Differences in placental pathology between COVID-19-induced preeclampsia-like syndrome and true preeclampsia

Abstract Background. Women with COVID-19 may develop preeclampsia-like syndrome, which shares some of the clinical features of preeclampsia (PE) but lacking its characteristic angiogenic imbalance (elevated soluble fms-like tyrosine kinase-1-to-placental growth factor ratio (sFlt-1/PlGF ratio)), suggesting the absence of placental involvement. The aim of this study was to investigate whether pathological placental changes associated with PE, such as maternal vascular malperfusion (MVM), may be useful to discriminate true PE from COVID-19-induced PE-like syndrome. Methods. Prospective cohort study conducted from February 2020 to September 2021. Inclusion criteria were pregnancies with SARS-CoV-2 infection that met the diagnostic criteria for PE at ≥ 20 weeks. Cases with a normal sFlt-1/PlGF ratio (≤ 38) were classified as PE-like syndrome and cases with an abnormal sFlt-1/PlGF ratio were classified as true PE. A perinatal pathologist blinded to group allocation performed the placental histopathological examination for signs of MVM following the Amsterdam criteria. Results. During the study period, 106 pregnant women with severe COVID-19 were admitted to the Intensive Care Unit. Among them, 15 (14.2%) met the diagnostic criteria for PE, and 11 placentas (73.3%) were available for histopathological examination. Of the 5 true PE cases (median sFlt-1/PlGF ratio of 137.9; IQR: 63.7-302.2), 80.0% had placentas with maternal vascular malperfusion (MVM). In contrast, none of the 6 PE-like syndrome cases (median sFlt-1/PlGF ratio of 5.53; IQR: 4.02–14.6) had placentas that met the MVM criteria. Conclusions. None of the placentas from cases with PE-like syndrome had histopathological criteria of MVM, while 80.0% of the placentas from cases with true PE showed high-grade MVM. The absence of MVM in PE-like syndrome supports the initial evidence based on angiogenic factors: PE-like syndrome and true PE are different conditions with similar clinical features, but different etiologies.