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First Author: Vincenzo Bronte  

Journal/preprint name: The Journal of Clinical Investigation 

Tags: SARS-CoV-2, COVID-19 patients, JAK/STAT3 


  • Observational 14-day trial of the selective and reversible JAK1/JAK2 kinase off-label inhibitor Baricitinib (n= 20 patients). 

  • Baricitinib treated patients had a lower mortality (5%) than patients who received other treatments (25/56 died) and were weaned off oxygen therapy earlier. 

  • Baricitinib reduced pSTAT3 in circulating immune cellsinflammatory cytokines, and increased circulating IgG/IgA 

  • Baricitinib appears to moderate inflammation in hospitalised COVID-19 patients, supporting another pilot study 12 COVID-19 patients (10.1016/j.jinf.2020.04.017) 

  • Improves understanding of how Baricitinib treatment alters COVID-19 progression and and suggests markers of target engagement which could be used in larger Baricitinib trials, e.g. Eli Lilly’s Phase III trial.  

Research Highlights 

  1. 20 COVID-19 patients received 2x 4mg for 2 days then 1x 4mg for 7 day, 56 COVID-19 controls received other treatments and 6 healthy donors. 

  1. Baricitinib treatment reduced inflammatory cytokines (IL-6, IL-1β and TNF-α) and C-reactive protein, increased circulating B/T cells, especially CD4+ T Cells, and SARS-CoV-2 spike protein antibodies.  

  1. Phosphotylated-STAT3 (p-Tyr705) was assessed in 6 Baricitinib treated patients in T cells, NK cells, monocytes and neutrophils leukocyte subsets, and was found to be reduced after 4 days of treatment. P-STAT1 (p-Tyr701) was unchanged in these patients. 

  1. Monocyte expansion was seen at day 7 irrespective of treatment received.  

  1. CD14+ monocytes assessed in one Baricitinib treated patient (n=1) were shown to suppress activated T-cells at a higher level in the ICU compared to when they were released from the ICU. 

Impact for COVID-19 research:  

This study suggests Baricitinib could be used to treat severe COVID-19 but needs to be validated in a larger cohort.  


  • Study TypeClinical Trial ID (NCT04438629). 

  • Key Techniques: ELISAs and Flow Cytometry used to measure various parameters in patient blood/serum.  


  1. Small number of patients (n=20), and some missing data from patient follow-up, monocyte function only studied in one patient. 

  1. Control group received other treatments (n=56). 

  1. Trial was held over a short timeline (14 days), long term impact of Baricitinib unknown.