The role of platelets, neutrophils and endothelium in COVID-19 infection

ABSTRACT

Introduction

COVID-19 is associated to an increased risk of thrombosis, as a result of a complex process that involves the activation of vascular and circulating cells, the release of soluble inflammatory and thrombotic mediators and blood clotting activation.

Areas covered

This article reviews the pathophysiological role of platelets, neutrophils, and the endothelium, and of their interactions, in the thrombotic complications of COVID-19 patients, and the current and future therapeutic approaches targeting these cell types.

Expert opinion

Virus-induced platelet, neutrophil, and endothelial cell changes are crucial triggers of the thrombotic complications and of the adverse evolution of COVID-19. Both the direct interaction with the virus and the associated cytokine storm concur to trigger cell activation in a classical thromboinflammatory vicious circle. Although heparin has proven to be an effective prophylactic and therapeutic weapon for the prevention and treatment of COVID-19-associated thrombosis, it acts downstream of the cascade of events triggered by SARS-CoV-2. The identification of specific molecular targets interrupting the thromboinflammatory cascade upstream, and more specifically acting either on the interaction of SARS-CoV-2 with blood and vascular cells or on the specific signaling mechanisms associated with their COVID-19-associated activation, might theoretically offer greater protection with potentially lesser side effects.

KEYWORDS:

• Antithrombotic therapy
• COVID-19
• cytokines
• endothelial cells
• extracellular microvescicles
• neutrophils
• platelets
• SARS-CoV-2
• thromboinflammation

Article highlights

• Besides respiratory involvement, an important cause of COVID-19 mortality is thrombosis, which can manifest as microvascular thrombosis, venous thromboembolism, or arterial thrombosis.

• Platelets, neutrophils, and endothelial cells display an hyper-activated phenotype in hospitalized COVID-19 patients, and their activation strongly associates with disease severity, thrombosis rate, or death.

• Both the direct interaction with SARS-CoV-2, causative agent of COVID-19, and the cytokine storm concur to trigger the activation of platelets, neutrophils, and endothelial cells in a classical thromboinflammatory vicious circle.

• In order to ameliorate COVID-19 outcomes and to reduce VTE risk, several therapeutic approaches have been proposed reducing systemic inflammation and targeting the three cell types involved in COVID-19 pathogenesis.

• However, COVID-19 mortality is still elevated and therapeutic efficacy and safety of current antithrombotic approaches is still suboptimal. Thus, there is an urgent need to identify new targets in order to block thromboinflammation at an early stage.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

A peer reviewer on this manuscript has received a research grant from Japan Blood Products Organization. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.