Increased levels of soluble fms‐like tyrosine kinase‐1 are associated with adverse outcome in pregnant women with COVID‐19

Abstract

Objective In addition to the lungs, the placenta and the endothelium can be affected by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Soluble fms‐like tyrosine kinase‐1 (sFlt‐1) and placental growth factor (PlGF) are markers of endothelial dysfunction and could potentially serve as predictors of severe coronavirus disease 2019 (COVID‐19). We aimed to investigate the association of serum concentrations of sFlt‐1 and PlGF with the severity of COVID‐19 in pregnancy. Methods This was a prospective cohort study carried out in a tertiary care hospital in Mexico City, Mexico. Symptomatic pregnant women with a positive reverse‐transcription quantitative polymerase chain reaction test for SARS‐CoV‐2 infection who fulfilled the criteria for hospitalization were included. The primary outcome was severe pneumonia due to COVID‐19. Secondary outcomes were intensive care unit (ICU) admission, viral sepsis and maternal death. sFlt‐1 levels were expressed as multiples of the median (MoM). The association between sFlt‐1 and each adverse outcome was explored by logistic regression analysis, adjusted for gestational age for outcomes occurring in more than five patients, and the predictive performance was assessed by receiver‐operating‐characteristics‐curve analysis. Results Among 113 pregnant women with COVID‐19, higher sFlt‐1 MoM was associated with an increased probability of severe pneumonia (adjusted odds ratio (aOR), 1.817 (95% CI, 1.365–2.418)), ICU admission (aOR, 2.195 (95% CI, 1.582–3.047)), viral sepsis (aOR, 2.318 (95% CI, 1.407–3.820)) and maternal death (unadjusted OR, 5.504 (95% CI, 1.079–28.076)). At a 10% false‐positive rate, sFlt‐1 MoM had detection rates of 45.2%, 66.7%, 83.3% and 100% for severe COVID‐19 pneumonia, ICU admission, viral sepsis and maternal death, respectively. PlGF values were similar between women with severe and those with non‐severe COVID‐19 pneumonia. Conclusion sFlt‐1 MoM is higher in pregnant women with severe COVID‐19 and has the capability to predict serious adverse pregnancy events, such as severe pneumonia, ICU admission, viral sepsis and maternal death. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Imbalanced Angiogenesis in Pregnancies Complicated by SARS-CoV-2 Infection

“…PlGF values were not significantly different between severe and non-severe pregnant cases of COVID-19 pneumonia. A subsequent publication by the same group has shown that sFlt-1 MoM values are higher in pregnant women with severe COVID-19 and they can be used as a predictor of medical complications, similarly to sFlt-1/ANG-II [ 19 ].…”

“…Recently, Espino-y-Sosa and colleagues have shown that high levels of sFlt-1/ANG-II are associated with adverse outcomes, including severe pneumonia, intensive care unit (ICU) admission, intubation, viral sepsis, and death, among SARS-CoV-2-infected pregnant women [ 18 ]. Subsequently, the same group has identified higher values of sFlt-1 MoM in pregnant women with severe COVID-19 and that these values could be used as a predictor of medical complications, similarly to sFlt-1/ANG-II [ 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 ).…”

“…Thus, PE and COVID-19 share a vascular–endothelial physiopathological pathway that may aggravate or worsen women's outcomes when both coexist. We hypothesize that this synergic effect is exemplified in sFlt-1 levels among PE and COVID-19 and that there may be an interaction between hypertensive disorders of pregnancy (HDP), COVID-19, and sFlt-1 levels that is reflected in the incidence of adverse maternal outcomes ( 15 ). Therefore, this study aims to evaluate the association between sFlt-1 levels and adverse maternal outcomes among positive SARS-CoV-2 pregnant women controlled by HDP.…”

COVID‐19 and stillbirth: direct vs indirect effect of the pandemic

“…Further research is needed into the risk factors associated with adverse outcomes due to COVID-19 in pregnant women 78,79 , such as gestational age at, and severity of, infection. This would enable early identification of those at increased risk, facilitating the development of antenatal surveillance and targeted intervention, and ensure that they are offered COVID-19 vaccination early.…”