Thrombocytopathy and endotheliopathy: crucial contributors to COVID-19 thromboinflammation

Nat Rev Cardiol. 2021 Mar;18(3):194-209. doi: 10.1038/s41569-020-00469-1. Epub 2020 Nov 19.

Abstract

The core pathology of coronavirus disease 2019 (COVID-19) is infection of airway cells by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that results in excessive inflammation and respiratory disease, with cytokine storm and acute respiratory distress syndrome implicated in the most severe cases. Thrombotic complications are a major cause of morbidity and mortality in patients with COVID-19. Patients with pre-existing cardiovascular disease and/or traditional cardiovascular risk factors, including obesity, diabetes mellitus, hypertension and advanced age, are at the highest risk of death from COVID-19. In this Review, we summarize new lines of evidence that point to both platelet and endothelial dysfunction as essential components of COVID-19 pathology and describe the mechanisms that might account for the contribution of cardiovascular risk factors to the most severe outcomes in COVID-19. We highlight the distinct contributions of coagulopathy, thrombocytopathy and endotheliopathy to the pathogenesis of COVID-19 and discuss potential therapeutic strategies in the management of patients with COVD-19. Harnessing the expertise of the biomedical and clinical communities is imperative to expand the available therapeutics beyond anticoagulants and to target both thrombocytopathy and endotheliopathy. Only with such collaborative efforts can we better prepare for further waves and for future coronavirus-related pandemics.

Publication types

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

MeSH terms

  • Administration, Inhalation
  • Anticoagulants / therapeutic use
  • Blood Coagulation Disorders / blood*
  • Blood Coagulation Disorders / drug therapy
  • Blood Coagulation Disorders / etiology
  • Blood Coagulation Disorders / physiopathology
  • Blood Platelet Disorders / blood*
  • Blood Platelet Disorders / drug therapy
  • Blood Platelet Disorders / etiology
  • Blood Platelet Disorders / physiopathology
  • COVID-19 / blood*
  • COVID-19 / complications
  • COVID-19 / drug therapy
  • COVID-19 / physiopathology
  • Endothelium, Vascular / physiopathology*
  • Endothelium-Dependent Relaxing Factors / therapeutic use
  • Epoprostenol / therapeutic use
  • Heart Disease Risk Factors
  • Humans
  • Iloprost / therapeutic use
  • Inflammation / blood*
  • Inflammation / etiology
  • Inflammation / physiopathology
  • Nitric Oxide / therapeutic use
  • Platelet Aggregation Inhibitors / therapeutic use
  • SARS-CoV-2
  • Systemic Inflammatory Response Syndrome / blood
  • Systemic Inflammatory Response Syndrome / drug therapy
  • Systemic Inflammatory Response Syndrome / physiopathology
  • Thrombosis / blood*
  • Thrombosis / etiology
  • Thrombosis / immunology
  • Thrombotic Microangiopathies / blood
  • Thrombotic Microangiopathies / drug therapy
  • Thrombotic Microangiopathies / etiology
  • Thrombotic Microangiopathies / physiopathology
  • Vascular Diseases / blood
  • Vascular Diseases / drug therapy
  • Vascular Diseases / etiology
  • Vascular Diseases / physiopathology
  • Vasodilator Agents / therapeutic use
  • Venous Thromboembolism / blood
  • Venous Thromboembolism / drug therapy
  • Venous Thromboembolism / etiology
  • Venous Thromboembolism / physiopathology

Substances

  • Anticoagulants
  • Endothelium-Dependent Relaxing Factors
  • Platelet Aggregation Inhibitors
  • Vasodilator Agents
  • Nitric Oxide
  • Epoprostenol
  • Iloprost

Supplementary concepts

  • COVID-19 drug treatment
  • pediatric multisystem inflammatory disease, COVID-19 related