SARS-CoV-2 & Long COVID on Reproductive System

SARS-CoV-2 & Long COVID on Reproductive System

Coronavirus Disease 2019 (COVID-19) has entered its fourth year since the end of 2019. At least 65 million people around the world suffer from Long COVID, sometimes called "post-acute sequelae of COVID-19”; may occur in at least 10% of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, affecting health problems including more than 200 symptoms with impacts on multiple organ systems.

According to the research by Hannah E. Davis and Eric J. Topol et.al. in "Nature Reviews Microbiology" this year (Jan. 2023), there are at least five to six hypotheses about the pathogenesis of COVID-19, including persisting reservoirs of SARS-CoV-2 in tissues , immune dysregulation, microbiota destruction, autoimmunity, microvascular blood clotting with endothelial dysfunction, and dysfunctional signaling in the brainstem and/or vagus nerve. Currently, there is no proven effective treatment.

Davis, Topol and others found that Long COVID are associated with all ages and acute phase disease severity. The proportion of diagnoses is highest between the ages of 36 and 50, and occurs in the group of non-hospitalized patients with a mild acute illness.

This study summarizes the main progress in the current scientific understanding of the Long COVID including:

1. Immunology and Virology
2. Vascular issues and organ damage
3. Neurological and Cognitive systems
4. ME/CFS, Dysautonomia and related conditions
5. Reproductive System
6. Respiratory System
7. Gastrointestinal system

Among them, the analysis of impacts on the reproductive system has been indicated that such symptoms are frequently reported in COVID-19 cases, but there are few studies to document the impact and sex-specific pathophysiology.

Research by Davis, Topol and others further explored the impact of Long COVID on the reproductive system : For the male group, the presence of viruses in reproductive organ tissues increases the risk of erectile dysfunction, which may be caused by endothelial dysfunction; and patients with Long COVID have impaired sperm count, sperm volume, motility, sperm morphology and sperm concentration, and was associated with elevated levels of cytokines and the presence of caspase 8,9, 3 in seminal fluid.

In terms of female group, it is currently known that the impact of the SARS-CoV-2 includes: menstruation and the week before menstruation are factors that trigger Long COVID, the decline of ovarian reserve and reproductive endocrine disorder and so on.

Infection with SARS-CoV-2 will also affect ovary hormone production and/or the endometrial response. People with both COVID-19 and menstruation changes are more prone to fatigue, headaches, body aches and shortness of breath. The most common menstrual changes include irregular menstruation, increased premenstrual symptoms and infrequent menstruation.

In addition, research on ME/CFS has shown that it is associated with:

  • Menstrual Cycle : premenstrual dysphoric disorder, menstrual cycle abnormalities, endometriosis/early menopause
  • Ovary: polycystic ovarian syndrome, ovarian cysts
  • Uterus : Inflammation, endometriosis

Pregnancy, postpartum changes, perimenopause, and menstrual cycle fluctuations also affect ME/CFS and as well as metabolic and immune system changes.

<Time> comprehensively reported the impact of SARS-Cov-2 and Long COVID on the reproductive health of men and women in April this year (2023), and analyzed the latest medical research, cases, as well as subsequent impact on people's reproductive choices. <Time> points out that the latest data from the U.S. Census Bureau (2023/3/22) shows that among 25% U.S. adults aged 18-39 of childbearing age suffering from COVID-19 with symptoms last for at least three months. Women are at higher risk than men for Long COVID risk.

Women with Long COVID interviewed by <Time>, they describe their situation, such as exacerbating a pre-existing neurological disease due to extreme fatigue, only having the strength to walk a short distance outside the house most of the time, or having only enough energy to take a shower once a week. They said it was difficult for them to imagine how such a state of health would be able to take care of pets, let alone the more energy-intensive raising of children.

On the other hand, Long COVID may affect the reproductive choices of adults, which can be observed from another issue. This <Time> report once again emphasized that after the diagnosis of COVID-19, SARS-CoV-2 may damage the quantity and quality of male sperm, testicular function and hormone levels, and may also reduce fertility and erectile dysfunction in the short term, making women getting pregnant becomes more difficult.

In women, certain fertility markers are low for at least a few months after SARS-CoV-2 infections, and the confirmed COVID-19 women during pregnancy may have disrupted menstrual cycles and increased complications such as preeclampsia and premature birth. For those with endometriosis, in addition to increasing the risk of developing Long COVID, pregnancy and ME/CFS may also be related to each other.

In an interview with <Time>, Kate Clancy, a professor at the University of Illinois at Urbana-Champaign, explained that inflammation may be a common link between Long COVID, menstrual changes, and symptom flares during menstruation because "The uterus is very much an immune organ” that keeps pathogens out while allowing the embryo to grow out of harm's way . The healthy uterus helps to shed and repair tissue on a regular basis, so it is highly sensitive to inflammation and other immune responses.

So this also raises another question: If the SARS-CoV-2 infection during pregnancy, will this affect the fetus?

Yes, the answer is provided by a new research, published on March 23, 2023 in JAMA Network Open. The team from Massachusetts General Hospital have uncovered the link between offspring (boys, not girls) and mothers with SARS-CoV-2 infection during pregnancy. This study indicates that these boys are more likely to develop neurodevelopmental disorders after birth and increase the risk of autism spectrum disorder.

Earlier studies have established a link between other infections during pregnancy and neurodevelopmental disorders in offspring, but the connection with COVID-19 takes that a step further.

Andrea Edlow, co-lead author of the paper from Massachusetts General Hospital and Harvard Medical School, said in an interview by SciTechDaily:”The neurodevelopmental risk associated with maternal SARS-CoV-2 infection was disproportionately high in male infants, consistent with the known increased vulnerability of males in the face of prenatal adverse exposures. “

Roy Perlis, another co-lead author, pointed out that further investigation through larger studies and extended long-term monitoring is necessary for the long-term  to assess this potential risk.

In this regard, there is a general lack of knowledge and misinformation after the SARS-CoV-2 is infected, which is why the research of Hannah E. Davis and Eric J. Topol et.al. finally called for long-term research on Long COVID and the lack of nursing knowledge is an urgent problem that needs to be solved at present. Among them, the influence on the reproductive system is particularly insufficient in the research on the mechanism of inflammatory diseases such as endometriosis, which should be paid attention to. In addition to providing education about Long COVID to the biomedical community, they also emphasized the need to carry out public awareness campaigns. Educate the public about the risks and consequences of growing COVID-19.


The latest study in the journal "Climacteric" (2023-08-30) points out: premature ovarian insufficiency (POI) related to infection with COVID-19


The aim of this study is to present the case report of a 36-year-old woman developing premature ovarian insufficiency (POI) after COVID-19 and review the literature referring to the possible impact of SARS-CoV-2 infection on female reproduction.

A 36-year-old nulligravida with normal menstrual cycles, non-smoker, with a normal body mass index and no pelvic surgery or oncological treatment in her medical history presented to the Infertility Center of the Institute of Mother and Child in Warsaw after a year of unsuccessful attempts to get pregnant. During diagnostic process she was affected by COVID-19 with a mild manifestation and thereafter she presented amenorrhea with intense hot flushes. Further diagnostic confirmed the diagnosis of POI.

There is a strong molecular basis for a possible effect of SARS-CoV-2 infection on the female reproductive system; however, the results of available research are conflicting. All of these aspects are discussed in detail.

K. Pankiewicz, E. Chotkowska, B. Nowakowska, M. Gos & T. Issat (2023) COVID-19-related premature ovarian insufficiency: case report and literature review, Climacteric, DOI: 10.1080/13697137.2023.2246878

Davis, H. E., McCorkell, L., Vogel, J. M., & Topol, E. J. (2023). Long COVID: major findings, mechanisms and recommendations. Nature Reviews Microbiology, 1-14. https://www.nature.com/articles/s41579-022-00846-2

Jamie Ducharme, Long COVID Is Making Some People Choose Not to Have Kids, Time, 2023/04/04. https://time.com/6268429/long-covid-reproductive-health/ 

SciTechDaily, COVID-19 Infection During Pregnancy Linked to Higher Risk of Neurodevelopmental Disorders. 2023/03/27. https://scitechdaily.com/covid-19-infection-during-pregnancy-linked-to-higher-risk-of-neurodevelopmental-disorders/