JAK inhibition reduces SARS-CoV-2 liver infectivity and modulates inflammatory responses to reduce morbidity and mortality.
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ABSTRACT:
SUBMITTER: Stebbing J
PROVIDER: S-EPMC7775747 | biostudies-literature | 2020 Nov
REPOSITORIES: biostudies-literature
Publications
JAK inhibition reduces SARS-CoV-2 liver infectivity and modulates inflammatory responses to reduce morbidity and mortality.
Stebbing Justin J Sánchez Nievas Ginés G Falcone Marco M Youhanna Sonia S Richardson Peter P Ottaviani Silvia S Shen Joanne X JX Sommerauer Christian C Tiseo Giusy G Ghiadoni Lorenzo L Virdis Agostino A Monzani Fabio F Rizos Luis Romero LR Forfori Francesco F Avendaño Céspedes Almudena A De Marco Salvatore S Carrozzi Laura L Lena Fabio F Sánchez-Jurado Pedro Manuel PM Lacerenza Leonardo Gianluca LG Cesira Nencioni N Caldevilla Bernardo David D Perrella Antonio A Niccoli Laura L Méndez Lourdes Sáez LS Matarrese Daniela D Goletti Delia D Tan Yee-Joo YJ Monteil Vanessa V Dranitsaris George G Cantini Fabrizio F Farcomeni Alessio A Dutta Shuchismita S Burley Stephen K SK Zhang Haibo H Pistello Mauro M Li William W Romero Marta Mas MM Andrés Pretel Fernando F Simón-Talero Rafaela Sánchez RS García-Molina Rafael R Kutter Claudia C Felce James H JH Nizami Zehra F ZF Miklosi Andras G AG Penninger Josef M JM Menichetti Francesco F Mirazimi Ali A Abizanda Pedro P Lauschke Volker M VM
Science advances 20210101 1
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-α2 increases ACE2 expression and SARS-Co ...[more]
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