ACE2: a key modulator of the renin-angiotensin system and pregnancy.

Angiotensin-converting enzyme 2 (ACE2) is a membrane-bound protein containing 805 amino acids. ACE2 shows approximately 42% sequence similarity to somatic ACE but has different biochemical activities. The key role of ACE2 is to catalyze the vasoconstrictor peptide angiotensin (ANG) II to Ang-(1-7), thus regulating the two major counterbalancing pathways of the renin-angiotensin system (RAS). In this way, ACE2 plays a protective role in end-organ damage by protecting tissues from the proinflammatory actions of ANG II. The circulating RAS is activated in normal pregnancy and is essential for maintaining fluid and electrolyte homeostasis and blood pressure. Renin-angiotensin systems are also found in the conceptus. In this review, we summarize the current knowledge on the regulation and function of circulating and uteroplacental ACE2 in uncomplicated and complicated pregnancies, including those affected by preeclampsia and fetal growth restriction. Since ACE2 is the receptor for SARS-CoV-2, and COVID-19 in pregnancy is associated with more severe disease and increased risk of abnormal pregnancy outcomes, we also discuss the role of ACE2 in mediating some of these adverse consequences. We propose that dysregulation of ACE2 plays a critical role in the development of preeclampsia, fetal growth restriction, and COVID-19-associated pregnancy pathologies and suggest that human recombinant soluble ACE2 could be a novel therapeutic to treat and/or prevent these pregnancy complications.

Measuring the Outcomes of Maternal COVID-19-related Prenatal Exposure (MOM-COPE): study protocol for a multicentric longitudinal project.

INTRODUCTION: COVID-19 is a highly infectious respiratory disease that rapidly emerged as an unprecedented epidemic in Europe, with a primary hotspot in Northern Italy during the first months of 2020. Its high infection rate and rapid spread contribute to set the risk for relevant psychological stress in citizens. In this context, mother-infant health is at risk not only because of potential direct exposure to the virus but also due to high levels of stress experienced by mothers from conception to delivery. Prenatal stress exposure associates with less-than-optimal child developmental outcomes, and specific epigenetic mechanisms (eg, DNA methylation) may play a critical role in mediating this programming association. METHODS AND ANALYSIS: We present the methodological protocol for a longitudinal, multicentric study on the behavioural and epigenetic effects of COVID-19-related prenatal stress in a cohort of mother-infant dyads in Northern Italy. The dyads will be enrolled at 10 facilities in Northern Italy. Saliva samples will be collected at birth to assess the methylation status of specific genes linked with stress regulation in mothers and newborns. Mothers will provide retrospective data on COVID-19-related stress during pregnancy. At 3, 6 and 12 months, mothers will provide data on child behavioural and socioemotional outcomes, their own psychological status (stress, depressive and anxious symptoms) and coping strategies. At 12 months, infants and mothers will be videotaped during semistructured interaction to assess maternal sensitivity and infant's relational functioning. ETHICS AND DISSEMINATION: This study was approved by the Ethics Committee (Pavia). Results will be published in peer-reviewed journals and presented at national and international scientific conferences. TRIAL REGISTRATION NUMBER: NCT04540029; Pre-results.

Uptrend in distress and psychiatric symptomatology in pregnant women during the coronavirus disease 2019 pandemic.

INTRODUCTION: Prenatal maternal distress has a negative impact on the course of pregnancy, fetal development, offspring development, and later psychopathologies. The study aimed to determine the extent to which the coronavirus disease 2019 (COVID-19) pandemic may aggravate the prenatal distress and psychiatric symptomatology of pregnant women. MATERIAL AND METHODS: Two cohorts of pregnant volunteer women were evaluated, one that was recruited before the COVID-19 pandemic (n = 496) through advertisements in prenatal clinics in Quebec, Canada, from April 2018 to March 2020; the other (n = 1258) was recruited online during the pandemic from 2 April to 13 April 2020. Prenatal distress and psychiatric symptomatology were measured with the Kessler Distress Scale (K10), Post-traumatic Checklist for DSM-5 (PCL-5), Dissociative Experiences Scale (DES-II), and Positive and Negative Affect Schedule (PANAS). RESULTS: The 1754 pregnant women (Mage  = 29.27, SD = 4.23) were between 4 and 41 gestational weeks (M = 24.80, SD = 9.42), were generally educated (91.3% had post-high-school training), and financially well-resourced (85.3% were above the low-income cut-off). A multivariate analysis of covariance controlling for age, gestational age, household income, education, and lifetime psychiatric disorders showed a large effect size (ES) in the difference between the two cohorts on psychiatric symptoms (Wilks' λ = 0.68, F6,1400  = 108.50, P < .001, partial η2  = 0.32). According to post-hoc analyses of covariance, the COVID-19 women reported higher levels of depressive and anxiety symptoms (ES = 0.57), dissociative symptoms (ES = 0.22 and ES = 0.25), symptoms of post-traumatic stress disorder (ES = 0.19), and negative affectivity (ES = 0.96), and less positive affectivity (ES = 0.95) than the pre-COVID-19 cohort. Women from the COVID-19 cohort were more likely than pre-COVID-19 women to present clinically significant levels of depressive and anxiety symptoms (OR = 1.94, χ2 [1] = 10.05, P = .002). Multiple regression analyses indicated that pregnant women in the COVID-19 cohort having a previous psychiatric diagnosis or low income would be more prone to elevated distress and psychiatric symptoms. CONCLUSIONS: Pregnant women assessed during the COVID-19 pandemic reported more distress and psychiatric symptoms than pregnant women assessed before the pandemic, mainly in the form of depression and anxiety symptoms. Given the harmful consequences of prenatal distress on mothers and offspring, the presently observed upsurge of symptoms in pregnant women calls for special means of clinical surveillance.

Management of Acute Severe Ulcerative Colitis in a Pregnant Woman With COVID-19 Infection: A Case Report and Review of the Literature.

First detected in Wuhan, China, the novel 2019 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped RNA beta-coronavirus responsible for an unprecedented, worldwide pandemic caused by COVID-19. Optimal management of immunosuppression in inflammatory bowel disease (IBD) patients with COVID-19 infection currently is based on expert opinion, given the novelty of the infection and the corresponding lack of high-level evidence in patients with immune-mediated conditions. There are limited data regarding IBD patients with COVID-19 and no data regarding early pregnancy in the era of COVID-19. This article describes a patient with acute severe ulcerative colitis (UC) during her first trimester of pregnancy who also has COVID-19. The case presentation is followed by a review of the literature to date on COVID-19 in regard to inflammatory bowel disease and pregnancy, respectively.