Placenta histological features in three cases of supposed SARS-CoV-2 vertical transmissions in second and third trimester of pregnancy

Objective. We described three cases of SARS-CoV-2 positive new-borns with both symptomatic and asymptomatic mothers. Materials and Methods. Placentas were analyzed in the pathology department and showed chronic histiocytic intervillositis with presence of CD68+ macrophages, syncytiotrophoblast necrosis and positivity of the syncytiotrophoblast for SARS-CoV-2 antigen or RNA. Results. The first case dates back to March 2020, when a symptomatic COVID-19 positive patient gave birth to a healthy neonate at 37.6 weeks of gestation. Skin to skin contact was not permitted but breastfeeding with a face mask was allowed. The newborn, that remained asymptomatic throughout the entire hospital stay, resulted positive to SARS-CoV-2 immediately after birth, at 24 hours of life and after 7 days. The second was delivered at 35.1 weeks of gestation by caesarean section for non-reassuring fetal status. The mother presented with fever, cough and a positive COVID-19 swab test. The newborn resulted positive on day 7, despite not having contact with the mother. No neonatal complications were observed. The third positive mother was admitted asymptomatic to the obstetric department in September 2021 due to preterm premature rupture of membranes at 20 weeks of gestation in a high-risk twin pregnancy. At 21.4 weeks of gestation her clinical conditions deteriorated, and she delivered two stillborn fetuses: SARSCoV- 2 was detected in all tissues samples. The lung of the first fetus only showed interstitial pneumonia features. Conclusions. We detected SARS-CoV-2 in placentas of both the second and third trimester, implying the passage of the virus through the placenta to the fetuses as the presence of SARSCoV- 2 RNA was demonstrated in swabs and foetal tissues.

Red Blood Cell-Derived Iron Alters Macrophage Function in COPD.

Lung macrophage iron levels are increased in COPD patients. Lung macrophage iron levels are thought to be increased by cigarette smoke, but the role of red blood cells (RBCs) as a source of iron has not been investigated. We investigate RBCs as a potential source of alveolar iron in COPD, and determine the effect of RBC-derived iron on macrophage function. We used lung tissue sections to assess RBC coverage of the alveolar space, iron and ferritin levels in 11 non-smokers (NS), 15 smokers (S) and 32 COPD patients. Lung macrophages were isolated from lung resections (n = 68) and treated with hemin or ferric ammonium citrate (50, 100 or 200 µM). Lung macrophage phenotype marker gene expression was measured by qPCR. The phagocytosis of Non-typeable Haemophilus influenzae (NTHi) was measured by flow cytometry. Cytokine production in response to NTHi in iron-treated macrophages was measured by ELISA. Lung macrophage iron levels were significantly correlated with RBC coverage of the alveolar space (r = 0.31, p = 0.02). Furthermore, RBC coverage and lung macrophage iron were significantly increased in COPD patients and correlated with airflow obstruction. Hemin treatment downregulated CD36, CD163, HLA-DR, CD38, TLR4, CD14 and MARCO gene expression. Hemin-treated macrophages also impaired production of pro-inflammatory cytokines in response to NTHi exposure, and decreased phagocytosis of NTHi (200 µM: 35% decrease; p = 0.03). RBCs are a plausible source of pulmonary iron overload in COPD. RBC-derived iron dysregulates macrophage phenotype and function.