key: cord-0822870-lb590qnp
authors: AL-LAMI, Rasha A.; ALRAMMAHI, Ali M.; ALGBURI, Ammar M.A.
title: Letter to the editor re: Coronavirus disease 2019 in pregnancy was associated with maternal morbidity and preterm birth
date: 2021-01-19
journal: Am J Obstet Gynecol
DOI: 10.1016/j.ajog.2021.01.007
sha: e7bff0e3cc43edf6195556474543d18958beb151
doc_id: 822870
cord_uid: lb590qnp

nan

Although the study reported non-causal association between preterm birth and COVID-19 and 34 that pregnant women with COVID-19 were labor induced before full term given their medical 35

conditions, there is biological evidence that SARS-CoV-2 might cause preterm labor in pregnant 36 women with no medical indication to induce preterm labor. It was reported that ACE-2 receptor 37 (which SARS-CoV-2 uses to enter the cell) is expressed in the female reproductive tract 38 including the uterus, placenta and ovary. ACE-2 is highly expressed during pregnancy, at least in 39 mid to late gestational age, which is speculated to provide vasodilatory effect driven by its 40 products, Angiotensin 1-7 2 . Testing for SARS-CoV-2 is mainly done by nasopharyngeal swab 41 RT-PCR, thus, women with SARS-CoV-2 viremia might be missed. Once the virus is in the 42 circulation, it is possible for SARS-CoV-2 to reach the reproductive tract (including the uterus) 43 and causes downregulation of ACE-2 and low levels of vasodilatory Angiotensin 1-7 leaving 44 unopposing vasoconstricting effects of Angiotensin-II that might lead to augmented uterine 45 contractions and subsequent preterm birth. Moreover, pre-eclampsia is associated with low levels 46 of angiotensin 1-7. Several reports showed that previously normotensive pregnant women with COVID-19 presented with pre-eclampsia or pre-eclampsia like symptoms (e.g., proteinuria). 48 49 Healthy pregnancy is associated with specific T lymphocytes balance (Treg/Th17), favoring T 50 regulatory abundance over Th17. While Treg lymphocytes maintain fetal tolerance and less local 51 immune response in pregnancy, Th17 is associated with fetal allograft rejection. Low Treg/T17 52 ratio was found in pregnant women with pre-eclampsia, abortion and preterm birth which is in 53 J o u r n a l P r e -p r o o f accordance to severe cases of COVID-19. While patients with COVID-19 might present with 54 lymphopenia, it is the type of lymphocytes that show disrupted levels with high Th17 and low 55

Treg which might ultimately alter the Treg/Th17 balance required for healthy pregnancy. 3 56 57 Glucocorticoids administration remains the common standard practice in anticipated preterm 58 birth; however, glucocorticoids was found to be associated with reduced ACE-2 expression and 59 subsequent reduction in vasodilatory angiotensin 1-7 in animal studies that might augment 60 preterm birth 4 . In sum, it is important to carefully manage pregnant women with COVID-19 61 with cautious administration of glucocorticoids in those with anticipated preterm birth and test 62

for viral presence in the circulation. 

Coronavirus disease 2019 in pregnancy 68 was associated with maternal morbidity and preterm birth

Is highly expressed 71 ACE 2 in pregnant women "a curse" in times of COVID-19 pandemic? Life sciences

COVID-19 and Treg/Th17 74 imbalance: Potential relationship to pregnancy outcomes. American journal of reproductive 75 immunology

-7) and Mas1 receptor axis in glucocorticoid-induced intrauterine growth 78 restriction