Baricitinib restrains the immune dysregulation in patients with severe COVID-19

Abstract

Background. COVID-19 patients develop pneumonia generally associated to lymphopenia and severe inflammatory response due to uncontrolled cytokine release. These mediators are transcriptionally regulated by the JAK-STAT signaling pathways, which can be disabled by small molecules. Methods. A group of subjects (n = 20) was treated with baricitinib according to an offlabel use of the drug. The study was designed as an observational longitudinal trial and approved by the local ethical committee. The patients were treated with baricitinib 4 mg twice daily for 2 days, followed by 4 mg per day for the remaining 7 days. Changes in the immune phenotype and expression of pSTAT3 in blood cells were evaluated and correlated with serum-derived cytokine levels and antibodies anti-SARS-CoV-2. In a single treated patient, we evaluated also the alteration of myeloid cell functional activity. Results. We provided evidence that baricitinib-treated patients have a marked reduction in serum levels of interleukin (IL)-6, IL-1β and tumor necrosis factor (TNF)-a, a rapid recovery in circulating T and B cell frequencies, and increased antibody production against SARS-CoV-2 spike protein, which were clinically associated with a reduction in oxygen flow need and progressive increase in the P/F. Conclusion. These data suggest that Baricitinib prevented the progression towards a severe/extreme form of the viral disease by modulating the patients' immune landscape and these changes were associated with a safer and favorable clinical outcome of patients with COVID-19 pneumonia. Trial registration. The ClinicalTrials.gov identifier of this project is protocol NCT04438629.

JAK-STAT Pathway Inhibition and their Implications in COVID-19 Therapy

“…Likewise, several on-going studies are to be progressed with Baricitinib. A report by Bronte et.al stated that it aids to amend the immune abnormalities in COVID-19 hospitalized patients [ 104 ]. Another phase III clinical trial evaluates the role of Baricitinib + Remdesivir combination (NCT04401579) for the treatment of COVID-19.…”

Potential immuno-nanomedicine strategies to fight COVID-19 like pulmonary infections

“… Baricitinib also blocks the viral entry by inhibiting AP2-associated protein kinase one and cyclin G-associated kinases. Under evaluation at various centers for severe COVID-19 cases [158] , [159] . TNF inhibitor Adalimumab (Humira) Adalimumab is a recombinant monoclonal antibody against TNF responses, which is approved for the treatment of autoimmune disease, particularly rheumatoid arthritis (RA) [160] .…”

Characteristics and Outcomes of IBD Patients with COVID-19 on Tofacitinib Therapy in the SECURE-IBD Registry

“… 3 Emerging data in non-IBD patients suggest that JAKi may blunt the cytokine storm that characterizes severe COVID-19 and potentially improve outcomes. 4 In fact, a number of JAKi such as tofacitinib, baricitinib and ruxolitinib are being studied in clinical trials for COVID-19 treatment.…”