Persistence of SARS-CoV-2 in the First Trimester Placenta Leading to Transplacental Transmission and Fetal Demise From an Asymptomatic Mother

Prajakta Shende; Pradip Gaikwad; Manisha Gandhewar; Pawankumar Ukey; Anshul Bhide; Vainav Patel; Sharad Bhagat; Vikrant Bhor; Smita Mahale; Rahul Gajbhiye; Deepak Modi

Disclosures

Hum Reprod. 2021;36(4):899-906. 

In This Article

Abstract and Introduction

Abstract

Coronavirus disease 2019 (COVID-19) is caused by infection of the respiratory tract by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which survives in the tissues during the clinical course of infection but there is limited evidence on placental infection and vertical transmission of SARS-CoV-2. The impact of COVID-19 in first trimester pregnancy remains poorly understood. Moreover, how long SARS-CoV-2 can survive in placenta is unknown. Herein, we report a case of a pregnant woman in the first trimester who tested positive for SARS-CoV-2 at 8 weeks of gestation, although her clinical course was asymptomatic. At 13 weeks of gestation, her throat swab tested negative for SARS-CoV-2 but viral RNA was detected in the placenta, and the Spike (S) proteins (S1 and S2) were immunolocalized in cytotrophoblast and syncytiotrophoblast cells of the placental villi. Histologically, the villi were generally avascular with peri-villus fibrin deposition and in some areas the syncytiotrophoblast layer appeared lysed. The decidua also had fibrin deposition with extensive leukocyte infiltration suggestive of inflammation. The SARS-CoV-2 crossed the placental barrier, as the viral RNA was detected in the amniotic fluid and the S proteins were detected in the fetal membrane. Ultrasonography revealed extensively subcutaneous edema with pleural effusion suggestive of hydrops fetalis and the absence of cardiac activity indicated fetal demise. This is the first study to provide concrete evidence of persistent placental infection of SARS-CoV-2 and its congenital transmission is associated with hydrops fetalis and intrauterine fetal demise in early pregnancy.

Introduction

In March 2020, the World Health Organization declared coronavirus disease 2019 (COVID-19) as a global pandemic. Caused by infection of the respiratory tract with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the numbers of confirmed cases have escalated rapidly. Despite this, the information on the effects of SARS-CoV-2 infection in pregnancy is limited to description of presenting symptoms and outcomes during late trimester infections (Allotey et al., 2020; Gajbhiye et al., 2020; Waghmare et al., 2021). Since the maternal physiology changes dynamically throughout pregnancy, the information on late trimester infections cannot be extrapolated directly to infection earlier in gestation.

During pregnancy, the placenta is an anatomical barrier that acts as the first line of defense to avoid transmission of pathogens from mother to fetus. However, some infectious agents can breach the placental barrier resulting in vertical transmission and activating innate immune responses causing major maternal and fetal complications (Parker et al., 2020). For pregnant women with COVID-19, vertical transmission of SARS-CoV-2 and the pregnancy complications like miscarriage, fetal malformations and/or stillbirth, are potentially serious concerns. The spike (S) proteins of SARS-CoV-2 bind to the host receptor ACE2 allowing the virus to enter the cells and replicate (Hoffmann et al., 2020; Jagtap et al., 2020). The placental syncytiotrophoblast, cytotrophoblasts and the extra-villous trophoblasts express the ACE2 receptors and also the genes necessary for S protein processing, viral replication and budding (Ashary et al., 2020; Colaco et al., 2020; Singh et al., 2020; Taglauer et al., 2020). These observations imply that the placenta is permissive for SARS-CoV-2 infection. Indeed, SARS-CoV-2 RNA and protein are detected in placenta of mothers with COVID-19 (Ashary et al., 2020; Hosier et al., 2020; Taglauer et al., 2020; Vivanti et al., 2020). In clinical cases and experimentally induced infections, SARS-CoV-2 is detected in multiple tissues (Best Rocha et al., 2020; Bradley et al., 2020; Chandrashekar et al., 2020; Costa et al., 2020; Yao et al., 2020; Zhang et al., 2020) during acute viremia; extended periods of viral shedding after clearing pulmonary infection have also been observed (Gupta et al., 2020; Wu et al., 2020; Zhang et al., 2020). Whether SARS-CoV-2 can also survive and shed from the placenta for extended periods is hitherto unknown.

Congenital infection of SARS-CoV-2 from feto-maternal interface is a matter of controversy. Some case series suggest that there is lack of vertical transmission of SARS-CoV-2 (Masmejan et al., 2020; Li et al., 2020b). However, large-scale systematic reviews reveal that a proportion of babies born to mother with COVID-19 are positive for viral RNA (Allotey et al., 2020; Gajbhiye et al., 2020). Whether this infection is due to transmission of SARS-CoV-2 in utero or the infection is acquired during the course of delivery or after birth remains unclear.

Herein, we report a case of first trimester asymptomatic SARS-CoV-2 infection associated with hydrops fetalis and fetal death. We observed that the viremia persisted in the placenta weeks after the mother cleared it from the pulmonary tract and there was transplacental transmission as SARS-CoV-2 could be detected in the amniotic fluid and fetal membranes.

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