Evidence map›Paper›PMID 32935119›Full record

ArticlemedRxiv : the preprint server for health sciences2020

Kynurenic acid underlies sex-specific immune responses to COVID-19.

Yuping Cai, Daniel J Kim, Takehiro Takahashi, David I Broadhurst, Shuangge Ma, Nicholas J W Rattray, Arnau Casanovas-Massana, Benjamin Israelow, Jon Klein, Carolina Lucas and 11 more

Open access · greenAbstract readPreprint
In one paragraph

Article in medRxiv : the preprint server for health sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed, 28 citations in OpenAlex.

  1. Article
  2. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

21 authors at 4 institutions in 3 countries.

Yuping CaiDepartment of Environmental Health Sciences, Yale School of Public Health, New Haven, CT 06510, USA.
Daniel J KimDepartment of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Takehiro TakahashiDepartment of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
David I BroadhurstCentre for Integrative Metabolomics & Computational Biology, School of Science, Edith Cowan University, Joondalup, 6027, Australia.
Shuangge MaDepartment of Biostatistics, Yale School of Public Health, New Haven, CT 06510, USA.
Nicholas J W RattrayStrathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, UK.
Arnau Casanovas-MassanaDepartment of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT 06510, USA.
Benjamin IsraelowDepartment of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Jon KleinDepartment of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Carolina LucasDepartment of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Tianyang MaoDepartment of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Adam J MooreDepartment of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT 06510, USA.
M Catherine MuenkerDepartment of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT 06510, USA.
Jieun OhDepartment of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Julio SilvaDepartment of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Patrick WongDepartment of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Yale IMPACT Research team
Albert I KoDepartment of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT 06510, USA.
Sajid A KhanDepartment of Surgery, Division of Surgical Oncology, Yale University School of Medicine, New Haven, CT 06520, USA.
Akiko IwasakiDepartment of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Caroline H JohnsonDepartment of Environmental Health Sciences, Yale School of Public Health, New Haven, CT 06510, USA.
Yale University · USEdith Cowan University · AUHoward Hughes Medical Institute · USUniversity of Strathclyde · GB

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
MEDICAL SCIENTIST TRAINING PROGRAMT32GM007205 · NIGMS · YALE UNIVERSITY · PI KAZMIERCZAK, BARBARA I · 1985 to 2019
$42.9M
Medical Scientist Training ProgramT32GM136651 · NIGMS · YALE UNIVERSITY · PI BARBARA I KAZMIERCZAK · 2020 to 2026
$16.5M
Exploring the Innate Sensors Underlying Cancer ImmunosurveillanceF30CA236466 · NCI · YALE UNIVERSITY · PI KIM, DANIEL J · 2019 to 2021
$111k
NCATS NIH HHS UL1 TR001863NCI NIH HHS F30 CA236466NIGMS NIH HHS T32 GM007205NIGMS NIH HHS T32 GM136651
6 · The paper itself

Abstract

Coronavirus disease-2019 (COVID-19) has poorer clinical outcomes in males compared to females, and immune responses underlie these sex-related differences in disease trajectory. As immune responses are in part regulated by metabolites, we examined whether the serum metabolome has sex-specificity for immune responses in COVID-19. In males with COVID- 19, kynurenic acid (KA) and a high KA to kynurenine (K) ratio was positively correlated with age, inflammatory cytokines, and chemokines and was negatively correlated with T cell responses, revealing that KA production is linked to immune responses in males. Males that clinically deteriorated had a higher KA:K ratio than those that stabilized. In females with COVID-19, this ratio positively correlated with T cell responses and did not correlate with age or clinical severity. KA is known to inhibit glutamate release, and we observed that serum glutamate is lower in patients that deteriorate from COVID-19 compared to those that stabilize, and correlates with immune responses. Analysis of Genotype-Tissue Expression (GTEx) data revealed that expression of kynurenine aminotransferase, which regulates KA production, correlates most strongly with cytokine levels and aryl hydrocarbon receptor activation in older males. This study reveals that KA has a sex-specific link to immune responses and clinical outcomes, in COVID-19 infection.

Identifiers

PMID32935119
PMCPMC7491534
OpenAlexW3084111371

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.