Placental lesions and SARS-Cov-2 infection: Diffuse placenta damage associated to poor fetal outcome

Abstract

Introduction Pregnant women with covid-19 are more likely to experience preterm birth. The virus seems to be associated with a wide range of placental lesions, none of them specific. Method We collected cases of Covid-19 maternal infection during pregnancy associated with poor pregnancy outcomes, for which we received the placenta. We studied clinical data and described pathological findings of placenta and post-mortem examination of fetuses. We performed an immunohistochemical study and RT-PCR of SARS-Cov-2 on placenta samples. Results We report 5 cases of poor fetal outcome, 3 fetal deaths and 2 extreme premature neonates, one with growth restriction, without clinical and biological sign of SARS-Cov-2 infection. All placenta presented massive perivillous fibrin deposition and large intervillous thrombi associated with strong SARS-Cov-2 expression in trophoblast and SARS-CoV-2 PCR positivity in amniotic fluid or on placenta samples. Chronic histiocytic intervillositis was present in 4/5 cases. Placental ultrasound was abnormal and the sFLT1-PIGF ratio was increased in one case. Timing between mothers’ infection and the poor fetal outcome was ≤10 days in 4 cases. The massive placental damage are directly induced by the virus whose receptors are expressed on trophoblast, leading to trophoblast necrosis and massive inflammation in villous chamber, in a similar way it occurs in diffuse alveolar damage in adults infected by SARS-Cov-2. Discussion SARS-Cov-2 can be associated to a rare set of placental lesions which can lead to fetal demise, preterm birth, or growth restriction. Stronger surveillance of mothers infected by SARS-Cov-2 is required.

Severe placental lesions due to maternal SARS-CoV-2 infection associated to intrauterine fetal death

“…This was supported by immunohistochemical studies showing positivity of villous trophoblast with SARS-CoV-2 antibodies. Otherwise, decidua arteriopathy was not seen but rather hemorrhagic changes dissociating the decidua, which is in agreement with literature [ 12 ]. Unlike other authors, we did not find fetal vascular thrombi [ 13 ].…”

“…On the clinical level, these lesions were observed between the 7 th day and the 20 th day after maternal infection occurred which is in agreement with observation in the literature [ 12 ].…”

COVID‐19 and vertical transmission: assessing the expression of ACE2/TMPRSS2 in the human fetus and placenta to assess the risk of SARS‐CoV‐2 infection

“…Furthermore, placental pathology including fibrin deposition and intervillous thrombosis associated with preterm labour, have been sporadically observed in SARS‐CoV2‐positive mothers, linked to immunochemical evidence of virus expression in the trophoblast. 13 , 40 One possible reason for discordant results within the published literature may be the widespread presence of Fc receptors in the human placenta, as these are known to bind antibodies to varying affinities 41 and may therefore lead to non‐specific staining. This emphasises the need for molecular validation, such as the RT‐qPCR or RNA‐seq data presented here together with the placental immunohistochemistry studies.…”

“…Therefore, understanding the potential for, and impact of, mid‐gestation fetal infection remains an ongoing public health question. Various mechanisms of vertical transmission have been hypothesised: direct infection of syncytiotrophoblast with subsequent transmission through the cytotrophoblast has been demonstrated in several histopathological and immunological studies 11 , 12 , 13 and appears not to involve the fetal‐origin Hofbauer cells in the majority of transplacental infections. 14 Infection via trafficked maternal cells has been suggested, as evidenced by an observed expression of ACE2 protein in infiltrating maternal cells in human placentas with chorioamnionitis.…”

Delayed Antiviral Immune Responses in Severe Acute Respiratory Syndrome Coronavirus Infected Pregnant Mice

“…Moreover, the SARS-CoV-2 virions had been found in the placenta of SARS-CoV-2 infected patients, which was complicated by severe preeclampsia and placental abruption (Hosier et al, 2020). The diffuse pathological changes in the placenta could be more likely associated with poor fetal outcomes rather than fetus infection (Bouachba et al, 2021;Cribiù et al, 2021). Some investigations revealed that the IgM or SARS-CoV-2 RNA had been detected in newborn infants (Juan et al, 2020;Song et al, 2021).…”