Lysosome activation in peripheral blood mononuclear cells and prognostic significance of circulating LC3B in COVID-19
© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissionsoup.com..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:22 |
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| Enthalten in: |
Briefings in bioinformatics - 22(2021), 2 vom: 22. März, Seite 1466-1475 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Fang, Shisong [VerfasserIn] |
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| Links: |
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| Themen: |
97C5T2UQ7J |
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| Anmerkungen: |
Date Completed 14.04.2021 Date Revised 14.04.2021 published: Print Citation Status MEDLINE |
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| doi: |
10.1093/bib/bbab043 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM321785487 |
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| 245 | 1 | 0 | |a Lysosome activation in peripheral blood mononuclear cells and prognostic significance of circulating LC3B in COVID-19 |
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| 520 | |a © The Author(s) 2021. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissionsoup.com. | ||
| 520 | |a 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 | ||
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| 700 | 1 | |a Xu, Wenye |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Weihua |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Ziheng |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Xin |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Hui |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Ying |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Renli |e verfasserin |4 aut | |
| 700 | 1 | |a Peng, Bo |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Xiaodong |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Xiao |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Jun |e verfasserin |4 aut | |
| 700 | 1 | |a Chan, Francis Ka Leung |e verfasserin |4 aut | |
| 700 | 1 | |a Ng, Siew Chien |e verfasserin |4 aut | |
| 700 | 1 | |a Wong, Sunny Hei |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Maggie Hai Tian |e verfasserin |4 aut | |
| 700 | 1 | |a Gin, Tony |e verfasserin |4 aut | |
| 700 | 1 | |a Joynt, Gavin Matthew |e verfasserin |4 aut | |
| 700 | 1 | |a Hui, David Shu Cheong |e verfasserin |4 aut | |
| 700 | 1 | |a Feng, Tiejian |e verfasserin |4 aut | |
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| 700 | 1 | |a Zou, Xuan |e verfasserin |4 aut | |
| 700 | 1 | |a Xia, Junjie |e verfasserin |4 aut | |
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