he7aguve

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?:abstract	Using AI we identified baricitinib as possessing anti-viral and anti-cytokine efficacy. We now show a 71% (95% CI 0.15-0.58) mortality benefit in 83 patients with moderate-severe SARS-CoV-2 pneumonia with few drug-induced adverse events, including a large elderly cohort (median age 81 years). A further 48 cases with mild-moderate pneumonia recovered uneventfully. Using organotypic 3D cultures of primary human liver cells, we demonstrate that interferon-alpha-2 (IFNα2) significantly increases ACE2 expression and SARS-CoV-2 infectivity in parenchymal cells by >5-fold. RNA-Seq reveals gene response signatures associated with platelet activation, fully inhibited by baricitinib. Using viral load quantifications and super-resolution microscopy, baricitinib exerts activity rapidly through the inhibition of host proteins (numb associated kinases), uniquely amongst anti-virals. This reveals mechanistic actions of a Janus kinase-1/2 inhibitor targeting viral entry, replication and the cytokine storm, and is associated with beneficial outcomes including in severely ill elderly patients, data that incentivizes further randomized controlled trials. Using AI, we identified baricitinib as having antiviral and anticytokine efficacy We now show a 71% (95% CI 0 15 to 0 58) mortality benefit in 83 patients with moderate-severe SARS-CoV-2 pneumonia with few drug-induced adverse events, including a large elderly cohort (median age, 81 years) An additional 48 cases with mild-moderate pneumonia recovered uneventfully Using organotypic 3D cultures of primary human liver cells, we demonstrate that interferon-alpha2 increases ACE2 expression and SARS-CoV-2 infectivity in parenchymal cells by greater than fivefold RNA-seq reveals gene response signatures associated with platelet activation, fully inhibited by baricitinib Using viral load quantifications and superresolution microscopy, we found that baricitinib exerts activity rapidly through the inhibition of host proteins (numb-associated kinases), uniquely among antivirals This reveals mechanistic actions of a Janus kinase-1/2 inhibitor targeting viral entry, replication, and the cytokine storm and is associated with beneficial outcomes including in severely ill elderly patients, data that incentivize further randomized controlled trials
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?:journal	Sci._Adv Science_Advances
?:license	unk
?:publication_isRelatedTo_Disease	<https://research.tib.eu/covid-19/entity/COVID-19>
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?:source	WHO
?:title	JAK inhibition reduces SARS-CoV-2 liver infectivity and modulates inflammatory responses to reduce morbidity and mortality
?:type	<https://research.tib.eu/covid-19/vocab/Publication>
?:who_covidence_id	#1066789 #927806
?:year	2020 2021

Property

Value

?:abstract

Using AI we identified baricitinib as possessing anti-viral and anti-cytokine efficacy. We now show a 71% (95% CI 0.15-0.58) mortality benefit in 83 patients with moderate-severe SARS-CoV-2 pneumonia with few drug-induced adverse events, including a large elderly cohort (median age 81 years). A further 48 cases with mild-moderate pneumonia recovered uneventfully. Using organotypic 3D cultures of primary human liver cells, we demonstrate that interferon-alpha-2 (IFNα2) significantly increases ACE2 expression and SARS-CoV-2 infectivity in parenchymal cells by >5-fold. RNA-Seq reveals gene response signatures associated with platelet activation, fully inhibited by baricitinib. Using viral load quantifications and super-resolution microscopy, baricitinib exerts activity rapidly through the inhibition of host proteins (numb associated kinases), uniquely amongst anti-virals. This reveals mechanistic actions of a Janus kinase-1/2 inhibitor targeting viral entry, replication and the cytokine storm, and is associated with beneficial outcomes including in severely ill elderly patients, data that incentivizes further randomized controlled trials.
Using AI, we identified baricitinib as having antiviral and anticytokine efficacy We now show a 71% (95% CI 0 15 to 0 58) mortality benefit in 83 patients with moderate-severe SARS-CoV-2 pneumonia with few drug-induced adverse events, including a large elderly cohort (median age, 81 years) An additional 48 cases with mild-moderate pneumonia recovered uneventfully Using organotypic 3D cultures of primary human liver cells, we demonstrate that interferon-alpha2 increases ACE2 expression and SARS-CoV-2 infectivity in parenchymal cells by greater than fivefold RNA-seq reveals gene response signatures associated with platelet activation, fully inhibited by baricitinib Using viral load quantifications and superresolution microscopy, we found that baricitinib exerts activity rapidly through the inhibition of host proteins (numb-associated kinases), uniquely among antivirals This reveals mechanistic actions of a Janus kinase-1/2 inhibitor targeting viral entry, replication, and the cytokine storm and is associated with beneficial outcomes including in severely ill elderly patients, data that incentivize further randomized controlled trials

is ?:annotates of