Vertical transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19), is still a controversial issue and studies on transplacental transmission correlations are still limited. We report on our experience with placental SARS-CoV-2 markers of infection in a series of mothers who received a diagnosis of COVID-19 in their third trimester of pregnancy.

SARS2‐CoV‐2 breakout in Italy caused a huge number of severely ill patients with a serious increase in mortality. Although lungs seem to be the main target of the infection, very few information are available about liver involvement, possibly evocating a systemic disease. Post‐mortem wedge liver biopsies from 48 patients died from severe pulmonary COVID‐19 disease with respiratory failure were collected from two main hospitals in northern Italy. No patient had clinical symptoms of liver disease or signs of liver failure before and during hospitalization; for each of them liver function tests were available. All liver samples showed minimal inflammation features. Histological pictures compatible with vascular alterations were observed, characterized by increase in number of portal vein branches associated with lumen massive dilatation, partial or complete luminal thrombosis of portal and sinusoidal vessels, fibrosis of portal tract, focally markedly enlarged and fibrotic. SARS‐CoV‐2 was found in 15 of 22 samples tested by in situ hybridization method. Our preliminary results confirm the clinical impression that liver failure is not a main concern and this organ is not the target of significant inflammatory damage. Histopathological findings are highly suggestive for marked derangement of intrahepatic blood vessel network secondary to systemic changes induced by virus that could target not only lung parenchyma but also cardiovascular system, coagulation cascade and endothelial layer of blood vessels. It still remains unclear if the mentioned changes are directly related to virus infection or if SARS‐CoV‐2 triggers a series of reactions leading to striking vascular alterations.

Context: Increasing numbers of neonates with systemic acute respiratory coronavirus 2 (SARS-CoV-2) infection are occurring, and in a small number there are reports of intrauterine infection. Objective: To characterize the placental pathology findings in a preselected cohort of neonates infected by transplacental transmission arising from maternal infection with SARS-CoV-2, and to identify pathology risk factors for placental and fetal infection. Design: Case-based retrospective analysis by a multinational group of 19 perinatal specialists of the placental pathology findings from 2 cohorts of infants delivered to mothers testing positive for SARS-CoV-2 - liveborn neonates infected via transplacental transmission who tested positive for SARS-CoV-2 after delivery and had SARS-CoV-2 identified in cells of the placental fetal compartment by molecular pathology; and stillborn infants with syncytiotrophoblast positive for SARS-CoV-2. Results: In placentas from all 6 liveborn neonates acquiring SARS-CoV-2 via transplacental transmission the syncytiotrophoblast was positive for coronavirus using immunohistochemistry, RNA in situ hybridization, or both. All 6 placentas had chronic histiocytic intervillositis and necrosis of the syncytiotrophoblast. The 5 stillborn/terminated infants had placental pathology findings that were similar including SARS-CoV-2 infection of the syncytiotrophoblast, chronic histiocytic intervillositis and syncytiotrophoblast necrosis. Conclusions: Chronic histiocytic intervillositis together with syncytiotrophoblast necrosis accompany SARS-CoV-2 infection of syncytiotrophoblast in liveborn and stillborn infants. Their coexistence in all placentas from liveborn infants acquiring their infection prior to delivery indicates that that these findings constitute a pathology risk factor for transplacental fetal infection. Potential mechanisms of infection of the placenta and fetus with SARS-CoV-2, and potential future studies, are discussed.

The mechanism(s) by which neonates testing positive for coronavirus disease 2019 (COVID-19) acquire their infection has been largely unknown. Transmission of the etiological agent, SARS-CoV-2, from mother to infant has been suspected but has been difficult to confirm. This communication summarizes the spectrum of pathology findings from pregnant women with COVID-19 based upon the infection status of their infants and addresses the potential interpretation of these results in terms of the effects of SARS-CoV-2 on the placenta and the pathophysiology of maternal-fetal infection. Placentas from pregnant women with COVID-19 and uninfected neonates show significant variability in the spectrum of pathology findings. In contrast, placentas from infected maternal-neonatal dyads are characterized by the finding of mononuclear cell inflammation of the intervillous space, termed chronic histiocytic intervillositis, together with syncytiotrophoblast necrosis. These placentas show prominent positivity of syncytiotrophoblast by SARS-CoV-2, fulfilling the published criteria for transplacental viral transmission as confirmed in fetal cells through identification of viral antigens by immunohistochemistry or viral nucleic acid using RNA in situ hybridization. The co-occurrence of chronic histiocytic intervillositis and trophoblast necrosis appears to be a risk factor for placental infection with SARS-CoV-2 as well as for maternal-fetal viral transmission, and suggests a potential mechanism by which the coronavirus can breach the maternal-fetal interface.

Increasing numbers of pregnant women with COVID-19 are being reported around from the world. The majority of neonates delivered to pregnant women infected with the new coronavirus SARS-CoV-2 have been negative for the virus, but a small number have tested positive for infection. It is important to determine whether vertical transmission of COVID-19 occurs and the mechanisms for its development. Based on a number of clinical and laboratory findings it has been suggested that transplacental transmission may be occurring, but a method to confirm this is necessary. This communication analyzes and evaluates the covariables that have been discussed as potential indicators of vertical and, specifically, intrauterine transmission including the timing of onset of neonatal illness, neonatal viral test positivity, neonatal antibody testing for IgG and IgM, and viral analysis of swabs of whole specimens of placental tissue. None of these methods can provide confirmatory evidence that infection developed prior to labor and delivery, or that transplacental transmission occurred. This commentary proposes that diagnosis of early-onset neonatal COVID-19 infection should be limited to neonates with positive RT-PCR testing for SARS-CoV-2 within the initial 72 hours of life. It also proposes that the occurrence of intrauterine transplacental SARS-CoV-2 among infected mother-infant dyads be based upon identification of SARS-CoV-2 in chorionic villous cells using immunohistochemistry or such nucleic acid methods such as in situ hybridization. Evaluating placentas from neonates with COVID-19 using these methods will be instrumental in determining the potential role and prevalence of transplacental transmission of the coronavirus.

High-resolution prenatal microarray testing is a reliable technique that increases diagnostic yield by at least 17.3% when compared with conventional karyotyping, without an increase in the frequency of variants of uncertain significance.

Intestinal ischemia in the COVID-19 era To the editor From the end of December, the world is facing the threat of a new zoonosis caused by Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS CoV-2) which gave rise to a pandemic which is currently ongoing. The Bergamo province has been one of the most affected regions worldwide with an increase in the mortality rate in the first trimester of 2020 of + 568% [1] if compared with the first trimester of the previous four years (2015-2019). Papa Giovanni XXIII Hospital was the most affected structure with over 20 0 0 admission for COVID-19 to date [2]. We describe a case of fatal intestinal infarction whit a difficult diagnosis, which was made possible throughout by using innovative technique. A 62-year-old unconscious man was admitted to the Emergency Department of Papa Giovanni XXIII Hospital (Bergamo, Italy) with severe hypotension during the month of April 2020. The recent medical history reported by phone from his wife included three days of abdominal pain and bilious vomiting. The patient's main comorbidities were obesity, arterial hypertension, diabetes mellitus type 2 and hepatic cirrhosis (non-alcoholic steatohepatitis + hepatitis B). Blood tests revealed an increase in the blood

Context.– Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can undergo maternal-fetal transmission, heightening interest in the placental pathology findings from this infection. Transplacental SARS-CoV-2 transmission is typically accompanied by chronic histiocytic intervillositis together with necrosis and positivity of syncytiotrophoblast for SARSCoV-2. Hofbauer cells are placental macrophages that have been involved in viral diseases including HIV and Zika virus, but their involvement in SARS-CoV-2 in unknown. Objective.– To determine whether SARS-CoV-2 can extend beyond the syncytiotrophoblast to enter Hofbauer cells, endothelium and other villous stromal cells in infected placentas of liveborn and stillborn infants. Design.– Case-based retrospective analysis by 29 perinatal and molecular pathology specialists of placental findings from a preselected cohort of 22 SARS-CoV-2-infected placentas delivered to pregnant women testing positive for SARS-CoV-2 from 7 countries. Molecular pathology methods were used to investigate viral involvement of Hofbauer cells, villous capillary endothelium, syncytiotrophoblast and other fetal-derived cells. Results.– Chronic histiocytic intervillositis and trophoblast necrosis was present in all 22 placentas (100%). SARS-CoV-2 was identified in Hofbauer cells from 4/22 placentas (18%). Villous capillary endothelial staining was positive in 2/22 cases (9%), both of which also had viral positivity in Hofbauer cells. Syncytiotrophoblast staining occurred in 21/22 placentas (95%). Hofbauer cell hyperplasia was present in 3/22 placentas (14%). In the 7 cases having documented transplacental infection of the fetus, 2 occurred in placentas with Hofbauer cell staining positive for SARS-CoV-2. Conclusions.– SARS-CoV-2 can extend beyond the trophoblast into the villous stroma, involving Hofbauer cells and capillary endothelial cells, in a small number of infected placentas. Most cases of SARS-CoV-2 transplacental fetal infection occur without Hofbauer cell involvement.