Association of laparoscopically-confirmed endometriosis with long COVID-19: a prospective cohort study

• Type of Material: Article
• Authors: Siwen Wang, Harvard T.H. Chan School of Public Health; Leslie V Farland, University of Arizona; Audrey Gaskins, Emory University; Jasmine Mortazavi, Michigan State University; Yi-Xin Wang, Harvard T.H. Chan School of Public Health; Rulla M Tamimi, Weill Cornell Medicine; Janet W Rich-Edwards, Harvard Medical School; Dan Zhang, Zhejiang University; Kathryn L Terry, Harvard T.H. Chan School of Public Health; Jorge E Chavarro, Harvard T.H. Chan School of Public Health; Stacey A Missmer, Michigan State University
• Language: English
• Date: 2023-06-01
• Publisher: MOSBY-ELSEVIER
• Publication Version: Final Published Version
• Copyright Statement: © 2023 Elsevier Inc. All rights reserved.
• Final Published Version (URL): http://dx.doi.org/10.1016/j.ajog.2023.03.030
• Title of Journal or Parent Work: AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
• Volume: 228
• Issue: 6
• Start Page: 714.e1
• End Page: 714.e13
• Grant/Funding Information: This study was supported by research grants HD96033 and HD96033-03S1, U01 HL145386, R24 ES028521, U01 CA176726, and R01 CA67262 from the National Institute of Health.
• Keywords: long COVID; Life Sciences & Biomedicine; RISK; laparoscopically-confirmed endometriosis; THROMBOSIS; Obstetrics & Gynecology; Science & Technology; endometriosis; VALIDITY; post-COVID-19 conditions; MULTIPLE IMPUTATION; inflammation; SARS-CoV-2

Abstract

Background: Women are at greater risk than men of developing chronic inflammatory conditions and “long COVID.” However, few gynecologic health risk factors for long COVID-19 have been identified. Endometriosis is a common gynecologic disorder associated with chronic inflammation, immune dysregulation, and comorbid presentation with autoimmune and clotting disorders, all of which are pathophysiological mechanisms proposed for long COVID-19. Therefore, we hypothesized that women with a history of endometriosis may be at greater risk of developing long COVID-19. Objective: This study aimed to investigate the association between history of endometriosis before SARS-CoV-2 infection and risk of long COVID-19. Study Design: We followed 46,579 women from 2 ongoing prospective cohort studies—the Nurses’ Health Study II and the Nurses’ Health Study 3—who participated in a series of COVID-19-related surveys administered from April 2020 to November 2022. Laparoscopic diagnosis of endometriosis was documented prospectively in main cohort questionnaires before the pandemic (1993–2020) with high validity. SARS-CoV-2 infection (confirmed by antigen, polymerase chain reaction, or antibody test) and long-term COVID-19 symptoms (≥4 weeks) defined by the Centers for Disease Control and Prevention were self-reported during follow-up. Among individuals with SARS-CoV-2 infection, we fit Poisson regression models to assess the associations between endometriosis and risk of long COVID-19 symptoms, with adjustment for potential confounding variables (demographics, body mass index, smoking status, history of infertility, and history of chronic diseases). Results: Among 3650 women in our sample with self-reported SARS-CoV-2 infections during follow-up, 386 (10.6%) had a history of endometriosis with laparoscopic confirmation, and 1598 (43.8%) reported experiencing long COVID-19 symptoms. Most women were non-Hispanic White (95.4%), with a median age of 59 years (interquartile range, 44–65). Women with a history of laparoscopically-confirmed endometriosis had a 22% greater risk of developing long COVID-19 (adjusted risk ratio, 1.22; 95% confidence interval, 1.05–1.42) compared with those who had never been diagnosed with endometriosis. The association was stronger when we defined long COVID-19 as having symptoms for ≥8 weeks (risk ratio, 1.28; 95% confidence interval, 1.09–1.50). We observed no statistically significant differences in the relationship between endometriosis and long COVID-19 by age, infertility history, or comorbidity with uterine fibroids, although there was a suggestive trend indicating that the association may be stronger in women aged <50 years (<50 years: risk ratio, 1.37; 95% confidence interval, 1.00–1.88; ≥50 years: risk ratio, 1.19; 95% confidence interval, 1.01–1.41). Among persons who developed long COVID-19, women with endometriosis reported on average 1 additional long-term symptom compared with women without endometriosis. Conclusion: Our findings suggest that those with a history of endometriosis may be at modestly increased risk for long COVID-19. Healthcare providers should be aware of endometriosis history when treating patients for signs of persisting symptoms after SARS-CoV-2 infection. Future studies should investigate the potential biological pathways underlying these associations.