Respiratory infections are common in pregnancy with conflicting evidence supporting their association with neonatal congenital anomalies, especially during the first trimester. We profiled cytokine ...and chemokine systemic responses in 242 pregnant women and their newborns after SARS-CoV-2 infection, acquired in different trimesters. Also, we tested transplacental IgG passage and maternal vaginal-rectal microbiomes. IgG transplacental passage was evident, especially with infection acquired in the first trimester. G-CSF concentration-involved in immune cell recruitment-decreased in infected women compared to uninfected ones: a beneficial event for the reduction of inflammation but detrimental to ability to fight infections at birth. The later the infection was acquired, the higher the systemic concentration of IL-8, IP-10, and MCP-1, associated with COVID-19 disease severity. All infected women showed dysbiosis of vaginal and rectal microbiomes, compared to uninfected ones. Two newborns tested positive for SARS-CoV-2 within the first 48 h of life. Notably, their mothers had acute infection at delivery. Although respiratory infections in pregnancy are reported to affect babies' health, with SARS-CoV-2 acquired early during gestation this risk seems low because of the maternal immune response. The observed vaginal and rectal dysbiosis could be relevant for neonatal microbiome establishment, although in our series immediate neonatal outcomes were reassuring.
Abstract Background Intrauterine fetal death (IUFD) is a tragic event and, despite efforts to reduce rates, its incidence remains difficult to reduce. The objective of the present study was to ...examine the etiological factors that contribute to the main causes and conditions associated with IUFD, over an 11-year period in a region of North-East Italy (Friuli Venezia Giulia) for which reliable data in available. Methods Retrospective analysis of all 278 IUFD cases occurred between 2005 and 2015 in pregnancies with gestational age ≥ 23 weeks. Results The incidence of IUFD was 2.8‰ live births. Of these, 30% were small for gestational age (SGA), with immigrant women being significantly over-represented. The share of SGA reached 35% in cases in which a maternal of fetal pathological condition was present, and dropped to 28% in the absence of associated pathology. In 78 pregnancies (28%) no pathology was recorded that could justify IUFD. Of all IUFDs, 11% occurred during labor, and 72% occurred at a gestational age above 30 weeks. Conclusion The percentage of IUFD cases for which no possible cause can be identified is quite high. Only the adoption of evidence-based diagnostic protocols, with integrated immunologic, genetic and pathologic examinations, can help reduce this diagnostic gap, contributing to the prevention of future IUFDs.
Intrauterine fetal death (IUFD) is a tragic event and, despite efforts to reduce rates, its incidence remains difficult to reduce. The objective of the present study was to examine the etiological ...factors that contribute to the main causes and conditions associated with IUFD, over an 11-year period in a region of North-East Italy (Friuli Venezia Giulia) for which reliable data in available.
Retrospective analysis of all 278 IUFD cases occurred between 2005 and 2015 in pregnancies with gestational age ≥ 23 weeks.
The incidence of IUFD was 2.8‰ live births. Of these, 30% were small for gestational age (SGA), with immigrant women being significantly over-represented. The share of SGA reached 35% in cases in which a maternal of fetal pathological condition was present, and dropped to 28% in the absence of associated pathology. In 78 pregnancies (28%) no pathology was recorded that could justify IUFD. Of all IUFDs, 11% occurred during labor, and 72% occurred at a gestational age above 30 weeks.
The percentage of IUFD cases for which no possible cause can be identified is quite high. Only the adoption of evidence-based diagnostic protocols, with integrated immunologic, genetic and pathologic examinations, can help reduce this diagnostic gap, contributing to the prevention of future IUFDs.
Abstract
Aims
Anticoagulation was associated with improved survival of hospitalized coronavirus disease 2019 (COVID-19) patients in large-scale studies. Yet, the development of COVID-19-associated ...coagulopathy (CAC) and the mechanism responsible for improved survival of anticoagulated patients with COVID-19 remain largely elusive. This investigation aimed to explore the effects of anticoagulation and low-molecular-weight heparin (LMWH) in particular on patient outcome, CAC development, thromboinflammation, cell death, and viral persistence.
Methods and results
Data of 586 hospitalized COVID-19 patients from three different regions of Austria were evaluated retrospectively. Of these, 419 (71.5%) patients received LMWH and 62 (10.5%) received non-vitamin-K oral anticoagulants (NOACs) during hospitalization. Plasma was collected at different time points in a subset of 106 patients in order to evaluate markers of thromboinflammation (H3Cit-DNA) and the cell death marker cell-free DNA (cfDNA). Use of LMWH was associated with improved survival upon multivariable Cox regression (hazard ratio = 0.561, 95% confidence interval: 0.348–0.906). Interestingly, neither LMWH nor NOAC was associated with attenuation of D-dimer increase over time, or thromboinflammation. In contrast, anticoagulation was associated with a decrease in cfDNA during hospitalization, and curtailed viral persistence was observed in patients using LMWH leading to a 4-day reduction of virus positivity upon quantitative polymerase chain reaction 13 (interquartile range: 6–24) vs. 9 (interquartile range: 5–16) days, P = 0.009.
Conclusion
Time courses of haemostatic and thromboinflammatory biomarkers were similar in patients with and without LMWH, indicating either no effects of LMWH on haemostasis or that LMWH reduced hypercoagulability to levels of patients without LMWH. Nonetheless, anticoagulation with LMWH was associated with reduced mortality, improved markers of cell death, and curtailed viral persistence, indicating potential beneficial effects of LMWH beyond haemostasis, which encourages use of LMWH in COVID-19 patients without contraindications.
Graphical Abstract
AXL and its corresponding ligand growth arrest–specific 6 (GAS‐6) are critically involved in hepatic immunomodulation and regenerative processes. Pleiotropic inhibitory effects on innate inflammatory ...responses might essentially involve the shift of macrophage phenotype from a pro‐inflammatory M1 to an anti‐inflammatory M2. We aimed to assess the relevance of the AXL/GAS‐6‐pathway in human liver regeneration and, consequently, its association with clinical outcome after hepatic resection. Soluble AXL (sAXL) and GAS‐6 levels were analyzed at preoperative and postoperative stages in 154 patients undergoing partial hepatectomy and correlated with clinical outcome. Perioperative dynamics of interleukin (IL)‐6, soluble tyrosine‐protein kinase MER (sMerTK), soluble CD163 (sCD163), and cytokeratin (CK) 18 were assessed to reflect pathophysiological processes. Preoperatively elevated sAXL and GAS‐6 levels predicted postoperative liver dysfunction (area under the curve = 0.721 and 0.722; P < 0.005) and worse clinical outcome. These patients failed to respond with an immediate increase of sAXL and GAS‐6 upon induction of liver regeneration. Abolished AXL pathway response resulted in a restricted increase of sCD163, suggesting a disrupted phenotypical switch to regeneratory M2 macrophages. No association with sMerTK was observed. Concomitantly, a distinct association of IL‐6 levels with an absent increase of AXL/GAS‐6 signaling indicated pronounced postoperative inflammation. This was further supported by increased intrahepatic secondary necrosis as reflected by CK18M65. sAXL and GAS‐6 represent not only potent and easily accessible preoperative biomarkers for the postoperative outcome but also AXL/GAS‐6 signaling might be of critical relevance in human liver regeneration. Refractory AXL/GAS‐6 signaling, due to chronic overactivation/stimulation in the context of underlying liver disease, appears to abolish their immediate release following induction of liver regeneration, causing overwhelming immune activation, presumably via intrahepatic immune regulation.
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