Evidence map›Paper›PMID 42049757›Full record

ArticleNature communications2026

Widespread gene-environment interactions shape the immune response to SARS-CoV-2 infection in hospitalized COVID-19 patients.

Haley E Randolph, Raúl Aguirre-Gamboa, Elsa Brunet-Ratnasingham, Tomoko Nakanishi, Zepeng Mu, Veronica Locher, Ellen Ketter, Cary Brandolino, Catherine Larochelle, Alexandre Prat and 7 more

Abstract read
In one paragraph

Article in Nature communications, 2026. 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.

  1. Article
  2. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors.

Haley E RandolphDepartment of Pediatrics, Columbia University Irving Medical Center, New York, NY, USA.ORCID http://orcid.org/0000-0003-2044-1180
Raúl Aguirre-GamboaSection of Genetic Medicine, Department of Medicine, University of Chicago, Chicago, IL, USA.
Elsa Brunet-RatnasinghamDepartment of Medicine, University of California, San Francisco, CA, USA.
Tomoko NakanishiLady Davis Institute for Medical Research, Jewish General Hospital, Montréal, QC, Canada.ORCID http://orcid.org/0000-0001-9510-5646
Zepeng MuCommittee on Genetics, Genomics, and Systems Biology, University of Chicago, Chicago, IL, USA.ORCID http://orcid.org/0000-0002-7717-3247
Veronica LocherCommittee on Immunology, University of Chicago, Chicago, IL, USA.
Ellen KetterCommittee on Microbiology, University of Chicago, Chicago, IL, USA.
Cary BrandolinoSection of Genetic Medicine, Department of Medicine, University of Chicago, Chicago, IL, USA.
Catherine LarochelleDepartment of Neurosciences, Faculty of Medicine, Université de Montréal, Montréal, QC, Canada.ORCID http://orcid.org/0000-0002-8724-4782
Alexandre PratDepartment of Neurosciences, Faculty of Medicine, Université de Montréal, Montréal, QC, Canada.ORCID http://orcid.org/0000-0001-6188-0580
Nathalie ArbourDepartment of Neurosciences, Faculty of Medicine, Université de Montréal, Montréal, QC, Canada.ORCID http://orcid.org/0000-0002-3718-1584
Anne DumaineSection of Genetic Medicine, Department of Medicine, University of Chicago, Chicago, IL, USA.
Andrés FinziCentre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada.ORCID http://orcid.org/0000-0002-4992-5288
Madeleine DurandCentre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada.
J Brent RichardsLady Davis Institute for Medical Research, Jewish General Hospital, Montréal, QC, Canada.ORCID http://orcid.org/0000-0002-3746-9086
Daniel E KaufmannCentre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada.
Luis B BarreiroCommittee on Genetics, Genomics, and Systems Biology, University of Chicago, Chicago, IL, USA. lbarreiro@uchicago.edu.ORCID http://orcid.org/0000-0001-9456-367X

Funding

Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada) 100558Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada) 169303Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada) 178344Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada) 365825Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada) 409511Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada) VR2-173203U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) F31-HL156419
6 · The paper itself

Abstract

Genome-wide association studies performed in COVID-19 patients have uncovered various loci significantly associated with susceptibility to SARS-CoV-2 infection and disease severity. However, the underlying cis-regulatory genetic factors contributing to heterogeneity in the response to SARS-CoV-2 infection and their impact on clinical phenotypes remain enigmatic. Here, we use single-cell RNA-sequencing to quantify genetic contributions to cis-regulatory variation in 361,119 peripheral blood mononuclear cells of 63 acute COVID-19 patients, 39 convalescent samples, and 106 healthy controls. Expression quantitative trait loci mapping across cell types within each disease state group reveals thousands of cis-associated variants, of which hundreds are detected exclusively in immune cells derived from acute patients. Patient-specific genetic effects dissipate as infection resolves, suggesting that distinct gene regulatory networks are at play in the active infection state. Further, 20.3% of tested loci demonstrate significant cell state interactions with genotype, with pathways related to interferon responses and oxidative phosphorylation showing pronounced cell state-dependent variation, predominantly in CD14

Indexed as

COVID-19Gene-Environment InteractionFemaleGene Regulatory NetworksGenetic Predisposition to DiseaseGenome-Wide Association StudyHospitalizationHumansLeukocytes, MononuclearMonocytesPolymorphism, Single NucleotideQuantitative Trait LociSARS-CoV-2Single-Cell Gene Expression Analysis

Identifiers

PMID42049757
PMCPMC13328456

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.