Elastase and Exacerbation of Neutrophil Innate Immunity are Involved in Multi-Visceral Manifestations of COVID-19

Abstract

Background: Many arguments suggest that neutrophils could play a prominent role in COVID-19. However, the role of key components of neutrophil innate immunity in severe forms of COVID-19 has deserved insufficient attention. We aimed to evaluate the involvement of Neutrophil Elastase, histone-DNA, and DNases in systemic and multi-organ manifestations of COVID-19. Methods: We performed a multicenter study of markers of neutrophil innate immunity in 155 cases consecutively recruited in a screening center (ambulatory subjects), local hospitals, and two regional university hospitals. The case were evaluated according to clinical and biological markers of severity and multi-organ manifestations and compared to 35 healthy controls. Results: Blood Neutrophil Elastase, histone-DNA, myeloperoxidase-DNA and free dsDNA were dramatically increased, and DNase activity decreased by 10-fold, compared to controls. Neutrophil Elastase and histone-DNA were associated with intensive care admission, body temperature, lung damage and markers of cardiovascular outcomes, renal failure and increased IL-6, IL-8 and CXCR2. Neutrophil Elastase was an independent predictor of the computed tomography score of COVID-19 lung damage and the number of affected organs, in multivariate analyses. The increased blood concentrations of NE and neutrophil extracellular traps were related to exacerbation of neutrophil stimulation through IL8 and CXCR2 increased concentrations and increased serum DAMPs, and to impaired degradation of NETs as a consequence of the dramatic decrease of blood DNase activity. Conclusion: Our results point out the key role of neutrophil innate immunity exacerbation in COVID-19. Neutrophil Elastase and DNase could be potential biomarkers and therapeutic targets of severe systemic manifestations of COVID-19.

A possible pathogenic correlation between neutrophil elastase (NE) enzyme and inflammation in the pathogenesis of coronavirus disease 2019 (COVID-19)

“…Also, our study findings displayed that NE levels in ICU patients were significantly elevated than in non-ICU patients. Our results were in line with a recent study conducted by Louis Guéant et al [30] who revealed that the NE levels were significantly elevated in COVID-19 patients. The recent evidence has represented the pathogenic role of NE in respiratory viral infections [36] and lung injury [27] , [37] , [38] .…”

“…Further evidence has highlighted the crucial function of NE in pathologic conditions, including chronic obstructive pulmonary disease and lung injury [27] , [28] , [29] . Besides, recently, it has been noticed that NE may be implicated in the pathogenesis of COVID-19 [30] . Therefore, the present study evaluated the association between dynamic changes in NE levels associated with inflammatory markers (IL-6 and IL-8), anti-inflammatory markers (IL-4, IL-10), and vitamin D levels on the three-time points (T1-T3) in ICU and non-ICU COVID-19 patients.…”

Variant-dependent oxidative and cytokine responses of human neutrophils to SARS-CoV-2 spike protein and anti-spike IgG1 antibodies

“…MPO has been indicated as a potential prognostic marker for the severity of COVID-19 (17). MPO has also been associated with lung epithelial and endothelial damage in cases of severe COVID-19 (23), potentially accelerating oxidative lung tissue injuries in patients infected with SARS-CoV-2.…”