Vascular endothelial damage in the pathogenesis of preeclampsia and SARS-CoV-2 infection in pregnancy

ABSTRACT

Background: Endothelial dysfunction is crucial in moderate to severe SARS-CoV-2 infection. Preeclampsia is an endothelial pregnancyrelated syndrome that shares some clinical and analytical features with COVID19. COVID19 signs in pregnant women might be misdiagnosed as preeclampsia leading to an iatrogenic preterm delivery. Aims: To address whether endothelial damage, microvascular thrombosis and dysregulated immune response exhibit different patterns in preeclampsia and COVID19 in pregnancy. Methods: Plasma samples were obtained from pregnant women with COVID19 pneumonia classified into moderate ( n = 10) or severe disease ( n = 9). Endothelial damage and immune response markers were assessed, including VCAM-1, TNF-receptor I (TNFRI), angiotensin II (ANGII), heparan sulfate (HS), PAI-1, dsDNA for neutrophil extracellular traps (NETs), C5b9, thrombomodulin (TM) and ADAMTS-13 activity. Results were compared to those in SARS-CoV-2 negative including healthy pregnant women as controls (C, n = 10), and patients with preeclampsia (PE, n = 13). Results: All endotheliopathy markers were significantly increased in severe COVID19 and PE patients compared to healthy pregnants ( p <0,05, Table 1), except TM and ADAMTS-13 activity. Patients with moderate COVID19 presented a biomarker profile similar to the observed in control patients. Severe COVID19 and PE profiles were distinctive among them regarding four markers VCAM-1, TNFRI and ANGII, clearly higher in PE, and HS, significantly lower in PE. The principal component analysis (PCA) in Figure 1, demonstrated the separation between severe COVID19 and PE from moderate COVID19 or uncomplicated pregnancies. The first and second components explained 29.1% and 18.4% of the variance between groups. (Figure Presented) Conclusions: Severe COVID19 exhibits signs of endothelial damage and immune dysregulation and some of them are shared with preeclampsia. However, there are specific markers with the potential to discriminate between both conditions. Investigation in this direction could help to develop new strategies for the prevention and treatment of both entities. Grants Fundació Clínic (HCB/2020/0401), JazzPharmaceuticals (IST-16-10355), Fundació La Marató de TV3 (202026-10).