COVID-19 is a viral disease caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), that can cause severe pneumonia and ARDS. Respiratory viral load may peak within 5 days after onset, while symptoms are still mild. Many patients rapidly (within 1 to 2 weeks of infection) develop dyspnea and pneumonia and require hospitalization for respiratory support.~Preliminary clinical data from COVID-19 patients indicate that severe symptoms with SARS-CoV-2 infection are associated with an exaggerated immune response driven by interleukin (IL)-6 IL-10, tumor necrosis factor (TNF)α, and other cytokines. The ultimate result is progressive destruction of the alveolar epithelium leading to pneumonia and/or ARDS. Moreover, the exudative phase of ARDS is thought to be due to an influx of myeloid cells (neutrophils and macrophages) and elevations of inflammatory cytokines, with higher levels of both IL-6 and IL-8 levels being correlated with increased mortality. Therefore, immunomodulatory therapy may be beneficial in reducing the deleterious effects of lung inflammation and mitigating progressive lung injury.~Tofacitinib is an inhibitor of Janus kinase (JAKs) 1 and 3, with partial selectivity to JAK 2. Tofacitinib suppresses pro-inflammatory signaling that may be important pathogenetically to progression to more severe lung disease and ARDS in patients with COVID-19.~The purpose of the study is to assess the safety and efficacy of tofacitinib plus standard pharmacologic and supportive measures in treating hospitalized participants with COVID-19 pneumonia.~Participants with laboratory confirmed SARS-CoV-2 infection as determined by a positive PCR, who have agreed to participate, will be screened within 72h hours after admission to the hospital to determine eligibility.~Eligible participants will be randomized on Day 1 to the tofacitinib plus standard of care treatment group or the placebo plus standard of care treatment group in a 1:1 ratio, stratified by site. Participants will receive treatment for up to 14 days or until discharge from the hospital, whichever is earlier.~Participants will be assessed daily (up to Day 28) while hospitalized for clinical, safety, and laboratory parameters. Follow-up visits will occur on Day 14 and on Day 28.
Tofacitinib suppresses pro-inflammatory signaling that may be important pathogenetically to progression to more severe lung disease and acute respiratory distress syndrome (ARDS) in patients with COVID-19. The purpose of the study is to assess the safety and efficacy of tofacitinib plus standard pharmacologic and supportive measures in treating hospitalized participants with COVID-19 pneumonia.