key: cord-0858353-c9rxmo44
authors: Algarroba, Gabriela N.; Rekawek, Patricia; Vahanian, Sevan A.; Khullar, Poonam; Palaia, Thomas; Peltier, Morgan R.; Chavez, Martin R.; Vintzileos, Anthony M.
title: Visualization of SARS-CoV-2 virus invading the human placenta using electron microscopy
date: 2020-05-13
journal: Am J Obstet Gynecol
DOI: 10.1016/j.ajog.2020.05.023
sha: 37e3dd4f931c1d22d39fbf3d3b8cabfbcdf62bce
doc_id: 858353
cord_uid: c9rxmo44

nan

The outbreak of the novel severe acute respiratory syndrome coronavirus (SARS-CoV-2), which 30 results in development of coronavirus disease (COVID-19) has been associated with significant morbidity 31 and mortality. The risk of vertical transmission from infected pregnant women to their fetuses is 32

controversial. Recent studies have revealed the possibility of vertical transmission (1, 2), contrary to 33 previous reports of no evidence of vertical transmission of SARS-CoV-2 (3). Whether vertical 34 transmission occurs and if so, with which frequency remains unknown (4). 35

We present a case of rapid clinical deterioration in a woman at 28 weeks' gestation due to 36 severe COVID-19 infection. Using electron microscopy to evaluate for potential viral transmission in the 37 placenta, we visualized and identified coronavirus virions invading into syncytiotrophoblasts in placental 38

villi. To our knowledge, this is the first report demonstrating direct evidence of SARS-CoV-2 virus 39 invasion in placental tissue and placental infection associated with SARS-CoV-2 virus. 40

A 40-year-old Hispanic female, G3P2002, at 28 weeks and 4 days, with no significant past medical 43 history, presented to the emergency department with worsening shortness of breath, cough, and 44 hypoxia in the setting of a known COVID-19 infection, on day 2 of 5 of an azithromycin course. She was 45 promptly admitted with the diagnosis of sepsis pneumonia secondary to COVID-19 infection. 46

Ten hours after the initial presentation, her clinical condition deteriorated with progressively increasing oxygen requirements. She was intubated, sedated, and started on a norepinephrine infusion 48 due to hypotension in order to maintain appropriate perfusion for the placenta. Antenatal 49 corticosteroids for fetal lung maturity were administered in anticipation of a preterm delivery. 50

Therapeutic anticoagulation with heparin was initiated due to risk of venous thromboembolism in the 51 setting of severe COVID-19 infection with elevated D-dimer. She received a one-time dose of 400 mg tocilizumab, an interleukin 6 receptor antagonist, while awaiting regulatory permission to start use of 53 the antiviral remdesivir. On HD 4, she developed a metabolic acidosis (pH 7.19, pCO2 26 mmHg, pO2 338 54 mmHg, HCO3 9.9 mmol/L, base deficit 17 mmol/L) and, despite a bicarbonate infusion, she continued to 55 deteriorate. The decision was made to proceed with delivery to optimize maternal treatment and 56 decrease fetal morbidity. She received a magnesium sulfate 4 g bolus for fetal neuroprotection. An 57 uncomplicated repeat cesarean delivery was performed in a negative pressure operating room with all 58 personnel in personal protective equipment of a female infant weighing 2 lbs and 15 oz (1340 grams). 59

The cord blood arterial gas was pH 7.26, PCO2 46, PO2 38, HCO3 20.6 and base deficit 7. APGARS were 60 3, 5, and 6 at 1, 5, and 10 minutes, respectively. PCR testing was not performed on the placenta or 61 amniotic fluid. 62

Postoperatively, the patient received a ten day course of remdesivir. She recovered well with 63 progressively lower oxygen requirements and resolution of metabolic acidosis. The patient was 64 discharged home on POD 10 with therapeutic enoxaparin for 12 weeks. The infant's COVID-19 testing 65 was negative on day of life (DOL) 2 and 3. 66

Patients with suspected COVID-19, including infants, are tested via SARS-CoV-2 PCR of a 68 nasopharyngeal swab, using the Cepheid Xpert TM Xpress SARS-CoV-2 RT-PCR assay under EUA as per our 69 institution's policy. All placentas from COVID-19 positive mothers are submitted for gross and histologic 70 evaluation in our institution. In this case, the placenta was submitted to the pathology laboratory 71 without fixative; fresh tissue was taken, using appropriate personal protective gear, under the Fisher 72

Scientific Safety Flow Lab Fume Hood. Two 1 mm fragments were taken, one from chorionic villi deep 73 within the placental parenchyma and one from the decidua on the maternal surface. The tissue was 74 fixed in 4% glutaraldehyde for electron microscopic evaluation. The placenta was then fixed in 10% 75 buffered formalin for 72 hours prior to sectioning. Ten representative, 3 mm thick tissue sections were 76 submitted from the placental parenchyma, membranes and umbilical cord for histologic evaluation. 

Preterm delivery 125 in pregnant woman with critical COVID-19 pneumonia and vertical transmission

From an Infected Mother to Her Newborn

Clinical characteristics and intrauterine 130 vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective 131 review of medical records

Evidence for and against 133 vertical transmission for SARS-CoV-2 (COVID-19)

Distribution of 136 angiotensin-(1-7) and ACE2 in human placentas of normal and pathological pregnancies

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