The influence of COVID-19 infection-associated immune response on the female reproductive system†

Coronavirus disease 2019 (COVID-19) is a multi-system disease that has led to a pandemic with unprecedented ramifications. The pandemic has challenged scientists for the past 2 years and brought back previously abandoned research topics. COVID-19 infection causes a myriad of symptoms ranging from mild flu-like symptoms to severe illness requiring hospitalization. Case reports showed multiple systemic effects of COVID-19 infection, including acute respiratory distress syndrome, fibrosis, colitis, thyroiditis, demyelinating syndromes, and mania, indicating that COVID-19 can affect most human body systems. Unsurprisingly, a major concern for women all over the globe is whether a COVID-19 infection has any long-term effects on their menstrual cycle, fertility, or pregnancy. Published data have suggested an effect on the reproductive health, and we hypothesize that the reported reproductive adverse effects are due to the robust immune reaction against COVID-19 and the associated cytokine storm. While the COVID-19 receptor (angiotensin converting enzyme, ACE2) is expressed in the ovaries, uterus, vagina, and placenta, we hypothesize that it plays a less important role in the adverse effects on the reproductive system. Cytokines and glucocorticoids act on the hypothalamo-pituitary gonadal axis, arachidonic acid pathways, and the uterus, which leads to menstrual disturbances and pregnancy-related adverse events such as preterm labor and miscarriages. This hypothesis is further supported by the apparent lack of long-term effects on the reproductive health in females, indicating that when the cytokine storm and its effects are dampened, the reproductive health of women is no longer affected.