Clinical Outcomes in a Cohort of Non-Ventilated COVID-19 Patients with Progressive Hypoxemia and Hyper-Inflammatory Response Treated with Baricitinib

Background: COVID-19, caused by SARS-CoV-2, is a respiratory disease that is causing significant morbidity and mortality globally and with limited effective treatment options. SARS-CoV-2 binds to the ACE2 receptors in pulmonary epithelial cells resulting in pulmonary infection with progression to acute respiratory distress syndrome and death in a subset of patients. Baricitinib is a Janus kinase (JAK) inhibitor that inhibits JAK1 and JAK2 receptors, which have been implicated in reducing SARS-CoV-2 endocytosis as well as reducing IL-6-mediated inflammation. Methods: We included non-mechanically ventilated (MV) patients with COVID-19 with progressive hypoxemia and elevated inflammatory markers (ferritin and C-reactive protein (CRP)) who received standard of care (SOC) treatment (either hydroxychloroquine +/- azithromycin or a protease inhibitor +/- ribavirin) plus baricitinib 2 mg daily for at least 50% doses of a seven-day standard drug course. The majority of patients were treated with corticosteroids and systemic anticoagulation as well. Patient demographics, clinical data, treatment regimens, and outcomes were collected through electronic medical records. Findings: Twenty-two patients, 50% males, received baricitinib. Median age was 57·5 (range 32–74) with a median Charlson Comorbidity Index (CCI) of 3·5 (interquartile range 2-5). Sixteen (72·7%) patients did not progress to MV or death. Seventeen (77·3%) patients had a reduction in supplemental oxygen requirements. Ferritin and CRP values decreased in the majority of patients. Interpretation: In non-MV COVID-19 patients with progressive hypoxemia and elevated markers of inflammation, standard of care treatment (SOC) plus baricitinib appears to improve supplemental oxygen requirements and reduce clinical progression in a subset of patients. Funding Statement: None Declaration of Interests: Patrick S. Milligan, MD: Nothing to disclose Jarrett R. Amsden, PharmD: Nothing to disclose Steven A. Norris, MD: Nothing to disclose Robert L. Baker, MD: Nothing to disclose Jaclyn Myers, PharmD: Nothing to disclose Felicia Preston, MS: Nothing to disclose Jessica Gregory, MS: Nothing to disclose Kathy A. Zoppi, PhD: Nothing to disclose Kaveh Tayebi, MD: Nothing to disclose Ramarao Yeleti, MD: Nothing to disclose Sandeep K. Gupta, MD is a consultant for Abbott, Allakos, Adare, Gossamer Bio, Receptos; has received research support from Shire; has royalties from UpToDate; and support from NIH U54 AI117804 Ethics Approval Statement: This study was approved by the Community Health Network, Indianapolis, IN., Institutional Review Board. Informed consent was waived, and researchers analyzed only deidentified (anonymized) data.