Placental SARS-CoV-2 in a patient with mild COVID-19 disease

Background

The full impact of COVID-19 on pregnancy remains uncharacterized. Current literature suggests minimal maternal, fetal, and neonatal morbidity and mortality,¹ and COVID-19 manifestations appear similar between pregnant and non-pregnant women.² We present a case of placental SARS-CoV-2 virus in a woman with an uncomplicated pregnancy and mild COVID-19 disease.

Methods

A pregnant woman was evaluated at University of Missouri Women and Children’s Hospital. Institutional review board approval was obtained; information was obtained from medical records. Reverse transcriptase-polymerase chain reaction (RT-PCR) was performed to detect SARS-CoV-2. A gynecological pathologist examined the placenta and performed histolopathology. Sections were formalin-fixed and paraffin-embedded; slides were cut and subjected to hematoxylin-and-eosin or immunohistochemistry (IHC) staining. IHC was performed with specific monoclonal antibodies to detect SARS-CoV-2 antigen or to identify trophoblasts.

Findings

A 29 year-old multigravida presented at 40-4/7 weeks for labor induction. With myalgias two days prior, she tested positive for SARS-CoV-2. Her parents were in self-isolation for COVID-19 positivity; husband was asymptomatic and tested negative for COVID-19, but exposed to a workplace (meatpacking facility) outbreak.

Prenatal course was uncomplicated, with no gestational hypertension. She was afebrile and asymptomatic with normal vital signs throughout hospitalization. Her myalgias improved prior to admission. A liveborn male infant was delivered vaginally. Newborn course was uneventful; he was appropriate for gestational age, physical was unremarkable, and he was discharged home at 36 hours. COVID-19 RT-PCR test was negative at 24 hours. At one-week follow-up, newborn was breastfeeding well, with no fevers or respiratory distress.

Overall placental histology is consistent with acute uterine hypoxia (subchorionic laminar necrosis) superimposed on chronic uterine hypoxia (extra-villous trophoblasts and focal chronic villitis). IHC using SARS-CoV-2 nucleocapsid-specific monoclonal antibody demonstrated SARS-CoV-2 antigens throughout the placenta in chorionic villi endothelial cells, and rarely in CK7-expressing trophoblasts. Negative control placenta (November 2019 delivery) and ferret nasal turbinate tissues (not shown) were negative for SARS-CoV-2.

Interpretation

In this report, SARS-CoV-2 was found in the placenta, but newborn was COVID-19 negative. Our case shows maternal vascular malperfusion, with no features of fetal vascular malperfusion.

To our knowledge, <underline>this is the first report of placental COVID-19 despite</underline><underline>mild</underline><underline>COVID-19 disease</underline> in pregnancy (with no symptoms of COVID-19 aside from myalgias); specifically, this patient had no fever, cough, or shortness of breath, but only myalgias and sick contacts. Despite her having mild COVID-19 disease in pregnancy, we demonstrate placental vasculopathy and presence of SARS-CoV-2 virus across the placenta. Evidence of placental COVID-19 raises concern for possible <underline>placental vasculopathy</underline> (potentially leading to fetal growth restriction, pre-eclampsia, and other pregnancy complications) as well as for <underline>potential vertical transmission</underline> – especially for pregnant women who may be exposed to COVID-19 in early pregnancy. Further studies are urgently needed, to determine whether women with mild, pre-symptomatic, or asymptomatic COVID-19 may have SARS-CoV-2 virus that can cross the placenta, cause fetal vascular malperfusion, and possibly affect the fetus. This raises important public health and public policy questions of whether future pregnancy guidance should include stricter pandemic precautions, such as screening for a wider array of COVID-19 symptoms, increased antenatal surveillance, and possibly routine COVID-19 testing on a regular basis throughout pregnancy.