Neutrophil extracellular traps in SARS-CoV2 related pneumonia in ICU patients: The NETCOV2 study

Introduction: Pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is poorly understood Neutrophil extracellular traps (NETs) have been involved in infection-related acute respiratory distress syndrome The role of NETs in SARS-CoV-2 related pneumonia in unknown Objectives: Investigate the association between the quantification of blood NETs at ICU admission and the respiratory failure evolution towards refractory hypoxemia in ICU patients with SARS-COV2 related pneumonia Methods: Prospective bicentric study including consecutive patients with SARS-CoV2 related pneumonia admitted in intensive care unit NETs blood levels were quantified in blood samples at day-1 and day-3 by flow cytometry (using myeloperoxidase [MPO] and citrullinated histones [Cit-H3] markers) The primary outcome was the association between the day-1 blood level of NETs and the number of days with refractory hypoxemia defined by a PaO2/FiO2 ratio < 100 mmHg Results: 58 patients (median age 62 [54, 69], mostly male (75 9%)) were included in the analysis The median number of days with severe hypoxemia (PaO2/FiO2 < 100 mmHg) was 4 [2, 6] days and day-28 mortality was 27 6% (n = 16) In multivariable negative binomial regression, MPO+ NETs were negatively associated with the number of days with severe hypoxemia within 7 days (0 84 [0 73, 0 97]), while neither single positive Cit-H3+ NETS nor double-positive NETS were significantly associated with the primary outcome The blood level of NETS was lower at day-1 than at day-3 in patients who died (32 6 [22 3, 70 3] vs 56 7 [23 3, 105 6] p < 0 001, 0 37 [0 0, 1 45] vs 2 2 [0 0, 4 3] p < 0 001 and 4 [1 2, 7 6] vs 6 8 [1 8, 15 0] p < 0 001 for MPO+, Cit-H3+ and double-positive NETS, respectively) Conclusion: The blood level of NETs at day-1 was negatively associated with the number of days with severe hypoxemia in patients admitted to the intensive care unit for SARS-CoV2 related pneumonia This could suggest a functional deficit of neutrophils in these patients that require further investigation