COVID-19 and preeclampsia: cause or consequence?

Abstract

Preeclampsia is a major cause of maternal morbidity and mortality worldwide, especially in low- and middle-income settings, where Covid-19 has also presented significant impact. The possible association between COVID-19 and PE is still controversial in the literature, with conflicting results. The physiological basis for such association is that the SARS-CoV-2 infection occurs within the renin-angiotensin system (RAS). Decreased levels of angiotensin converting enzyme 2 (ACE2) are associated with increased risk of preeclampsia (PE), and ACE2 is the pathway to viral infection in different cell types. Furthermore, both conditions progress with intense inflammatory and vascular activation. Objective: to evaluate whether the infection by SARS-CoV-2 during pregnancy increases the risk for the occurrence of preeclampsia and adverse outcomes and if the determination of angiogenesis-related factors (sFLIT-1 and PlGF) can assist the diagnosis of preeclampsia in COVID-19 infected women. Method: Study in two phases at a referral maternity hospital. First phase with retrospective assessment and dosage of biomarkers (automated Elecsys® sFlt-1 / PlGF) in 100 samples of pregnant, non-vaccinated, women with suspected or confirmed COVID-19, correlating with maternal and perinatal outcomes and PE diagnosis. At this stage, the limitation is at the time of collection of maternal serum, a single collection, in suspected COVID-19, and not necessarily at the time of PE diagnosis, but it may provide relevant initial results. Phase 2 will be a prospective cohort study, with monitoring of 300 pregnant women during antenatal care and serial investigation for COVID-19 (with serology and RT-qPCR in 3 moments: antenatal care admission, 28 weeks and childbirth), defining exposed cases and not exposed to SARS-CoV-2 infection, to compare the frequency of pre-eclampsia, maternal and perinatal outcomes and biomarker measurements. Vaccination (type of vaccine and number of doses) will be considered, introducing this variable in the assessment of exposed and unexposed. Quantitative data obtained, and statistical analysis will be assessed for normality of data distribution. For the comparison of two variables with normal distribution, Student's t test will be considered and for three or more variables with normal distribution the ANOVA test will be the chosen statistical test. For comparisons of dichotomous variables, the Chi-square or Fisher's exact will be considered. (AU)