Avaliação de marcadores de armadilhas extracelulares de neutrófilos no desfecho clínico de pacientes com Covid-19 grave

Abstract

Severe cases of COVID-19, a disease caused by SARS-CoV, can progress to Severe Acute Respiratory Syndrome, multiple organ failure and death, requiring Intensive Care Units (ICUs) support. Studies report different factors of poor prognosis for this portion of the infected. Three months after the declaration of COVID-19 as a pandemic, the presence of elevated levels of constituents of Neutrophil Extracellular Traps (NETs) was reported in patients with the disease. NETs are a mechanism of innate immunity, in which their excessive production or their decreased elimination are involved in the immunopathogenesis of inflammatory diseases. Few studies have evaluated the influence of NETs on the clinical outcome of COVID-19. Thus, the aim of this study was to evaluate the influence of NETs markers, as well as the sociodemographic and laboratory profile, on the clinical outcome of patients with severe COVID-19 admitted to the ICU of a reference hospital in Fortaleza/CE, in increased cases periods in 2020 and 2021. A total of 78 plasma samples, from ICU admission, were used for the investigation of myeloperoxidase (MPO), neutrophil elastase (NE), citrullinated histone H3 (H3Cit) and cell-free DNA (cfDNA), using enzyme immunoassay and fluorimetry. Of the 78 patients, 40 (51.2%) died during hospitalization and 38 (48.8%) had a clinical outcome of hospital discharge. A total of 50 (64.1%) were male and 28 (35.9%) were female. Patients who died were older (median: 69.50; IQR: 55-76), had lower platelet concentrations (median: 193.5 x 10³/mm³; IQR: 154-278 x 10³/mm³) and higher neutrophil/lymphocyte ratio (NLR) (median: 12.79; IQR: 9.21-21.44) when compared to discharged patients. Of the four markers indicative of NETs measured, three of them (MPO, H3Cit and cfDNA) were higher (p<0.05) in the death group compared to the discharged group. There was a significant correlation (p<0.05) strong positive between NE and MPO (r=0.8561), moderate positive correlation between H3Cit and MPO (r=0.4075), and MPO and cfDNA (r=0.4965). Weak positive correlations were found between NE and cfDNA, H3Cit and EN, H3Cit and cfDNA. Furthermore, MPO and NE correlated with NLR (r=0.2430, r=0.3029) and Neutrophils (r=0.3074, r=0.2858). Thus, the highest levels of NETs markers in patients who died and the correlations found between them point to the contribution of this mechanism in the worsening of COVID-19 to an unfavorable outcome, and should be studied as a therapeutic strategy in individuals infected with the severe form of the disease, improving its prognosis.