Placental Vascular Malperfusion and Perinatal Outcomes During the Vasculotropic Viral Surge of Endemic SARS-CoV-2: A 50-Month Multicenter Longitudinal Study

Abstract

The re-emergence of seasonal respiratory pathogens has complicated obstetric care following the transition of coronavirus disease 2019 to an endemic state. The study examined the epidemiological impact and pathogenetic characteristics associated with endemic viruses among pregnant women. A multicenter retrospective cohort study was conducted using an epidemiological dataset of 9647 consecutive deliveries from 2022 to 2026. A nested clinical sub-cohort of 140 hospitalized patients was divided into coronavirus disease 2019 (67 cases) and other respiratory infections (73 cases) groups. The study compared epidemiological trends, predictive biomarkers (neutrophil-to-lymphocyte ratio and C-reactive protein level), and placental histopathology. The analysis showed an asymmetric U-shaped trend in adverse perinatal events over the study period (N = 9647). Following the nadir of eight stillbirths in 2024, a viral resurgence in 2025 resulted in a 2.6-fold increase in stillbirth risk, primarily linked to preeclampsia and placental abruption. Furthermore, within the clinical sub-cohort, the coronavirus disease 2019 group exhibited a significantly elevated neutrophil-to-lymphocyte ratio, which effectively predicted subclinical maternal vascular malperfusion. The increase in stillbirths between 2025 and 2026 may be exacerbated by waning population immunity and the vasculotropic properties of endemic coronavirus disease 2019. The neutrophil-to-lymphocyte ratio can serve as a useful biomarker for detecting subclinical thrombotic risk.