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

Abstract

We read with great interest the article “Coronavirus disease 2019 in pregnancy was associated with maternal morbidity and preterm birth.” Sentilhes et al1Sentilhes L. De Marcillac F. Jouffrieau C. et al.Coronavirus disease 2019 in pregnancy was associated with maternal morbidity and preterm birth.Am J Obstet Gynecol. 2020; 223: 914.e1-914.e15Abstract Full Text Full Text PDF PubMed Scopus (109) Google Scholar supported with evidence the hypothesis that pregnant women with coronavirus disease 2019 (COVID-19) can have adverse obstetrical outcomes and preterm deliveries. Although the study reported a noncausal association between preterm birth and COVID-19 and that pregnant women with COVID-19 were induced for labor before full term because of their medical conditions, there is a biological evidence that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) might cause preterm labor in pregnant women with no medical indication for preterm labor induction. It was reported that the angiotensin-converting enzyme type-2 (ACE-2) receptor (which SARS-CoV-2 uses to enter the cell) is expressed by the female reproductive tract including the uterus, placenta, and ovaries. ACE-2 is highly expressed during pregnancy, at least during mid- to late-gestation, which is speculated to provide a vasodilatory effect driven by its products, namely angiotensin 1 to 7.2Dhaundiyal A. Kumari P. Jawalekar S.S. Chauhan G. Kalra S. Navik U. Is highly expressed ACE 2 in pregnant women “a curse” in times of COVID-19 pandemic?.Life Sci. 2021; 264: 118676Crossref PubMed Scopus (21) Google Scholar Testing for the presence of SARS-CoV-2 is mainly done by a reverse transcription-polymerase chain reaction of a nasopharyngeal swab, and thus women with SARS-CoV-2 viremia might be missed. Once the virus is in the circulation system, it is possible for SARS-CoV-2 to reach the reproductive tract (including the uterus) and to cause down-regulation of the ACE-2 receptors and subsequently low levels of vasodilatory angiotensin 1 to 7, thereby leaving the vasoconstricting effects of angiotensin II unopposed, which might lead to augmented uterine contractions and subsequently preterm birth. Moreover, preeclampsia is associated with low levels of angiotensin 1 to 7. Several reports showed that previously normotensive pregnant women with COVID-19 presented with preeclampsia or preeclampsia-like symptoms (eg, proteinuria). Moreover, healthy pregnancy is associated with a specific T lymphocytes balance (regulatory T cells [Treg] to T helper 17 cells [Th17]), favoring Treg abundance over Th17. Although Treg lymphocytes maintain fetal tolerance and a reduced local immune response in pregnancy, Th17 is associated with fetal allograft rejection. A low Treg to Th17 ratio was found in pregnant women with preeclampsia, those who aborted, and those who underwent preterm deliveries, which is in accordance with the ratios in severe cases of COVID-19. Although patients with COVID-19 might present with lymphopenia, it is the type of lymphocytes that show disrupted levels (with high Th17 and low Treg levels), which might ultimately alter the Treg to Th17 balance required for a healthy pregnancy.3Muyayalo K.P. Huang D.H. Zhao S.J. Xie T. Mor G. Liao A.H. COVID-19 and Treg/Th17 imbalance: potential relationship to pregnancy outcomes.Am J Reprod Immunol. 2020; 84: e13304Crossref PubMed Scopus (53) Google Scholar The administration of corticosteroids remains the common standard practice in anticipated preterm birth cases; however, corticosteroids was found to be associated with a reduced ACE-2 receptor expression and a subsequent reduction in vasodilatory angiotensin 1 to 7 in animal studies, which might augment preterm birth.4Ghadhanfar E. Alsalem A. Al-Kandari S. Naser J. Babiker F. Al-Bader M. The role of ACE2, angiotensin-(1-7) and Mas1 receptor axis in glucocorticoid-induced intrauterine growth restriction.Reprod Biol Endocrinol. 2017; 15: 97Crossref PubMed Scopus (38) Google Scholar In conclusion, it is important to carefully manage pregnant women with COVID-19, with cautious administration of corticosteroids in those with anticipated preterm deliveries, and to test for viral presence in the circulation system. Coronavirus disease 2019 in pregnancy was associated with maternal morbidity and preterm birthAmerican Journal of Obstetrics & GynecologyVol. 223Issue 6PreviewDespite the mainly reassuring outcomes for pregnant women with coronavirus disease 2019 reported by previous case series with small sample sizes, some recent reports of severe maternal morbidity requiring intubation and of maternal deaths show the need for additional data about the impact of coronavirus disease 2019 on pregnancy outcomes. Full-Text PDF Coronavirus disease 2019 in pregnancy was associated with maternal morbidity and preterm birthAmerican Journal of Obstetrics & GynecologyVol. 224Issue 5PreviewWe thank Dr Al-Lami and colleagues for their interest regarding our work. In our case series of 54 pregnant women with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, we aimed to report the impact of coronavirus disease 2019 (COVID-19) on pregnancy and neonatal outcomes.1 However, our data are limited to answer the specific comments made by Dr Al-Lami and colleagues. Full-Text PDF