p9gf76s5

Property	Value
?:abstract	BACKGROUNDPatients 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.METHODSWe 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.RESULTSWe provide evidence that patients treated with baricitinib had a marked reduction in serum levels of IL-6, IL-1ß, 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.CONCLUSIONThese 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.TRIAL REGISTRATIONClinicalTrials.gov NCT04438629.FUNDINGThis work was supported by the Fondazione Cariverona (ENACT Project) and the Fondazione TIM.
is ?:annotates of	<https://research.tib.eu/covid-19/entity/p9gf76s5_hasAnnotation_C0013227> <https://research.tib.eu/covid-19/entity/p9gf76s5_hasAnnotation_C1096117> <https://research.tib.eu/covid-19/entity/p9gf76s5_hasAnnotation_C1155266> <https://research.tib.eu/covid-19/entity/p9gf76s5_hasAnnotation_C1328819> <https://research.tib.eu/covid-19/entity/p9gf76s5_hasAnnotation_C1367307> <https://research.tib.eu/covid-19/entity/p9gf76s5_hasAnnotation_C1419208> <https://research.tib.eu/covid-19/entity/p9gf76s5_hasAnnotation_C5203676>
?:creator	<https://research.tib.eu/covid-19/entity/Bronte%2C_Vincenzo%3B_Ugel%2C_Stefano%3B_Tinazzi%2C_Elisa%3B_Vella%2C_Antonio%3B_De_Sanctis%2C_Francesco%3B_Can%C3%A8%2C_Stefania%3B_Batani%2C_Veronica%3B_Trovato%2C_Rosalinda%3B_Fiore%2C_Alessandra%3B_Petrova%2C_Varvara%3B_Hofer%2C_Francesca%3B_Barouni%2C_Roza_Maria%3B_Musiu%2C_Chiara%3B_Caligola%2C_Simone%3B_Pinton%2C_Laura%3B_Torroni%2C_Lorena%3B_Polati%2C_Enrico%3B_Donadello%2C_Katia%3B_Friso%2C_Simonetta%3B_Pizzolo%2C_Francesca%3B_Iezzi%2C_Manuela%3B_Facciotti%2C_Federica%3B_Pelicci%2C_Pier_Giuseppe%3B_Righetti%2C_Daniela%3B_Bazzoni%2C_Paolo%3B_Rampudda%2C_Mariaelisa%3B_Comel%2C_Andrea%3B_Mosaner%2C_Walter%3B_Lunardi%2C_Claudio%3B_Olivieri%2C_Oliviero>
?:journal	J._clin._invest
?:license	unk
?:publication_isRelatedTo_Disease	<https://research.tib.eu/covid-19/entity/COVID-19>
is ?:relation_isRelatedTo_publication of	<https://research.tib.eu/covid-19/entity/p9gf76s5_HAS_C0024312_COEXISTS_WITH_C0032285> <https://research.tib.eu/covid-19/entity/p9gf76s5_HAS_C1155266_COEXISTS_WITH_C0032285>
?:source	WHO
?:title	Baricitinib restrains the immune dysregulation in patients with severe COVID-19
?:type	<https://research.tib.eu/covid-19/vocab/Publication>
?:who_covidence_id	#721245
?:year	2020

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Value

?:abstract

BACKGROUNDPatients 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.METHODSWe 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.RESULTSWe provide evidence that patients treated with baricitinib had a marked reduction in serum levels of IL-6, IL-1ß, 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.CONCLUSIONThese 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.TRIAL REGISTRATIONClinicalTrials.gov NCT04438629.FUNDINGThis work was supported by the Fondazione Cariverona (ENACT Project) and the Fondazione TIM.

is ?:annotates of