Excessive Neutrophils and Neutrophil Extracellular Traps in COVID-19

Wang, Jun; Li, Qian; Yin, Yongmei; Zhang, Yingying; Cao, Yingying; Lin, Xiao; Huang, Lihua; Hoffmann, Daniel; Lu, Mengji; Qiu, Yuanwang

doi:10.3389/fimmu.2020.02063

Cited by 230 publications

(215 citation statements)

References 46 publications

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“…Tests on peripheral neutrophil count, thrombocyte count, and plasma IL-6 level are commonly conducted. Higher numbers of neutrophils in the peripheral blood correlated with the severity of lung damage (30). In our cohort, patients in the HFNC failure group had significantly higher neutrophil counts than those in the HFNC success group, but no difference in the proportion of neutrophilia was observed between the two groups.…”

Section: Discussionmentioning

confidence: 49%

A Novel Risk-Stratification Models of the High-Flow Nasal Cannula Therapy in COVID-19 Patients With Hypoxemic Respiratory Failure

Yang

Huang

et al. 2020

Front. Med.

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Background: High-flow nasal cannula (HFNC) has been recommended as a suitable choice for the management of coronavirus disease 2019 (COVID-19) patients with acute hypoxemic respiratory failure before mechanical ventilation (MV); however, delaying MV with HFNC therapy is still a dilemma between the technique and clinical management during the ongoing pandemic.Methods: Retrospective analysis of COVID-19 patients treated with HFNC therapy from four hospitals of Wuhan, China. Demographic information and clinical variables before, at, and shortly after HFNC initiation were collected and analyzed. A risk-stratification model of HFNC failure (the need for MV) was developed with the 324 patients of Jin Yin-tan Hospital and validated its accuracy with 69 patients of other hospitals.Results: Among the training cohort, the median duration of HFNC therapy was 6 (range, 3–11), and 147 experienced HFNC failure within 7 days of HFNC initiation. Early predictors of HFNC failure on the basis of a multivariate regression analysis included age older than 60 years [odds ratio (OR), 1.93; 95% confidence interval (CI), 1.08–3.44; p = 0.027; 2 points], respiratory rate-oxygenation index (ROX) <5.31 (OR, 5.22; 95% CI, 2.96–9.20; p < 0.001; 5 points) within the first 4 h of HFNC initiation, platelets < 125 × 109/L (OR, 3.04; 95% CI, 1.46–6.35; p = 0.003; 3 points), and interleukin 6 (IL-6) >7.0 pg/mL (OR, 3.34; 95% CI, 1.79–6.23; p < 0.001; 3 points) at HFNC initiation. A weighted risk-stratification model of these predictors showed sensitivity of 80.3%, specificity of 71.2% and a better predictive ability than ROX index alone [area under the curve (AUC) = 0.807 vs. 0.779, p < 0.001]. Six points were used as a cutoff value for the risk of HFNC failure stratification. The HFNC success probability of patients in low-risk group (84.2%) was 9.84 times that in the high-risk group (34.8%). In the subsequent validation cohort, the AUC of the model was 0.815 (0.71–0.92).Conclusions: Aged patients with lower ROX index, thrombocytopenia, and elevated IL-6 values are at increased risk of HFNC failure. The risk-stratification models accurately predicted the HFNC failure and early stratified COVID-19 patients with HFNC therapy into relevant risk categories.

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Section: Discussionmentioning

confidence: 49%

A Novel Risk-Stratification Models of the High-Flow Nasal Cannula Therapy in COVID-19 Patients With Hypoxemic Respiratory Failure

Yang

Huang

et al. 2020

Front. Med.

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“…Although NETosis is a very powerful mechanism fighting for the infection, the ability of NETs to damage tissues is well-documented in infection and sterile disease. NETs directly kill epithelial and endothelial cells [11,38], and excessive NETosis damages the epithelium in pulmonary fungal infection [12] and the endothelium in transfusion-related acute lung injury [39].…”

Section: Ag Proteins and Their Role In Netosismentioning

confidence: 99%

Proteins associated with neutrophil degranulation are upregulated in nasopharyngeal swabs from SARS-CoV-2 patients

et al. 2020

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COVID-19 or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) appeared throughout the World and currently affected more than 9 million people and caused the death of around 470,000 patients. The novel strain of the coronavirus disease is transmittable at a devastating rate with a high rate of severe hospitalization even more so for the elderly population. Naso-oro-pharyngeal swab samples as the first step towards detecting suspected infection of SARS-CoV-2 provides a non-invasive method for PCR testing at a high confidence rate. Furthermore, proteomics analysis of PCR positive and negative nasooropharyngeal samples provides information on the molecular level which highlights disease pathology. Samples from 15 PCR positive cases and 15 PCR negative cases were analyzed with nanoLC-MS/MS to identify the differentially expressed proteins. Proteomic analyses identified 207 proteins across the sample set and 17 of them were statistically significant. Protein-protein interaction analyses emphasized pathways like Neutrophil degranulation, Innate Immune System, Antimicrobial Peptides. Neutrophil Elastase (ELANE), Azurocidin (AZU1), Myeloperoxidase (MPO), Myeloblastin (PRTN3), Cathepsin G (CTSG) and Transcobalamine-1 (TCN1) were found to be significantly altered in naso-oropharyngeal samples of SARS-CoV-2 patients. The identified proteins are linked to alteration in the innate immune system specifically via neutrophil degranulation and NETosis.

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“…Increased neutrophil counts in the peripheral blood have been associated with a worsening of the patient's prognosis. In fact, the neutrophil-to-lymphocyte ratio (NLR) has been used as a marker of severe disease [95][96][97]. In COVID-19 patients, reactive oxygen species (ROS) produced by neutrophils are augmented which can also contribute to organ failure [98].…”

Section: Nets and Covid-19mentioning

confidence: 99%

“…Neutrophil degranulation and NET markers have been associated with severe illness during COVID-19 [99]. In fact, higher levels of NETs have been correlated with an increased death rate in COVID-19 patients, in which an overreactive neutrophilic response leads to a general multi-organ failure [97]. Neutrophils appear to be decorated with thrombocytes in severe cases of COVID-19, the number of NETs identified in the circulation is significantly increased in these patients [100][101][102] and this correlates with the evidence of increased platelet factor 4 detected in these patients [101].…”

Section: Nets and Covid-19mentioning

confidence: 99%

“NETs and EETs, a Whole Web of Mess”

et al. 2020

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Neutrophils and eosinophils are granulocytes that have very distinct functions. Neutrophils are first responders to external threats, and they use different mechanisms to control pathogens. Phagocytosis, reactive oxygen species, and neutrophil extracellular traps (NETs) are some of the mechanisms that neutrophils utilize to fight pathogens. Although there is some controversy as to whether NETs are in fact beneficial or detrimental to the host, it mainly depends on the biological context. NETs can contribute to disease pathogenesis in certain types of diseases, while they are also undeniably critical components of the innate immune response. On the contrary, the role of eosinophils during host immune responses remains to be better elucidated. Eosinophils play an important role during helminthic infections and allergic responses. Eosinophils can function as effector cells in viral respiratory infections, gut bacterial infections, and as modulators of immune responses by driving the balance between Th1 and Th2 responses. In particular, eosinophils have biological activities that appear to be quite similar to those of neutrophils. Both possess bactericidal activity, can activate proinflammatory responses, can modulate adaptive immune responses, can form extracellular traps, and can be beneficial or detrimental to the host according to the underlying pathology. In this review we compare these two cell types with a focus on highlighting their numerous similarities related to extracellular traps.

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Excessive Neutrophils and Neutrophil Extracellular Traps in COVID-19

Cited by 230 publications

References 46 publications

A Novel Risk-Stratification Models of the High-Flow Nasal Cannula Therapy in COVID-19 Patients With Hypoxemic Respiratory Failure

A Novel Risk-Stratification Models of the High-Flow Nasal Cannula Therapy in COVID-19 Patients With Hypoxemic Respiratory Failure

Proteins associated with neutrophil degranulation are upregulated in nasopharyngeal swabs from SARS-CoV-2 patients

“NETs and EETs, a Whole Web of Mess”

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