Lysosome activation in peripheral blood mononuclear cells and prognostic significance of circulating LC3B in COVID-19
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AbstractCoronavirus 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.
Acceptance Date28/01/2021
All Author(s) ListFang S, Zhang L, Liu Y, Xu W, Wu W, Huang Z, Wang X, Liu H, Sun Y, Zhang R, Peng B, Liu X, Sun X, Yu J, Chan FKL, Ng SC, Wong SH, Wang MHT, Gin T, Joynt GM, Hui DSC, Feng T, Wu WKK, Chan MTV, Zou X, Xia J
Journal nameBriefings in Bioinformatics
Volume Number22
Issue Number2
Pages1466 - 1475
LanguagesEnglish-United Kingdom
KeywordsCOVID-19, LC3B, autophagy

Last updated on 2021-13-06 at 18:06