Blood Test Identifies Stillbirth, Placentitis in Women with COVID-19

Recent reports have identified an increased risk of stillbirth in pregnant people infected with SARS-CoV-2. Perinatal pathologists have identified specific placental pathology, termed COVID placentitis, associated with a high risk of stillbirth and poor neonatal outcome.

COVID placentitis, characterized by histiocytic intervillositis, increased perivillous fibrin deposition, and villous trophoblast necrosis, has been associated with direct viral infection of the syncytiotrophoblast layer of the placenta. A blood test may identify pregnant women with COVID-19 who are at higher risk for stillbirth and placentitis.

Image: CloneJET PCR Cloning Kit is an advanced positive selection system for high-efficiency cloning of PCR products generated with any thermostable DNA polymerase (Photo courtesy of ThermoFisher Scientific)

Clinical Scientists at the Northwestern University Feinberg School of Medicine (Chicago, IL, USA) and their colleagues identified six patients diagnosed with COVID placentitis on pathologic examination and with maternal plasma samples collected and 12 matched controls that had SARS-CoV-2 infection without COVID placentitis. The control cases were matched for gestational age at birth and time between SARS-CoV-2 infection and delivery.

COVID placentitis was diagnosed based on the presence of histiocytic intervillositis confirmed with immunohistochemical staining for CD68 and increased perivillous fibrin deposition in the context of maternal SARS-CoV-2 infection. The percentage of villous parenchyma involved was estimated using both gross and microscopic evidence of involvement. Viral RNA was extracted from clinical specimens utilizing the QIAamp Viral RNA Minikit (Qiagen, Hilden, Germany). Testing for SARS-CoV-2 presence was performed by qRT-PCR with the CDC 2019-nCoV RT-PCR Diagnostic Panel utilizing the N1 probe in SARS-CoV-2 and RNASE P probe for sample quality control. All replicates were amplified and on-target amplification was verified by TOPO cloning (CloneJET PCR Cloning Kit, Thermo Fisher Scientific, Waltham, MA, USA) and Sanger sequencing of the N1 qPCR product.

The investigators reported that among the patients with placentitis, one had asymptomatic SARS-CoV-2 infection, four had mild infections and one had moderate infection. There was one stillbirth in the placentitis group. Two women with placentitis were viremic, including the patient who had a stillbirth, while viremia was not detected in the group without placentitis. Cloning and Sanger sequencing of the qRT-PCR products confirmed specific on-target amplification of SARS-CoV-2 in two samples.

Leena B. Mithal, MD, an assistant professor of pediatric infectious diseases and the lead author of the study, said, “Right now, we don’t know if there’s placentitis until after delivery. We’re laying groundwork for further studies so that in the future, people who are diagnosed with COVID during pregnancy may be able to get a test that will help identify pregnancies that may be at higher risk of stillbirth or fetal distress.” The study was published in the April, 2022 issue of the journal Placenta.

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Northwestern University Feinberg School of Medicine 
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