AUTHOR=Godement Mathieu , Zhu Jaja , Cerf Charles , Vieillard-Baron Antoine , Maillon Agathe , Zuber Benjamin , Bardet Valérie , Geri Guillaume 

TITLE=Neutrophil Extracellular Traps in SARS-CoV2 Related Pneumonia in ICU Patients: The NETCOV2 Study

JOURNAL=Frontiers in Medicine

VOLUME=8

YEAR=2021

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2021.615984

DOI=10.3389/fmed.2021.615984

ISSN=2296-858X

ABSTRACT=<p><bold>Background:</bold> Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a poorly understood disease involving a high inflammatory status. Neutrophil extracellular traps (NETs) have been described as a new pathway to contain infectious diseases but can also participate in the imbalance of the inflammatory and the coagulation systems. NETs could be a therapeutic target in COVID-19 patients.</p><p><bold>Methods:</bold> Consecutive patients with SARS-CoV2 related pneumonia admitted to the intensive care unit were included in a prospective bicentric study. Neutrophil extracellular trap concentrations were quantified in whole blood samples at day-1 and day-3 by flow cytometry. The primary outcome was the association between the blood NET quantification at ICU admission and the number of days with refractory hypoxemia defined by a PaO<sub>2</sub>/FIO<sub>2</sub> ratio ≤100 mmHg.</p><p><bold>Results:</bold> Among 181 patients admitted to the ICUs for acute respiratory failure related to SARS-CoV2 pneumonia, 58 were included in the analysis. Patients were 62 [54, 69] years old in median, mostly male (75.9%). The median number of days with severe hypoxemia was 4 [2, 6] days and day-28 mortality was 27.6% (<italic>n</italic> = 16). The blood level of NETs significantly decreased between day-1 and day-3 in patients who survived (59.5 [30.5, 116.6] to 47 [33.2, 62.4] <italic>p</italic> = 0.006; 8.6 [3.4, 18.0] to 4 [1.4, 10.7] <italic>p</italic> = 0.001 and 7.4 [4.0, 16.7] to 2.6 [1.0, 8.3] <italic>p</italic> = 0.001 for MPO+, Cit-H3+, and MPO+ Cit-H3+ NETs, respectively) while it remained stable in patients who died (38.4 [26.0, 54.8] to 44.5 [36.4, 77.7] <italic>p</italic> = 0.542; 4.9 [1.3, 13.0] to 5.5 [2.8, 6.9] <italic>p</italic> = 0.839 and 4 [1.3, 13.6] to 2.7 [1.4, 4.5] <italic>p</italic> = 0.421 for MPO+, Cit-H3+, and MPO+ Cit-H3+ NETs, respectively). In multivariable negative binomial regression, the blood level of MPO+ NETs was negatively associated with the number of days with severe hypoxemia within 7 days (0.84 [0.73, 0.97]), while neither Cit-H3+ NETs nor double-positive NETs were significantly associated with the primary outcome.</p><p><bold>Conclusion:</bold> The whole 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. The lack of decrease of the blood level of NETs between day-1 and day-3 discriminated patients who died within day-28.</p>