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
  • 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.
Products