Commonalities Between ARDS, Pulmonary Fibrosis and COVID-19: The Potential of Autotaxin as a Therapeutic Target

Front Immunol. 2021 Oct 4:12:687397. doi: 10.3389/fimmu.2021.687397. eCollection 2021.

Abstract

Severe COVID-19 is characterized by acute respiratory distress syndrome (ARDS)-like hyperinflammation and endothelial dysfunction, that can lead to respiratory and multi organ failure and death. Interstitial lung diseases (ILD) and pulmonary fibrosis confer an increased risk for severe disease, while a subset of COVID-19-related ARDS surviving patients will develop a fibroproliferative response that can persist post hospitalization. Autotaxin (ATX) is a secreted lysophospholipase D, largely responsible for the extracellular production of lysophosphatidic acid (LPA), a pleiotropic signaling lysophospholipid with multiple effects in pulmonary and immune cells. In this review, we discuss the similarities of COVID-19, ARDS and ILDs, and suggest ATX as a possible pathologic link and a potential common therapeutic target.

Keywords: ARDS; Autotaxin; COVID-19; lysophosphatidic acid; pulmonary fibrosis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anti-Inflammatory Agents / therapeutic use
  • COVID-19 / blood
  • COVID-19 / pathology*
  • Dexamethasone / therapeutic use
  • Humans
  • Lung / pathology
  • Lysophospholipase D
  • Lysophospholipids / metabolism
  • Phosphoric Diester Hydrolases / blood
  • Phosphoric Diester Hydrolases / metabolism*
  • Pulmonary Fibrosis / blood
  • Pulmonary Fibrosis / pathology*
  • Respiratory Distress Syndrome / blood
  • Respiratory Distress Syndrome / pathology*
  • SARS-CoV-2
  • Signal Transduction / immunology

Substances

  • Anti-Inflammatory Agents
  • Dexamethasone
  • Lysophospholipids
  • Phosphoric Diester Hydrolases
  • Lysophospholipase D
  • lysophosphatidic acid