Evidence map›Paper›PMID 38076862›Full record

ArticlemedRxiv : the preprint server for health sciences2023

SARS-CoV-2 Orphan Gene ORF10 Contributes to More Severe COVID-19 Disease.

Jeffrey Haltom, Nidia S Trovao, Joseph Guarnieri, Pan Vincent, Urminder Singh, Sergey Tsoy, Collin A O'Leary, Yaron Bram, Gabrielle A Widjaja, Zimu Cen and 9 more

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

Article in medRxiv : the preprint server for health sciences, 2023. 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, 8 citations in OpenAlex.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors at 8 institutions in 2 countries.

Jeffrey HaltomDepartment of Genetics Development and Cell Biology, Iowa State University, Ames, IA 50011, USA.
Nidia S TrovaoDivision of International Epidemiology and Population Studies, Fogarty International Center, National Institutes of Health, Bethesda, Maryland, 20892, USA.
Joseph GuarnieriCenter for Mitochondrial and Epigenomic Medicine, Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Pan VincentDivision of International Epidemiology and Population Studies, Fogarty International Center, National Institutes of Health, Bethesda, Maryland, 20892, USA.
Urminder SinghBioinformatics and Computational Biology Program, and Genetics Program, Iowa State University, Ames, IA 50011, USA.
Sergey TsoyDivision of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medicine, New York, NY, USA.
Collin A O'LearyRoy J. Carver Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, IA 50011, USA.
Yaron BramDivision of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medicine, New York, NY, USA.
Gabrielle A WidjajaCenter for Mitochondrial and Epigenomic Medicine, Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Zimu CenCenter for Mitochondrial and Epigenomic Medicine, Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Robert MellerMorehouse School of Medicine, Atlanta, GA , 30310-1495, USA.
Stephen B BaylinDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21231.
Walter N MossBioinformatics and Computational Biology Program, and Genetics Program, Iowa State University, Ames, IA 50011, USA.
Basil J NikolauBioinformatics and Computational Biology Program, and Genetics Program, Iowa State University, Ames, IA 50011, USA.
Francisco J EnguitaInstituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal.
Douglas C WallaceCenter for Mitochondrial and Epigenomic Medicine, Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Afshin BeheshtiCOVID-19 International Research Team, Medford, MA 02155, USA.
Robert SchwartzDivision of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medicine, New York, NY, USA.
Eve Syrkin WurteleBioinformatics and Computational Biology Program, and Genetics Program, Iowa State University, Ames, IA 50011, USA.
Children's Hospital of Philadelphia · USIowa State University · USCornell University · USNational Institutes of Health · USBroad Institute · USMorehouse School of Medicine · USUniversity of Lisbon · PTVan Andel Institute · US

Funding

Genetic Viral and Host Adaptations to Breach Species Barriers of HCVR01AI107301 · NIAID · PRINCETON UNIVERSITY · PI Thomas Pietschmann, Alexander Ploss · 2013 to 2026
$6.0M
Finding, folding and characterizing the functions of disease-relevant RNA structuresR01GM133810 · NIGMS · IOWA STATE UNIVERSITY · PI Walter Moss · 2019 to 2026
$2.8M
Optimization of the engineered 3D hepatic microenvironment enhances pluripotent stem cell derived hepatocyteR01DK121072 · NIDDK · WEILL MEDICAL COLL OF CORNELL UNIV · PI SCHWARTZ, ROBERT E · 2020 to 2024
$2.6M
NIAID NIH HHS R01 AI107301NIDDK NIH HHS R01 DK121072NIGMS NIH HHS R01 GM133810
6 · The paper itself

Abstract

The orphan gene of SARS-CoV-2, ORF10, is the least studied gene in the virus responsible for the COVID-19 pandemic. Recent experimentation indicated ORF10 expression moderates innate immunity in vitro. However, whether ORF10 affects COVID-19 in humans remained unknown. We determine that the ORF10 sequence is identical to the Wuhan-Hu-1 ancestral haplotype in 95% of genomes across five variants of concern (VOC). Four ORF10 variants are associated with less virulent clinical outcomes in the human host: three of these affect ORF10 protein structure, one affects ORF10 RNA structural dynamics. RNA-Seq data from 2070 samples from diverse human cells and tissues reveals ORF10 accumulation is conditionally discordant from that of other SARS-CoV-2 transcripts. Expression of ORF10 in A549 and HEK293 cells perturbs immune-related gene expression networks, alters expression of the majority of mitochondrially-encoded genes of oxidative respiration, and leads to large shifts in levels of 14 newly-identified transcripts. We conclude ORF10 contributes to more severe COVID-19 clinical outcomes in the human host.

Indexed as

COVID-19de novo geneNovel geneORF10Orphan genePandemicRNA-SeqSARS-CoV-2Viral diversityViral evolution

Identifiers

PMID38076862
PMCPMC10705665
OpenAlexW4389132122

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.