Lysosome activation in peripheral blood mononuclear cells and prognostic significance of circulating LC3B in COVID-19.
Brief Bioinform
; 22(2): 1466-1475, 2021 03 22.
Article
in En
| MEDLINE
| ID: mdl-33620066
ABSTRACT
Coronavirus disease 2019 (COVID-19) has spread rapidly worldwide, causing significant mortality. There is a mechanistic relationship between intracellular coronavirus replication and deregulated autophagosome-lysosome system. We performed transcriptome analysis of peripheral blood mononuclear cells (PBMCs) from COVID-19 patients and identified the aberrant upregulation of genes in the lysosome pathway. We further determined the capability of two circulating markers, namely microtubule-associated proteins 1A/1B light chain 3B (LC3B) and (p62/SQSTM1) p62, both of which depend on lysosome for degradation, in predicting the emergence of moderate-to-severe disease in COVID-19 patients requiring hospitalization for supplemental oxygen therapy. Logistic regression analyses showed that LC3B was associated with moderate-to-severe COVID-19, independent of age, sex and clinical risk score. A decrease in LC3B concentration <5.5 ng/ml increased the risk of oxygen and ventilatory requirement (adjusted odds ratio 4.6; 95% CI 1.1-22.0; P = 0.04). Serum concentrations of p62 in the moderate-to-severe group were significantly lower in patients aged 50 or below. In conclusion, lysosome function is deregulated in PBMCs isolated from COVID-19 patients, and the related biomarker LC3B may serve as a novel tool for stratifying patients with moderate-to-severe COVID-19 from those with asymptomatic or mild disease. COVID-19 patients with a decrease in LC3B concentration <5.5 ng/ml will require early hospital admission for supplemental oxygen therapy and other respiratory support.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Leukocytes, Mononuclear
/
SARS-CoV-2
/
COVID-19
/
Lysosomes
/
Microtubule-Associated Proteins
Type of study:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Brief Bioinform
Journal subject:
BIOLOGIA
/
INFORMATICA MEDICA
Year:
2021
Document type:
Article
Affiliation country:
China