Biomarkers of cell damage, neutrophil and macrophage activation associated with in-hospital mortality in geriatric COVID-19 patients.
Alu
COVID-19
Geriatric patients
Neutrophil elastase
Prognostic biomarker
SARS-CoV-2
cfDNA
in-hospital mortality
sCD163
Journal
Immunity & ageing : I & A
ISSN: 1742-4933
Titre abrégé: Immun Ageing
Pays: England
ID NLM: 101235427
Informations de publication
Date de publication:
15 Dec 2022
15 Dec 2022
Historique:
received:
26
04
2022
accepted:
10
10
2022
entrez:
15
12
2022
pubmed:
16
12
2022
medline:
16
12
2022
Statut:
epublish
Résumé
The risk for symptomatic COVID-19 requiring hospitalization is higher in the older population. The course of the disease in hospitalised older patients may show significant variation, from mild to severe illness, ultimately leading to death in the most critical cases. The analysis of circulating biomolecules involved in mechanisms of inflammation, cell damage and innate immunity could lead to identify new biomarkers of COVID-19 severity, aimed to improve the clinical management of subjects at higher risk of severe outcomes. In a cohort of COVID-19 geriatric patients (n= 156) who required hospitalization we analysed, on-admission, a series of circulating biomarkers related to neutrophil activation (neutrophil elastase, LL-37), macrophage activation (sCD163) and cell damage (nuclear cfDNA, mithocondrial cfDNA and nuclear cfDNA integrity). The above reported biomarkers were tested for their association with in-hospital mortality and with clinical, inflammatory and routine hematological parameters. Aim of the study was to unravel prognostic parameters for risk stratification of COVID-19 patients. Lower n-cfDNA integrity, higher neutrophil elastase and higher sCD163 levels were significantly associated with an increased risk of in-hospital decease. Median (IQR) values observed in discharged vs. deceased patients were: 0.50 (0.30-0.72) vs. 0.33 (0.22-0.62) for n-cfDNA integrity; 94.0 (47.7-154.0) ng/ml vs. 115.7 (84.2-212.7) ng/ml for neutrophil elastase; 614.0 (370.0-821.0) ng/ml vs. 787.0 (560.0-1304.0) ng/ml for sCD163. The analysis of survival curves in patients stratified for tertiles of each biomarker showed that patients with n-cfDNA integrity < 0.32 or sCD163 in the range 492-811 ng/ml had higher risk of in-hospital decease than, respectively, patients with higher n-cfDNA integrity or lower sCD163. These associations were further confirmed in multivariate models adjusted for age, sex and outcome-related clinical variables. In these models also high levels of neutrophil elastase (>150 ng/ml) appeared to be independent predictor of in-hospital death. An additional analysis of neutrophil elastase in patients stratified for n-cfDNA integrity levels was conducted to better describe the association of the studied parameters with the outcome. On the whole, biomarkers of cell-free DNA integrity, neutrophil and macrophage activation might provide a valuable contribution to identify geriatric patients with high risk of COVID-19 in-hospital mortality.
Sections du résumé
BACKGROUND
BACKGROUND
The risk for symptomatic COVID-19 requiring hospitalization is higher in the older population. The course of the disease in hospitalised older patients may show significant variation, from mild to severe illness, ultimately leading to death in the most critical cases. The analysis of circulating biomolecules involved in mechanisms of inflammation, cell damage and innate immunity could lead to identify new biomarkers of COVID-19 severity, aimed to improve the clinical management of subjects at higher risk of severe outcomes. In a cohort of COVID-19 geriatric patients (n= 156) who required hospitalization we analysed, on-admission, a series of circulating biomarkers related to neutrophil activation (neutrophil elastase, LL-37), macrophage activation (sCD163) and cell damage (nuclear cfDNA, mithocondrial cfDNA and nuclear cfDNA integrity). The above reported biomarkers were tested for their association with in-hospital mortality and with clinical, inflammatory and routine hematological parameters. Aim of the study was to unravel prognostic parameters for risk stratification of COVID-19 patients.
RESULTS
RESULTS
Lower n-cfDNA integrity, higher neutrophil elastase and higher sCD163 levels were significantly associated with an increased risk of in-hospital decease. Median (IQR) values observed in discharged vs. deceased patients were: 0.50 (0.30-0.72) vs. 0.33 (0.22-0.62) for n-cfDNA integrity; 94.0 (47.7-154.0) ng/ml vs. 115.7 (84.2-212.7) ng/ml for neutrophil elastase; 614.0 (370.0-821.0) ng/ml vs. 787.0 (560.0-1304.0) ng/ml for sCD163. The analysis of survival curves in patients stratified for tertiles of each biomarker showed that patients with n-cfDNA integrity < 0.32 or sCD163 in the range 492-811 ng/ml had higher risk of in-hospital decease than, respectively, patients with higher n-cfDNA integrity or lower sCD163. These associations were further confirmed in multivariate models adjusted for age, sex and outcome-related clinical variables. In these models also high levels of neutrophil elastase (>150 ng/ml) appeared to be independent predictor of in-hospital death. An additional analysis of neutrophil elastase in patients stratified for n-cfDNA integrity levels was conducted to better describe the association of the studied parameters with the outcome.
CONCLUSIONS
CONCLUSIONS
On the whole, biomarkers of cell-free DNA integrity, neutrophil and macrophage activation might provide a valuable contribution to identify geriatric patients with high risk of COVID-19 in-hospital mortality.
Identifiants
pubmed: 36522763
doi: 10.1186/s12979-022-00315-7
pii: 10.1186/s12979-022-00315-7
pmc: PMC9751505
doi:
Types de publication
Journal Article
Langues
eng
Pagination
65Informations de copyright
© 2022. The Author(s).
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