SARS–CoV-2 infection of the placenta
Hillary Hosier, Shelli F. Farhadian, Raffaella A. Morotti, Uma Deshmukh, Alice Lu-Culligan, Katherine H. Campbell, Yuki Yasumoto, Chantal B.F. Vogels, Arnau Casanovas-Massana, Pavithra Vijayakumar, Bertie Geng, Camila D. Odio, John Fournier, Anderson F. Brito, Joseph R. Fauver, Feimei Liu, Tara Alpert, Reshef Tal, Klara Szigeti-Buck, Sudhir Perincheri, Christopher Larsen, Aileen M. Gariepy, Gabriela Aguilar, Kristen L. Fardelmann, Malini Harigopal, Hugh S. Taylor, Christian M. Pettker, Anne L. Wyllie, Charles Dela Cruz, Aaron M. Ring, Nathan D. Grubaugh, Albert I. Ko, Tamas L. Horvath, Akiko Iwasaki, Uma M. Reddy, Heather S. Lipkind
Hillary Hosier, Shelli F. Farhadian, Raffaella A. Morotti, Uma Deshmukh, Alice Lu-Culligan, Katherine H. Campbell, Yuki Yasumoto, Chantal B.F. Vogels, Arnau Casanovas-Massana, Pavithra Vijayakumar, Bertie Geng, Camila D. Odio, John Fournier, Anderson F. Brito, Joseph R. Fauver, Feimei Liu, Tara Alpert, Reshef Tal, Klara Szigeti-Buck, Sudhir Perincheri, Christopher Larsen, Aileen M. Gariepy, Gabriela Aguilar, Kristen L. Fardelmann, Malini Harigopal, Hugh S. Taylor, Christian M. Pettker, Anne L. Wyllie, Charles Dela Cruz, Aaron M. Ring, Nathan D. Grubaugh, Albert I. Ko, Tamas L. Horvath, Akiko Iwasaki, Uma M. Reddy, Heather S. Lipkind
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Clinical Research and Public Health Reproductive biology

SARS–CoV-2 infection of the placenta

Abstract

BACKGROUND The effects of the novel coronavirus disease 2019 (COVID-19) in pregnancy remain relatively unknown. We present a case of second trimester pregnancy with symptomatic COVID-19 complicated by severe preeclampsia and placental abruption.METHODS We analyzed the placenta for the presence of severe acute respiratory syndrome coronavirus 2 (SARS–CoV-2) through molecular and immunohistochemical assays and by and electron microscopy and measured the maternal antibody response in the blood to this infection.RESULTS SARS–CoV-2 localized predominantly to syncytiotrophoblast cells at the materno-fetal interface of the placenta. Histological examination of the placenta revealed a dense macrophage infiltrate, but no evidence for the vasculopathy typically associated with preeclampsia.CONCLUSION This case demonstrates SARS–CoV-2 invasion of the placenta, highlighting the potential for severe morbidity among pregnant women with COVID-19.FUNDING Beatrice Kleinberg Neuwirth Fund and Fast Grant Emergent Ventures funding from the Mercatus Center at George Mason University. The funding bodies did not have roles in the design of the study or data collection, analysis, and interpretation and played no role in writing the manuscript.

Authors

Hillary Hosier, Shelli F. Farhadian, Raffaella A. Morotti, Uma Deshmukh, Alice Lu-Culligan, Katherine H. Campbell, Yuki Yasumoto, Chantal B.F. Vogels, Arnau Casanovas-Massana, Pavithra Vijayakumar, Bertie Geng, Camila D. Odio, John Fournier, Anderson F. Brito, Joseph R. Fauver, Feimei Liu, Tara Alpert, Reshef Tal, Klara Szigeti-Buck, Sudhir Perincheri, Christopher Larsen, Aileen M. Gariepy, Gabriela Aguilar, Kristen L. Fardelmann, Malini Harigopal, Hugh S. Taylor, Christian M. Pettker, Anne L. Wyllie, Charles Dela Cruz, Aaron M. Ring, Nathan D. Grubaugh, Albert I. Ko, Tamas L. Horvath, Akiko Iwasaki, Uma M. Reddy, Heather S. Lipkind

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Figure 2

Examination of SARS–CoV-2 RNA in maternal and fetal tissue.

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Examination of SARS–CoV-2 RNA in maternal and fetal tissue. (A) SARS–CoV...
(A) SARS–CoV-2 qRT-PCR results of fetal and maternal samples using the CDC assay which consists of the N1 and N2 primers and probes targeting the coronavirus nucleocapsid and the RP primers and probe targeting human RNase P as an internal control. Ct values from both N1 and N2 must be below 38 for the result to be positive, as internally validated. Virus titers are shown as the average calculation from N1 and N2 Ct values. For the tissues, 80–160 mg was used for extractions, and for the swabs in viral transport media and other liquid samples, 0.25–0.4 mL was used. ND, not detected. (B) The SARS–CoV-2 genome sequenced from the infected placenta was combined with 289 other genomes available from GISAID from around the world. The phylogenetic tree was constructed using IQ-TREE (http://www.iqtree.org/) within the Nextstrain Augur pipeline, and the results were visualized using Auspice (28). Genetic divergence is shown as substitutions per site from the root. An enlarged view of the 18 genomes in the clade that contains the SARS–CoV-2 genome sequenced from the placenta (USA/Connecticut-Yale-050) is shown. The clade is defined by 3 nucleotide substitutions, A28881A, G28882A, and G28883C, providing the equivalent of approximately 95% branch support. The consensus SARS–CoV-2 genome from the placenta (Yale-050) can be found using NCBI’s BioProject PRJNA614976 and the phylogenetic data can be visualized at Nexstrain (https://nextstrain.org/community/grubaughlab/CT-SARS-CoV-2/paper2). The Acknowledgments for the sequences obtained from GISAID can be found at Nexstrain (https://github.com/grubaughlab/CT-SARS-CoV-2/tree/master/paper2).