Case report: Tissue positivity for SARS-CoV-2 in a preterm born infant death of thrombosis: possible intrauterine transmission.

Intrauterine transmission of SARS-CoV-2 (Severe Acute Respiratory Syndrome Corona Virus 2) is still matter of debate among scientists and there is limited information concerning this aspect of research. This could lead to severe complications of the growing fetus and, theoretically, of the newborn as well. We report the case of a male infant of 1,100 grams, born at 27th week of gestation to a SARS-CoV-2 mother, tested negative for viral detection at delivery. He was immediately admitted to neonatal Intensive Care Unit (ICU) for severe complications, where he died after 37 days by pulmonary embolism and thrombosis of the superior vena cava. After autopsy, SARS-CoV-2 N-protein and Spike RBD were detected in several tissues, particularly in the esophagus, stomach, spleen, and heart, with a significantly higher H-Score than the placenta. In conclusion, immunohistochemical analysis demonstrated SARS-CoV-2 NP and Spike RBD positivity in different tissues suggesting a possible intrauterine transmission. Newborn thrombo-embolism could be a complication of SARS-CoV-2 infection as observed in adult patients.

Effect of SARS-CoV-2 infection in pregnancy on CD147, ACE2 and HLA-G expression.

INTRODUCTION: Recent studies reported a differential expression of both ACE2 and CD147 in pregnant women associated to SARS-CoV-2 placental infection. The aim of this study is to further investigate the placental SARS-CoV-2 infection and the potential effect on protein expression (ACE2, CD147, HLA-G and CD56). METHODS: The study was on three subgroups: i) 18 subjects positive for SARS-CoV-2 swab at delivery; ii) 9 subjects that had a positive SARS-CoV-2 swab during pregnancy but resulted negative at delivery; iii) 11 control subjects with physiological pregnancy and with no previous or concomitant SARS-CoV-2 swab positivity. None of the subjects were vaccinated for SARS-CoV-2 infection. The placenta samples were analyzed for SARS-CoV-2 NP (Nucleocapsid protein) positivity and the expression of ACE2, CD147, HLA-G and CD56. RESULTS: We observed a higher percentage of SARS-CoV-2 NP positive placenta samples in the group of SARS-CoV-2 PCR positive at delivery in comparison with SARS-CoV-2 PCR negative at delivery. The localization of SARS-CoV-2 NP positivity in placenta samples was mainly in syncytiotrophoblast (ST) of SARS-CoV-2 PCR positive at delivery group and in extra-villous trophoblast (EVT) of SARS-CoV-2 PCR negative at delivery group. CD147, HLA-G positivity was higher in ST of SARS-CoV-2 PCR positive at delivery group, while CD56-expressing immune cells were decreased in comparison with control subjects. DISCUSSION: We confirmed the ability of SARS-CoV-2 to infect placenta tissues. The simultaneous SARS-CoV-2 swab positivity at delivery and the positivity of the placenta tissue for SARS-CoV-2 NP seems to create an environment that modifies the expression of specific molecules, as CD147 and HLA-G. These data suggest a possible impact of SARS-CoV-2 infection during pregnancy, that might be worthy to be monitored also in vaccinated subjects.

Relevance of VEGF and CD147 in different SARS-CoV-2 positive digestive tracts characterized by thrombotic damage.

Several evidence suggests that, in addition to the respiratory tract, also the gastrointestinal tract is a main site of severe acute respiratory syndrome CoronaVirus 2 (SARS-CoV-2) infection, as an example of a multi-organ vascular damage, likely associated with poor prognosis. To assess mechanisms SARS-CoV-2 responsible of tissue infection and vascular injury, correlating with thrombotic damage, specimens of the digestive tract positive for SARS-CoV-2 nucleocapsid protein were analyzed deriving from three patients, negative to naso-oro-pharyngeal swab for SARS-CoV-2. These COVID-19-negative patients came to clinical observation due to urgent abdominal surgery that removed different sections of the digestive tract after thrombotic events. Immunohistochemical for the expression of SARS-CoV-2 combined with a panel of SARS-CoV-2 related proteins angiotensin-converting enzyme 2 receptor, cluster of differentiation 147 (CD147), human leukocyte antigen-G (HLA-G), vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 was performed. Tissue samples were also evaluated by electron microscopy for ultrastructural virus localization and cell characterization. The damage of the tissue was assessed by ultrastructural analysis. It has been observed that CD147 expression levels correlate with SARS-CoV-2 infection extent, vascular damage and an increased expression of VEGF and thrombosis. The confirmation of CD147 co-localization with SARS-CoV-2 Spike protein binding on gastrointestinal tissues and the reduction of the infection level in intestinal epithelial cells after CD147 neutralization, suggest CD147 as a possible key factor for viral susceptibility of gastrointestinal tissue. The presence of SARS-CoV-2 infection of gastrointestinal tissue might be consequently implicated in abdominal thrombosis, where VEGF might mediate the vascular damage.