At a Glance Commentary: Scientific knowledge on the Subject: severe SARS-CoV-2 infections leading to the Coronavirus disease 2019 (COVID-19) and the acute respiratory distress syndrome (ARDS) are associated with high mortality and prolonged durations of intensive care unit stay. Profound lymphopenia and elevated serum levels of pro-inflammatory cytokines, also characterized as cytokine storm, have been associated with clinical severity. However, few data compared the immunopathology of COVID-19 ARDS to that of non-COVID-19 ARDS, so that specific traits of the immune responses to severe SARS-CoV-2 infections have not been well identified. What This Study Adds to the Field: COVID-19 ARDS patients showed a phenotype of impaired adaptive immune response with profound lymphopenia and impaired/delayed lymphocyte activation. We also report a "chemokine signature" with increased serum concentrations of IP-10 and GM-CSF in COVID-19 patients. Serum concentrations of IP-10 and GM-CSF and nasopharyngeal viral loads were associated with outcomes in COVID-19 patients. Such results highlight the contribution of myeloid cells and impaired adaptive immune

Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Neutrophil extracellular traps have been associated with tissue damage. Whether these are involved in the pathogenesis of human acute respiratory distress syndrome (ARDS) and could be a potential therapeutic target is unknown. The authors quantified bronchoalveolar and blood neutrophil extracellular traps in patients with pneumonia-related ARDS and assessed their relationship with ventilator-free days. Methods Immunocompetent patients with pneumonia and moderate or severe ARDS (n = 35) and controls (n = 4) were included in a prospective monocentric study. Neutrophil extracellular trap concentrations were quantified (as DNA–myeloperoxidase complexes) in bronchoalveolar lavage fluid and serum by enzyme-linked immunosorbent assay. The relationship between bronchoalveolar lavage neutrophil extracellular trap concentrations and the primary clinical endpoint (i.e., the number of live ventilator-free days at day 28) was assessed using linear regression analyses. Results There was no significant relationship between bronchoalveolar lavage neutrophil extracellular trap concentrations and ventilator-free days by multiple regression analysis (β coefficient = 2.40; 95% CI, −2.13 to 6.92; P = 0.288). Neutrophil extracellular trap concentrations were significantly higher in bronchoalveolar lavage than in blood of ARDS patients (median [first to third quartiles]:154 [74 to 1,000] vs. 26 [4 to 68] arbitrary units, difference: −94; 95% CI, −341 to −57; P < 0.0001). Bronchoalveolar concentrations of patients were higher than those of controls (154 [74 to 1,000] vs. 4 [4 to 4] arbitrary units, difference: −150; 95% CI, −996 to −64; P < 0.001) and associated with bronchoalveolar interleukin-8 (Spearman’s ρ = 0.42; P = 0.012) and neutrophil concentrations (ρ = 0.57; P < 0.0001). Intensive care unit mortality (12%, n = 2 of 17 vs. 17%, n = 3 of 18; P > 0.99) and the number of ventilator-free days at day 28 (22 [14 to 25] vs. 14 [0 to 21] days; difference: −5; 95% CI, −15 to 0; P = 0.066) did not significantly differ between patients with higher (n = 17) versus lower (n = 18) bronchoalveolar neutrophil extracellular trap concentrations. Conclusions Bronchoalveolar neutrophil extracellular trap concentration was not significantly associated with mechanical ventilation duration in pneumonia-related ARDS.