Authors' reply re: Pre‐eclampsia‐like syndrome induced by severe COVID‐19: a prospective observational study

Sir, Thank you for the opportunity to respond to the letter from Leavitt and colleagues. We would like to thank them for their interest in our study and their valuable observations. We agree with Leavitt and colleagues that a similar underlying pathophysiology (endothelial damage) may exist in both pre-eclampsia (PE) and COVID19, which may explain most of their common clinical manifestations. Other authors have suggested that the signs and symptoms of PE present in some pregnant women with COVID-19 could be a consequence of the placental dysfunction due to intravascular inflammation associated with the infection, leading to a prothrombotic state in the placenta. This hypothesis is supported by the higher rates of maternal vascular malperfusion features observed from placentas of women with COVID-19. Although this hypothesis has biological plausibility, previous studies have shown a correlation between placental histological findings consistent with maternal underperfusion and anti-angiogenic status. By contrast, in our study we did not find increased soluble fms-like tyrosine kinase-1/placental growth factor values in most of the women with COVID-19 and signs and symptoms of PE. For this reason, we believe that the placental malperfusion due to COVID-19 is unlikely to be the main aetiology of the PE-like syndrome. Thus, we agree with Leavitt and colleagues that the shared pathophysiology between COVID-19 and PE is probably related to immunothrombosis and decreased alpha-1antitrypsin (AAT) and that further research is needed to better understand the causes of PE and PE-like syndrome in order to achieve appropriate treatments for these conditions.&