SARS-CoV-2 Infection Exacerbates Hypertensive Disorders in Pregnancy Through Vascular and Immune Pathways

Background: SARS-CoV-2 infection has been linked to an increased risk of hypertensive disorders during pregnancy, particularly preeclampsia (PE). As both conditions involve vascular and endothelial dysfunction, a mechanistic overlap has been proposed. This study examines the relationship between maternal COVID-19 and preeclampsia by analyzing inflammatory, endothelial, and angiogenic biomarkers in pregnancies with and without these complications. Methods: A case–control study was conducted, including four groups: healthy pregnancies before 2020 (n = 10), preeclampsia cases before 2020 (n = 10), COVID-19 cases without preeclampsia (n = 10), and COVID-19 cases with preeclampsia (n = 10). The groups were selected to be comparable in terms of gestational age at blood sampling. Biomarkers related to endothelial, inflammatory, and angiogenic pathways were measured. Results: Significant differences in biomarker levels were detected among the four groups. Regarding endothelial damage, sICAM1 levels were significantly higher in the COVID-PE group compared with the COVID-noPE group (p = 0.002). Additionally, vWF (p = 0.006), END1 (p < 0.001), and sVCAM1 (p = 0.030) levels varied significantly across groups. IL8 levels showed significant differences (p < 0.001), and were particularly elevated in preeclampsia cases (preCOVID-PE and COVID-PE groups) compared with controls (p = 0.005 and p < 0.001, respectively). Angiogenic markers sFlt-1, PLGF, and sFlt-1/PLGF exhibited significant group differences (p < 0.001). In contrast, maternal SARS-CoV-2 infection in the absence of preeclampsia was not associated with a significant alteration of the sFlt-1/PlGF ratio. Discussion: PE associated with SARS-CoV-2 infection preserved the classical angiogenic signature of preeclampsia, but showed additional endothelial and inflammatory biomarker alterations. These findings support an association between SARS-CoV-2 infection and a distinct endothelial and inflammatory biomarker profile in PE, warranting confirmation in larger prospective studies.