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

Abstract

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 Childrens 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, this is the first report of placental COVID-19 despite mild COVID-19 disease 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 placental vasculopathy (potentially leading to fetal growth restriction, pre-eclampsia, and other pregnancy complications) as well as for potential vertical transmission -- 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.

A structured review of placental morphology and histopathological lesions associated with SARS-CoV-2 infection

“…Eighteen studies, involving 45 pregnancies, reported no evidence of pregnancy complications in their cases [ 16 , 22 , 23 , 26 , 27 , [37] , [38] , [39] , [40] , [41] , [42] , [43] , [44] , [45] , [46] , [47] , [48] , [49] ]. There was no apparent increase in the frequency of maternal pregnancy complications in the remaining cases (see Table 2 ).…”

“…Hypoxia induced by maternal SARS-CoV-2 infection may lead to maternal vascular malperfusion (MVM) [ 54 ]; features or diagnoses of MVM were noted in 69 cases (46% of placentas examined, 95% confidence interval (CI) 38.1–53.9%) by 12 studies [ 25 , [28] , [29] , [30] , [31] , [32] , 34 , 43 , 44 , 51 , 52 , 55 ] ( Fig. 2 ).…”

“…High grade chronic villitis was detected in one of the placentas of a twin pregnancy, with an additional case of high grade chronic villitis and associated avascular villi and two cases of chronic villitis were also reported [ 31 ]. Villitis was reported in five placentas [ 29 , 43 , 44 , 57 ], whilst histiocytic villitis was found in two placentas [ 55 , 57 ]. In one study, chorioamnionitis was reported in placentas from three stillborn infants, with one also having the finding of villitis [ 30 ].…”

“…The same authors also compared complement staining and found that the level of staining was similar to controls. Hsu et al reported the finding of the SARS-CoV-2 antigen throughout the placenta, including in endothelial cells, but rarely in the syncytium [ 43 ], whilst two studies identified SARS-CoV-2 in the syncytiotrophoblast, including two placentas from stillborn twins [ 34 , 57 ]. Vivanti et al identified the SARS-Cov-2 N protein in the cytoplasm of trophoblast [ 44 ].…”

Assistência a gemelares com risco de infecção congênita por COVID-19, relato de experiência

“…Em estudo realizado com 10 recémnascidos de genitoras infectadas pelo vírus, seis apresentaram dificuldade respiratória, dois febre e um, taquicardia. Além disso, 4 desenvolveram sintomas gastrointestinais como sangramento gástrico, intolerância alimentar e inchaço, e 7 apresentaram alterações na radiografia torácica devido a infecções (Hsu et al, 2020).…”