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
Affiliations
Barbara J. Mann
Department of Medicine, Division of Infectious Diseases, University of Virginia School of Medicine, Charlottesville, VA 22908, USA; Microbiology, Immunology, and Cancer Biology, University of Virginia School of Medicine, Charlottesville, VA 22908, USA; Corresponding author. Department of Medicine, Division of Infectious Diseases, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
Preeti Chhabra
Department of Surgery, University of Virginia School of Medicine, Charlottesville, VA 22908, USA
Mingyang Ma
Department of Surgery, University of Virginia School of Medicine, Charlottesville, VA 22908, USA
Savannah G. Brovero
Department of Medicine, Division of Infectious Diseases, University of Virginia School of Medicine, Charlottesville, VA 22908, USA
Riley T. Hannan
Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of Virginia School of Medicine, Charlottesville, VA 22908, USA
Jeffrey M. Sturek
Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of Virginia School of Medicine, Charlottesville, VA 22908, USA
Marieke K. Jones
Claude Moore Health Sciences Library, University of Virginia School of Medicine, Charlottesville, VA 22908, USA
Joel Linden
Department of Medicine, Division of Nephrology, University of Virginia School of Medicine, Charlottesville, VA 22908, USA
Kenneth L. Brayman
Department of Surgery, University of Virginia School of Medicine, Charlottesville, VA 22908, USA
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 A2A receptors (A2AR) 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 A2AR agonists as therapies for treating cytokine storm due to COVID-19.
