Antenatal SARS-CoV-2 infection has been proposed as a risk factor for development of hypertensive disorders of pregnancy (HDP) [1], [2], [3], [4], [5], [6], [7], [8]. An association between SARS-CoV-2 infection and HDP has been shown in some studies [2], [8], [9], [10], while no association has been found in others [11], [12], [13], [14]. In general, the pathophysiological mechanisms of HDP have yet to be fully elucidated, however delivery of the placenta leads to resolution of symptoms, suggesting a central role for the placenta in HDP pathogenesis [15]. Antenatal SARS-CoV-2 infection results in endothelial dysfunction and microangiopathy both systemically and specifically in the placenta [16], [17], [18], [19], [20], [21]. Placentas from SARS-CoV-2 positive mothers have shown features associated with fetal and maternal vascular malperfusion, including the presence of fibrin deposition, abnormal maternal vessels, intervillous thrombi, and avascular villi [5], [18], [19], [20], [21]. Given evidence of endothelial dysfunction in the placenta in both diseases, it is plausible that SARS-CoV-2 and HDP share similar downstream pathophysiologic pathways.

While these observations imply an association between SARS-CoV-2 infection and HDP, clinical evidence is conflicting. Various meta-analyses report an association between antenatal SARS-CoV-2 and increased incidence of HDP and pre-eclampsia [1], [2], [3], [4], [5], [6], [7], [8]. Others including both retrospective cohort studies and larger meta-analyses have found no association [2], [14], [22]. One of the major limitations of the literature is the heterogeneity of SARS-CoV-2 testing protocols which changed and evolved throughout the pandemic. As many of the currently published retrospective studies did not utilize universal testing for SARS-CoV-2, it is likely that individuals with asymptomatic infection are underrepresented or aberrantly classified as SARS-CoV-2 negative participants.

This analysis specifically investigates the impact of antenatal SARS-CoV-2 infection and subsequent development of HDP in a large, diverse, prospective pregnancy cohort early in the pandemic.