Inhibition of cytokine signaling by ruxolitinib and implications for COVID-19 treatment

Approximately 15% of patients with coronavirus disease 2019 (COVID-19) experience severe disease, and 5% progress to critical stage that can result in rapid death. No vaccines or antiviral treatments have yet proven effective against COVID-19. Patients with severe COVID-19 experience elevated plasma levels of pro-inflammatory cytokines, which can result in cytokine storm, followed by massive immune cell infiltration into the lungs leading to alveolar damage, decreased lung function, and rapid progression to death. As many of the elevated cytokines signal through Janus kinase (JAK)1/JAK2, inhibition of these pathways with ruxolitinib has the potential to mitigate the COVID-19–associated cytokine storm and reduce mortality. This is supported by preclinical and clinical data from other diseases with hyperinflammatory states, where ruxolitinib has been shown to reduce cytokine levels and improve outcomes. The urgent need for treatments for patients with severe disease support expedited investigation of ruxolitinib for patients with COVID-19. •Severe coronavirus disease 2019 (COVID-19) cases are associated with cytokine storm.•Pro-inflammatory cytokines implicated in the sequelae signal through JAK1/JAK2.•Ruxolitinib, a JAK1/JAK2 inhibitor, could mitigate the cytokine storm in COVID-19.•Ruxolitinib may therefore have potential to reduce mortality in severe COVID-19.