Emerging mechanisms of pulmonary vasoconstriction in SARS-CoV-2-induced acute respiratory distress syndrome (ARDS) and potential therapeutic targets

Harry Karmouty-Quintana, Rajarajan A. Thandavarayan, Steven P. Keller, Sandeep Sahay, Lavannya M. Pandit, Bindu Akkanti

Research output: Contribution to journalReview articlepeer-review

34 Scopus citations


The 1918 influenza killed approximately 50 million people in a few short years, and now, the world is facing another pandemic. In December 2019, a novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused an international outbreak of a respiratory illness termed coronavirus disease 2019 (COVID-19) and rapidly spread to cause the worst pandemic since 1918. Recent clinical reports highlight an atypical presentation of acute respiratory distress syndrome (ARDS) in COVID-19 patients characterized by severe hypoxemia, an imbalance of the renin–angiotensin system, an increase in thrombogenic processes, and a cytokine release storm. These processes not only exacerbate lung injury but can also promote pulmonary vascular remodeling and vasoconstriction, which are hallmarks of pulmonary hypertension (PH). PH is a complication of ARDS that has received little attention; thus, we hypothesize that PH in COVID-19-induced ARDS represents an important target for disease amelioration. The mechanisms that can promote PH following SARS-CoV-2 infection are described. In this review article, we outline emerging mechanisms of pulmonary vascular dysfunction and outline potential treatment options that have been clinically tested.

Original languageEnglish (US)
Article number8081
Pages (from-to)1-21
Number of pages21
JournalInternational journal of molecular sciences
Issue number21
StatePublished - Oct 29 2020


  • Acute lung injury
  • COVID-19
  • Cytokine release storm
  • Endothelin
  • Hypoxic-adenosinergic response
  • Kallikrein–Kinin System
  • Renin angiotensin system
  • Respiratory viral infection
  • Severe Acute Respiratory Syndrome/drug therapy
  • Pandemics
  • Renin-Angiotensin System/physiology
  • Cytokine Release Syndrome/drug therapy
  • Kallikrein-Kinin System/physiology
  • Acute Lung Injury/pathology
  • SARS-CoV-2
  • Betacoronavirus
  • Pneumonia, Viral/drug therapy
  • Coronavirus Infections/drug therapy
  • Vasoconstriction/drug effects

ASJC Scopus subject areas

  • Molecular Biology
  • Spectroscopy
  • Catalysis
  • Inorganic Chemistry
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry


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