2. Academic Validation
  3. Chitinase 3-like-1 is a therapeutic target that mediates the effects of aging in COVID-19

Chitinase 3-like-1 is a therapeutic target that mediates the effects of aging in COVID-19

  • JCI Insight. 2021 Nov 8;6(21):e148749. doi: 10.1172/jci.insight.148749.
Suchitra Kamle 1,  Bing Ma 1,  Chuan Hua He 1,  Bedia Akosman 1,  Yang Zhou 1,  Chang-Min Lee 1,  Wafik S El-Deiry 2 3 4 5,  Kelsey Huntington 2 3 4 5,  Olin Liang 3 4 5,  Jason T Machan 6,  Min-Jong Kang 7,  Hyeon Jun Shin 7,  Emiko Mizoguchi 1 8,  Chun Geun Lee 1,  Jack A Elias 1 4 5 9
Affiliations

Affiliations

  • 1 Molecular Microbiology and Immunology.
  • 2 Pathology and Laboratory Medicine.
  • 3 Hematology-Oncology Division, Department of Medicine.
  • 4 The Joint Program in Cancer Biology.
  • 5 Cancer Center at Brown University, and.
  • 6 Department of Biostatistics, Lifespan Health System, Warren Alpert Medical School, Brown University, Providence, Rhode Island, USA.
  • 7 Section of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
  • 8 Department of Immunology, Kurume University, School of Medicine, Kurume, Fukuoka, Japan.
  • 9 Department of Medicine, Brown University, Providence, Rhode Island, USA.
PMID: 34747367 DOI: 10.1172/jci.insight.148749
Abstract

COVID-19 is caused by SARS-CoV-2 (SC2) and is more prevalent and severe in elderly and patients with comorbid diseases (CM). 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.

Keywords

COVID-19; Immunotherapy; Molecular pathology; Therapeutics.

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