Fetal and placental infection with SARS‐CoV‐2 in early pregnancy
María Yolotzín Valdespino-Vázquez, Addy Cecilia Helguera‐Repetto, Moisés León‐Juárez, Oscar Villavicencio‐Carrisoza, Arturo Flores‐Pliego, Elsa Romelia Moreno‐Verduzco, Diana L. Díaz‐Pérez, Maria Isabel Villegas-Mota, Elba Carrasco‐Ramírez, Irma López-Martı́nez, David M. Giraldo‐Gómez, Rosalía Lira, Martha Yocupicio‐Monroy, Mario Rodríguez‐Bosch, Edgar Sevilla-Reyes, Manuel Cortés‐Bonilla, Sandra Acevedo‐Gallegos, Horacio Merchant‐Larios, Jorge Arturo Cardona–Pérez, Claudine Irles
Abstract
To date, mother-to-fetus transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the coronavirus disease 2019 (COVID-19) pandemic, remains controversial. Although placental COVID-19 infection has been documented in some cases during the second- and third-trimesters, no reports are available for the first trimester of pregnancy, and no SARS-CoV-2 protein has been found in fetal tissues. We studied the placenta and fetal organs from an early pregnancy miscarriage in a COVID-19 maternal infection by immunohistochemical, reverse transcription quantitative real-time polymerase chain reaction, immunofluorescence, and electron microscopy methods. SARS-CoV-2 nucleocapsid protein, viral RNA, and particles consistent with coronavirus were found in the placenta and fetal tissues, accompanied by RNA replication revealed by double-stranded RNA (dsRNA) positive immunostain. Prominent damage of the placenta and fetal organs were associated with a hyperinflammatory process identified by histological examination and immunohistochemistry. The findings provided in this study document that congenital SARS-CoV-2 infection is possible during the first trimester of pregnancy and that fetal organs, such as lung and kidney, are targets for coronavirus. The infection and multi-organic fetal inflammation produced by SARS-CoV-2 during early pregnancy should alert clinicians in the assessment and management of pregnant women for possible fetal consequences and adverse perinatal outcomes.