Excessive Matrix Metalloproteinase-1 and Hyperactivation of Endothelial Cells Occurred in COVID-19 Patients and Were Associated With the Severity of COVID-19

J Infect Dis. 2021 Jul 2;224(1):60-69. doi: 10.1093/infdis/jiab167.

Abstract

Background: Systemic vascular injury occurs in coronavirus disease 2019 (COVID-19) patients; however, the underlying mechanisms remain unknown.

Methods: To clarify the role of inflammatory factors in COVID-19 vascular injury, we used a multiplex immunoassay to profile 65 inflammatory cytokines/chemokines/growth factors in plasma samples from 24 hospitalized (severe/critical) COVID-19 patients, 14 mild/moderate cases, and 13 healthy controls (HCs).

Results: COVID-19 patients had significantly higher plasma levels of 20 analytes than HCs. Surprisingly, only 1 cytokine, macrophage migration inhibitory factor (MIF), was among these altered analytes, while the rest were chemokines/growth factors. Additionally, only matrix metalloproteinase-1 (MMP-1) and vascular endothelial growth factor A (VEGF-A) were significantly elevated in hospitalized COVID-19 patients when compared to mild/moderate cases. We further studied MMP-1 enzymatic activity and multiple endothelial cell (EC) activation markers (soluble forms of CD146, intercellular adhesion molecule 1 [ICAM-1], and vascular cell adhesion molecule 1 [VCAM-1]) and found that they were highly dysregulated in COVID-19 patients.

Conclusions: COVID-19 patients have a unique inflammatory profile, and excessive MMP-1 and hyperactivation of ECs are associated with the severity of COVID-19.

Keywords: COVID-19; MMP-1; endothelial cell; inflammation; vascular injury.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers
  • COVID-19 / blood
  • COVID-19 / diagnosis
  • COVID-19 / metabolism*
  • COVID-19 / virology*
  • Cytokines / metabolism
  • Endothelial Cells / metabolism*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Hospitalization
  • Host-Pathogen Interactions*
  • Humans
  • Inflammation Mediators / metabolism
  • Male
  • Matrix Metalloproteinase 1 / blood
  • Matrix Metalloproteinase 1 / metabolism*
  • Middle Aged
  • SARS-CoV-2*
  • Severity of Illness Index

Substances

  • Biomarkers
  • Cytokines
  • Inflammation Mediators
  • Matrix Metalloproteinase 1