Special Report
A standardized definition of placental infection by SARS-CoV-2, a consensus statement from the National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health and Human Development SARS-CoV-2 Placental Infection Workshop

https://doi.org/10.1016/j.ajog.2021.07.029Get rights and content

Pregnant individuals infected with SARS-CoV-2 have higher rates of intensive care unit admission, oxygen requirement, need for mechanical ventilation, and death than nonpregnant individuals. Increased COVID-19 disease severity may be associated with an increased risk of viremia and placental infection. Maternal SARS-CoV-2 infection is also associated with pregnancy complications such as preeclampsia and preterm birth, which can be either placentally mediated or reflected in the placenta. Maternal viremia followed by placental infection may lead to maternal-fetal transmission (vertical), which affects 1% to 3% of exposed newborns. However, there is no agreed-upon or standard definition of placental infection. The National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health and Human Development convened a group of experts to propose a working definition of placental infection to inform ongoing studies of SARS-CoV-2 during pregnancy. Experts recommended that placental infection be defined using techniques that allow virus detection and localization in placental tissue by one or more of the following methods: in situ hybridization with antisense probe (detects replication) or a sense probe (detects viral messenger RNA) or immunohistochemistry to detect viral nucleocapsid or spike proteins. If the abovementioned methods are not possible, reverse transcription polymerase chain reaction detection or quantification of viral RNA in placental homogenates, or electron microscopy are alternative approaches. A graded classification for the likelihood of placental infection as definitive, probable, possible, and unlikely was proposed. Manuscripts reporting placental infection should describe the sampling method (location and number of samples collected), method of preservation of tissue, and detection technique. Recommendations were made for the handling of the placenta, examination, and sampling and the use of validated reagents and sample protocols (included as appendices).

Key words

COVID-19
fetal death
immunohistochemistry
in situ hybridization
placental infection
placentitis
preeclampsia
preterm birth
SARS-CoV-2
stillbirth
syncytiotrophoblast
vertical transmission

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D.J.R., A.G.E., and R.J.R. share first authorship.

Meeting date: March 9, 2021.

D.J.R. received royalties for authorship on perinatal pathology topics for UpToDate and Cambridge University Press, neither of which should impact this manuscript. J.L.H. is a consultant for Aadi Bioscience and TRACON Pharmaceuticals, unrelated to the topic of this manuscript. D.T.T. is a consultant for ROME Therapeutics, NanoString Technologies, Pfizer, Merrimack Pharmaceuticals, Ventana Roche, Foundation Medicine, Inc, and EMD Millipore Sigma, which are not related to this work. D.T.T. is a founder and has equity in ROME Therapeutics, PanTher Therapeutics, and TellBio, Inc, which is not related to this work. D.T.T. receives sponsored research support from ACD Bio-Techne for RNA in situ hybridization, which is related to this manuscript. D.T.T.’s interests were reviewed and are managed by Mass General Brigham in accordance with their conflict of interest policies. T.D.M. is a site principal investigator (PI) and medical consultant for a Pfizer trial of SARS-CoV-2 vaccination in pregnancy. T.D.M. receives UpToDate royalties and was the site PI for a Novavax and GestVision trial, which are unrelated to this work. The remaining authors report no conflict of interest.

This research was supported, in part, by the Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, United States Department of Health and Human Services (NICHD/NIH/DHHS), and, in part, with federal funds from NICHD/NIH/DHHS under contract number HHSN275201300006C. R.J.R. has contributed to this work as part of his official duties as an employee of the United States Federal Government.

The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

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