Novel Ratio Soluble Fms-like Tyrosine Kinase-1/Angiotensin-II (sFlt-1/ANG-II) in Pregnant Women Is Associated with Critical Illness in COVID-19

Abstract

Background: In healthy pregnancies, components of the Renin-Angiotensin system (RAS) are present in the placental villi and contribute to invasion, migration, and angiogenesis. At the same time, soluble fms-like tyrosine kinase 1 (sFlt-1) production is induced after binding of ANG-II to its receptor (AT-1R) in response to hypoxia. As RAS plays an essential role in the pathogenesis of COVID-19, we hypothesized that angiogenic marker (sFlt-1) and RAS components (ANG-II and ACE-2) may be related to adverse outcomes in pregnant women with COVID-19; Methods: Prospective cohort study. Primary outcome was severe pneumonia. Secondary outcomes were ICU admission, intubation, sepsis, and death. Spearman’s Rho test was used to analyze the correlation between sFlt-1 and ANG-II levels. The sFlt-1/ANG-II ratio was determined and the association with each adverse outcome was explored by logistic regression analysis and the prediction was assessed using receiver-operating-curve (ROC); Results: Among 80 pregnant women with COVID-19, the sFlt-1/ANG-II ratio was associated with an increased probability of severe pneumonia (odds ratio [OR]: 1.31; p = 0.003), ICU admission (OR: 1.05; p = 0.007); intubation (OR: 1.09; p = 0.008); sepsis (OR: 1.04; p = 0.008); and death (OR: 1.04; p = 0.018); Conclusion: sFlt-1/ANG-II ratio is a good predictor of adverse events such as pneumonia, ICU admission, intubation, sepsis, and death in pregnant women with COVID-19.

sFlt-1 Is an Independent Predictor of Adverse Maternal Outcomes in Women With SARS-CoV-2 Infection and Hypertensive Disorders of Pregnancy

“…In our population, SARS-CoV-2 infection is an independent inflammation factor, added to the pre-existing due to preeclampsia; the significant increases in sFlt-1 concentrations can explain this compared with women with SARS-CoV-2 infection without preeclampsia. Previously, we suggested that interaction between viral spike protein (S) of SARS-CoV-2 and ACE-2 reduces ACE-2 levels in the cell membrane and generates an imbalance of Ang-II/Ang1-7, causing acute hypoxia, which induction and overproduction of sFlt-1, leading to systemic endothelial damage ( 15 , 37 ).…”

SARS-CoV-2 impacts the transcriptome and epigenome at the maternal-fetal interface in pregnancy

“…Apart from the increased risks of fetal demise and preterm birth, increased incidence of “preeclampsia-like syndrome” has been noted in pregnant patients with SARS-CoV-2 infection ( 2 ). Indeed, evidence suggests that preeclampsia and COVID-19 share similar clinical phenotypes of endothelial dysfunction and may have common pathophysiological mechanisms, especially those involving the renin-angiotensin system (RAS) ( 70–72 ). In healthy pregnancies, the RAS components contribute to invasion, migration, and angiogenesis of trophoblast cells ( 73, 74 ).…”

Placental Syndromes—A New Paradigm in Perinatology

“…Angiotensin-converting enzyme 2 was also found on trophoblast cells. Pregnant women with severe COVID-19 were found to have elevated maternal plasma concentration of sFlt-1 and a high sFlt-1/PlGF ratio, similar to those developing PE [ 56 ].…”