Evidence map›Paper›PMID 37441066›Full record

ArticleFrontiers in immunology2023

Circulating Reelin promotes inflammation and modulates disease activity in acute and long COVID-19 cases.

Laurent Calvier, Aleksandra Drelich, Jason Hsu, Chien-Te Tseng, Yair Mina, Avindra Nath, Maria Z Kounnas, Joachim Herz

Open access · goldAbstract read
In one paragraph

Article in Frontiers in immunology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
2.2field-weighted citation impact, top 12% 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

12 citing papers in PubMed, 18 citations in OpenAlex.

  1. Article
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  4. Genetic or therapeutic disruption of the Reelin/Apoer2 signaling pathway improves inflammatory arthritis outcomes.Proceedings of the National Academy of Sciences of the United States of America · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 5 institutions in 2 countries.

Laurent CalvierDepartment of Molecular Genetics, University of Texas (UT) Southwestern Medical Center, Dallas, TX, United States.
Aleksandra DrelichDepartment of Biochemistry, Cellular, and Molecular Biology, University of Texas Medical Branch (UTMB) Health, Galveston, TX, United States.
Jason HsuDepartment of Biochemistry, Cellular, and Molecular Biology, University of Texas Medical Branch (UTMB) Health, Galveston, TX, United States.
Chien-Te TsengDepartment of Biochemistry, Cellular, and Molecular Biology, University of Texas Medical Branch (UTMB) Health, Galveston, TX, United States.
Yair MinaNational Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States.
Avindra NathNational Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States.
Maria Z KounnasReelin Therapeutics Inc., San Diego, CA, United States.
Joachim HerzDepartment of Molecular Genetics, University of Texas (UT) Southwestern Medical Center, Dallas, TX, United States.
The University of Texas Medical Branch at Galveston · USNational Institute of Neurological Disorders and Stroke · USNational Institutes of Health · USSouthwestern Medical CenterThe University of Texas Southwestern Medical Center · US

Funding

Metabolism of the VLDL receptor and ApoE receptor 2R37HL063762 · NHLBI · UT SOUTHWESTERN MEDICAL CENTER · PI HERZ, JOACHIM J · 2010 to 2019
$4.0M
Physiology and Pathophysiology of Apolipoprotein E receptor-2 splicing in Alzheimer's diseaseRF1AG053391 · NIA · UT SOUTHWESTERN MEDICAL CENTER · PI HERZ, JOACHIM J · 2016 to 2020
$2.4M
Molecular Basis of Synaptic Suppression by ApoER01NS093382 · NINDS · UT SOUTHWESTERN MEDICAL CENTER · PI HERZ, JOACHIM J · 2016 to 2020
$2.0M
NHLBI NIH HHS R37 HL063762NIA NIH HHS RF1 AG053391NINDS NIH HHS R01 NS093382
6 · The paper itself

Abstract

Thromboembolic complications and excessive inflammation are frequent in severe COVID-19, potentially leading to long COVID. In non-COVID studies, we and others demonstrated that circulating Reelin promotes leukocyte infiltration and thrombosis. Thus, we hypothesized that Reelin participates in endothelial dysfunction and hyperinflammation during COVID-19. We showed that Reelin was increased in COVID-19 patients and correlated with the disease activity. In the severe COVID-19 group, we observed a hyperinflammatory state, as judged by increased concentration of cytokines (IL-1α, IL-4, IL-6, IL-10 and IL-17A), chemokines (IP-10 and MIP-1β), and adhesion markers (E-selectin and ICAM-1). Reelin level was correlated with IL-1α, IL-4, IP-10, MIP-1β, and ICAM-1, suggesting a specific role for Reelin in COVID-19 progression. Furthermore, Reelin and all of the inflammatory markers aforementioned returned to normal in a long COVID cohort, showing that the hyperinflammatory state was resolved. Finally, we tested Reelin inhibition with the anti-Reelin antibody CR-50 in hACE2 transgenic mice infected with SARS-CoV-2. CR-50 prophylactic treatment decreased mortality and disease severity in this model. These results demonstrate a direct proinflammatory function for Reelin in COVID-19 and identify it as a drug target. This work opens translational clinical applications in severe SARS-CoV-2 infection and beyond in auto-inflammatory diseases.

Indexed as

COVID-19AnimalsChemokine CCL4Chemokine CXCL10HumansInflammationIntercellular Adhesion Molecule-1Interleukin-4MicePost-Acute COVID-19 SyndromeSARS-CoV-2Chemokine CCL4Chemokine CXCL10Intercellular Adhesion Molecule-1Interleukin-4adhesion markersCOVID-19cytokine stormendothelial dysfunctioninflammationleukocytelong COVIDReelin

Identifiers

PMID37441066
PMCPMC10333573
OpenAlexW4382243208

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.