COVID-19 during Pregnancy: Clinical and In Vitro Evidence against Placenta Infection at Term by SARS-CoV-2

Colson, Arthur; Depoix, Christophe L.; Dessilly, Géraldine; Baldin, Pamela; Danhaive, Olivier; Hubinont, Corinne; Sonveaux, Pierre; Debiève, Frédéric

Despite occasional reports of SARS-CoV-2 vertical transmission during pregnancy, the question of placental infection and its consequences for the newborn remain questionable. Here, we analyzed the placentas of 31 COVID-19-positive mothers by RT-PCR, immunohistochemistry and in situ hybridization. We only detected one case of placental infection, which was associated with intrauterine demise of the fetus. We then isolated and differentiated primary trophoblasts from non-pathological human placentas at term, and exposed them to SARS-CoV-2 virions. Unlike for positive control cells Vero E6, we were not able to detect the virus inside cytotrophoblasts and syncytiotrophoblasts or in the supernatant four days after infection. As a mechanism of defense, we hypothesized that trophoblasts at term do not express ACE2 and TMPRSS, the two main host membrane receptors for SARS-CoV-2 entry. The quantification of these proteins in the placenta during pregnancy confirmed the absence of TMPRSS2 at the surface of the syncytium. Surprisingly, a transiently induced experimental expression of TMPRSS2 did not allow the entry or replication of the virus in differentiated trophoblasts. Altogether, these results underline that trophoblasts are not likely to be infected by SARS-CoV-2 at term, but the reported case raises concern about preterm infection.