Evidence map›Paper›PMID 34375313›Full record

ArticleJCI insight2021

SARS-CoV-2-associated ssRNAs activate inflammation and immunity via TLR7/8.

Valentina Salvi, Hoang Oanh Nguyen, Francesca Sozio, Tiziana Schioppa, Carolina Gaudenzi, Mattia Laffranchi, Patrizia Scapini, Mauro Passari, Ilaria Barbazza, Laura Tiberio and 7 more

Open access · goldAbstract read
In one paragraph

Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
104citing papers in PubMed, 2 pooled it
9.7field-weighted citation impact, top 1% 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

104 citing papers in PubMed, 2 syntheses or guidelines pooled it, 143 citations in OpenAlex.

  1. Mucosal immune response in biology, disease prevention and treatment.Signal transduction and targeted therapy · 2025
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  7. Defective RNA Polymerase III sensing of mitochondrial DNA in pulmonary epithelial cells impairs type I IFN immunity to SARS-CoV-2.Proceedings of the National Academy of Sciences of the United States of America · 2026
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44 more citing papers are in PubMed but not listed here.

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

17 authors at 5 institutions in 2 countries.

Valentina SalviDepartment of Molecular and Translational Medicine, University of Brescia, Italy.
Hoang Oanh NguyenDepartment of Molecular and Translational Medicine, University of Brescia, Italy.
Francesca SozioDepartment of Molecular and Translational Medicine, University of Brescia, Italy.
Tiziana SchioppaDepartment of Molecular and Translational Medicine, University of Brescia, Italy.
Carolina GaudenziDepartment of Molecular and Translational Medicine, University of Brescia, Italy.
Mattia LaffranchiDepartment of Molecular and Translational Medicine, University of Brescia, Italy.
Patrizia ScapiniDepartment of Medicine, Section of General Pathology, University of Verona, Italy.
Mauro PassariDepartment of Molecular and Translational Medicine, University of Brescia, Italy.
Ilaria BarbazzaDepartment of Molecular and Translational Medicine, University of Brescia, Italy.
Laura TiberioDepartment of Molecular and Translational Medicine, University of Brescia, Italy.
Nicola TamassiaDepartment of Medicine, Section of General Pathology, University of Verona, Italy.
Cecilia GarlandaIRCCS Humanitas Research Hospital, Rozzano (MI), Italy.
Annalisa Del PreteDepartment of Molecular and Translational Medicine, University of Brescia, Italy.
Marco A CassatellaDepartment of Medicine, Section of General Pathology, University of Verona, Italy.
Alberto MantovaniIRCCS Humanitas Research Hospital, Rozzano (MI), Italy.
Silvano SozzaniLaboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy.
Daniela BosisioDepartment of Molecular and Translational Medicine, University of Brescia, Italy.
University of Brescia · ITIRCCS Humanitas Research Hospital · ITUniversity of Verona · ITHumanitas University · ITIstituto Neurologico Mediterraneo · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The inflammatory and IFN pathways of innate immunity play a key role in the resistance and pathogenesis of coronavirus disease 2019 (COVID-19). Innate sensors and SARS-CoV-2-associated molecular patterns (SAMPs) remain to be completely defined. Here, we identified single-stranded RNA (ssRNA) fragments from the SARS-CoV-2 genome as direct activators of endosomal TLR7/8 and MyD88 pathway. The same sequences induced human DC activation in terms of phenotype and function, such as IFN and cytokine production and Th1 polarization. A bioinformatic scan of the viral genome identified several hundreds of fragments potentially activating TLR7/8, suggesting that products of virus endosomal processing potently activate the IFN and inflammatory responses downstream of these receptors. In vivo, SAMPs induced MyD88-dependent lung inflammation characterized by accumulation of proinflammatory and cytotoxic mediators and immune cell infiltration, as well as splenic DC phenotypical maturation. These results identified TLR7/8 as a crucial cellular sensor of ssRNAs encoded by SARS-CoV-2 involved in host resistance and the disease pathogenesis of COVID-19.

Indexed as

Immunity, InnateCOVID-19HumansLungRNA, ViralSARS-CoV-2Toll-Like Receptor 7RNA, ViralToll-Like Receptor 7CytokinesDendritic cellsImmunologyInnate immunity

Identifiers

PMID34375313
PMCPMC8492321
OpenAlexW3191892183

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.