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.