Godement Mathieu, Zhu Jaja, Cerf Charles, Vieillard-Baron Antoine, Maillon Agathe, Zuber Benjamin, Bardet Valérie, Geri Guillaume
Medical Intensive Care Unit, Ambroise Paré Hospital, APHP, Paris, France.
Paris Saclay University, Saint-Aubin, France.
Front Med (Lausanne). 2021 Feb 23;8:615984. doi: 10.3389/fmed.2021.615984. eCollection 2021.
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. 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/FIO ratio ≤100 mmHg. 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% ( = 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] = 0.006; 8.6 [3.4, 18.0] to 4 [1.4, 10.7] = 0.001 and 7.4 [4.0, 16.7] to 2.6 [1.0, 8.3] = 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] = 0.542; 4.9 [1.3, 13.0] to 5.5 [2.8, 6.9] = 0.839 and 4 [1.3, 13.6] to 2.7 [1.4, 4.5] = 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. 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.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）是一种了解甚少的疾病，伴有高度炎症状态。中性粒细胞胞外诱捕网（NETs）被认为是控制传染病的一条新途径，但也可能参与炎症和凝血系统的失衡。NETs可能是新冠肺炎患者的一个治疗靶点。入住重症监护病房的连续SARS-CoV2相关肺炎患者被纳入一项前瞻性双中心研究。在第1天和第3天通过流式细胞术对全血样本中的中性粒细胞胞外诱捕网浓度进行定量。主要结局是入住重症监护病房时血液中NETs定量与由动脉血氧分压/吸入氧分数比（PaO₂/FiO₂）≤100 mmHg定义的难治性低氧血症天数之间的关联。在因SARS-CoV2肺炎导致急性呼吸衰竭而入住重症监护病房的181例患者中，58例被纳入分析。患者年龄中位数为62[54,69]岁，大多数为男性（75.9%）。严重低氧血症的天数中位数为4[2,6]天，第28天死亡率为27.6%（n = 16）。存活患者的血液NETs水平在第1天和第3天之间显著下降（MPO⁺、Cit-H3⁺和MPO⁺Cit-H3⁺ NETs分别从59.5[30.5,116.6]降至47[33.2,62.4]，P = 0.006；从8.6[3.4,18.0]降至4[1.4,10.7]，P = 0.001；从7.4[4.0,16.7]降至2.6[1.0,8.3]，P = 0.001），而死亡患者的血液NETs水平保持稳定（MPO⁺、Cit-H3⁺和MPO⁺Cit-H3⁺ NETs分别从38.4[26.0,54.8]降至44.5[36.4,77.7]，P = 0.542；从4.9[1.3,13.0]降至5.5[2.8,6.9]，P = 0.839；从4[1.3,13.6]降至2.7[1.4,4.5]，P = 0.421）。在多变量负二项回归中，MPO⁺ NETs的血液水平与7天内严重低氧血症的天数呈负相关（0.84[0.73,0.97]），而Cit-H3⁺ NETs和双阳性NETs均与主要结局无显著关联。对于因SARS-CoV2相关肺炎入住重症监护病房的患者，第1天全血中NETs水平与严重低氧血症的天数呈负相关。第1天和第3天血液中NETs水平缺乏下降可区分出在第28天内死亡的患者。
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