Improved survival of SARS COV-2-infected K18- hACE2 mice treated with adenosine A2AR agonist

Barbara J Mann; Preeti Chhabra; Mingyang Ma; Savannah G Brovero; Riley T Hannan; Jeffrey M Sturek; Marieke K Jones; Joel Linden; Kenneth L Brayman

doi:10.1016/j.heliyon.2023.e19226

Improved survival of SARS COV-2-infected K18- hACE2 mice treated with adenosine A_2AR agonist

Heliyon. 2023 Aug 18;9(8):e19226. doi: 10.1016/j.heliyon.2023.e19226. eCollection 2023 Aug.

Authors

Barbara J Mann^{1

2}, Preeti Chhabra³, Mingyang Ma³, Savannah G Brovero¹, Riley T Hannan⁴, Jeffrey M Sturek⁴, Marieke K Jones⁵, Joel Linden⁶, Kenneth L Brayman³

Affiliations

¹ Department of Medicine, Division of Infectious Diseases, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
² Microbiology, Immunology, and Cancer Biology, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
³ Department of Surgery, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
⁴ Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
⁵ Claude Moore Health Sciences Library, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
⁶ Department of Medicine, Division of Nephrology, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.

Abstract

A life-threatening manifestation of Covid-19 infection is a cytokine storm that requires hospitalization and supplemental oxygen. Various strategies to reduce inflammatory cytokines have had some success in limiting cytokine storm and improving survival. Agonists of adenosine A_2A receptors (A_2AR) reduce cytokine release from most immune cells. Apadenoson is a potent and selective anti-inflammatory adenosine analog that reduces inflammation. When administered by subcutaneous osmotic pumps to mice infected with SARS CoV-2, Apadenoson was found to improve the outcomes of infection as measured by a decrease in weight loss, improved clinical symptoms, reduced levels of proinflammatory cytokines and chemokines in bronchial lavage (BAL) fluid, and enhanced survival of K18-hACE2 transgenic mice. These results support further examination of A_2AR agonists as therapies for treating cytokine storm due to COVID-19.

Keywords: Adenosine agonists; Apadenoson; COVID-19; SARS CoV2; Therapy.