Observational studyScience advances2021
JAK inhibition reduces SARS-CoV-2 liver infectivity and modulates inflammatory responses to reduce morbidity and mortality.
Open access · goldAbstract readMulticenter StudyObservational Study
In one paragraph
Observational study in Science advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 papers, 8 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
124citing papers in PubMed, 8 pooled it
4.8field-weighted citation impact, top 3% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
124 citing papers in PubMed, 8 syntheses or guidelines pooled it, 215 citations in OpenAlex.
- Does baricitinib reduce mortality and disease progression in SARS-CoV-2 virus infected patients? A systematic review and meta analysis.Respiratory medicine · 2022Pooled it
- Janus kinase inhibitors for the treatment of COVID-19.The Cochrane database of systematic reviews · 2022Pooled it
- Clinical efficacy and adverse events of baricitinib treatment for coronavirus disease-2019 (COVID-19): A systematic review and meta-analysis.Journal of medical virology · 2022Pooled it
- JAK inhibitors and COVID-19.Journal for immunotherapy of cancer · 2022Pooled it
- Janus kinase (JAK)-inhibitors and coronavirus disease 2019 (Covid-19) outcomes: a systematic review and meta-analysis.Expert review of anti-infective therapy · 2022Pooled it
- Janus kinases inhibitors for coronavirus disease-2019: A pairwise and Bayesian network meta-analysis.Frontiers in medicine · 2022Pooled it
- A meta-analysis on the risk factors adjusted association between cardiovascular disease and COVID-19 severity.BMC public health · 2021Pooled it
- The Efficacy and Safety of Janus Kinase Inhibitors for Patients With COVID-19: A Living Systematic Review and Meta-Analysis.Frontiers in medicine · 2021Pooled it
- Efficacy and safety of baricitinib plus standard of care for the treatment of critically ill hospitalised adults with COVID-19 on invasive mechanical ventilation or extracorporeal membrane oxygenation: an exploratory, randomised, placebo-controlled trial.The Lancet. Respiratory medicine · 2022Trial
- Efficacy and safety of baricitinib for the treatment of hospitalised adults with COVID-19 (COV-BARRIER): a randomised, double-blind, parallel-group, placebo-controlled phase 3 trial.The Lancet. Respiratory medicine · 2021Trial
- Body mass index and baricitinib treatment effect in hospitalized adults with COVID-19: A secondary analysis of ACTT-2.Heart & lung : the journal of critical careTrial
- The protective efficacy of baricitinib against lipopolysaccharide / D-Galactosamine-Induced acute liver Injury.Frontiers in pharmacology · 2026Article
- Cardiomyocyte Janus kinase 1 (JAK1) signaling is required for cardiac homeostasis and cytokine-dependent activation of STAT3.Journal of molecular and cellular cardiology · 2025Article
- A Review: Can Cytokines Induce Vascular Inflammation as a Sequela of Viral Infections?Health science reports · 2025Article
- ALBACOVIDIOL Study: Effect of Calcifediol Treatment on Mortality in Patients Hospitalized for COVID-19: A Retrospective Analysis.Nutrients · 2025Observational
- Identification of Dinaciclib and Ganetespib as anti-inflammatory drugs using a novel HTP screening assay that targets IFNγ-dependent PD-L1.Frontiers in immunology · 2025Article
- AI-based hardware and software tools in microscopy to boost research in immunology and virology.Frontiers in immunology · 2025Review
- Development and Validation of a UPLC-MS/MS Detection Method of Baricitinib for Therapeutic Drug Monitoring in COVID-19 Patients.Drug design, development and therapy · 2025Article
- Honeysuckle extracts as a potential inhibitor of SARS-CoV-2 infection.Frontiers in pharmacology · 2025Article
- Sclareol exerts an anti-inflammatory effect, possibly through COXs inhibition pathway:Pharmaceutical science advances · 2024Article
64 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
50 authors at 20 institutions in 9 countries.
Justin StebbingDepartment of Surgery and Cancer, Imperial College, London, UK. j.stebbing@imperial.ac.uk volker.lauschke@ki.se.ORCID 0000-0002-1117-6947
Ginés Sánchez NievasDepartment of Rheumatology, Complejo Hospitalario Universitario de Albacete, Albacete, Spain.ORCID 0000-0003-3910-2955
Marco FalconeDepartment of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Sonia YouhannaDepartment of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0002-9376-8478
Peter RichardsonBenevolentAI, Maple Street, London, UK.
Silvia OttavianiDepartment of Surgery and Cancer, Imperial College, London, UK.ORCID 0000-0002-8830-9947
Joanne X ShenDepartment of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Christian SommerauerDepartment of Microbiology, Tumor, and Cell Biology, Karolinska Institutet, Science for Life Laboratory, Solna, Sweden.ORCID 0000-0001-7132-7172
Giusy TiseoDepartment of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Lorenzo GhiadoniDepartment of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Agostino VirdisDepartment of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Fabio MonzaniDepartment of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.ORCID 0000-0003-1676-098X
Luis Romero RizosDepartment of Geriatric Medicine, Complejo Hospitalario Universitario de Albacete, Albacete, Spain.
Francesco ForforiDepartment of Surgical, Medical and Molecular Pathology and Critical Care Medicine, Pisa, University of Pisa, Italy.ORCID 0000-0001-8201-8076
Almudena Avendaño CéspedesDepartment of Geriatric Medicine, Complejo Hospitalario Universitario de Albacete, Albacete, Spain.
Salvatore De MarcoDepartment of Internal Medicine, Azienda Ospedaliera Universitaria Pisana, Pisa, Italy.ORCID 0000-0002-5013-0220
Laura CarrozziDepartment of Surgical, Medical and Molecular Pathology and Critical Care Medicine, Pisa, University of Pisa, Italy.
Fabio LenaDepartment of Pharmaceutical Medicine, Misericordia Hospital, Grosseto, Italy.ORCID 0000-0002-4920-9898
Pedro Manuel Sánchez-JuradoDepartment of Geriatric Medicine, Complejo Hospitalario Universitario de Albacete, Albacete, Spain.
Leonardo Gianluca LacerenzaDepartment of Pharmaceutical Medicine, Misericordia Hospital, Grosseto, Italy.ORCID 0000-0002-9315-1654
Nencioni CesiraDepartment of Medicine, Misericordia Hospital, Grosseto, Italy.ORCID 0000-0002-9133-8562
David Caldevilla BernardoDepartment of Radiology, Complejo Hospitalario Universitario de Albacete, Albacete, Spain.ORCID 0000-0002-4836-3738
Antonio PerrellaDepartment of Medicine, Misericordia Hospital, Grosseto, Italy.
Laura NiccoliDepartment of Rheumatology, Hospital of Prato, Prato, Italy.
Lourdes Sáez MéndezDepartment of Internal Medicine, Complejo Hospitalario Universitario de Albacete, Albacete, Spain.
Daniela MatarreseHospital Network ASL Toscana Centro, Toscana, Italy.ORCID 0000-0002-3479-4545
Delia GolettiDepartment of Epidemiology and Preclinical Research, National Institute for Infectious Diseases-IRCCS, Rome, Italy.ORCID 0000-0001-8360-4376
Yee-Joo TanUniversity of Singapore, Infectious Diseases Programme, Immunology Programme, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore and Institute of Molecular and Cell Biology (IMCB), A*STAR (Agency for Science, Technology and Research), Singapore, Singapore.ORCID 0000-0002-2278-4497
Vanessa MonteilKarolinska Institutet, Department of Laboratory Medicine, Unit of Clinical Microbiology, and SE-17177, Stockholm, Sweden.ORCID 0000-0002-2652-5695
George DranitsarisDepartment of Hematology, School of Medicine, University of Ioannina, Ioannina, Greece.
Fabrizio CantiniDepartment of Rheumatology, Hospital of Prato, Prato, Italy.
Alessio FarcomeniDepartment of Economics and Finance, University of Rome Tor Vergata, Rome Italy.ORCID 0000-0002-7104-5826
Shuchismita DuttaRCSB Protein Data Bank, Rutgers, The State University of New Jersey, Piscataway, NJ, USA.ORCID 0000-0002-2109-5411
Stephen K BurleyRCSB Protein Data Bank, Rutgers, The State University of New Jersey, Piscataway, NJ, USA.
Haibo ZhangDepartments of Anesthesia, Medicine, and Physiology, University of Toronto, Toronto, ON, Canada.ORCID 0000-0002-1714-3038
Mauro PistelloVirology Unit, Department of Translational Research, University of Pisa, Pisa, Italy.ORCID 0000-0003-0908-6253
William LiThe Angiogenesis Foundation, Cambridge, MA, USA.ORCID 0000-0003-3344-1403
Marta Mas RomeroDepartment of Geriatric Medicine, Complejo Hospitalario Universitario de Albacete, Albacete, Spain.
Fernando Andrés PretelDepartment of Statistics, Complejo Hospitalario Universitario de Albacete, Albacete, Spain.
Rafaela Sánchez Simón-TaleroDepartment of Pneumology, Complejo Hospitalario Universitario de Albacete, Albacete, Spain.
Rafael García-MolinaDepartment of Geriatric Medicine, Complejo Hospitalario Universitario de Albacete, Albacete, Spain.ORCID 0000-0003-3498-1049
Claudia KutterDepartment of Microbiology, Tumor, and Cell Biology, Karolinska Institutet, Science for Life Laboratory, Solna, Sweden.ORCID 0000-0002-8047-0058
James H FelceOxford Nanoimaging, Oxford, UK.ORCID 0000-0001-5531-9244
Zehra F NizamiOxford Nanoimaging, Oxford, UK.ORCID 0000-0003-3308-3247
Andras G MiklosiOxford Nanoimaging, Oxford, UK.
Josef M PenningerInstitute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria.ORCID 0000-0002-8194-3777
Francesco MenichettiDepartment of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Ali MirazimiKarolinska Institutet, Department of Laboratory Medicine, Unit of Clinical Microbiology, and SE-17177, Stockholm, Sweden.
Pedro AbizandaDepartment of Geriatric Medicine, Complejo Hospitalario Universitario de Albacete, Albacete, Spain.ORCID 0000-0002-4707-2963
Volker M LauschkeDepartment of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden. j.stebbing@imperial.ac.uk volker.lauschke@ki.se.ORCID 0000-0002-1140-6204
University of Pisa · ITComplejo Hospitalario Universitario de Albacete · ESKarolinska Institutet · SEMinistry of Economy, Industry and Competitiveness · ESOspedale Misericordia - Grosseto · ITOxford Nanoimaging (United Kingdom) · GBAgency for Science, Technology and Research · SGHospital of Prato · ITImperial College London · GBRutgers, The State University of New Jersey · USScience for Life Laboratory · SEAngiogenesis Foundation · USAzienda Ospedaliera Universitaria Pisana · ITAzienda Usl Toscana Centro · ITBenevolentAI (United Kingdom) · GBCenter for Prevention and Treatment of Infections · USInstitute of Molecular Biotechnology · ATUniversity of Ioannina · GRUniversity of Rome Tor Vergata · ITUniversity of Toronto · CA
Funding
PDB MANAGEMENT BY THE RESEARCH COLLABORATORY FOR STRUCTURAL BIOINFORMATICSR01GM133198 · NIGMS · RUTGERS, THE STATE UNIV OF N.J. · PI BURLEY, STEPHEN K · 2019 to 2023
$19.3MDepartment of Health NIHR-RP-011-053NIGMS NIH HHS R01 GM133198
Abstract
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-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.
Indexed as
AdultAgedAged, 80 and overAntiviral AgentsAzetidinesCOVID-19COVID-19 Drug TreatmentCytokine Release SyndromeCytokinesDrug Evaluation, PreclinicalEnzyme InhibitorsFemaleGene Expression ProfilingHumansInterferon alpha-2ItalyAntiviral AgentsAzetidinesbaricitinibCytokinesEnzyme InhibitorsInterferon alpha-2Janus KinasesPurinesPyrazolesSulfonamides
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Read underepoch 390
Registered trials
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.