INTRODUCTION
Coronavirus disease 2019 (COVID-19) produces thromboembolic events and multi-organ manifestations, including in heart, liver and kidneys1, 2. They result in part from the exacerbation of innate immunity 3 and a cytokine storm produced by lymphocyte and macrophage activation 4-6. Arguments suggest that neutrophils also play a prominent role in the severe and life-threatening forms of the disease 6-9. However, the involvement of neutrophils in systemic and multi-organ outcomes of COVID-19 has deserved insufficient attention8.
Neutrophils have an arsenal of defensive strategies that include the release of antimicrobial granules and neutrophil elastase (NE), and the formation of neutrophil extracellular traps (NETs) 6, 8. NETs are histone-DNA components of dying neutrophils involved in the host defense against pathogens 6, 8. A study reported that two markers of NETs, cell-free DNA and myeloperoxidase (MPO)-DNA, were increased in hospitalized COVID-19 patients compared to 30 controls and were correlated with C-reactive protein, D-dimer, lactate dehydrogenase and absolute neutrophil count 9. Another study from our group showed that MPO-DNA level is increased in the early phase of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, in ambulatory cases 10. The homeostasis of circulating NETs is dependent on NE and DNase 1 and DNase 11L36. Excessive NE and NETs in blood produces vascular and tissue lesions in acute viral pneumonia, which resemble those observed in COVID-19 infection 6, 11, 12. Despite these evidences, whether NE, DNases and histone-DNA are involved in the multi-visceral manifestations of COVID-19 has not been evaluated to date.
We aimed to study the blood level of NE, total DNase activity, histone-DNA and other NET components in patients with COVID-19 infection according to disease severity and multi-organ manifestations. We found that NE was an independent predictor of the multi-organ injury produced by COVID-19. The release of NE and NETs was related to neutrophil activation by serum damage-associated molecular patterns (DAMPs) and IL-8/CXCR2 pathway.