Patients with coronavirus disease 2019 (COVID-19) develop pneumonia generally associated with lymphopenia and a 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. We treated a group of patients (n = 20) with baricitinib according to an off-label use of the drug. The study was designed as an observational, longitudinal trial and approved by the local ethics committee. The patients were treated with 4 mg baricitinib twice daily for 2 days, followed by 4 mg per day for the remaining 7 days. Changes in the immune phenotype and expression of phosphorylated STAT3 (p-STAT3) in blood cells were evaluated and correlated with serum-derived cytokine levels and antibodies against severe acute respiratory syndrome–coronavirus 2 (anti–SARS-CoV-2). In a single treated patient, we also evaluated the alteration of myeloid cell functional activity. RESULTS. We provide evidence that patients treated with baricitinib had a marked reduction in serum levels of IL-6, IL-1β, and TNF-α, a rapid recovery of circulating T and B cell frequencies, and increased antibody production against the SARS-CoV-2 spike protein, all of which were clinically associated with a reduction in the need for oxygen therapy and a progressive increase in the P/F (PaO2, oxygen partial pressure/FiO2, fraction of inspired oxygen) ratio. CONCLUSION. These data suggest that baricitinib prevented the progression to a severe, extreme form of the viral disease by modulating the patients’ immune landscape and that these changes were associated with a safer, more favorable clinical outcome for patients with COVID-19 pneumonia.

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

Bronte, V.
;
Ugel, S.;Vella, A.;de Sanctis, F.;Batani, V.;Trovato, R.;Petrova, V.;Hofer, F.;Musiu, C.;Caligola, S.;Pinton, L.;Torroni, L.;Polati, E.;Donadello, K.;Pizzolo, F.;Comel, A.;
2020-01-01

Abstract

Patients with coronavirus disease 2019 (COVID-19) develop pneumonia generally associated with lymphopenia and a 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. We treated a group of patients (n = 20) with baricitinib according to an off-label use of the drug. The study was designed as an observational, longitudinal trial and approved by the local ethics committee. The patients were treated with 4 mg baricitinib twice daily for 2 days, followed by 4 mg per day for the remaining 7 days. Changes in the immune phenotype and expression of phosphorylated STAT3 (p-STAT3) in blood cells were evaluated and correlated with serum-derived cytokine levels and antibodies against severe acute respiratory syndrome–coronavirus 2 (anti–SARS-CoV-2). In a single treated patient, we also evaluated the alteration of myeloid cell functional activity. RESULTS. We provide evidence that patients treated with baricitinib had a marked reduction in serum levels of IL-6, IL-1β, and TNF-α, a rapid recovery of circulating T and B cell frequencies, and increased antibody production against the SARS-CoV-2 spike protein, all of which were clinically associated with a reduction in the need for oxygen therapy and a progressive increase in the P/F (PaO2, oxygen partial pressure/FiO2, fraction of inspired oxygen) ratio. CONCLUSION. These data suggest that baricitinib prevented the progression to a severe, extreme form of the viral disease by modulating the patients’ immune landscape and that these changes were associated with a safer, more favorable clinical outcome for patients with COVID-19 pneumonia.
COVID-19, pneumonia, baricitinib, immune response
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11562/1078326
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