Evidence map›Paper›PMID 32702726›Full record

ArticleResearch square2020

SARS-CoV2 drives JAK1/2-dependent local and systemic complement hyper-activation.

Bingyu Yan, Tilo Freiwald, Daniel Chauss, Luopin Wang, Erin West, Jack Bibby, Matthew Olson, Shahram Kordasti, Didier Portilla, Arian Laurence and 4 more

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in Research square, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed, 32 citations in OpenAlex.

  1. Trial
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 4 institutions in 2 countries.

Bingyu YanDepartments of Biochemistry and Computer Science, Purdue University, West Lafayette, IN, USA.
Tilo FreiwaldImmunoregulation Section, Kidney Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH, Bethesda, MD, USA.
Daniel ChaussImmunoregulation Section, Kidney Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH, Bethesda, MD, USA.
Luopin WangDepartments of Biochemistry and Computer Science, Purdue University, West Lafayette, IN, USA.
Erin WestLaboratory of Molecular Immunology and the Immunology Center, National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD, USA.
Jack BibbyLaboratory of Molecular Immunology and the Immunology Center, National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD, USA.
Matthew OlsonDepartment of Biological Sciences, Purdue University, West Lafayette, IN, USA.
Shahram KordastiSchool of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK.
Didier PortillaImmunoregulation Section, Kidney Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH, Bethesda, MD, USA.
Arian LaurenceNuffield Department of Medicine, University of Oxford, UK.
Michail S LionakisFungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, MD, USA.
Claudia KemperLaboratory of Molecular Immunology and the Immunology Center, National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD, USA.
Behdad AfzaliImmunoregulation Section, Kidney Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH, Bethesda, MD, USA.
Majid KazemianDepartments of Biochemistry and Computer Science, Purdue University, West Lafayette, IN, USA.
National Institutes of Health · USPurdue University West Lafayette · USKing's College London · GBUniversity of Oxford · GB

Funding

Immunopathogenesis of Fungal InfectionsZIAAI001175 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI LIONAKIS, MICHAIL · 2012 to 2025
$23.9M
Unravelling immunoregulatory circuits of tissue inflammationZIADK075149 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI AFZALI, BEHDAD · 2019 to 2025
$19.3M
Tissue Engineering and RegenerationT32DE007057 · NIDCR · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI DAVID H. KOHN · 1985 to 2026
$17.3M
Joint submission for administrative supplement proposal: HIPAA aligned storage and computing solutionR35GM138283 · NIGMS · PURDUE UNIVERSITY · PI KAZEMIAN, MAJID · 2020 to 2024
$2.0M
A New Therapy for Bowel Ischemia-Reperfusion InjuryR44DK075149 · NIDDK · THERASOURCE, LLC · PI JACOB, ASHA · 2010 to 2012
$1.2M
Expression, regulation, and role of enhancer RNAs in T helper cellsK22HL125593 · NHLBI · PURDUE UNIVERSITY · PI KAZEMIAN, MAJID · 2017 to 2019
$747k
New Therapy for Bowel Ischemia-Reperfusion InjuryR43DK075149 · NIDDK · THERASOURCE, LLC · PI WU, RONGQIAN · 2006 to 2007
$288k
INHIBITION OF PLASMODIUM/HEPATOCYTE INTERACTIONK11AI001175 · NIAID · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI SINNIS, PHOTINI · 1993 to 1997
–
Intramural NIH HHS ZIA AI001175Intramural NIH HHS ZIA DK075149NHLBI NIH HHS K22 HL125593NIAID NIH HHS K11 AI001175NIDCR NIH HHS T32 DE007057NIDDK NIH HHS R43 DK075149NIDDK NIH HHS R44 DK075149NIGMS NIH HHS R35 GM138283
6 · The paper itself

Abstract

Patients with coronavirus disease 2019 (COVID-19) present with a range of devastating acute clinical manifestations affecting the lungs, liver, kidneys and gut. The best-characterized entry receptor for the disease-causing virus SARS-CoV2, angiotensin converting enzyme (ACE) 2, is highly expressed in these tissues. However, the pathways that underlie the disease are still poorly understood. Here we show that the complement system is unexpectedly one of the intracellular pathways most highly induced by SARS-CoV2 infection in lung epithelial and liver cells. Within cells of the bronchoalveolar lavage of patients, distinct signatures of complement activation in myeloid, lymphoid and epithelial cells tracked with disease severity. Modelling the regulome of host genes induced by COVID-19 and the drugs that could normalize these genes both implicated the JAK1/2-STAT1 signaling system downstream of type I interferon receptors, and NF-kB. Ruxolitinib, a JAK1/2 inhibitor and the top predicted pharmaceutical candidate, normalized interferon signature genes, IL-6 (the best characterized severity marker in COVID-19) and all complement genes induced by SARS-CoV2, but did not affect NF-kB-regulated genes. We predict that combination therapy with JAK inhibitors and other agents with the potential to normalize NF-kB-signaling, such as anti-viral agents, may serve as an effective clinical strategy.

Identifiers

PMID32702726
PMCPMC7336704
OpenAlexW3044474866

What OpenQuestion holds

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LicenceCC BY
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.