Evidence map›Paper›PMID 40435967›Full record

ArticleJournal of innate immunity2025

Patients Hospitalized with COVID-19 Demonstrate Distinct Plasma Cytokine and Chemokine Concentrations in vivo and TLR-Mediated Cytokine and Chemokine Production in Whole Blood in vitro.

Athena N Nguyen, Thomas S Kouyate, Kevin Ryff, Alec L Plotkin, Simon Doss-Gollin, Sanya Thomas, Kerry McEnaney, Al Ozonoff, Joann Diray-Arce, Ofer Levy and 5 more

Abstract read
In one paragraph

Article in Journal of innate immunity, 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. Review
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

15 authors.

Athena N NguyenPrecision Vaccines Program, Department of Pediatrics, Boston Children's Hospital, Boston, Massachusetts, USA.
Thomas S KouyatePrecision Vaccines Program, Department of Pediatrics, Boston Children's Hospital, Boston, Massachusetts, USA, thomas.kouyate@childrens.harvard.edu.
Kevin RyffPrecision Vaccines Program, Department of Pediatrics, Boston Children's Hospital, Boston, Massachusetts, USA.
Alec L PlotkinPrecision Vaccines Program, Department of Pediatrics, Boston Children's Hospital, Boston, Massachusetts, USA.
Simon Doss-GollinPrecision Vaccines Program, Department of Pediatrics, Boston Children's Hospital, Boston, Massachusetts, USA.
Sanya ThomasPrecision Vaccines Program, Department of Pediatrics, Boston Children's Hospital, Boston, Massachusetts, USA.
Kerry McEnaneyPrecision Vaccines Program, Department of Pediatrics, Boston Children's Hospital, Boston, Massachusetts, USA.
Al OzonoffPrecision Vaccines Program, Department of Pediatrics, Boston Children's Hospital, Boston, Massachusetts, USA.
Joann Diray-ArcePrecision Vaccines Program, Department of Pediatrics, Boston Children's Hospital, Boston, Massachusetts, USA.
Ofer LevyPrecision Vaccines Program, Department of Pediatrics, Boston Children's Hospital, Boston, Massachusetts, USA.
Oludare A OdumadePrecision Vaccines Program, Department of Pediatrics, Boston Children's Hospital, Boston, Massachusetts, USA.
Lindsey R BadenBrigham and Women's Hospital, Boston, Massachusetts, USA.
Simon D van HarenPrecision Vaccines Program, Department of Pediatrics, Boston Children's Hospital, Boston, Massachusetts, USA.
Kinga K SmolenPrecision Vaccines Program, Department of Pediatrics, Boston Children's Hospital, Boston, Massachusetts, USA.
IMPACC - Boston Team

Funding

Transcriptomics to define biomarkers of neonatal vaccine immunogenicityU19AI118608 · NIAID · BOSTON CHILDREN'S HOSPITAL · PI LEVY, OFER · 2017 to 2021
$24.7M
NIAID NIH HHS U19 AI118608
6 · The paper itself

Abstract

introductionSARS-CoV-2's continued global health impact underscores the importance of ongoing pathogenesis research. Insights into the host's first line of defense against severe COVID-19 identify actionable biomarkers, informing disease management or therapeutics. Yet, the innate immune response, including cytokines, chemokines, adenosine deaminases (ADAs) and Toll-like receptors (TLRs), relevant to COVID-19 remain incompletely characterized.

methodsPeripheral blood was longitudinally collected between May 2020 and March 2021 from COVID-19 hospitalized adults (N = 79) and healthy controls (HCs) (N = 14; not tested, assumed COVID-negative, no viral exposure or symptoms). Heparinized blood was fractionated for plasma cryopreservation and in vitro whole blood TLR-stimulation employing TLR-3, -4, and -7/8 agonists. Post-stimulation culture supernatants were analyzed using multiplex and enzymatic assays.

resultsUpon hospitalization, plasma concentrations of IFNγ, IL-6, CXCL10, and ADAs were significantly upregulated compared to convalescent time points and HCs. Participants with fatal COVID-19 exhibited higher IL-27, CXCL10, and ADAs concentrations upon admission. Plasma cytokines, chemokines, and ADAs were positively correlated and associated with distinct temporal patterns. TLR-stimulated cell cultures from patients produced reduced IFNα2, IFNγ, IL-12p40, and IL-12p70 compared to HCs or later time points.

conclusionHigher plasma concentrations of IL-27, CXCL10, and ADAs at admission were associated with severe COVID-19 and mortality. Reduced TLR-mediated IFNα2, IFNγ, and IL-12p70 production suggests COVID dampens Th1-polarizing innate immune responses, providing insight into immunological sequelae of SARS-CoV-2 infection.

Indexed as

ChemokinesCOVID-19CytokinesSARS-CoV-2Toll-Like ReceptorsAdultAgedFemaleHospitalizationHumansImmunity, InnateMaleMiddle AgedChemokinesCytokinesToll-Like ReceptorsCOVID-19Innate immunitySARS-CoV-2Toll-like receptors

Identifiers

PMID40435967
PMCPMC12185065

What OpenQuestion holds

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Registered trials

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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.