COVID-19 and preeclampsia (preE) share the ANG-II mediated endothelial dysfunction, resulting from a significant dysregulation of RAS and an imbalanced proportion of anti-angiogenic and pro-angiogenic soluble plasmatic factors. Of note, an increased incidence of preE has been reported among COVID-19-infected mothers compared to the general pregnant population. The two most promising angiogenic markers are the soluble fms-like tyrosine kinase receptor-1 (sFlt-1), the major antiangiogenic factor, and the placental growth factor (PlGF), a powerful angiogenic factor. Since these markers have proven useful in the prediction, diagnosis, and severity of preE, this study aimed to evaluate their maternal serum levels in pregnancies complicated by SARS-CoV-2 infection and to assess their potential use to guide the management of these women. A retrospective analysis of SARS-CoV-2-positive pregnant women was performed. The serum levels of sFlt-1 and PlGF were collected at the diagnosis of SARS-CoV-2 infection at the hospital, before the beginning of steroid/hydroxychloroquine and/or antithrombotic therapy. The sFlt-1/PlGF ratio was stratified using cut-off values clinically utilized in the diagnosis and prediction of preE (low < 38, intermediate 38–85/110* and high >85/110*, * if before or after the 34th week of gestation). A total of 57 women were included, of whom 20 (35%) had signs and symptoms of COVID-19 at hospital presentation and 37 (65%) were asymptomatic. None were vaccinated. The mean gestational age at diagnosis of SARS-CoV-2 infection was 32 weeks in symptomatic patients and 37 weeks and 5 days in asymptomatic ones (p = 0.089). sFlt-1 serum levels were higher in SARS-CoV-2 positive asymptomatic patients compared to women with COVID-19 related symptoms (4899 ± 4357 pg/mL vs. 3187 ± 2426 pg/mL, p = 0.005). sFlt-1/PlGF at admission was <38 in 18 of the 20 symptomatic women (90%) compared to 22 (59%) of the asymptomatic patients (p = 0.018). Of note, two of the three women admitted to the intensive care unit had a very low ratio ( 85/110 were not significantly different between the two groups: 11% in asymptomatic patients (4/37) vs. none of the symptomatic patients (p = 0.286), and all of them presented a placental dysfunction, like preE (n = 1) and FGR (n = 3). Of note, there were no stillbirths or maternal or neonatal deaths among symptomatic patients; also, no cases of preE, FGR, or small for gestational age neonates were diagnosed. In conclusion, our data suggest that SARS-CoV-2 infection during pregnancy could influence the angiogenic balance. A significant pathological alteration of the sFlt-1/PlGF ratio cannot be identified during the symptomatic phase; however, if left untreated, SARS-CoV-2 infection could potentially trigger placental dysfunction.

COVID-19 has been primarily identified as a respiratory infection characterized by signs and symptoms associated with the dysfunction of the renin-angiotensin system (RAS). This is attributed to the SARS-CoV-2 virus invading the respiratory mucosa via angiotensin-converting enzyme 2 (ACE2), which is an important element of the RAS. Meanwhile, preeclampsia is an obstetric pathology that, surprisingly, resembles the pathology of COVID-19. It is a systemic syndrome that occurs during the second half of pregnancy and is determined to be a major cause of maternal and perinatal morbidity and mortality. This disease typically presents with new-onset hypertension and proteinuria or other specific end-organ dysfunctions. RAS-mediated mechanisms may explain its primary clinical-pathological features, which are suggestive of an underlying microvascular dysfunction in both diseases, with induction of vasculopathy, coagulopathy, and inflammation. In this report, we review the medical literature on this subject. Further, the underlying similarities between the two conditions are discussed to assess preeclampsia as a model for COVID-19. These considerations are valid in the case of original SARS-CoV-2 primary infection. Emerging SARS-CoV-2 variants as well as the vaccination could alter various aspects of the virus biology, including human ACE-2 receptor binding affinity and therefore the RAS mediated consequences.

To evaluate the clinical utility of placental growth factor (PlGF) for the prediction of preeclampsia (PE). This prospective cohort study included women divided into three groups: (1) pregnancies w...

The ratio between sFlt-1 (soluble fms-like tyrosine kinase-1) and PlGF (Placental Growth Factor) was recently introduced to aid in the management of hypertensive disorders of pregnancy and fetal growth restriction, but it has limitations. This study proposes a new angiogenic classification of PlGF and sFlt-1 to enhance maternal and fetal risk assessment in pregnancies with suspected placental dysfunction. A retrospective analysis was conducted on hospitalized singleton pregnancies beyond the 20th week complicated by hypertensive disorders of pregnancy and/or fetal growth restriction. Patients were classified based on sFlt-1/PlGF (low, medium, high, very high) and into the nine possible combinations using PlGF and sFlt-1 gestational age-specific levels: (1) PlGF and sFlt-1 within range; (2) PlGF in range, sFlt-1 < range; (3) PlGF in range, sFlt-1 > range; (4) PlGF < range, sFlt-1 in range; (5) PlGF and sFlt-1 < range; (6) PlGF < range, sFlt-1 > range; (7) PlGF > range, sFlt-1 in range; (8) PlGF > range, sFlt-1 < range; (9) PlGF and sFlt-1 > range. The cohort included 227 patients. The most common categories were 1, 3, 4, and 6. Categories 4 and 6 had a higher proportion of fetal growth restriction, whereas categories 3 and 6, presented a greater risk of severe maternal complications. Category 6 exhibited the highest risk of adverse maternal-fetal outcomes; conversely, category 1 was the category at the lowest risk for complications. Notably, 40 % of patients classified as low or medium risk by the sFlt-1/PlGF were high-risk by our classification. Evaluation of actual PlGF and sFlt-1 levels rather than set cut-off ratios can improve the risk stratification of clinical manifestations of placental pathology.

We read with interest the work by Espino-y-Sosa and colleagues

Background: several studies have demonstrated that angiogenic markers can improve the clinical management of hypertensive disorders (HDs) and fetal growth restriction (FGR) in singleton pregnancies, but few studies have evaluated the performance of these tests in multiple pregnancies. Our aim was to investigate the role of soluble fms-like tyrosine kinase 1 (sFlt-1) in predicting adverse obstetric outcomes in hospitalized multiple pregnancies with HD (preeclampsia/gestational hypertension/uncontrolled chronic hypertension) and/or FGR in one or more fetuses. Methods: A retrospective analysis of multiple pregnancies with HD/FGR occurring after the 20th gestational week. Pregnant women were divided into two groups: women with high levels of sFlt-1 and those with low levels of sFlt-1. A value of sFlt-1 greater than or equal to 15,802 pg/mL was considered arbitrarily high, as it is equivalent to two times the 90th percentile expected in an uncomplicated full-term singleton pregnancy based on data from a prospective multicenter study (7901 pg/mL). Results: The cohort included 39 multiple pregnancies. There were no cases of birth <34 weeks, HELLP syndrome, ICU admission, and urgent cesarean sections for HD/FGR complications reported among women with low levels of sFlt-1. Conclusions: A cut-off value of sFlt-1 ≥ 15,802 pg/mL could represent a valuable tool for predicting adverse obstetric outcomes in multiple pregnancies hospitalized for HD/FGR disorders, regardless of gestational age and chorionicity.