sFlt-1/PlGF ratio in hypertensive disorders of pregnancy in patients affected by COVID-19

Abstract

Objectives To analyze soluble Fms-like tyrosine Kinase 1 (sFlt-1) and Placental Growth Factor (PlGF) ratio concentrations in COVID-19 pregnant patients with and without Hypertensive Disorders of Pregnancy (HDP), compared with non COVID-19 pregnant patients with HDP and a control group. Study design : We recruited and obtained a complete follow-up of 19 COVID-19 pregnant patients with HDP and of 24 COVID-19 normotensive pregnant patients. Demographic, clinical and sFlt-1/PlGF ratio findings were compared with a group of 185 non COVID-19 pregnant patients with HDP and 41 non COVID normotensive patients. Findings were based on univariate analysis and on a multivariate adjusted model, and a case by case analysis of COVID-19 pregnant patients with an abnormal sFlt-1/PlGF ratio >38 at recruitment. Main outcome measures : sFlt-1/PlGF ratio. Results We confirmed a significant higher prevalence of HDP in women affected by COVID-19 compared to control population. sFlt-1/PlGF ratio was found high in HDP patients, with and without of Sars-Cov2 infection. COVID-19 patients with worse evolution of the disease showed greater rates of obesity and other comorbidities. sFlt/PlGF ratio proved not to be helpful in the differential diagnosis of the severity of this infection. Conclusions COVID-19 pregnant patients showed a higher prevalence of HDP compared to non COVID-19 controls, as well as higher comorbidity rates. In spite of the possible common endothelial target and damage, between Sars-Cov-2 infection and HDP, the sFlt1/PlGF ratio did not correlate with the severity of this syndrome.

Role of biomarkers (sFlt-1/PlGF) in cases of COVID-19 for distinguishing preeclampsia and guiding clinical management

“…Increased sFlt-1/PlGF ratio or decreased PlGF values have been associated to adverse maternal and perinatal outcomes. [3] , [13] , [24] , [25] , [26] Studies indicate that COVID-19 in pregnancy can induce higher incidence of adverse perinatal outcomes, as well as PE-like syndrome. [24] , [25] , [26] The same studies suggest that the biomarkers testing (such as PlGF and sFlt-1/PlGF ratio) could be used to differentiate PE from severe COVID-19 and improve clinical management.…”

“…Adequate diagnosis is key in ascertaining appropriate clinical management, especially in cases of preterm gestation since the decision on the timing of delivery has a significant impact on perinatal outcomes. Because clinical parameters of hypertension, proteinuria, and target organ damage can be similar, biomarkers could be a useful tool in distinguishing and guiding such decision-making for cases that involve COVID-19 and preeclampsia [ 13 ]. The sFlt-1/PlGF ratio at a threshold of below 38 can provide reassurance for the absence of PE at that given time, as well as indicate a low likelihood of onset in the following week.…”

sFlt-1/PlGF Ratio Is Not a Good Predictor of Severe COVID-19 nor of Adverse Outcome in Pregnant Women with SARS-CoV-2 Infection—A Case-Control Study

“…Significant differences were observed between COVID-19 hypertensive and normotensive women and between non-COVID-19 hypertensive and COVID-19 normotensive patients. COVID-19 did not deteriorate the angiogenic imbalance in pregnant women [ 9 ].…”

“…sFlt-1 is a protein associated with endothelial damage, acute lung injury and syncytiotrophoblast hypoxia [ 8 ]. It impairs nitric oxide production and makes endothelial cells more sensitive to ANG II, which, in turn, makes them more vulnerable to damage [ 9 ]. sFlt-1 and placental growth factor (PlGF) are well known markers of placental hypoxia and predictors of preeclampsia (PE) [ 10 ].…”

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

“…In the participating hospitals, a substantial increase in preeclampsia is observed among women with pregnancy complicated by SARS-CoV-2 infection compared to women with a negative test (National Institute of Perinatology: 18 vs. 9%, General Hospital of Mexico: 12 vs. 5%). At a molecular level, there is an interaction between COVID-19 and PE, characterized by altered levels of angiogenic markers soluble fms-like tyrosine kinase (sFlt-1) and placental growth factor (PlGF) and higher sFlt-1/PlGF ratio ( 6 , 11 – 13 ). Serum sFlt-1 is an antiangiogenic protein released from many tissues that antagonizes serum PlGF and vascular endothelial growth factor [VEGF, promoting endothelial dysfunction ( 14 )].…”