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Published on: May 12, 2023
Excessive Neutrophils and Neutrophil Extracellular Traps in COVID-19
Jun Wang1,2,3, Qian Li3,4, Yongmei Yin5
1Center of Clinical Laboratory, The Fifth People's Hospital of Wuxi, Jiangnan University, Wuxi, China.
Insights
Severe COVID-19 pneumonia involves excessive neutrophils and neutrophil extracellular traps (NETs). These findings help explain the lung injury observed in patients with coronavirus disease.
Area of Science:
- Immunology
- Pulmonology
- Virology
Background:
- Severe coronavirus disease (COVID-19) is associated with elevated neutrophil counts.
- Pathological findings show neutrophil infiltration in COVID-19 autopsies.
- Understanding neutrophil-driven pathogenesis in severe COVID-19 pneumonia is critical.
Purpose of the Study:
- To investigate the role of neutrophils in the pathogenesis of severe pneumonia in COVID-19 patients.
- To correlate neutrophil counts with lung injury progression in COVID-19.
- To explore the molecular mechanisms of neutrophil involvement in COVID-19.
Main Methods:
- Retrospective analysis of 55 COVID-19 patients categorized by disease severity.
- Bayesian inference to quantify trends between leukocyte counts and lung lesions on chest CT scans.
- RNA sequencing of lung specimens and bronchoalveolar lavage fluid (BALF) to analyze host immune cell transcriptional signatures.
Main Results:
- Neutrophilia was observed in 6 of 8 severe COVID-19 patients, correlating with lesion progression.
- Increasing neutrophil counts paralleled increased lesion severity on CT scans, indicating neutrophilia-induced lung injury.
- Transcriptome analysis linked neutrophil activation to 17 neutrophil extracellular trap (NET)-associated genes, involving innate immunity and interactions with T, NK, and B cells.
Conclusions:
- Excessive neutrophils and associated NETs are implicated in the pathogenesis of lung injury in COVID-19 pneumonia.
- Neutrophil activation and NET formation may be key drivers of severe lung damage in COVID-19.
- These findings highlight neutrophils as a potential therapeutic target for COVID-19.
Abstract:
Background: Cases of excessive neutrophil counts in the blood in severe coronavirus disease (COVID-19) patients have drawn significant attention. Neutrophil infiltration was also noted on the pathological findings from autopsies. It is urgent to clarify the pathogenesis of neutrophils leading to severe pneumonia in COVID-19. Methods: A retrospective analysis was performed on 55 COVID-19 patients classified as mild (n = 22), moderate (n = 25), and severe (n = 8) according to the Guidelines released by the National Health Commission of China. Trends relating leukocyte counts and lungs examined by chest CT scan were quantified by Bayesian inference. Transcriptional signatures of host immune cells of four COVID19 patients were analyzed by RNA sequencing of lung specimens and BALF. Results: Neutrophilia occurred in 6 of 8 severe patients at 7-19 days after symptom onset, coinciding with lesion progression. Increasing neutrophil counts paralleled lesion CT values (slope: 0.8 and 0.3-1.2), reflecting neutrophilia-induced lung injury in severe patients. Transcriptome analysis revealed that neutrophil activation was correlated with 17 neutrophil extracellular trap (NET)-associated genes in COVID-19 patients, which was related to innate immunity and interacted with T/NK/B cells, as supported by a protein-protein interaction network analysis. Conclusion: Excessive neutrophils and associated NETs could explain the pathogenesis of lung injury in COVID-19 pneumonia.
