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 autopsy. 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 lung estimated by chest CT scan, were quantified by Bayesian inference. Transcriptional signatures of host immune cells of four COVID19 patients were analysed by RNA sequencing of lung specimens and BALF. Findings: Neutrophilia occurred in 6 of 8 severe patients at 7 to 19 days after symptom onset, coinciding with lesion progression. Increasing neutrophil counts paralleled lesion CT values (slope: 0·8, 0·3–1·2), reflecting neutrophilia-induced lung injury in severe patients. Transcriptome analysis revealed that neutrophil activation was correlated with 17 neutrophil extracellular traps (NETs) associated genes in COVID-19 patients, which related with innate immunity and interacted with T/NK /B cells, as supported by protein-protein interaction network analysis. Interpretation: Excessive neutrophils and associated NETs could explain pathogenesis of lung injury in COVID-19 pneumonia. Funding: This work was supported by the foundation of Wuxi Medical Development Discipline for Infectious Disease (FZXK006) and Wuxi Young Medical Talents (Q201743), Health and Science Bureau of Wuxi (MS201731, CSE31N1712). Declaration of Interests: All authors disclose that there are no conflicts of interest. Ethics Approval Statement: The study was approved by the Ethics Committee of the Fifth People’s Hospital, Wuxi (No. 2020-006-1).
Highlights
As of early May 2020, more than 3 million cases of coronavirus disease 2019 (COVID-19) have been confirmed worldwide, resulting in hundreds of thousands of deaths [1]
Lymphopenia occurred in seven of eight severe patients and 11 of 25 moderate cases within 7 d, acute respiratory distress syndrome (ARDS) occurred in all eight severe patients within 8 d, and neutrophilia occurred in six of eight severe patients and one of 25 moderate cases within 9 d (Figure 1)
These findings suggest that higher neutrophil counts, the neutrophil-to-lymphocyte ratio (NLR), and C-reactive protein (CRP), FIB, and TT levels as potential prognostic factors
Summary
As of early May 2020, more than 3 million cases of coronavirus disease 2019 (COVID-19) have been confirmed worldwide, resulting in hundreds of thousands of deaths [1]. Severe patients develop acute respiratory distress syndrome (ARDS) or multiple organ failure, with a 4–15% death rate [2, 3]. It is not well-understood what drives the exacerbated host response involving a cytokine storm in severe COVID-19 [4]. Neutrophil infiltration was noted in three recent reports on the pathological findings from autopsied COVID-19 patients [5,6,7]. Increased neutrophil counts were reported to occur simultaneously in the peripheral blood of severe and non-surviving COVID-19 patients [3, 8]. Cases of excessive neutrophil counts in the blood in severe coronavirus disease (COVID-19) patients have drawn significant attention. It is urgent to clarify the pathogenesis of neutrophils leading to severe pneumonia in COVID-19
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