Potential impact of COVID-19 pandemic on endometriosis

Chen-Yang Huang, Chenyang Huang, Huang CY, Haixiang Sun, Sun HX, Hai-xiang Sun, Jie Mei, Mei J
Reproductive and developmental medicine · 2022 · vol. 6(3) , pp. 138–143 · doi:10.1097/rd9.0000000000000015 · PMID:37521529 · PMC9924788 · W4285085985
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⚙ AI-generated summary by claude@2026-06, 2026-06-10 ⓘ

COVID-19 may impact endometriosis pathogenesis and symptoms through cytokine storms and immune suppression, while pandemic-related isolation and healthcare disruption exacerbate psychological distress and delay treatment.

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⚙ AI-generated deep summary by claude@2026-07, 2026-07-08 · read from full text ⓘ

This paper is a narrative review that examines how the COVID-19 pandemic might affect endometriosis by comparing immune and inflammatory features of SARS-CoV-2 infection with known immunopathology in endometriosis, and by discussing reported pandemic-related disruptions to care (e.g., delayed exams, suspended surgeries, cancelled outpatient appointments) and psychological impacts. It highlights overlapping mechanisms including immune dysregulation (reduced NK cell cytotoxicity, altered T-cell polarization toward Th2, increased macrophage involvement, and changes in inflammatory cytokines/chemokines) and suggests that COVID-19–associated cytokine release and angiogenic factor changes (including VEGF) could create inflammatory and pro-angiogenic conditions relevant to ectopic lesion growth, while gut microbiota disruptions in COVID-19 are also discussed as a possible contributor to endometriosis development. The authors state that there are no exact reports at present directly quantifying the COVID-19 pandemic’s impact on endometriosis occurrence or progression. This paper is centrally about endometriosis — it reviews potential impacts of COVID-19 mechanisms and pandemic-related care disruption on endometriosis pathogenesis and symptoms.

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Abstract

The impact of coronavirus disease 2019 (COVID-19) on endometriosis (EM) is currently unclear. Here, we aimed to describe the potential influence of COVID-19 on the pathogenesis, clinical symptoms, and treatment of EM. The cytokine storm caused by COVID-19 may induce the occurrence and progression of EM, and immunosuppression of COVID-19 may help the ectopic endometrium escape from immune clearance. Consequently, the forced social isolation and the cancelation of non-emergency medical treatment during the COVID-19 pandemic aggravate anxiety and psychological pressure, which can aggravate the symptoms related to EM and delay routine medical services.
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Em

Endometriosis is a disease in which activated endometrial glands or stroma are implanted outside of the uterine cavity. Endometriosis usually leads to the progressive exacerbation of secondary dysmenorrhea, abnormal menstruation, and even infertility [ 16 ] . Studies have suggested that there are other regulatory mechanisms leading to the occurrence and development of EM, in addition to retrograde menstruation [ 17 , 18 ] . Abnormal immune system function might be an important mechanism of EM [ 19 , 20 ] . Several studies further revealed that the following phenomena can be observed in EM patients: decreased T-cell response activity and NK cell cytotoxicity, increased polyclonal activation and antibody production of B cells, increased number and activation of peritoneal macrophages, and changes in infl am matory mediators [ 21 ] . In patients with EM, the transformation of T cells into helper T cells (Th2) increases, and the activation of systemic and local humoral reactions caused by the change of Th1/Th2 cell ratio is closely related to EM [ 22 , 23 ] . In addition, IL-27 triggers Th17 cells to secrete IL-10 through the c-Maf/RORγt/Blimp-1 signaling pathway, which promotes the growth and implantation of ectopic lesions [ 24 ] . Forkhead box P3 (Foxp3) was detected in the lesions of deep rectosigmoid EM/ovarian EM, and the number of Treg cells in the peritoneal fluid and endometrium of patients with EM was significantly increased, indicating that Treg cells may play a role in the immune pathogenesis of EM [ 23 24 25 26 ] . B lymphocytes may also play a role in the pathogenesis of EM by secreting autoantibodies [ 27 ] , while studies have shown that NK cells in EM show reduced cytotoxicity due to increased expression of killer inhibitory receptors (KIR), resulting in immune escape of ectopic endometrium and further adhesion and invasion of the ectopic endometrium [ 21 , 28 ] . Neutrophils produce pro-inflammatory cytokines such as vascular endothelial growth factor (VEGF), IL-8, IL-12, C-X-C motif chemokine ligand (CXCL) 10, CXCL12, and so on, which can promote EM progression [ 29 ] . Moreover, recent studies have shown that macrophages migrate to the M2 type during EM, which may increase the local production of factors that promote angiogenesis and endometrial cell invasion [ 30 ] .

Intro

The coronavirus disease 2019 (COVID-19) has caused patients to become unable to go to medical institutions, which has an adverse impact on many chronic diseases [ 1 ] . Several studies have reported the possible impact of the COVID-19 epidemic on endometriosis (EM), such as suspending surgical treatment, canceling outpatient appointments, delaying ultrasound ex am ination, and the psychological impact of forced self-isolation [ 2 , 3 ] . Here, we summarize the similarities in the pathogenesis of COVID-19 and EM, and the impact of COVID-19 on the common clinical symptoms and treatment of EM is reviewed to elaborate the comprehensive impact of the COVID-19 pandemic on EM. Our review aims to provide research ideas and directions for further exploration of the specific impact of COVID-19 on EM.

Author

C.Y.H. and J.M. contributed to concept, design, and critical discussion. C.Y.H. and H.X.S. contributed to literature search, manuscript preparation, manuscript editing, and manuscript drafting. All authors read and approved the final manuscript.

Covid 19

COVID-19 is caused by a novel coronavirus, severe acute respiratory syndrome-associated coronavirus 2 (SARS-CoV-2), a positive-sense single-stranded RNA virus with high infectivity and pathogenicity [ 4 ] . Angiotensin-converting enzyme 2 (ACE2), which is expressed in various tissues and cells, is the molecular target of the SARS-CoV-2 when invading target tissues [ 4 ] . Then, SARS-CoV-2 can interact with the immune system of the body, leading to individual immune system disorders, which can explain the various clinical manifestations of this disease [ 5 ] . Autopsies of patients with COVID-2019 have shown a high macrophage infiltration rate, suggesting an initial immune response of macrophages to the virus [ 6 ] . It has been reported that more than 60% of patients have a decrease in lymphocyte count (less than 1.0 × 10 9 /L) in their peripheral blood, and this proportion could exceed 80% [ 7 ] in patients diagnosed with severe COVID-19. Moreover, neutrophilia could be detected in patients with severe COVID-19, and the neutrophils-to-lymphocytes ratio has been associated with a poor prognosis of this disease [ 8 ] . Studies have also reported that an increase in the number of monocytes could be observed in the d am aged vessels of patients with COVID-19 [ 9 ] . In addition, the numbers of T and natural killer (NK) cells in patients with COVID-19 significantly decreased. Simultaneously, the regulatory cell (Treg) count decreased significantly in severe COVID-19 patients [ 10 ] . These results suggest that the dual reduction of innate immunity and adaptive immunity in patients with COVID-19 significantly leads to an impaired ability of the immune system to eliminate the virus [ 10 ] . At present, it is believed that this immune response is not simply activated or inhibited but is reflected in the disorder of the body’s defense mechanism. Studies have shown that there are significant increases in the levels of infl am matory cytokines such as interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-7, IL-8, IL-10, interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), monocyte chemotactic protein-1 (MCP-1), C-C motif chemokine ligand 4 (CCL4), chemokine (CK), and colony stimulating factor (CSF) in patients with COVID-19 [ 7 , 8 ] . The continuous interaction of SARS-CoV-2 with the target cells leads to the recruitment of infl am mation-related cells, the continuous release of pro-infl am matory cytokines, and the continuous aggravation of the systemic infl am matory response, which is considered as the cytokine release syndrome and is commonly known as the cytokine storm (CS) [ 11 ] . Severe acute respiratory syndrome-associated coronavirus 2 only inhibits the IFN signaling pathway, specifically, the expression of IFN-1, and the secretion of chemokines is not inhibited [ 12 ] , in fact, the expression of many infl am matory cytokines (IL-6, CCL-2, CCL-3, and CCL-5) is increased [ 11 ] . In addition, increased plasma IL-2 and IL-6 levels have been observed in patients with severe COVID-19 [ 10 ] . After the activation of primary cytokines, CD8  +  T cells, NK cells, Treg cells, and Th2 cells can secrete secondary cytokines such as IFN-γ, bidirectional regulatory protein, or IL-5 to clear the virus and inhibit infl am mation [ 13 ] . Severe acute respiratory syndrome-associated coronavirus 2 repeatedly acts on super-activated T cells and produces a large number of granulocyte macrophage CSF (GM-CSF) and IL-6, which further activate CD14  +  CD16  +  monocytes, resulting in a CS and multi-organ dysfunction [ 8 , 14 ] . Therefore, SARS-CoV-2 can over-activate immune cells and inhibit negative regulation, so that the immune process will be continuously am plified, causing corresponding d am age to the body [ 15 ] .

Potential

COVID-19 may have an impact on the occurrence and development of EM but also on the typical clinical symptoms of women with EM, such as pelvic pain, emotional anxiety, and infertility. Pelvic pain is the most common symptom in EM. Women with EM may experience periodic or a periodic pelvic pain such as dysmenorrhea [ 53 ] , and pain-related symptoms may worsen under stress [ 54 ] . Given the added anxiety because of the pandemic, patients with EM may be more sensitive to pelvic pain from EM. Studies have found that changes in social distancing may exacerbate pain intensity during the COVID-19 pandemic [ 55 ] . On the contrary, other studies suggested that the change in social distance did not cause significant deterioration of pain intensity, and not all psychological stress aggravated chronic pain [ 55 ] . During the COVID-19 pandemic, the burden on most women was even heavier due to the increase in housework, childcare, and more study time of children at home instead of in school [ 56 ] . Thus, these may aggravate the pain symptoms of EM, which may even lead to the need for an increased dosage of painkillers [ 57 ] . Some scholars speculate that this phenomenon may also occur because COVID-19 prevents EM patients from receiving routine treatment or selective surgical treatment in hospitals [ 58 ] . Therefore, during social isolation caused by COVID-19, more patients with EM experience pain and anxiety [ 59 ] . In addition, previous studies have shown that care and concern from other people also seem to have beneficial effects in alleviating pain [ 60 ] . Social disconnection and loneliness caused by the COVID-19 pandemic affect the intensity of pain and may lead to the aggravation of pain-related symptoms [ 61 ] . In addition to the common symptoms of pelvic pain, EM can also lead to female infertility. Patients with EM-related infertility have been under pressure from their f am ilies and themselves, and many of them require assisted reproductive technology (ART). There is no conclusive evidence that ART or pregnancy increases the risk of COVID-19. However, during the COVID-19 pandemic, it is recommended to suspend ART and postpone all non-emergency operations (such as artificial insemination and embryo transfer). Moreover, during the COVID-19 pandemic, the incidence of psychological and mental diseases has increased [ 62 ] . Infertile women in urgent need of pregnancy may be more vulnerable to negative psychosocial effects. The COVID-19 epidemic and infertility stress are both important sources of stress [ 63 ] . Some patients are unable to face the temporary closure of reproductive medicine centers, and even a small number of patients have a strong sense of despair, resulting in deterioration of health status and impairment of mental health [ 64 ] . From the perspective of female fertility, a delay in ART treatment will reduce the probability of successful pregnancy, especially in older women. In addition, the anxiety of elderly women is becomes more severe, which may adversely affect ovarian function [ 65 ] . At the s am e time, studies have shown that only about one-third of patients experience EM-related changes, suggesting that the impact of COVID-19 on clinical problems related to EM may be over-estimated. Patients with EM will not bear pressure similar to that of infertile patients, owing to the temporary suspension of ART treatment [ 3 ] .

Conclusion

This review focuses on the potential impact of the COVID-19 pandemic on EM. The occurrence and development of COVID-19 and EM are accompanied by abnormalities in the immune system. Many infl am matory factors are released in patients with COVID-19, which may increase the risk of EM occurrence or aggravate the severity of EM. At the s am e time, the body of patients with COVID-19 is in a condition of severe immunosuppression, which also provides a suitable environment for ectopic endometrium to escape from clearance. Whether the impact of COVID-19 on the endometrial microenvironment can lead to the occurrence and development of EM is worthy of further investigation. On the other hand, the occurrence of COVID-19 has no association with sex and age, while EM mostly occurs in women of gestational age. These findings show that COVID-19 not only has an important impact on the occurrence and development of EM (Fig. 1 ) but also has a certain impact on the typical clinical symptoms of EM (Fig. 2 ). Mandatory isolation and increased psychological pressure during the COVID-19 pandemic may aggravate the feeling of pelvic pain from EM. For EM-infertile patients, delayed ART treatment will bring greater psychological pressure and even promote the further development of EM. In conclusion, the COVID-19 pandemic has had a significant impact on EM. During the COVID-19 pandemic, more attention should be paid to women prone to EM or with EM and effective methods should be further explore to reduce these impacts. Potential roles of coronavirus disease 2019 (COVID-19) on the pathogenesis of endometriosis. ACE2: angiotensin-converting enzyme 2; CCL: chemokine ligand; EM: endometriosis; IL: interleukin; SARS-CoV-2: severe acute respiratory syndrome-associated coronavirus 2; TNF: tumor necrosis factor; VEGF: vascular endothelial growth factor. Potential roles of coronavirus disease 2019 (COVID-19) on the clinical symptoms of endometriosis. ART: assisted reproductive technology; EM: endometriosis.

Funding(S)

This work was supported by grants from the National Natural Science Foundation of China (82071646, 81801530).

Coi Statement

All authors declare no conflict of interest.

Acknowledgments

None.

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