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

Suchitra Kamle1, Bing Ma1, Chuan Hua He1

  • 1Molecular Microbiology and Immunology.

JCI Insight
|November 8, 2021
PubMed

Insights

Chitinase 3-like-1 (CHI3L1) significantly increases SARS-CoV-2 (SC2) severity in older adults and those with comorbidities by stimulating the SC2 receptor ACE2 and proteases. Targeting CHI3L1 may offer a new COVID-19 therapeutic strategy.

Area of Science:

  • Virology
  • Immunology
  • Gerontology

Background:

  • COVID-19, caused by SARS-CoV-2 (SC2), presents higher prevalence and severity in elderly individuals and those with comorbid diseases (CM).
  • Chitinase 3-like-1 (CHI3L1) levels are known to increase with aging and in the presence of CM.

Purpose of the Study:

  • To investigate the relationship between CHI3L1 and SC2 infection.
  • To determine the role of CHI3L1 in the heightened severity of COVID-19 in vulnerable populations.

Main Methods:

  • Investigated CHI3L1's effect on SC2 receptor (ACE2) and spike protein priming proteases (SPP).
  • Examined the induction of ACE2 and SPP during aging.
  • Assessed the impact of anti-CHI3L1, kasugamycin, and phosphorylation inhibitors.
  • Correlated circulating CHI3L1 levels with COVID-19 severity in human studies.

Main Results:

  • CHI3L1 was identified as a potent stimulator of ACE2 and SPP.
  • ACE2 and SPP were found to be induced during aging.
  • Anti-CHI3L1, kasugamycin, and phosphorylation inhibitors effectively blocked ACE2 and SPP induction.
  • Elevated CHI3L1 levels in elderly and comorbid patients correlated with increased COVID-19 severity.

Conclusions:

  • CHI3L1 significantly contributes to the pathogenesis of SC2 infection, particularly in aging individuals.
  • CHI3L1 enhances SC2 infection by stimulating ACE2 and SPP, representing a key mechanism in age-related COVID-19 severity.
  • CHI3L1 emerges as a promising therapeutic target for COVID-19.