Airway epithelial cells and macrophages trigger IL-6-CD95/CD95L axis and mediate initial immunopathology of COVID-19.

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-1ß 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.

MMP-2 and MMP-9 levels in plasma are altered and associated with mortality in COVID-19 patients.

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 < 0.0001) compared to Controls. MMP-9 levels in COVID-19 patients were not affected by comorbidity such as hypertension or obesity. MMP-2 levels were affected by hypertension (p < 0.05), but unaffected by obesity status. Notably, hypertensive COVID-19 patients had higher MMP-2 levels compared to the non-hypertensive COVID-19 group, albeit still lower than Controls (p < 0.05). No association between MMP-2 and MMP-9 plasmatic levels and corticosteroid treatment or acute kidney injury was found in COVID-19 patients. The survival analysis showed that COVID-19 mortality was associated with increased MMP-2 and MMP-9 levels. Age, hypertension, BMI, and MMP-2 and MMP-9 were better predictors of mortality during hospitalization than SAPS3 and SOFA scores at hospital admission. In conclusion, a significant association between MMP-2 and MMP-9 levels and COVID-19 was found. Notably, MMP-2 and MMP-9 levels predicted the risk of in-hospital death suggesting possible pathophysiologic and prognostic roles.

Alcohol-based surgical hand preparation: translating scientific evidence into clinical practice.

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 < 0.001). The individual risk of developing a surgical site infection did not significantly change between the pre-intervention and the intervention phase (Adjusted RR = 0.66; 95% CI 0. 16-2.70, p = 0.563). Conclusion: Our results demonstrate that, when compared to the traditional surgical scrub, alcohol-based surgical hand preparation improves the quality and reduces the duration of the preparation, being at least equally effective for the prevention of surgical site infections.

Could dysnatremias play a role as independent factors to predict mortality in surgical critically ill patients?

Several studies have demonstrated the impact of dysnatremias on mortality of intensive care unit (ICU) patients. The objective of this study was to assess whether dysnatremia is an independent factor to predict mortality in surgical critically ill patients admitted to ICU in postoperative phase.One thousand five hundred and ninety-nine surgical patients (58.8% males; mean age of 60.6 ±â€Š14.4 years) admitted to the ICU in the postoperative period were retrospectively studied. The patients were classified according to their serum sodium levels (mmol/L) at admission as normonatremia (135-145), hyponatremia (<135), and hypernatremia (>145). APACHE II, SAPS III, and SOFA were recorded. The capability of each index to predict mortality of ICU and hospital mortality of patients was analyzed by multiple logistic regression.Hyponatremia did not have an influence on mortality in the ICU with a relative risk (RR) = 0.95 (0.43-2.05) and hospital mortality of RR = 1.40 (0.75-2.59). However, this association was greater in patients with hypernatremia mortality in the ICU (RR = 3.33 [95% confidence interval, CI 1.58-7.0]) and also in hospital mortality (RR = 2.9 [ 95% CI = 1.51-5.55). The pairwise comparison of ROC curves among the different prognostic indexes (APACHE II, SAPS III, SOFA) did not show statistical significance. The comparison of these indexes with serum sodium levels for general population, hyponatremia, and normonatremia was statistically significant (P < .001). For hypernatremia, the AUC and 95% CI for APACHE II, SAPS III, SOFA, and serum sodium level were 0.815 (0.713-0.892), 0.805 (0.702-0.885), 0.885 (0.794-0.945), and 0.663 (0.549-0.764), respectively. The comparison among the prognostic indexes was not statistically significant. Only SOFA score had a statistic difference compared with hypernatremia (P < .02).The serum sodium levels at admission, especially hypernatremia, may be used as an independent predictor of outcome in the surgical critically ill patients.

Effectiveness of a dental care intervention in the prevention of lower respiratory tract nosocomial infections among intensive care patients: a randomized clinical trial.

OBJECTIVE: To evaluate whether dental treatment may enhance oral antisepsis, thus preventing more effectively lower respiratory tract infections (LRTIs) among critically ill patients. DESIGN: Observer-blind randomized clinical trial. SETTING: General intensive care unit (ICU) for adult patients. PATIENTS: We analyzed data from 254 adult patients who stayed for at least 48 hours in the ICU. INTERVENTION: Patients were randomized by means of rolling dice. The experimental group (n = 127) had access to dental care provided by a dental surgeon, 4-5 times a week. Besides routine oral hygiene, care also included teeth brushing, tongue scraping, removal of calculus, atraumatic restorative treatment of caries, and tooth extraction. The control group (n = 127) had access to routine oral hygiene only, which included the use of chlorhexidine as a mouth rinse, which was performed by the ICU nurse staff. RESULTS: The primary study outcome was the LRTI incidence, which was 8.7% in the experimental group and 18.1% in the control group (adjusted relative risk [RR], 0.44 [95% confidence interval (CI), 0.20-0.96]; P = .04). Ventilator-associated pneumonia rates per 1,000 ventilator-days were 16.5 (95% CI, 9.8-29.5) in the control group and 7.6 (95% CI, 3.3-15.0) in the experimental group (P < .05). Mortality rates were similar between both study groups: 31.5% in the control group versus 29.1% in the experimental group (adjusted RR, 0.93 [95% CI, 0.52-1.65]; P = .796). No severe adverse events related to oral care were observed during the study. CONCLUSION: Dental treatment was safe and effective in the prevention of LRTI among critically ill patients who were expected to stay at least 48 hours in the ICU. TRIAL REGISTRATION: Brazilian Clinical Trials Registry, affiliated with the World Health Organization's International Clinical Trial Registry Platform: U1111-1152-2671.