The cytokine storm of COVID-19: a spotlight on prevention and protection

ABSTRACT

Introduction

The cytokine release syndrome (CRS) of COVID-19 is associated with the development of critical illness requiring multi-organ support. Further research is required to halt progression of multi-organ injury induced by hyper-inflammation.

Areas covered

PubMed/MEDLINE^TM databases were accessed between May 9^th-June 9^th, 2020, to review the latest perspectives on the treatment and pathogenesis of CRS.

Expert opinion

Over-activity of chemotaxis triggers a macrophage activation syndrome (MAS) resulting in the release of pro-inflammatory cytokines. IL-6 and TNF- α are at the forefront of hyper-inflammation. The inflammatory cascade induces endothelial activation and capillary leak, leading to circulatory collapse and shock. As endothelial dysfunction persists, there is activation of the clotting cascade and microvascular obstruction. Continued endothelial activation results in multi-organ failure, regardless of pulmonary tissue damage. We propose that targeting the endothelium may interrupt this cycle. Immuno-modulating therapies have been suggested, however, further data is necessary to confirm that they do not jeopardize adaptive immunity. Inhibition of IL-6 and the Janus Kinase, signal transducer and activator of transcription proteins pathway (JAK/STAT), are favorable targets. Remote ischemic conditioning (RIC) reduces the inflammation of sepsis in animal models and should be considered as a low risk intervention, in combination with cardiovascular protection.

KEYWORDS:

• Cytokine-Storm
• cytokine release Syndrome
• COVID-19
• endothelial activation
• cardiovascular protection

Article highlights

• IL-6 and TNF- α are key mediators of the cytokine release syndrome in COVID-19

• Macrophage activation syndrome and endothelial activation are cornerstone in persistent inflammation

• Endothelial involvement is associated with microvascular thrombi and pro-thrombotic state

• Risk to the adaptive immune response should be considered when developing cytokine suppression therapy

• Remote Ischemic conditioning and cardiovascular protection should be considered in the prevention and protection of COVID-19 CRS

This box summarizes key points contained in the article.

Acknowledgments

We specifically thank the Thompson Family Charitable Trust for their support of our COVID-19 research. We also thank the Hatter Foundation for continued support of our research.

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

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

This paper was not funded.