Evaluating the role of chemokines and chemokine receptors involved in coronavirus infection

ABSTRACT

Introduction

Coronaviruses are a large family of positive-stranded nonsegmented RNA viruses with genomes of 26–32 kilobases in length. Human coronaviruses are commonly associated with mild respiratory illness; however, the past three decades have seen the emergence of severe acute respiratory coronavirus (SARS-CoV), middle eastern respiratory coronavirus (MERS-CoV), and SARS-CoV-2 which is the etiologic agent for COVID-19. Severe forms of COVID-19 include acute respiratory distress syndrome (ARDS) associated with cytokine release syndrome that can culminate in multiorgan failure and death. Among the proinflammatory factors associated with severe COVID-19 are the chemokines CCL2, CCL3, CXCL8, and CXCL10. Infection of susceptible mice with murine coronaviruses, such as mouse hepatitis virus (MHV), elicits a similar chemokine response profile as observed in COVID-19 patients and these in vivo models have been informative and show that targeting chemokines reduces the severity of inflammation in target organs.

Areas covered

PubMed was used using keywords: Chemokines and coronaviruses; Chemokines and mouse hepatitis virus; Chemokines and COVID-19. Clinicaltrials.gov was used using keywords: COVID-19 and chemokines; COVID-19 and cytokines; COVID-19 and neutrophil

Expert opinion

Chemokines and chemokine receptors are clinically relevant therapeutic targets for reducing coronavirus-induced inflammation.

KEYWORDS:

• Coronavirus
• chemokines
• chemokine receptors
• inflammation
• clinical targets

Article highlights

• Coronaviruses elicit an orchestrated expression of chemokines following infection and this is regulated, in part, by stage of disease.

• Coronavirus-induced expression of chemokines attracts targeted populations of leukocytes that aid in host defense or contribute to ongoing inflammation and disease pathology.

• Chemokines represent promising markers for evaluating disease severity in COVID-19 patients as circulating levels of specific chemokines have been associated with ARDS as well as other multiorgan failure.

• Ongoing clinical trials targeting chemokines may offer new therapeutic pathways in dampening tissue inflammation and improve clinical outcome.

Declaration of interest

The authors have no other 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 apart from those disclosed.

Reviewer disclosures

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

Additional information

Funding

This work was supported by funding from National Institutes of Health (NIH) research grants R01NS041249 and R35NS116835 and National Multiple Sclerosis Society Grant CA-1607-25040 to T Lane. G Olivarria was supported by (NIH) Immunology Research Training Grant 5T32AI060573-15. The authors declare no other financial interests.