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Summary: Airway epithelial cells (AEC) infected with SARS-CoV-2 may drive the dysfunction of macrophages during COVID-19. We hypothesized that the direct interaction of AEC with macrophages mediated by CD95/CD95L or indirect interaction mediated by IL-6 signaling are key steps for the COVID-19 severe acute inflammation. The interaction of macrophages with apoptotic and infected AEC increased CD95 and CD163 expression, and induced macrophage death. Macrophages exposed to tracheal aspirate with high IL-6 levels from intubated patients with COVID-19 or to recombinant human IL-6 exhibited decreased HLA-DR expression, increased CD95 and CD163 expression and IL-1β production. IL-6 effects on macrophages were prevented by both CD95/CD95L antagonist and by IL-6 receptor antagonist and IL-6 or CD95 deficient mice showed significant reduction of acute pulmonary inflammation post-infection. Our findings show a non-canonical CD95L-CD95 pathway that simultaneously drives both macrophage activation and dysfunction and point to CD95/CD95L axis as therapeutic target.

Respiratory symptoms are one of COVID-19 manifestations, and the metalloproteinases (MMPs) have essential roles in the lung physiology. We sought to characterize the plasmatic levels of matrix metalloproteinase-2 and 9 (MMP-2 and MMP-9) in patients with severe COVID-19 and to investigate an association between plasma MMP-2 and MMP-9 levels and clinical outcomes and mortality. MMP-2 and MMP-9 levels in plasma from patients with COVID-19 treated in the ICU (COVID-19 group) and Control patients were measured with the zymography. The study groups were matched for age, sex, hypertension, diabetes, BMI, and obesity profile. MMP-2 levels were lower and MMP-9 levels were higher in a COVID-19 group (p

Abstract Background Although alcohol-based surgical hand preparation offers potential advantages over the traditional surgical scrubbing technique, implementing it may be challenging due to resistance of surgeons in changing their practice. We aimed to implement alcohol-based surgical hand preparation in the hospital setting evaluating the impact of that on the quality and duration of the procedure, as well as on the prevention of surgical site infections. Methods A quasi-experimental study conducted at a tertiary-care university hospital from April 01 to November 01, 2017. Participants were cardiac and orthopedic surgical teams (n = 56) and patients operated by them (n = 231). Intervention consisted of making alcohol-based handrub available in the operating room, convincing and training surgical teams for using it, promoting direct observation of surgical hand preparation, and providing aggregated feedback on the quality of the preparation. The primary study outcome was the quality of the surgical hand preparation, inferred by the compliance with each one of the steps predicted in the World Health Organization (WHO) technique, evaluated through direct observation. Secondary study outcome was the patient’s individual probability of developing surgical site infection in both study periods. We used the Wilcoxon for paired samples and McNemar’s test to assess the primary study outcome and we build a logistic regression model to assess the secondary outcome. Results We observed 534 surgical hand preparation events. Among 33 participants with full data available for both study periods, we observed full compliance with all the steps predicted in the WHO technique in 0.03% (1/33) of them in the pre-intervention period and in 36.36% (12/33) of them in the intervention period (OR:12.0, 95% CI: 2. 4-59.2, p = 0.002). Compared to the pre-intervention period, the intervention reduced the duration of the preparation (4.8 min vs 2.7 min, respectively; p