Association of Laparoscopically-confirmed Endometriosis with Long COVID: A Prospective Cohort Study.

Overview

abstract

BACKGROUND: Women are at greater risk than men of developing chronic inflammatory conditions and of developing 'long COVID.' However, few gynecologic health risk factors for long COVID have been identified. Endometriosis is a common gynecological disorder associated with chronic inflammation, immune dysregulation, and comorbid presentation with autoimmune and clotting disorders, all of which are pathophysiologic mechanisms proposed for long COVID. Therefore, we hypothesized that women with a history of endometriosis may be at greater risk of developing long COVID. OBJECTIVE: To investigate the association between history of endometriosis prior to SARS-CoV-2 infection and risk of long COVID. METHODS: We followed 46,579 women from two 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 prior to the pandemic (1993-2020) with high validity. SARS-CoV-2 infection (confirmed by antigen, PCR, or antibody test) and CDC-defined long-term COVID-19 symptoms (≥4 weeks) 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 symptoms. The majority of 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 (adjusted RR=1.22, 95% CI=1.05-1.42), compared to those who had never been diagnosed with endometriosis. The association was stronger when we defined long COVID as having symptoms ≥8 weeks (RR=1.28, 95% CI=1.09-1.50). We observed no statistically significant differences in the relationship between endometriosis and long COVID by age, infertility history, or comorbidity with uterine fibroids, although there was a suggestive trend that women <50 years may be at higher risk (<50 years, RR=1.37, 95% CI=1.00-1.88; ≥50 years, RR=1.19, 95% CI=1.01-1.41). Among persons who developed long COVID, women with endometriosis reported on average one additional long-term symptom compared to women without endometriosis. CONCLUSIONS AND RELEVANCE: Our findings suggest that those with a history of endometriosis may be at modestly increased risk for long COVID. Health care providers should be aware of endometriosis history when treating patients for signs of persisting symptoms post-SARS-CoV-2 infection. Future studies should investigate the potential biological pathways underlying these associations.