Evidence map›Paper›PMID 32473600›Full record

ArticleEMBO molecular medicine2020

Mechanism of baricitinib supports artificial intelligence-predicted testing in COVID-19 patients.

Justin Stebbing, Venkatesh Krishnan, Stephanie de Bono, Silvia Ottaviani, Giacomo Casalini, Peter J Richardson, Vanessa Monteil, Volker M Lauschke, Ali Mirazimi, Sonia Youhanna and 13 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in EMBO molecular medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 173 papers, 8 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
173citing papers in PubMed, 8 pooled it
5.9field-weighted citation impact, top 3% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

173 citing papers in PubMed, 8 syntheses or guidelines pooled it, 267 citations in OpenAlex.

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  4. JAK inhibitors and COVID-19.Journal for immunotherapy of cancer · 2022
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113 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

23 authors at 8 institutions in 5 countries.

Justin Stebbing *Department of Surgery and Cancer, Imperial College, London, UK.ORCID 0000-0002-1117-6947
Venkatesh Krishnan *Eli Lilly and Company, Indianapolis, IN, USA.ORCID 0000-0002-3295-6598
Stephanie de BonoEli Lilly and Company, Indianapolis, IN, USA.
Silvia OttavianiDepartment of Surgery and Cancer, Imperial College, London, UK.
Giacomo CasaliniLuigi Sacco, Department of Clinical and Biomedical Sciences, University of Milan, Milan, Italy.
Peter J RichardsonBenevolentAI, London, UK.
Vanessa MonteilUnit of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
Volker M LauschkeUnit of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
Ali MirazimiUnit of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
Sonia YouhannaUnit of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
Yee-Joo TanInfectious Diseases Programme, Immunology Programme, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore City, Singapore.
Fausto BaldantiDepartment of Clinical, Surgical, Diagnostics and Pediatric Sciences, University of Pavia, Pavia, Italy.
Antonella SarasiniDepartment of Clinical, Surgical, Diagnostics and Pediatric Sciences, University of Pavia, Pavia, Italy.
Jorge A Ross TerresEli Lilly and Company, Indianapolis, IN, USA.
Brian J NickoloffEli Lilly and Company, Indianapolis, IN, USA.
Richard E HiggsEli Lilly and Company, Indianapolis, IN, USA.
Guilherme RochaEli Lilly and Company, Indianapolis, IN, USA.
Nicole L ByersEli Lilly and Company, Indianapolis, IN, USA.
Douglas E SchlichtingEli Lilly and Company, Indianapolis, IN, USA.
Ajay NirulaEli Lilly and Company, Indianapolis, IN, USA.
Anabela Cardoso *Eli Lilly and Company, Indianapolis, IN, USA.
Mario Corbellino *Division of Infectious Diseases, ASST Fatebenefratelli Sacco, Milan, Italy.
Sacco Baricitinib Study Group
Eli Lilly (United States) · USKarolinska University Hospital · SEImperial College London · GBUniversity of Pavia · ITAgency for Science, Technology and Research · SGASST Fatebenefratelli Sacco · ITBenevolentAI (United Kingdom) · GBUniversity of Milan · IT

Funding

Department of Health NIHR-RP-011-053Eli Lilly and Company (Lilly)Sacco Baricitininb Study Group
6 · The paper itself

Abstract

Baricitinib is an oral Janus kinase (JAK)1/JAK2 inhibitor approved for the treatment of rheumatoid arthritis (RA) that was independently predicted, using artificial intelligence (AI) algorithms, to be useful for COVID-19 infection via proposed anti-cytokine effects and as an inhibitor of host cell viral propagation. We evaluated the in vitro pharmacology of baricitinib across relevant leukocyte subpopulations coupled to its in vivo pharmacokinetics and showed it inhibited signaling of cytokines implicated in COVID-19 infection. We validated the AI-predicted biochemical inhibitory effects of baricitinib on human numb-associated kinase (hNAK) members measuring nanomolar affinities for AAK1, BIKE, and GAK. Inhibition of NAKs led to reduced viral infectivity with baricitinib using human primary liver spheroids. These effects occurred at exposure levels seen clinically. In a case series of patients with bilateral COVID-19 pneumonia, baricitinib treatment was associated with clinical and radiologic recovery, a rapid decline in SARS-CoV-2 viral load, inflammatory markers, and IL-6 levels. Collectively, these data support further evaluation of the anti-cytokine and anti-viral activity of baricitinib and support its assessment in randomized trials in hospitalized COVID-19 patients.

Indexed as

Artificial IntelligenceBetacoronavirusPandemicsAdultAgedAntiviral AgentsAzetidinesCoronavirus InfectionsCOVID-19COVID-19 Drug TreatmentCytokinesDrug Evaluation, PreclinicalDrug RepositioningFemaleHumansIntracellular Signaling Peptides and ProteinsAntiviral AgentsAzetidinesbaricitinibCytokinesIntracellular Signaling Peptides and ProteinsProtein Kinase InhibitorsProtein Serine-Threonine KinasesPurinesPyrazolesSulfonamidesanti-cytokineanti-viralbaricitinibcase seriesCOVID-19

Identifiers

PMID32473600
PMCPMC7300657
OpenAlexW3029848232

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.