Lysosome activation in peripheral blood mononuclear cells and prognostic significance of circulating LC3B in COVID-19

Fang, Shisong; Zhang, Lin; Liu, Yingzhi; Xu, Wenye; Wu, Weihua; Huang, Ziheng; Wang, Xin; Liu, Hui; Sun, Ying; Zhang, Renli; Peng, Bo; Liu, Xiaodong; Sun, Xiao; Yu, Jun; Chan, Francis Ka Leung; Ng, Siew Chien; Wong, Sunny Hei; Wang, Maggie Hai Tian; Gin, Tony; Joynt, Gavin Matthew; Hui, David Shu Cheong; Feng, Tiejian; Wu, William Ka Kei; Chan, Matthew Tak Vai; Zou, Xuan; Xia, Junjie

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.