Circulating rather than alveolar extracellular DNA levels predict outcomes in influenza: a cohort study

Abstract Background: We have reported that high levels of circulating neutrophil extracellular traps (NETs) are associated with a poor prognosis in patients with severe influenza A infection. It remains unclear whether NETs in the bronchoalveolar lavage fluid (BALF) are a superior biomarker for predicting clinical outcomes in influenza.Methods: One hundred eighteen patients who were diagnosed with H1N1 influenza in 2017-2018 were recruited. NETs were assessed in plasma and BALF samples by quantifying cell-free DNA (cfDNA) and protein-DNA complexes. Predictions of severe illness and 60-day mortality were analyzed with receiver operating characteristic curves.Results: The NET levels were significantly elevated in the BALF and contributed to the pathological injury of lungs, yet it was not associated with disease severity or mortality in patients severely infected with H1N1. Plasma NET levels were significantly increased in the patients with severe influenza and positively correlated with the oxygen index and sequential organ failure assessment scores. High levels of plasma cfDNA (> 286.6 ng/ml) or histone-bound DNA (> 9.4 ng/ml) on the day of admission predicted severe influenza, and even higher levels of cfDNA (> 306.3 ng/ml) or histone-bound DNA (> 23.1 ng/ml) predicted fatal outcomes in severely ill patients.Conclusions: Alveolar NETs contribute to lung damage but do not correlate with outcomes in patients with severe H1N1 infection. Plasma cfDNA and histone-bound DNA represent early predictive biomarkers for the prognosis of influenza.