Evidence map›Paper›PMID 41453867›Full record

ArticleCell death discovery2025

Modelling severe COVID-19 in TLR3-mutated hiPSCs-derived lung organoids.

Andrea Latini, Paola Spitalieri, Federica Centofanti, Barbara Rizzacasa, Donatella Amatore, Giorgia Grilli, Riccardo De Santis, Lorenzo Vaccaro, Vito Luigi Colona, Giulio Puleri and 10 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell death discovery, 2025. 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.

  1. Article
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

20 authors.

Andrea LatiniDepartment of Biomedicine and Prevention, Genetics Section, University of Rome Tor Vergata, Rome, Italy.
Paola SpitalieriDepartment of Biomedicine and Prevention, Genetics Section, University of Rome Tor Vergata, Rome, Italy.
Federica CentofantiDepartment of Biomedicine and Prevention, Genetics Section, University of Rome Tor Vergata, Rome, Italy.ORCID http://orcid.org/0000-0001-5731-2812
Barbara RizzacasaDepartment of Biomedicine and Prevention, Genetics Section, University of Rome Tor Vergata, Rome, Italy.
Donatella AmatoreDefence Institute for Biomedical Sciences, Rome, Italy.
Giorgia GrilliDefence Institute for Biomedical Sciences, Rome, Italy.
Riccardo De SantisDefence Institute for Biomedical Sciences, Rome, Italy.
Lorenzo VaccaroTelethon Institute of Genetics and Medicine (TIGEM), Armenise/Harvard Laboratory of Integrative Genomics, Pozzuoli, Italy.
Vito Luigi ColonaUnit of Neurorehabilitation, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.ORCID http://orcid.org/0000-0002-9660-7397
Giulio PuleriDepartment of Biomedicine and Prevention, Genetics Section, University of Rome Tor Vergata, Rome, Italy.
Anna Maria NardoneMedical Genetics Laboratory, Policlinico Tor Vergata Hospital, Rome, Italy.
Michela BiancolellaDepartment of Biology, University of Rome "Tor Vergata", Rome, Italy.
Elena CampioneDermatology Unit, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.
Loredana SarmatiClinical Infectious Diseases, Department of System Medicine, Tor Vergata University, Rome, Italy.
Paola RoglianiUnit of Respiratory Medicine, Department of Experimental Medicine, University of Rome Tor Vergata, Rome, Italy.
Davide CacchiarelliTelethon Institute of Genetics and Medicine (TIGEM), Armenise/Harvard Laboratory of Integrative Genomics, Pozzuoli, Italy.ORCID http://orcid.org/0000-0002-9621-6716
Antonio NovelliLaboratory of Medical Genetics, Translational Cytogenomics Research Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Federica SangiuoloDepartment of Biomedicine and Prevention, Genetics Section, University of Rome Tor Vergata, Rome, Italy.ORCID http://orcid.org/0000-0002-6227-4248
Florigio ListaDefence Institute for Biomedical Sciences, Rome, Italy.
Giuseppe NovelliDepartment of Biomedicine and Prevention, Genetics Section, University of Rome Tor Vergata, Rome, Italy. novelli@med.uniroma2.it.ORCID http://orcid.org/0000-0002-7781-602X

Funding

Fondazione Telethon (Telethon Foundation) Core GrantGiovanni Armenise-Harvard Foundation Career Development AwardMinistero della Salute (Ministry of Health, Italy) genOMICAMinistero della Salute (Ministry of Health, Italy) T3-AN-09 Genomed
6 · The paper itself

Abstract

Clinical variability in COVID-19 is partly explained by host genetic factors, including inborn errors of immunity. We investigated a patient with a heterozygous nonsense mutation in the TLR3 gene (p.Trp769*) by generating human-induced pluripotent stem cells (hiPSCs) and differentiating them into lung organoids (hLORGs). TLR3-mutated hLORGs showed reduced basal expression of TLR3 and downstream signaling genes. Following infection with a pseudotyped SARS-CoV-2 virus and live SARS-CoV-2, RNA-Seq and qPCR analyses revealed significant upregulation of fibrinogen genes (FGA, FGG), which are associated with severe COVID-19. Interestingly, TLR3 expression remained inducible upon infection, despite the loss-of-function mutation. Our patient-derived hLORG model recapitulates the pathophysiological features of the patient and provides a platform to investigate host-virus interactions and test targeted therapies for genetically at-risk individuals.

Identifiers

PMID41453867
PMCPMC12858893

What Socratic 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 Socratic graph.