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Because chitinase 3-like-1 (CHI3L1) is induced during aging and CM, the relationships between CHI3L1 and SC2 were investigated. Here, we demonstrate that CHI3L1 is a potent stimulator of the SC2 receptor angiotensin converting enzyme 2 (ACE2) and viral spike protein priming proteases (SPP), that ACE2 and SPP are induced during aging, and that anti-CHI3L1, kasugamycin, and inhibitors of phosphorylation abrogate these ACE2- and SPP-inductive events. Human studies also demonstrate that the levels of circulating CHI3L1 are increased in the elderly and patients with CM, where they correlate with COVID-19 severity. These studies demonstrate that CHI3L1 is a potent stimulator of ACE2 and SPP, that this induction is a major mechanism contributing to the effects of aging during SC2 infection, and that CHI3L1 co-opts the CHI3L1 axis to augment SC2 infection. CHI3L1 plays a critical role in the pathogenesis of and is an attractive therapeutic target in COVID-19.<\/jats:p>","DOI":"10.1172\/jci.insight.148749","type":"journal-article","created":{"date-parts":[[2021,11,7]],"date-time":"2021-11-07T14:00:55Z","timestamp":1636293655000},"source":"Crossref","is-referenced-by-count":36,"title":["Chitinase 3-like-1 is a therapeutic target that mediates the effects of aging in COVID-19"],"prefix":"10.1172","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9847-1211","authenticated-orcid":true,"given":"Suchitra","family":"Kamle","sequence":"first","affiliation":[{"name":"Molecular Microbiology and Immunology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5640-283X","authenticated-orcid":true,"given":"Bing","family":"Ma","sequence":"additional","affiliation":[{"name":"Molecular Microbiology and Immunology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuan 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