjdltzGDNTCwyaNT4v8jBw2yT8gLfxvzIolt9UT1sJwI4dNGmyLRI4Z48dthwlrMbiRZiYtY5AM1PLGWJpx23EeNmYCfpGfkfxM8s0fu8T5/TmGH39uq7bnZ29++Bivw5ABMw+YJFY5CDD+IEX1KBgFo2AUjBgAADIVP7PZNAoJAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0001-5772-8711","institution":"Iran University of Medical Sciences","correspondingAuthor":true,"prefix":"","firstName":"Shahla","middleName":"","lastName":"Chaichian","suffix":""},{"id":2851571,"identity":"b5d7a6d1-b899-49ea-95fd-03b876b7405a","order_by":2,"name":"Saeed Samie","email":"","orcid":"","institution":"Iran University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Saeed","middleName":"","lastName":"Samie","suffix":""},{"id":2851572,"identity":"04552faf-716e-4bd2-aba7-bd7a12b50a81","order_by":3,"name":"Masoumeh Majidi Zolbin","email":"","orcid":"","institution":"Tehran University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Masoumeh","middleName":"Majidi","lastName":"Zolbin","suffix":""},{"id":2851573,"identity":"2841ece5-45c3-4718-961c-9e52b07a3fc7","order_by":4,"name":"Fatemeh Jesmi","email":"","orcid":"","institution":"Iran University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Fatemeh","middleName":"","lastName":"Jesmi","suffix":""},{"id":2851574,"identity":"ee5f13cf-6b58-46b1-ae2d-322377ddb61c","order_by":5,"name":"Meisam Akhlaghdoust","email":"","orcid":"","institution":"Iran University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Meisam","middleName":"","lastName":"Akhlaghdoust","suffix":""},{"id":2851575,"identity":"b6788127-d43f-49f0-8e19-0ac050266808","order_by":6,"name":"Mahin Ahmadi Pishkuhi","email":"","orcid":"","institution":"Tehran University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Mahin","middleName":"Ahmadi","lastName":"Pishkuhi","suffix":""},{"id":2851576,"identity":"cbb53ccd-2b73-47fb-b68f-139af79b6af0","order_by":7,"name":"Zahra Sadat Mirshafiei","email":"","orcid":"","institution":"Iran University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Zahra","middleName":"Sadat","lastName":"Mirshafiei","suffix":""},{"id":2851577,"identity":"d548fe0d-d267-4d17-a749-734ec54e9a29","order_by":8,"name":"Fereshteh Khalilzadeh","email":"","orcid":"","institution":"Iran University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Fereshteh","middleName":"","lastName":"Khalilzadeh","suffix":""},{"id":2851578,"identity":"8576e3ad-5d4d-4e62-a689-fe404b4a822a","order_by":9,"name":"Dorsa Safari","email":"","orcid":"","institution":"Iran University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Dorsa","middleName":"","lastName":"Safari","suffix":""}],"badges":[],"createdAt":"2020-08-04 11:18:12","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-53422/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-53422/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12905-021-01270-z","type":"published","date":"2021-03-22T15:00:32+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":13597830,"identity":"14e9a63b-0215-4143-848d-a40e1e192819","added_by":"auto","created_at":"2021-09-17 05:33:42","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":538796,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-53422/v1/d53d20d5-b63b-468d-bfaa-503ba7958d83.pdf"}],"financialInterests":"","formattedTitle":"Does Endometriosis Increase Susceptibility to COVID–19 Infections? A case-control study in Women of Reproductive Age","fulltext":[{"header":"Plain English Summary","content":"Coronavirus disease 2019 (COVID–19 infection) is today the most critical health issue, infecting more and more people each day without vaccination or definite treatment. It is thus important to determine the risk factors of COVID–19 infection. Several diseases are considered risk factor for susceptibility to infection or higher severity of COVID–19. Endometriosis is a common benign gynecologic disease and it has been suggested that it may increases the risk of COVID–19 infections, because in both diseases immunologic pathways are involved. In the present study, 507 women with endometriosis (case group) were compared with 520 women without endometriosis (control group) showed that endometriosis is not a risk factor for COVID–19 infection."},{"header":"Background","content":" \u003cp\u003eCoronavirus disease 2019 (COVID\u0026ndash;19 infection), is one of the most critical pandemics ever, resulting in about a 15% mortality rate in hospitalized patients (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). As a newly emerging disease, ongoing researches are running on different aspects of the disease; yet, no vaccination or definite treatment has been found (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). The virus mainly affects the respiratory system, presenting with cough, difficult breathing, pneumonia, and in severe cases, acute respiratory distress syndrome (ARDS), need for intensive care unit (ICU) admission and mechanical ventilation (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Some cases of COVID\u0026ndash;19 may be complicated by multiple organ failure (MOF) which results in death (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eSusceptibility of specific organs to COVID\u0026ndash;19 has provoked research towards the disease mechanisms (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e), which resulted in identification that the spike glycoprotein (S protein), one of the main structural components of SARS\u0026ndash;CoV-2, facilitates binding of envelope viruses to host cells by forming homotrimers protruding on the viral surface, which attracts angiotensin-converting enzyme 2 (ACE\u003csub\u003e2\u003c/sub\u003e) (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Therefore, SARS\u0026ndash;CoV-2 can directly damage organs which express ACE\u003csub\u003e2\u003c/sub\u003e, including lungs, heart, kidneys and intestines (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e) and the virus entry through this receptor depends on the cleavage of the S protein, which varies in different virus strains and cell types (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eACE\u003csub\u003e2\u003c/sub\u003e protein is also effective in the physiology and pathology of the reproductive system, including the testicles and ovaries, and fertility processes (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). COVID\u0026ndash;19 may also affect the quality and quantity of sperm production, as well as the production of sex hormones, leading to decreased libido (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). Considering endometrial infection by SARS\u0026ndash;CoV, it has been suggested that endometrium has a low risk of COVID\u0026ndash;19 infection, due to the low expression of ACE\u003csub\u003e2\u003c/sub\u003e and transmembrane protease serine protease\u0026ndash;2 (TMPRSS2), but the expression of these host receptors increase at specific stages of the menstrual cycle and varies based on the woman\u0026rsquo;s age (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). Previous studies on the endometrial disease have also determined the presence of ACE\u003csub\u003e2\u003c/sub\u003e in the glandular epithelium, stroma, perivascular space, and endothelium, and its significant increase in endometrial cancer tissue (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). Therefore, clinical studies are required to determine the risk of COVID\u0026ndash;19 infection in the endometrial tissue (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eEndometriosis is a common benign gynecologic disease, in which the endometrial tissue is implanted anywhere in the female\u0026rsquo;s body outside the uterus, most commonly in the abdominal and pelvic cavities (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). The association of immune system disturbances with the incidence of endometriosis has been discovered previously (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). It has been suggested that intratracheal endometriosis may induce and/or worsen pulmonary symptoms of COVID\u0026ndash;19 infection (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). An expert opinion has suggested specific treatment guidelines, in order to reduce the susceptibility of endometriosis patients to COVID\u0026ndash;19 infection (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). However, to date, there is no evidence about the risk of COVID\u0026ndash;19 infections in patients with endometriosis. Accordingly, the present study aimed to compare the risk of COVID\u0026ndash;19 among women with or without endometriosis.\u003c/p\u003e "},{"header":"Methods","content":"\u003cdiv id=\"Sec2\" class=\"Section2\"\u003e \u003cdiv id=\"Sec3\" class=\"Section3\"\u003e \u003ch2\u003eStudy design\u003c/h2\u003e \u003cp\u003eThe included participants were asked to complete a researcher\u0026ndash;designated checklist via email or social networks or cell phone for evaluation of Real-Time polymerase chain reaction (rt-PCR) screening test and symptoms of COVID\u0026ndash;19, the recent history of traveling to the high-risk areas, social distancing, relationship with a patient infected with COVID\u0026ndash;19, positive COVID\u0026ndash;19 rt-PCR Test, isolation due to COVID\u0026ndash;19 infection, and hospitalization due to COVID\u0026ndash;19. History of H1N1 infection and vaccination during last year, and a positive history of medical diseases. The symptoms included fever, sore throat, nasal congestion, cough, shortness of breath, headache, weakness and muscle pain, reduced sense of smell and/or taste, ocular problems, and other (including gastrointestinal, skin, hematologic, and neuronal) complications. Patients, younger than 18 or older than 45 were excluded from the study.\u003c/p\u003e \u003cp\u003eThis study was designed as a case-control study and conducted at Pars general hospital from May 21st to July 3rd, 2020. The study the population consisted of women with histologic confirmation of endometriosis (extracted sample during laparoscopy), compared with an age-matched control group, selected from women without endometriosis who referred to the gynecologic clinic for screening Pap smear test and had no complaints of any symptom related to endometriosis. The sample size of the study was considered at a minimum of 500 in each group, considering the estimated period prevalence of COVID\u0026ndash;19 of 13% in the population, based on the study by Signorelli and colleagues (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e), the power of the study was 80% and an alpha error of .05. The researcher selected the eligible participants according to the inclusion criteria, explained the study design and objectives to the eligible participants, and asked them to read and sign the written informed consent, and included the eligible participants (who gave consent) into the study by census method. The protocol of the present study was approved by the Ethics Committee of Pars Advanced and Minimally Invasive Medical Manners research center, Pars Hospital, Tehran, Iran. (code: 99G5018).\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eFor describing the categorical variables, frequency (percentage) was reported. For numeric variables, first, Kolmogorov\u0026ndash;Smirnov test was used to assess the normal distribution of data and according to the results of this test, the numeric variables were described by mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD) or median and compared between the groups using independent \u003cem\u003et-test\u003c/em\u003e or Mann\u0026ndash;Whitney U test, whenever the data did not appear to have normal distribution or when the assumption of equal variances was violated across the study groups. Categorical variables were, on the other hand, compared using chi-square or Fisher\u0026rsquo;s exact test. The association of variables was tested by Spearman\u0026rsquo;s correlation coefficient. For the statistical analysis, the statistical software IBM SPSS Statistics for Windows version 21.0 (IBM Corp. 2012. Armonk, NY: IBM Corp.) was used. P values of .05 or less were considered statistically significant.\u003c/p\u003e \u003c/div\u003e "},{"header":"Results","content":" \u003cp\u003eA total of 507 women were evaluated in the case group and 520 women in the control group. The mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD of the women\u0026rsquo;s age was 29.08\u0026thinsp;\u0026plusmn;\u0026thinsp;14.29 in the case group and 33.00\u0026thinsp;\u0026plusmn;\u0026thinsp;7.06 in the control group (P\u0026thinsp;=\u0026thinsp;.379). The majority of the case group had stage IV endometriosis (N\u0026thinsp;=\u0026thinsp;110, 63.2%), 17.2% had stage III (N\u0026thinsp;=\u0026thinsp;30), 8% had stage II (N\u0026thinsp;=\u0026thinsp;14), 11.4% had stage I endometriosis (N\u0026thinsp;=\u0026thinsp;20). In the case group, 18.3% (N\u0026thinsp;=\u0026thinsp;93) had a positive history of infertility.\u003c/p\u003e \u003cp\u003eThe results of comparing the COVID\u0026ndash;19 characteristics between the case and control groups, as shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, showed no difference between the groups in terms of COVID\u0026ndash;19 infection (P\u0026thinsp;=\u0026thinsp;.942), frequency of H1N1 vaccination, recent traveling to high-risk provinces, social distancing, close contact with an infected patient, as well as the frequency of performing screening test, admission and isolation due to COVID\u0026ndash;19 (P\u0026thinsp;\u0026gt;\u0026thinsp;.05); but, the frequency of symptoms (P\u0026thinsp;\u0026lt;\u0026thinsp;.05) and H1N1 infection were significantly different between the groups (P\u0026thinsp;\u0026lt;\u0026thinsp;.001). As shown in Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, the frequency of asymptomatic cases and the frequency of fever was higher in the control group (P\u0026thinsp;\u0026lt;\u0026thinsp;.001 and .004, respectively), and the frequency of other symptoms was higher in the case group (P\u0026thinsp;\u0026lt;\u0026thinsp;.001). The average disease period was 14 days in both groups (P\u0026thinsp;=\u0026thinsp;.694).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThe results of comparing the coronavirus disease characteristics between the case and control groups\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eCase group (N\u0026thinsp;=\u0026thinsp;507)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eControl group 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\u003cp\u003e97.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e.212\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eYes\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eTravel\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eNo\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e470\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e92.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e370\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e69.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e.059\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eYes\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eSocial distancing\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eNo\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e397\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e78.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e267\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e67.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e.256\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eYes\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e109\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e127\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e32.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eClose contact\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eNo\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e475\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e93.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e358\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e91.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e.979\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eYes\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e8.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eCOVID\u0026ndash;19 infection\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eNo\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e490\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e96.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e515\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e97\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e.942\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eYes\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"10\" rowspan=\"11\"\u003e \u003cp\u003e\u003cb\u003esymptoms\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eNone\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e479\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e94.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e508\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e95.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eFever\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e.004\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eSore throat\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e.745\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eNasal congestion\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e.050\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eCough\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e.747\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eShortness of breath\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e.558\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eHeadache\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e.486\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eWeakness and muscle pain\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e.094\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eReduced sense of smell and/or taste\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e.622\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eOcular problems\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e.179\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eOther\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eScreening\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eNo\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e477\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e94.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e476\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e89.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e.137\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eYes\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e7.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eAdmission\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eNo\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e505\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e99.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e520\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e.494\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eYes\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eIsolation\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eNo\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e493\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e97.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e420\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e97.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e.790\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eYes\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eResults of: \u003csup\u003e*\u003c/sup\u003eChi square test, \u0026dagger;: Fisher\u0026rsquo;s exact test\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe frequency of underlying diseases is shown in Table \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. As demonstrated in this table, 80.5% in the case group and 72.3% in the control had no underlying disease (P\u0026thinsp;=\u0026thinsp;.002) and the frequency of diabetes mellitus (P\u0026thinsp;=\u0026thinsp;.038), cardiovascular disease, hypertension, and lupus erythematosus were higher in the control (all P\u0026thinsp;\u0026lt;\u0026thinsp;.001; Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThe results of comparing the frequency of underlying diseases between the study groups\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eCase group (N\u0026thinsp;=\u0026thinsp;507)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eControl group (N\u0026thinsp;=\u0026thinsp;520)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eP\u0026ndash;value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eFrequency\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003ePercent\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003eFrequency\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003ePercent\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNone\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e408\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e80.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e376\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e72.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e.002\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eThyroid disease\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e.98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e.501\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDiabetes mellitus\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e.038\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCardiovascular disease\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e7.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHypertension\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e8.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAsthma\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e.124\u0026dagger;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAllergy\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e.057\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCancer\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e.097\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSinusitis\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e.173\u0026dagger;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLupus erythematosus\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e.156\u0026dagger;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRheumatoid arthritis\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e5.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u0026dagger;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eOther\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e.314\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eResults of: \u003csup\u003e*\u003c/sup\u003eChi-square test, \u0026dagger;Fisher\u0026rsquo;s exact test\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eStudying the association of the study variables with COVID\u0026ndash;19 infection identified close contact with a patient infected with COVID\u0026ndash;19 as a significant risk factor, both in the case (r\u0026thinsp;=\u0026thinsp;.331, P\u0026thinsp;\u0026lt;\u0026thinsp;.001) and the control group (r\u0026thinsp;=\u0026thinsp;.244, P\u0026thinsp;\u0026lt;\u0026thinsp;.001), while other variables such as social distancing, traveling, underlying diseases, thyroid disease, and endometriosis stage were not associated with COVID\u0026ndash;19 infection (P\u0026thinsp;\u0026gt;\u0026thinsp;.05; Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThe association of COVID\u0026ndash;19 infections with the study variables in each study group\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003e \u003cp\u003eCOVID\u0026ndash;19\u0026ndash;positive cases in the case group (N\u0026thinsp;=\u0026thinsp;16)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e \u003cp\u003eCOVID\u0026ndash;19\u0026ndash;positive cases in the control group (N\u0026thinsp;=\u0026thinsp;16)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eN (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003ePearson\u0026rsquo;s coefficient\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003ep-value\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003eN (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003ePearson\u0026rsquo;s coefficient\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003ep-value\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"5\" rowspan=\"6\"\u003e \u003cp\u003e\u003cb\u003eUnderlying diseases\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eDiabetes mellitus\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026ndash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"5\" rowspan=\"6\"\u003e \u003cp\u003e.108\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"5\" rowspan=\"6\"\u003e \u003cp\u003e.611\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1 (6.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"5\" rowspan=\"6\"\u003e \u003cp\u003e.202\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\" morerows=\"5\" rowspan=\"6\"\u003e \u003cp\u003e.533\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eCardiovascular disease\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026ndash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1 (6.2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eHypertension\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026ndash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2 (12.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eAsthma\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026ndash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1 (6.2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eAllergy\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026ndash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1 (6.2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eRheumatoid arthritis\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (12.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1 (6.2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eThyroid disease\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (31%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.032\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.471\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3 (18.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e.026\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e.588\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAdmission due to COVID\u0026ndash;19\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (6.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.246\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026ndash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u0026ndash;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eH1N1 vaccination\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (6.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.026\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.445\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e13 (81.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e.026\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e.554\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTravel\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (6.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.006\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4 (25%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e.803\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e.465\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSocial distancing\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (31%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.043\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.355\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4 (25%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e.089\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e.510\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eClose contact\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (50%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.331\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6 (37.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e.244\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e "},{"header":"Discussion","content":" \u003cp\u003eComparing two groups of women with and without endometriosis showed no difference in the frequency of COVID\u0026ndash;19 infection. The prevalence of the disease depends on the interaction between the virus and the individual\u0026rsquo;s immune system. Our studies\u0026rsquo; findings represent that women with endometriosis do not have a higher risk of COVID\u0026ndash;19 and the risk of COVID\u0026ndash;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\u0026ndash;19 pandemic has forced researchers to focus on the different aspects of this disease, and studying factors that can predispose the individual to disease (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). Studies have investigated the effect of nutrition (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e), serum parameters, such as blood group (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e) and elevated plasmin(ogen) (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e), as well as underlying autoimmune diseases, such as tuberculosis (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e) and lupus erythematosus (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e), on COVID\u0026ndash;19 susceptibility. However, as far as the authors are concerned, the risk of COVID\u0026ndash;19 infection in women with endometriosis has not been clinically evaluated, to date.\u003c/p\u003e \u003cp\u003eThe endometrial susceptibility to COVID\u0026ndash;19 is still under investigation. In a molecular genetic study by Henarejos\u0026ndash;Castillo et al., analyzing data of 112 women with normal endometrial cells demonstrated that the lower expression of host proteases, related to SARS\u0026ndash;CoV-2 infection, such as ACE\u003csub\u003e2\u003c/sub\u003e and TMPRSS2 may result in a lower risk of endometrial susceptibility to COVID\u0026ndash;19 infection, but the expression varies in different phases of the menstrual cycle and increases during implantation and in older women (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). It is also assumed that COVID\u0026ndash;19 can induce changes in endometrial tissue and affect the female reproductive potential (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). However, the susceptibility of endometrial tissue to COVID\u0026ndash;19 has not been confirmed in the clinical setting (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). Studying large databases has shown that the uterine corpus endometrial carcinoma tissue is more susceptible to SARS\u0026ndash;CoV-2 infection, which also affected the tumor prognosis after COVID\u0026ndash;19 infection (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). Other cancer types, including gastrointestinal and urinary tract tumors have also shown higher susceptibility to COVID\u0026ndash;19 infection, attributed to the expression of ACE\u003csub\u003e2\u003c/sub\u003e and TMPRSS2 in cancer tissues (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e). 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 (\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e). The main immunologic changes during endometriosis include reduction of T cell reactivity, natural killer (NK) cell\u0026rsquo;s cytotoxicity, increased antibody production, macrophages polarization and inflammatory mediators release (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e). The increased infiltration level of immune cells, including B cell, CD4\u003csup\u003e+\u003c/sup\u003eT cell, neutrophil, and dendritic cells as well as increased expression of ACE\u003csub\u003e2\u003c/sub\u003e has been correlated with SARS\u0026ndash;CoV-2 susceptibility in endometrial cancer (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). However, such association has not been found in endometriosis and the results of our study showed no difference in susceptibility to COVID\u0026ndash;19 infection in endometriosis women, which maybe due to the fact that the inflammatory and immunologic pathways in endometriosis is chronic (\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e), while that of COVID\u0026ndash;19 is acute.\u003c/p\u003e \u003cp\u003eIn the current study, it was found that the frequency of COVID\u0026ndash;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\u0026ndash;19 infection, as they mainly do not present common symptoms. Of note, many of the asymptomatic cases with COVID\u0026ndash;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 (\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e). COVID\u0026ndash;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\u0026rsquo;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 (\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e). Asymptomatic COVID\u0026ndash;19 is considered the Achilles\u0026rsquo; heel for disease control, due to the strong infectivity and transmission during this period, and the major role of asymptomatic carriers in the person\u0026ndash;to\u0026ndash;person disease transmission (\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e). 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 (\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e). We supposed that the different frequency of asymptomatic COVID\u0026ndash;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 (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). 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\u0026ndash;19 (\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e). The immune system should fight against SARS\u0026ndash;CoV-2 by activation of cellular and innate inflammatory responses (\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e), which may be altered by the underlying immune dysfunction in the patient (\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e) and hence cause the different response of women with endometriosis to COVID\u0026ndash;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\u0026ndash;19 disease course is the underlying disease in the patient (\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e). 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.\u003c/p\u003e \u003cp\u003eWe also analyzed factors associated with COVID\u0026ndash;19 infection and the results revealed that close contact with a patient infected with COVID\u0026ndash;19 was the only risk factor in both groups that resulted in a slightly increased chance (.3\u0026ndash; and .2\u0026ndash;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\u0026ndash;19 infection. As far as no vaccination and definite treatment are available for COVID\u0026ndash;19, preventive measures should be considered by everyone to reduce the transmission rate and the prevalence of this epidemic (\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e). Accordingly, several guidelines have been devised for flattening the curve of COVID\u0026ndash;19 (\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e). 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 (\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe limitations of the present study include the cross-sectional nature of the study and lack of follow\u0026ndash;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.\u003c/p\u003e "},{"header":"Conclusions","content":" \u003cp\u003eThe results of the present study showed that endometriosis does not increase the susceptibility to COVID\u0026ndash;19 infection, but changes the presenting symptoms. Therefore, more attention should be paid for accurate diagnosis of COVID\u0026ndash;19 in women with endometriosis. The lower rate of fever and higher rate of uncommon symptoms in women with endometriosis may be due to the immune interactions of these two diseases. Since the exact mechanism of infection with this virus is not fully understood and no specific drug or vaccine has been designed for it so far, the most important task at present is to eliminate the transmission cycle. Identifying the predisposing factors can help diagnose the high-risk patients and achieve this aim.\u003c/p\u003e "},{"header":"Abbreviations","content":"\u003cul\u003e\n\u003cli\u003eCOVID\u0026ndash;19 infection: Coronavirus disease 2019\u003c/li\u003e\n\u003cli\u003eARDS: acute respiratory distress syndrome\u003c/li\u003e\n\u003cli\u003eICU: intensive care unit\u003c/li\u003e\n\u003cli\u003eMOF: multiple organ failure\u003c/li\u003e\n\u003cli\u003eACE\u003csub\u003e2\u003c/sub\u003e: angiotensin-converting enzyme 2\u003c/li\u003e\n\u003cli\u003eTMPRSS2: transmembrane protease serine protease\u0026ndash;2\u003c/li\u003e\n\u003cli\u003ert-PCR: Real-Time polymerase chain reaction\u003c/li\u003e\n\u003cli\u003eSD: standard deviation\u003c/li\u003e\n\u003cli\u003eNK: natural killer\u003c/li\u003e\n\u003cli\u003ePRR: Pattern Recognition Receptor\u003c/li\u003e\n\u003cli\u003eCT: computed tomography\u003c/li\u003e\n\u003c/ul\u003e"},{"header":"Declarations","content":"\u003cul\u003e\n\u003cli\u003e\u003cstrong\u003eEthics approval and consent to participate: \u003c/strong\u003eWritten informed was obtained from the participants.\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003eConsent for publication: \u003c/strong\u003eAll participants gave consent for anonymous publication of their results.\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003eAvailability of data and materials: Available upon request.\u003c/strong\u003e\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003eCompeting interests: \u003c/strong\u003eThe authors of the present study declare that they have no competing interests.\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003eFunding: \u003c/strong\u003eThis study is supported by, Pars General hospital, Tehran, Iran. The funder had role in data collection, but had no role in decision to publish, or preparation of the manuscript.\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003eAuthors' contributions:\u003c/strong\u003e Study concept and design: SC and BM, drafting of the manuscript FJ and MA and DS and critical revision of the manuscript: SC, and ZSM Statistical Analysis: MAP and FK. All of the authors have given final approval of the version to be published.\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003eAcknowledgements: \u003c/strong\u003eThe authors of the present study sincerely thank patients who answered the questions very carefully and by patience in the critical ere of COVID\u0026ndash;19.\u003c/li\u003e\n\u003c/ul\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e \u003cspan\u003eHarapan H, Itoh N, Yufika A, Winardi W, Keam S, Te H, et al. Coronavirus disease 2019 (COVID\u0026ndash;19): A literature review. 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COVID\u0026ndash;19 in Italy: impact of containment measures and prevalence estimates of infection in the general population. Acta bio\u0026ndash;medica: Atenei Parmensis. 2020;91(3\u0026ndash;S):175\u0026ndash;9.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eJordan RE, Adab P, Cheng K. Covid\u0026ndash;19: risk factors for severe disease and death. British Medical Journal Publishing Group; 2020.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eButler MJ, Barrientos RM. The impact of nutrition on COVID\u0026ndash;19 susceptibility and long\u0026ndash;term consequences. Behavior: Brain; 2020.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eZhao J, Yang Y, Huang H\u0026ndash;P, Li D, Gu D\u0026ndash;F, Lu X\u0026ndash;F, et al. Relationship between the ABO Blood Group and the COVID\u0026ndash;19 Susceptibility. medRxiv. 2020.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eJi H\u0026ndash;L, Zhao R, Matalon S, Matthay MA. 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Molecular Human Reproduction. 2020.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eYang J, Li H, Hu S, Zhou Y. ACE2 correlated with immune infiltration serves as a prognostic biomarker in endometrial carcinoma and renal papillary cell carcinoma: implication for COVID\u0026ndash;19. Aging. 2020;12(8):6518.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eCai C, Ahmed OA, Shen H, Zeng S. Which cancer type has the highest risk of COVID\u0026ndash;19 infection? The Journal of Infection. 2020.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eKr\u0026aacute;l\u0026iacute;čkov\u0026aacute; M, Vetvicka V. Immunological aspects of endometriosis: a review. Annals of translational medicine. 2015;3(11).\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eRiccio LdGC, Santulli P, Marcellin L, Abr\u0026atilde;o MS, Batteux F, Chapron C. Immunology of endometriosis. 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COVID\u0026ndash;19 infection: the perspectives on immune responses. Nature Publishing Group; 2020.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eEmami A, Javanmardi F, Pirbonyeh N, Akbari A. Prevalence of underlying diseases in hospitalized patients with COVID\u0026ndash;19: a systematic review and meta\u0026ndash;analysis. Archives of academic emergency medicine. 2020;8(1).\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eWu Y\u0026ndash;C, Chen C\u0026ndash;S, Chan Y\u0026ndash;J. The outbreak of COVID\u0026ndash;19: An overview. Journal of the Chinese Medical Association. 2020;83(3):217.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eThunstrom L, Newbold S, Finnoff D, Ashworth M, Shogren JF. The benefits and costs of flattening the curve for COVID\u0026ndash;19. Available at SSRN 3561934. 2020.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eSohrabi C, Alsafi Z, O\u0026rsquo;Neill N, Khan M, Kerwan A, Al\u0026ndash;Jabir A, et al. World Health Organization declares global emergency: A review of the 2019 novel coronavirus (COVID\u0026ndash;19). International Journal of Surgery. 2020.\u003c/span\u003e \u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-womens-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmwh","sideBox":"Learn more about [BMC Women's Health](http://bmcwomenshealth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmwh/default.aspx","title":"BMC Women's Health","twitterHandle":"","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Endometriosis, Coronavirus, Covid-19 Infections, Risk Factors, PCR","lastPublishedDoi":"10.21203/rs.3.rs-53422/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-53422/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eIn today\u0026rsquo;s world, coronavirus disease 2019 (COVID\u0026ndash;19) is the most critical health problem and research is continued on studying the associated factors. But it is not clear whether endometriosis increases the risk of COVID\u0026ndash;19.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWomen who referred to the gynecology clinic were evaluated and 507 women with endometriosis (case group) were compared with 520 women without endometriosis (control group). COVID\u0026ndash;19 infection, symptoms, exposure, hospitalization, isolation, H1N1 infection and vaccination, and past medical history of the participants were recorded and compared between the groups using IBM SPSS Statistics for Windows version 21.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eComparison between the groups represent COVID\u0026ndash;19 infection in 3.2% of the case group and 3% of the control group (P\u0026thinsp;=\u0026thinsp;.942). The control group had a higher frequency of asymptomatic infection (95.7% vs. 94.5%; P\u0026thinsp;\u0026lt;\u0026thinsp;.001) and fever (1.6% vs. 0%; P\u0026thinsp;=\u0026thinsp;.004), while the frequency of rare symptoms was more common in the case group (P\u0026thinsp;\u0026lt;\u0026thinsp;.001). The average disease period was 14 days in both groups (P\u0026thinsp;=\u0026thinsp;.694). COVID\u0026ndash;19 infection was correlated with close contact (r\u0026thinsp;=\u0026thinsp;.331; P\u0026thinsp;\u0026lt;\u0026thinsp;.001 in the case group and r\u0026thinsp;=\u0026thinsp;.244; P\u0026thinsp;\u0026lt;\u0026thinsp;.001 in the control group), but not with the history of thyroid disorders, H1N1 vaccination, traveling to high-risk areas, and social isolation (P\u0026thinsp;\u0026gt;\u0026thinsp;.05).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eEndometriosis does not increase the susceptibility to COVID\u0026ndash;19 infections, but alters the manifestation of the disease. The prevalence of the disease may depend on the interaction between the virus and the individual\u0026rsquo;s immune system but further studies are required in this regard.\u003c/p\u003e","manuscriptTitle":"Does Endometriosis Increase Susceptibility to COVID–19 Infections? A case-control study in Women of Reproductive Age","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2020-09-30 17:40:27","doi":"10.21203/rs.3.rs-53422/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2020-11-23T00:00:00+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2020-11-22T00:00:00+00:00","index":2,"fulltext":"Recommendation: Major revisions required\nForm responses:\n---\n\nComments to Author:\n---\nThe study should be better justified and references should be support the reason to research the susceptibility of COVID -19 in endometriosis patients, for example, if it would be in relation to ACE2, or if it would be in relation to other aspects of the immune system. In this study, the justification was not clear. \nIn addition, the study should be conducted with a larger number of patients, aiming a better statistical result, and it could be conducted with a more homogeneous group, with less bias.\n\nIn relation to Background - the study starts by contextualizing the COVID -19 and its relation with the ACE2 expression - lines 52 to 67. However, when describing the relationship of ACE2 with the female reproductive system, it is not done in a clear and adequate way. Initially in lines 68-69, it is mentioned that the ACE2 protein is related with the testicles, ovaries and fertility processes. But what is the effect on physiology and pathology, is it an important role?\nIn the sequence lines 70-71, reference 10 is cited, where the relationship between COVID-19 and male gametogenesis. However, the question is what about the female gametogenesis? What would be the impact of COVID-19?\nIt follows the description of the relation between COVID-19 and endometrial infection, and the description of ACE2 expression in the endometrium. After that, the presence of ACE2 and endometrial cancer. However, the study is about endometriosis, and there is no reference about the expression of ACE2 in endometriosis lesions.\nThen, there is the description of endometriosis in lines 80-82. After that, on lines 82-83, the relation of endometriosis with alterations in the immune system is mentioned, but what are these relations? And what relation could there be with COVID-19? It is not clear on the text.\nNext, on lines 83-85, the sentence is not supported by the reference.\nAt the end of background, there is no justification for the study. There are not clear evidences about why endometriosis could increase the susceptibility to COVID-19.\n\nRegarding the methodology, the number of 500 patients in each group was based on the prevalence of 13% of the population (data presented in the study by Signorelli), but in this study it was reported that the prevalence of COVID-19 varied from 0.35-13%, being 13% only in the region of Lombardy, while the prevalence of Italy in general was 4%.\nThe 4% of prevalence was found in each group of women in this study. The study found in each group 3.2% of women with COVID-19 in the case group and 3% in the control group, and that is so different from the 13% that was used to base the sample size.\nIn the 500 women group, they found just 16 patients in each group with COVID-19, a small number to study the susceptibility of COVID-19 in endometriosis patients. The study should be conducted with more women for a better statistical result.\nIn addition, the study presents an important bias, the women in the control group have many comorbidities. And they should use concomitant medications, which could have an impact on the difference in symptoms found in both groups. Thus, the study should be conducted with more homogeneous groups.\n\nAfter the Discussion, in lines 171-186, it is described the relation that COVID-19 can have in endometrial cells and in endometrial cancer, and other types of cancer that can also increase the susceptibility to COVID-19 are cited. However, this study is about endometriosis and it is not about endometrial cancer.\nThe physiopathology of endometrial cancer differs from endometriosis, so what is the relationship between endometrial cancer, COVID-19 and endometriosis?\nAfter the lines 186-196, the description of the physiopathology of endometriosis with immune system begins. However, in the following lines 192-194, changes in the immune system are correlated with increased ACE2 expression, and the susceptibility of SARS-COv2 with endometrial cancer. The authors should search for references to support the relationship between ACE2 and endometriosis.\nAfter that, in lines 194-198, authors justify that an increase in the susceptibility to COVID-19 in endometriosis patients was not found, because endometriosis is a chronic inflammatory disease while COVID- 19 is acute. This was an early statement made, without any justification or support in the literature.\nOn lines 199-204, there is a description of the relationship between the differences in symptoms of each group, but it is important to highlight that besides the groups are small, they are different in terms of comorbidities, which can be the confounding factor in terms of symptoms, what is said after lines 233-235.\n* Publons Reviewer Recognition. Springer Nature can send verification of this review directly to Publons (a subsidiary of Clarivate Analytics). If you would like to take advantage of this service, please click on the “Yes” option below. Your name, email address, title of the reviewed manuscript, name of the journal, and date of your review submission (the “Review Data”) will then be transmitted to Publons upon publication of the manuscript. If you have already registered at Publons, they will notify you of the receipt of this review and update your profile as per your settings and their policy. If you are not registered with Publons, you will receive an email from them asking you to register in order for them to be able to recognize your review on your new profile page. Publons may use the Review Data to generate derivative metadata for the benefit of Publons and you as a reviewer, carefully considering the sensitivity of such information. For example, Publons may verify your record as a reviewer by updating your profile published on its webservice if you have registered for such service or help editors to identify candidate reviewers. Please find the details of processing in Publons’ privacy policy https://publons.com/about/terms: **No**\n* Declaration of competing interests: **'I declare that I have no competing interests'**\n* Reviewer Publication Consent. I agree for my report to be made available under an Open Access Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manuscript is accepted for publication. Any comments that I do not wish to be included in the published report have been included as confidential comments to the editor, which will not be published.: **I agree to the terms of the CC-BY 4.0 license; please do not publish my name with my report. (default)**\n* Is the study design appropriate to answer the research question (including the use of appropriate controls), and are the conclusions supported by the evidence presented?: **No**\n* Are the methods sufficiently described to allow the study to be repeated?: **No**\n* Is the use of statistics and treatment of uncertainties appropriate?: **No**\n* Is the presentation of the work clear?: **No**\n* Are the images in this manuscript (including electrophoretic gels and blots) free from apparent manipulation?: **Yes**\n"},{"type":"editorInvitedReview","content":"","date":"2020-11-16T00:00:00+00:00","index":1,"fulltext":"Recommendation: Accept after discretionary revisions\nForm responses:\n---\n\nComments to Author:\n---\nDear Authors,\nthank you very much for the opportunity to review this paper that is about a case control study of patients affected by endometriosis versus not regarding the prevalence of Covid-19 prevalence.\nWith regards to the methodology of the study the prevalence used to calculate sample size, can reppresent a Bias, given that the authors might use the prevalence of the region where the population were enrolled, however I think we can consider it appropriate anyway, but should be stated among limitations.\nAgain authors should describe the degree of covid19 severity, when the patient was tested, which test they used, how far from surgery, before? after?\nEnglish proofreading is suggested.\nBest regards\n\n\n\n* Publons Reviewer Recognition. Springer Nature can send verification of this review directly to Publons (a subsidiary of Clarivate Analytics). If you would like to take advantage of this service, please click on the “Yes” option below. Your name, email address, title of the reviewed manuscript, name of the journal, and date of your review submission (the “Review Data”) will then be transmitted to Publons upon publication of the manuscript. If you have already registered at Publons, they will notify you of the receipt of this review and update your profile as per your settings and their policy. If you are not registered with Publons, you will receive an email from them asking you to register in order for them to be able to recognize your review on your new profile page. Publons may use the Review Data to generate derivative metadata for the benefit of Publons and you as a reviewer, carefully considering the sensitivity of such information. For example, Publons may verify your record as a reviewer by updating your profile published on its webservice if you have registered for such service or help editors to identify candidate reviewers. Please find the details of processing in Publons’ privacy policy https://publons.com/about/terms: **Yes**\n* Declaration of competing interests: **none**\n* Reviewer Publication Consent. I agree for my report to be made available under an Open Access Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manuscript is accepted for publication. Any comments that I do not wish to be included in the published report have been included as confidential comments to the editor, which will not be published.: **I agree to the terms of the CC-BY 4.0 license; please do not publish my name with my report. (default)**\n* Is the study design appropriate to answer the research question (including the use of appropriate controls), and are the conclusions supported by the evidence presented?: **Yes**\n* Are the methods sufficiently described to allow the study to be repeated?: **Yes**\n* Is the use of statistics and treatment of uncertainties appropriate?: **Yes**\n* Is the presentation of the work clear?: **Yes**\n* Are the images in this manuscript (including electrophoretic gels and blots) free from apparent manipulation?: **Yes**\n"},{"type":"reviewerAgreed","content":"","date":"2020-11-02T00:00:00+00:00","index":2,"fulltext":""},{"type":"reviewerAgreed","content":"","date":"2020-10-25T12:00:00+00:00","index":1,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2020-10-02T12:00:00+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2020-10-01T12:00:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2020-09-28T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2020-09-24T12:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-womens-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmwh","sideBox":"Learn more about [BMC Women's Health](http://bmcwomenshealth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmwh/default.aspx","title":"BMC Women's Health","twitterHandle":"","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"479676d2-31d8-41ed-80d5-581ac88cf184","owner":[],"postedDate":"September 30th, 2020","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":650013,"name":"Internal Medicine"},{"id":650014,"name":"Preventive Medicine"}],"tags":[],"updatedAt":"2021-03-29T15:00:54+00:00","versionOfRecord":{"articleIdentity":"rs-53422","link":"https://doi.org/10.1186/s12905-021-01270-z","journal":{"identity":"bmc-womens-health","isVorOnly":false,"title":"BMC Women's Health"},"publishedOn":"2021-03-22 15:00:32","publishedOnDateReadable":"March 22nd, 2021"},"versionCreatedAt":"2020-09-30 17:40:27","video":"","vorDoi":"10.1186/s12905-021-01270-z","vorDoiUrl":"https://doi.org/10.1186/s12905-021-01270-z","workflowStages":[]},"version":"v1","identity":"rs-53422","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-53422","identity":"rs-53422","version":["v1"]},"buildId":"WvIrzKhiLBfengagbw6Ux","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}