{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T13:20:21Z","timestamp":1740144021397,"version":"3.37.3"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2021,2,23]],"date-time":"2021-02-23T00:00:00Z","timestamp":1614038400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Shenzhen bay laboratory grant","award":["SZBL202002271005","SZBL202002271004"],"award-info":[{"award-number":["SZBL202002271005","SZBL202002271004"]}]},{"name":"Shenzhen Science and Technology Programme, Shenzhen Science and Technology Innovation Commission","award":["202002073000003","JCYJ20180307102005105","C.06.19.00301"],"award-info":[{"award-number":["202002073000003","JCYJ20180307102005105","C.06.19.00301"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["8187631","8187356"],"award-info":[{"award-number":["8187631","8187356"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,3,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Coronavirus disease 2019 (COVID-19) has spread rapidly worldwide, causing significant mortality. There is a mechanistic relationship between intracellular coronavirus replication and deregulated autophagosome\u2013lysosome 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\u2009&amp;lt;5.5\u00a0ng\/ml increased the risk of oxygen and ventilatory requirement (adjusted odds ratio: 4.6; 95% CI: 1.1\u201322.0; P\u2009=\u20090.04). 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\u2009&amp;lt;5.5\u00a0ng\/ml will require early hospital admission for supplemental oxygen therapy and other respiratory support.<\/jats:p>","DOI":"10.1093\/bib\/bbab043","type":"journal-article","created":{"date-parts":[[2021,1,29]],"date-time":"2021-01-29T12:11:57Z","timestamp":1611922317000},"page":"1466-1475","source":"Crossref","is-referenced-by-count":14,"title":["Lysosome activation in peripheral blood mononuclear cells and prognostic significance of circulating LC3B in COVID-19"],"prefix":"10.1093","volume":"22","author":[{"given":"Shisong","family":"Fang","sequence":"first","affiliation":[{"name":"Shenzhen Center for Disease Control and Prevention, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Zhang","sequence":"additional","affiliation":[{"name":"CUHK-Shenzhen Research Institute, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingzhi","family":"Liu","sequence":"additional","affiliation":[{"name":"CUHK-Shenzhen Research Institute, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenye","family":"Xu","sequence":"additional","affiliation":[{"name":"Chinese University of Hong Kong, Hong Kong"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weihua","family":"Wu","sequence":"additional","affiliation":[{"name":"Shenzhen Center for Disease Control and Prevention, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ziheng","family":"Huang","sequence":"additional","affiliation":[{"name":"Chinese University of Hong Kong, Hong Kong"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Wang","sequence":"additional","affiliation":[{"name":"Shenzhen Center for Disease Control and Prevention, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Liu","sequence":"additional","affiliation":[{"name":"Shenzhen Center for Disease Control and Prevention, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Sun","sequence":"additional","affiliation":[{"name":"Shenzhen Center for Disease Control and Prevention, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renli","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shenzhen Center for Disease Control and Prevention, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo","family":"Peng","sequence":"additional","affiliation":[{"name":"Shenzhen Center for Disease Control and Prevention, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaodong","family":"Liu","sequence":"additional","affiliation":[{"name":"Chinese University of Hong Kong, Hong Kong"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao","family":"Sun","sequence":"additional","affiliation":[{"name":"Chinese University of Hong Kong, Hong Kong"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Yu","sequence":"additional","affiliation":[{"name":"Chinese University of Hong Kong, Hong Kong"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francis Ka Leung","family":"Chan","sequence":"additional","affiliation":[{"name":"Chinese University of Hong Kong, Hong Kong"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siew Chien","family":"Ng","sequence":"additional","affiliation":[{"name":"Chinese University of Hong Kong, Hong Kong"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sunny Hei","family":"Wong","sequence":"additional","affiliation":[{"name":"Chinese University of Hong Kong, Hong Kong"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maggie Hai Tian","family":"Wang","sequence":"additional","affiliation":[{"name":"Chinese University of Hong Kong, Hong Kong"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tony","family":"Gin","sequence":"additional","affiliation":[{"name":"Chinese University of Hong Kong, Hong Kong"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gavin Matthew","family":"Joynt","sequence":"additional","affiliation":[{"name":"Chinese University of Hong Kong, Hong Kong"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David Shu Cheong","family":"Hui","sequence":"additional","affiliation":[{"name":"Chinese University of Hong Kong, Hong Kong"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiejian","family":"Feng","sequence":"additional","affiliation":[{"name":"Shenzhen Center for Disease Control and Prevention, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5662-5240","authenticated-orcid":false,"given":"William Ka Kei","family":"Wu","sequence":"additional","affiliation":[{"name":"CUHK-Shenzhen Research Institute, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew Tak Vai","family":"Chan","sequence":"additional","affiliation":[{"name":"Chinese University of Hong Kong, Hong Kong"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuan","family":"Zou","sequence":"additional","affiliation":[{"name":"Shenzhen Center for Disease Control and Prevention, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junjie","family":"Xia","sequence":"additional","affiliation":[{"name":"Shenzhen Center for Disease Control and Prevention, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2021,2,23]]},"reference":[{"key":"2021032314363584800_ref1","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.semcdb.2019.07.014","article-title":"Autophagy in intracellular bacterial infection","volume":"101","author":"Hu","year":"2020","journal-title":"Semin Cell Dev Biol"},{"key":"2021032314363584800_ref2","first-page":"369","article-title":"Features of 20 133 UK patients in hospital with covid-19 using the ISARIC WHO Clinical Characterisation Protocol: prospective observational cohort study","volume":"m1985","author":"Docherty","year":"2020","journal-title":"BMJ"},{"issue":"10","key":"2021032314363584800_ref3","doi-asserted-by":"crossref","first-page":"1724","DOI":"10.7150\/ijbs.45498","article-title":"Targeting the endocytic pathway and autophagy process as a novel therapeutic strategy in COVID-19","volume":"16","author":"Yang","year":"2020","journal-title":"Int J Biol Sci"},{"issue":"6","key":"2021032314363584800_ref4","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1038\/s41579-018-0003-6","article-title":"Autophagy during viral infection\u2014a double-edged sword","volume":"16","author":"Choi","year":"2018","journal-title":"Nat Rev Microbiol"},{"issue":"8","key":"2021032314363584800_ref5","doi-asserted-by":"crossref","first-page":"1426","DOI":"10.4161\/auto.29309","article-title":"Coronavirus NSP6 restricts autophagosome expansion","volume":"10","author":"Cottam","year":"2014","journal-title":"Autophagy"},{"key":"2021032314363584800_ref6","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/s41420-019-0181-7","article-title":"SARS-Coronavirus Open Reading Frame-8b triggers intracellular stress pathways and activates NLRP3 inflammasomes","volume":"5","author":"Shi","year":"2019","journal-title":"Cell Death Dis"},{"issue":"9","key":"2021032314363584800_ref7","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1038\/s41419-018-0917-y","article-title":"SARS-Coronavirus Open Reading Frame-3a drives multimodal necrotic cell death","volume":"9","author":"Yue","year":"2018","journal-title":"Cell Death Dis"},{"issue":"3","key":"2021032314363584800_ref8","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.cell.2010.01.028","article-title":"Methods in mammalian autophagy research","volume":"140","author":"Mizushima","year":"2010","journal-title":"Cell"},{"volume-title":"Laboratory Testing for Coronavirus Disease (COVID-19) in Suspected Human Cases: Interim Guidance","author":"WHO","key":"2021032314363584800_ref9"},{"key":"2021032314363584800_ref10","article-title":"Epidemiology and transmission of COVID-19 in 391 cases and 1286 of their close contacts in Shenzhen, China: a retrospective cohort study","volume":"20","author":"Bi","journal-title":"Lancet Infect Dis"},{"issue":"1","key":"2021032314363584800_ref11","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1096\/fj.201601393R","article-title":"Defective lysosomal clearance of autophagosomes and its clinical implications in nonalcoholic steatohepatitis","volume":"32","author":"Wang","year":"2018","journal-title":"FASEB J"},{"key":"2021032314363584800_ref12","article-title":"Mild or moderate Covid-19","volume":"383","author":"Gandhi","journal-title":"N Engl J Med"},{"issue":"7","key":"2021032314363584800_ref13","doi-asserted-by":"crossref","first-page":"e45","DOI":"10.1164\/rccm.201908-1581ST","article-title":"Diagnosis and treatment of adults with community-acquired pneumonia. An official clinical practice guideline of the American Thoracic Society and Infectious Diseases Society of America","volume":"200","author":"Metlay","year":"2019","journal-title":"Am J Respir Crit Care Med"},{"issue":"1","key":"2021032314363584800_ref14","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1097\/01.ede.0000147512.81966.ba","article-title":"Optimal cut-point and its corresponding Youden Index to discriminate individuals using pooled blood samples","volume":"16","author":"Schisterman","year":"2005","journal-title":"Epidemiology"},{"key":"2021032314363584800_ref15","doi-asserted-by":"crossref","first-page":"388","DOI":"10.3389\/fcimb.2018.00388","article-title":"The role of host cholesterol during flavivirus infection","volume":"8","author":"Osuna-Ramos","year":"2018","journal-title":"Front Cell Infect Microbiol"},{"issue":"33","key":"2021032314363584800_ref16","doi-asserted-by":"crossref","first-page":"9852","DOI":"10.1021\/jp504516a","article-title":"Computational investigation of cholesterol binding sites on mitochondrial VDAC","volume":"118","author":"Weiser","year":"2014","journal-title":"J Phys Chem B"},{"key":"2021032314363584800_ref17","doi-asserted-by":"crossref","first-page":"14893","DOI":"10.1038\/ncomms14893","article-title":"Cholesterol-mediated allosteric regulation of the mitochondrial translocator protein structure","volume":"8","author":"Jaipuria","year":"2017","journal-title":"Nat Commun"},{"issue":"5","key":"2021032314363584800_ref18","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1161\/ATVBAHA.119.312136","article-title":"Lysosomal acid lipase in lipid metabolism and beyond","volume":"39","author":"Li","year":"2019","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"2021032314363584800_ref19","doi-asserted-by":"crossref","first-page":"e50832","DOI":"10.7554\/eLife.50832","article-title":"Intracellular cholesterol trafficking is dependent upon NPC2 interaction with lysobisphosphatidic acid","volume":"8","author":"McCauliff","year":"2019","journal-title":"Elife"},{"issue":"8","key":"2021032314363584800_ref20","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1172\/JCI8574","article-title":"Macrophage scavenger receptor CD36 is the major receptor for LDL modified by monocyte-generated reactive nitrogen species","volume":"105","author":"Podrez","year":"2000","journal-title":"J Clin Invest"},{"issue":"1","key":"2021032314363584800_ref21","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1038\/s41392-020-00292-7","article-title":"COVID-19-activated SREBP2 disturbs cholesterol biosynthesis and leads to cytokine storm","volume":"5","author":"Lee","year":"2020","journal-title":"Signal Transduct Target Ther"},{"issue":"1","key":"2021032314363584800_ref22","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.immuni.2019.11.015","article-title":"Targeting 7-dehydrocholesterol reductase integrates cholesterol metabolism and IRF3 activation to eliminate infection","volume":"52","author":"Xiao","year":"2020","journal-title":"Immunity"},{"issue":"4","key":"2021032314363584800_ref23","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1189\/jlb.0603298","article-title":"Activation of primary T lymphocytes results in lysosome development and polarized granule exocytosis in CD4+ and CD8+ subsets, whereas expression of lytic molecules confers cytotoxicity to CD8+ T cells","volume":"80","author":"Shen","year":"2006","journal-title":"J Leukoc Biol"},{"issue":"9","key":"2021032314363584800_ref24","doi-asserted-by":"crossref","first-page":"5062","DOI":"10.4049\/jimmunol.165.9.5062","article-title":"Regulation of cell surface expression of CTLA-4 by secretion of CTLA-4-containing lysosomes upon activation of CD4+T cells","volume":"165","author":"Iida","year":"2000","journal-title":"J Immunol"},{"issue":"18","key":"2021032314363584800_ref25","doi-asserted-by":"crossref","first-page":"8051","DOI":"10.7150\/thno.43507","article-title":"Autophagy-lysosome inhibitor chloroquine prevents CTLA-4 degradation of T cells and attenuates acute rejection in murine skin and heart transplantation","volume":"10","author":"Cui","year":"2020","journal-title":"Theranostics"},{"issue":"9","key":"2021032314363584800_ref26","doi-asserted-by":"crossref","first-page":"5495","DOI":"10.4049\/jimmunol.172.9.5495","article-title":"Cathepsin G, and not the asparagine-specific endoprotease, controls the processing of myelin basic protein in lysosomes from human B lymphocytes","volume":"172","author":"Burster","year":"2004","journal-title":"J Immunol"},{"issue":"1","key":"2021032314363584800_ref27","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1073\/pnas.0405737102","article-title":"Rapid biogenesis and sensitization of secretory lysosomes in NK cells mediated by target-cell recognition","volume":"102","author":"Liu","year":"2004","journal-title":"Proc Natl Acad Sci"},{"issue":"8","key":"2021032314363584800_ref28","doi-asserted-by":"crossref","first-page":"102597","DOI":"10.1016\/j.autrev.2020.102597","article-title":"Covid-19 and autoimmunity","volume":"19","author":"Ehrenfeld","year":"2020","journal-title":"Autoimmun Rev"},{"issue":"12","key":"2021032314363584800_ref29","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1038\/s41590-020-00814-z","article-title":"Extrafollicular B cell responses correlate with neutralizing antibodies and morbidity in COVID-19","volume":"21","author":"Woodruff","year":"2020","journal-title":"Nat Immunol"},{"issue":"8","key":"2021032314363584800_ref30","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1038\/s41584-020-0448-7","article-title":"Autoimmune and inflammatory diseases following COVID-19","volume":"16","author":"Galeotti","year":"2020","journal-title":"Nat Rev Rheumatol"}],"container-title":["Briefings in Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/bib\/article-pdf\/22\/2\/1466\/36654729\/bbab043.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/bib\/article-pdf\/22\/2\/1466\/36654729\/bbab043.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,3,23]],"date-time":"2021-03-23T15:04:14Z","timestamp":1616511854000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bib\/article\/22\/2\/1466\/6146553"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,23]]},"references-count":30,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2021,2,23]]},"published-print":{"date-parts":[[2021,3,22]]}},"URL":"https:\/\/doi.org\/10.1093\/bib\/bbab043","relation":{},"ISSN":["1467-5463","1477-4054"],"issn-type":[{"type":"print","value":"1467-5463"},{"type":"electronic","value":"1477-4054"}],"subject":[],"published-other":{"date-parts":[[2021,3]]},"published":{"date-parts":[[2021,2,23]]}}}