Finding of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Within Placental Tissue 11 Weeks After Maternal Infection.

Abstract

To the Editor.—We read with particular attention the article of Schwartz et al1 recently published in your journal.We want to discuss a case of long persistence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in placental specimens, associated with histiocytic intervillositis, marked increase in perivillous fibrin deposition, and chronic high-grade villitis. The mother was previously hospitalized for a symptomatic SARS-CoV-2 infection at gestational week (GW) 26, and spontaneous delivery occurred at GW 37. The reverse transcription polymerase chain reaction result of the nasopharyngeal swab taken at delivery was negative in both mother and child. Placental weight was less than the third centile for gestational age, no intrauterine growth restriction was recorded during pregnancy, and the neonatal outcome was unremarkable.Here we show a pattern of histiocytic intervillositis associated with the immunohistochemical permanence of SARS-CoV-2 in Hofbauer cells and in the walls of intravillous fetal vessels, not in trophoblastic cells. The clone used to identify the virus (anti-nucleocapsid GTX135361, GeneTex) was previously tested for this purpose.2 In addition, we found other hallmarks of chronic persisting damage, such as a marked increase in perivillous fibrin deposition, chronic high-grade villitis, and chronic deciduitis (Figure, A through D).Viruses can be vertically transmitted from mother to infant through intrauterine (hematogenous or ascending paths), intrapartum, and postpartum routes. Even though a large majority of infants born to pregnant women with coronavirus disease 2019 (COVID-19) have been uninfected, new evidence shows that vertical transmission can occur. A recent analysis revealed that nearly 70% of SARS-CoV-2–positive neonates acquired the infection through postpartum transmission, with the remaining 30% through intrauterine or intrapartum mechanisms. Among all (122), 5.7% were stated to have confirmed congenital infection.3It has been reported that, once the transmission has taken place, its effect on the fetus and the newborn can be relevant, leading to preterm delivery, admission to neonatal intensive care, or even stillbirth. A review of literature has shown only a case of persistence of the virus associated with placental lesions suggestive of inflammation after a previous SARS-CoV-2 infection. However, in this case, the infection occurred at GW 8, leading to a spontaneous abortion at GW 13.4Although the placental lesions previously described in the work of Schwartz et al1 were related to an acute, symptomatic infection, here we demonstrate a histiocytic intervillositis with specific viral persistence, even after 11 weeks from the previous maternal symptomatic infection, in an otherwise healthy mother and newborn.All these findings may be the consequence of an immune-mediated persistent injury to the maternal-fetal interface. Trophoblast destruction may act as a potential mechanism to allow the virus to penetrate the chorionic villi and, once it has reached the fetal vessels, to become widespread in the fetal circulation, persisting in fetal vessels and macrophages, as shown (Figure, D).Besides confirming the pathogenesis of damage previously hypothesized, our findings add new relevant information about how long SARS-CoV-2 can survive in human placentas. This may be crucial for clarifying the viral mechanism of persistence in all the tissue involved after primary infection, not only in trophoblastic-derived cells.