Neutrophil extracellular traps (NETs) have been observed in the airway in patients with chronic obstructive pulmonary disease (COPD), but their clinical and pathophysiologic implications have not been defined. We sought to determine whether NETs are associated with disease severity in patients with COPD and how they are associated with microbiota composition and airway neutrophil function. NET protein complexes (DNA-elastase and histone-elastase complexes), cell-free DNA, and neutrophil biomarkers were quantified in soluble sputum and serum from patients with COPD during periods of disease stability and during exacerbations and compared with clinical measures of disease severity and the sputum microbiome. Peripheral blood and airway neutrophil function were evaluated by means of flow cytometry ex vivo and experimentally after stimulation of NET formation. Sputum NET complexes were associated with the severity of COPD evaluated by using the composite Global Initiative for Obstructive Lung Disease scale (P < .0001). This relationship was due to modest correlations between NET complexes and FEV1, symptoms evaluated by using the COPD assessment test, and higher levels of NET complexes in patients with frequent exacerbations (P = .002). Microbiota composition was heterogeneous, but there was a correlation between NET complexes and both microbiota diversity (P = .009) and dominance of Haemophilus species operational taxonomic units (P = .01). Ex vivo airway neutrophil phagocytosis of bacteria was reduced in patients with increased sputum NET complexes. Consistent results were observed regardless of the method of quantifying sputum NETs. Failure of phagocytosis could be induced experimentally by incubating healthy control neutrophils with soluble sputum from patients with COPD. NET formation is increased in patients with severe COPD and associated with more frequent exacerbations and a loss of microbiota diversity.

To assess the characteristics and risk factors for mortality in patients with severe coronavirus disease-2019 (COVID-19) treated with tocilizumab (TCZ), alone or in combination with corticosteroids (CS). From March 17 to April 7, 2020, a real-world observational retrospective analysis of consecutive hospitalized adult patients receiving TCZ to treat severe COVID-19 was conducted at our 750-bed university hospital. The main outcome was all-cause in-hospital mortality. A total of 1,092 patients with COVID-19 were admitted during the study period. Of them, 186 (17%) were treated with TCZ, of which 129 (87.8%) in combination with CS. Of the total 186 patients, 155 (83.3 %) patients were receiving noninvasive ventilation when TCZ was initiated. Mean time from symptoms onset and hospital admission to TCZ use was 12 (±4.3) and 4.3 days (±3.4), respectively. Overall, 147 (79%) survived and 39 (21%) died. By multivariate analysis, mortality was associated with older age (HR = 1.09, p < 0.001), chronic heart failure (HR = 4.4, p = 0.003), and chronic liver disease (HR = 4.69, p = 0.004). The use of CS, in combination with TCZ, was identified as a protective factor against mortality (HR = 0.26, p < 0.001) in such severe COVID-19 patients receiving TCZ. No serious superinfections were observed after a 30-day follow-up. In patients with severe COVID-19 receiving TCZ due to systemic host-immune inflammatory response syndrome, the use of CS in addition to TCZ therapy, showed a beneficial effect in preventing in-hospital mortality.

BACKGROUND: Patients with coronavirus disease 2019 (COVID-19) can develop severe bilateral pneumonia leading to respiratory failure. We aimed to study the potential role of lung ultrasound score (LUS) in subjects with COVID-19. METHODS: We conducted an observational, prospective pilot study, including consecutive subjects admitted to an intermediate care unit due to COVID-19 pneumonia. LUS is a 12-zone examination method for lung parenchyma assessment. LUS was performed with a portable convex transducer, scores from 0 to 36 point s . Clinical and demographic data were collected at LUS evaluation. Survival analysis was performed using a composite outcome including ICU admission or death. Subjects were followed for 30 d from LUS assessment. RESULTS: Of 36 subjects included, 69.4% were male, and mean age was 60.19 ± 12.75 y. A cutoff LUS ≥ 24 points showed 100% sensitivity, 69.2% specificity, and an area under the receiver operating characteristic curve of 0.85 for predicting worse prognosis. The composite outcome was present in 10 subjects (55.6%) with LUS ≥ 24 points, but not in the group with lower LUS scores ( P < .001). Subjects with LUS ≥ 24 points had a higher risk of ICU admission or death (hazard ratio 9.97 [95% CI 2.75–36.14], P < .001). Significant correlations were observed between LUS and S pO 2 /F IO 2 , serum D-dimer, C-reactive protein, lactate dehydrogenase, and lymphocyte count. CONCLUSIONS: LUS ≥ 24 points can help identify patients with COVID-19 who are likely to require ICU admission or to die during follow-up. LUS also correlates significantly with clinical and laboratory markers of COVID-19 severity.