Severe COVID-19 infections present with cytokine storms, hypercoagulation, and acute respiratory distress syndrome, with extracellular vesicles (EVs) being involved in coagulation and inflammation. This study aimed to determine whether coagulation profiles and EVs reflect COVID-19 disease severity. Thirty-six patients with symptomatic COVID-19 infection with mild/moderate/severe disease (12 in each group) were analyzed. Sixteen healthy individuals served as controls. Coagulation profiles and EV characteristics were tested by nanoparticle tracking analysis (NTA), flow cytometry, and Western blot. While coagulation factors VII, V, VIII, and vWF were comparable, significant differences were found in patients’ D-Dimer/fibrinogen/free protein S levels compared to controls. Severe patients’ EVs displayed higher percentages of small EVs (<150 nm) with increased expression of exosome marker CD63. Severe patients’ EVs displayed high levels of platelet markers (CD41) and coagulation factors (tissue factor activity, endothelial protein C receptor). EVs of patients with moderate/severe disease expressed significantly higher levels of immune cell markers (CD4/CD8/CD14) and contained higher levels of IL-6. We demonstrated that EVs, but not the coagulation profile, may serve as biomarkers for COVID-19 severity. EVs demonstrated elevated levels of immune- and vascular-related markers in patients with moderate/severe disease, and may play a role in disease pathogenesis.

Chronic graft-versus-host disease (cGVHD) presents with dermal inflammation and fibrosis. We investigated the characteristics of extracellular vesicles (EVs) obtained from cGVHD patients, and their potential effects on human dermal fibroblast (NHDF) cells. The anti-inflammatory and anti-fibrotic effects of placental EVs were also explored given their known anti-inflammatory properties. Fourteen cGVHD patients’ EVs contained higher levels of fibrosis-related proteins, TGFβ and α-smooth muscle actin (αSMA), compared to EVs from thirteen healthy subjects. The exposure of NHDF cells to the patients’ EVs increased the NHDF cells’ TGFβ and αSMA expressions. Placental EVs derived from placental-expanded cells (PLX) (Pluri Inc.) and human villous trophoblast (HVT) cells expressing the mesenchymal markers CD29, CD73, and CD105, penetrated into both the epidermal keratinocytes (HACATs) and NHDF cells. Stimulation of the HACAT cells with cytokine TNFα/INFγ (0.01–0.1 ng/µL) reduced cell proliferation, while the addition of placental EVs attenuated this effect, increasing and normalizing cell proliferation. The treatment of NHDF cells with a combination of TGFβ and placental HVT EVs reduced the stimulatory effects of TGFβ on αSMA production by over 40% (p = 0.0286). In summary, EVs from patients with cGVHD can serve as a biomarker for the cGVHD state. Placental EVs may be used to regulate dermal inflammation and fibrosis, warranting further investigation of their therapeutic potential.

Objectives: To determine whether in a labor floor housed continuously by senior physicians the risk of adverse maternal and neonatal outcome is affected by time of delivery. Methods: This retrospective cohort study, conducted at a tertiary medical center, assessed singleton term deliveries from 1 January 2011 to 30 January 2020. Participants were categorized based on delivery timing, correlating with nursing shifts, to evaluate perinatal outcomes. The primary endpoint included adverse maternal outcomes such as emergency Cesarean section, anal sphincter injuries, blood product transfusions, and postpartum surgeries (laparotomy/laparoscopy). Secondary outcomes focused on neonatal health indicators, including low Apgar scores, ICU admissions, respiratory issues, extended hospital stays, and neurological complications. Results: 87,863 deliveries were available for analysis with equal distribution during the day. The risk of adverse composite maternal outcome was highest during the evening (aOR 1.25, 95% CI 1.18–1.32) and lowest during the night (aOR 0.94, 95% CI 0.88–0.99) compared to daytime deliveries. This difference was primarily driven by the highest rate of emergency CD in the evening. Neonatal outcomes were comparable, except for length of stay > 5 days, which was more frequent among newborns delivered during the evening and night shifts compared to the morning shift (aOR 1.19, 95% CI 1.07–1.33 and aOR 1.17, 95% CI 1.05–1.31, respectively). Conclusions: In term pregnancies, the evening shift is associated with the highest risk of adverse maternal and neonatal outcomes despite physician seniority.