SARS-CoV-2 outbreak is the first pandemic of the century. SARS-CoV-2 infection is transmitted through droplets; other transmission routes are hypothesized but not confirmed. So far, it is unclear whether and how SARS-CoV-2 can be transmitted from the mother to the fetus. We demonstrate the transplacental transmission of SARS-CoV-2 in a neonate born to a mother infected in the last trimester and presenting with neurological compromise. The transmission is confirmed by comprehensive virological and pathological investigations. In detail, SARS-CoV-2 causes: (1) maternal viremia, (2) placental infection demonstrated by immunohistochemistry and very high viral load; placental inflammation, as shown by histological examination and immunohistochemistry, and (3) neonatal viremia following placental infection. The neonate is studied clinically, through imaging, and followed up. The neonate presented with neurological manifestations, similar to those described in adult patients.

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Transplacental transmission of SARS-CoV-2 infection.

https://research-information.bris.ac.uk/ws/files/72868282/Clean_Revised_Stillbirths_Recall_to_action_in_HIC.pdf

Stillbirths: recall to action in high-income countries

Objectives To describe histopathologic findings in the placentas of women with coronavirus disease 2019 (COVID-19) during pregnancy. Methods Pregnant women with COVID-19 delivering between March 18, 2020, and May 5, 2020, were identified. Placentas were examined and compared to historical controls and women with placental evaluation for a history of melanoma. Results Sixteen placentas from patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were examined (15 with live birth in the third trimester, 1 delivered in the second trimester after intrauterine fetal demise). Compared to controls, third trimester placentas were significantly more likely to show at least one feature of maternal vascular malperfusion (MVM), particularly abnormal or injured maternal vessels, and intervillous thrombi. Rates of acute and chronic inflammation were not increased.The placenta from the patient with intrauterine fetal demise showed villous edema and a retroplacental hematoma. Conclusions Relative to controls, COVID-19 placentas show increased prevalence of decidual arteriopathy and other features of MVM, a pattern of placental injury reflecting abnormalities in oxygenation within the intervillous space associated with adverse perinatal outcomes. Only 1 COVID-19 patient was hypertensive despite the association of MVM with hypertensive disorders and preeclampsia. These changes may reflect a systemic inflammatory or hypercoagulable state influencing placental physiology.

/pdf/placental-pathology-in-covid-19-554bpwlx0d.pdf

Placental Pathology in COVID-19.

Importance Biological data are lacking with respect to risk of vertical transmission and mechanisms of fetoplacental protection in maternal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Objective To quantify SARS-CoV-2 viral load in maternal and neonatal biofluids, transplacental passage of anti–SARS-CoV-2 antibody, and incidence of fetoplacental infection. Design, Setting, and Participants This cohort study was conducted among pregnant women presenting for care at 3 tertiary care centers in Boston, Massachusetts. Women with reverse transcription–polymerase chain reaction (RT-PCR) results positive for SARS-CoV-2 were recruited from April 2 to June 13, 2020, and follow-up occurred through July 10, 2020. Contemporaneous participants without SARS-CoV-2 infection were enrolled as a convenience sample from pregnant women with RT-PCR results negative for SARS-CoV-2. Exposures SARS-CoV-2 infection in pregnancy, defined by nasopharyngeal swab RT-PCR. Main Outcomes and Measures The main outcomes were SARS-CoV-2 viral load in maternal plasma or respiratory fluids and umbilical cord plasma, quantification of anti–SARS-CoV-2 antibodies in maternal and cord plasma, and presence of SARS-CoV-2 RNA in the placenta. Results Among 127 pregnant women enrolled, 64 with RT-PCR results positive for SARS-CoV-2 (mean [SD] age, 31.6 [5.6] years) and 63 with RT-PCR results negative for SARS-CoV-2 (mean [SD] age, 33.9 [5.4] years) provided samples for analysis. Of women with SARS-CoV-2 infection, 23 (36%) were asymptomatic, 22 (34%) had mild disease, 7 (11%) had moderate disease, 10 (16%) had severe disease, and 2 (3%) had critical disease. In viral load analyses among 107 women, there was no detectable viremia in maternal or cord blood and no evidence of vertical transmission. Among 77 neonates tested in whom SARS-CoV-2 antibodies were quantified in cord blood, 1 had detectable immunoglobuilin M to nucleocapsid. Among 88 placentas tested, SARS-CoV-2 RNA was not detected in any. In antibody analyses among 37 women with SARS-CoV-2 infection, anti–receptor binding domain immunoglobin G was detected in 24 women (65%) and anti-nucleocapsid was detected in 26 women (70%). Mother-to-neonate transfer of anti–SARS-CoV-2 antibodies was significantly lower than transfer of anti-influenza hemagglutinin A antibodies (mean [SD] cord-to-maternal ratio: anti–receptor binding domain immunoglobin G, 0.72 [0.57]; anti-nucleocapsid, 0.74 [0.44]; anti-influenza, 1.44 [0.80];P  Conclusions and Relevance In this cohort study, there was no evidence of placental infection or definitive vertical transmission of SARS-CoV-2. Transplacental transfer of anti-SARS-CoV-2 antibodies was inefficient. Lack of viremia and reduced coexpression and colocalization of placental angiotensin-converting enzyme 2 and transmembrane serine protease 2 may serve as protective mechanisms against vertical transmission.

/pdf/assessment-of-maternal-and-neonatal-sars-cov-2-viral-load-33qof606st.pdf

Assessment of Maternal and Neonatal SARS-CoV-2 Viral Load, Transplacental Antibody Transfer, and Placental Pathology in Pregnancies During the COVID-19 Pandemic.

This study describes the pathology and clinical information on 20 placentas whose mother tested positive for the novel Coronovirus (2019-nCoV) cases. Ten of the 20 cases showed some evidence of fetal vascular malperfusion or fetal vascular thrombosis. The significance of these findings is unclear and needs further study.

https://journals.sagepub.com/doi/pdf/10.1177/1093526620925569

Placental Pathology in Covid-19 Positive Mothers: Preliminary Findings.

Context.—The value of placental examination in investigations of adverse pregnancy outcomes may be compromised by sampling and definition differences between laboratories. Objective.—To establish an agreed-upon protocol for sampling the placenta, and for diagnostic criteria for placental lesions. Recommendations would cover reporting placentas in tertiary centers as well as in community hospitals and district general hospitals, and are also relevant to the scientific research community. Data Sources.—Areas of controversy or uncertainty were explored prior to a 1-day meeting where placental and perinatal pathologists, and maternal-fetal medicine specialists discussed available evidence and subsequently reached consensus where possible. Conclusions.—The group agreed on sets of uniform sampling criteria, placental gross descriptors, pathologic terminologies, and diagnostic criteria. The terminology and microscopic descriptions for maternal vascular malperfusion, fetal vascular malperfusion, delayed villous m...

/pdf/sampling-and-definitions-of-placental-lesions-amsterdam-2xnjc9vkzt.pdf

Nathalie C.M. Balmus

Papers

Sampling and Definitions of Placental Lesions: Amsterdam Placental Workshop Group Consensus Statement