Molecular and Physiological Aspects of SARS-CoV-2 Infection in Women and Pregnancy

Abstract

Whilst scientific knowledge about SARS-CoV-2 and COVID-19 is rapidly increasing, much of the effects on pregnant women is still unknown. To accommodate pregnancy, the human endometrium must undergo a physiological transformation called decidualization. These changes encompass the remodeling of endometrial immune cells leading to immunotolerance of the semi-allogenic conceptus as well as defense against pathogens. The angiotensin converting enzyme 2 (ACE2) plays an important regulatory role in the renin-angiotensin-system (RAS) and has been shown to be protective against comorbidities known to worsen COVID-19 outcomes. Furthermore, ACE2 is also crucial for decidualization and thus for early gestation. An astounding gender difference has been found in COVID-19 with male patients presenting with more severe cases and higher mortality rates. This could be attributed to differences in sex chromosomes, hormone levels and behavior patterns. Despite profound changes in the female body during pregnancy, expectant mothers do not face worse outcomes compared with non-pregnant women. Whereas mother-to-child transmission through respiratory droplets during labor or in the postnatal period is known, another question of in utero transmission remains unanswered. Evidence of placental SARS-CoV-2 infection and expression of viral entry receptors at the maternal-fetal interface suggests the possibility of in utero transmission. SARS-CoV-2 can cause further harm through placental damage, maternal systemic inflammation, and hindered access to health care during the pandemic. More research on the effects of COVID-19 during early pregnancy as well as vaccination and treatment options for gravid patients is urgently needed.

ACE inhibitors on ACE1, ACE2, and TMPRSS2 expression and spheroid attachment on human endometrial Ishikawa cells

“…In conclusion, the human endometrium expresses ACE1, ACE2, and TMPRSS2 transcripts and proteins. Similar findings have been reported in recent studies [35] , [36] , [37] . The commonly used human receptive endometrial Ishikawa and RL95–2 cells both express ACE1, ACE2, and TMPRSS2 transcripts and proteins making them suitable for in vitro studies on endometrial receptivity and embryo implantation.…”