Evidence map›Paper›PMID 36266337›Full record

Trial reportNature microbiology2022

Integrated host-microbe plasma metagenomics for sepsis diagnosis in a prospective cohort of critically ill adults.

Katrina L Kalantar, Lucile Neyton, Mazin Abdelghany, Eran Mick, Alejandra Jauregui, Saharai Caldera, Paula Hayakawa Serpa, Rajani Ghale, Jack Albright, Aartik Sarma and 15 more

Registry-linked trialAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Nature microbiology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06181669 (Pneumonia Direct Pilot), which is not on this map. Cited by 84 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
84citing papers in PubMed, 1 pooled it
–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.

NCT06181669 completednot on this mapstarted 2024, after this paper: background citation

Pneumonia Direct Pilot

TypeobservationalSponsorDuke UniversityRan2024 to 2025Enrolled173ConditionsPneumonia, Bacterial, Ventilator Associated PneumoniaArmsPathogen and Host Directed testing
3 · Its place in the literature

Who cites it

84 citing papers in PubMed, 1 synthesis or guideline pooled it.

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  15. Reply to Liu et al. and Chen et al.American journal of respiratory and critical care medicine · 2026
    Article
  16. Diagnostic Yield of Repeat Blood Cultures and Risk Factors for Bloodstream Infection in Persistent Febrile Neutropenia.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2026
    Article
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24 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

25 authors.

Katrina L Kalantar *Chan Zuckerberg Initiative, San Francisco, CA, USA.
Lucile Neyton *Department of Medicine, Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California San Francisco, San Francisco, CA, USA.
Mazin AbdelghanyDepartment of Medicine, Division of Infectious Diseases, University of California San Francisco, San Francisco, CA, USA.
Eran MickDepartment of Medicine, Division of Infectious Diseases, University of California San Francisco, San Francisco, CA, USA.ORCID 0000-0002-7299-808X
Alejandra JaureguiDepartment of Medicine, Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California San Francisco, San Francisco, CA, USA.
Saharai CalderaDepartment of Medicine, Division of Infectious Diseases, University of California San Francisco, San Francisco, CA, USA.
Paula Hayakawa SerpaDepartment of Medicine, Division of Infectious Diseases, University of California San Francisco, San Francisco, CA, USA.
Rajani GhaleDepartment of Medicine, Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California San Francisco, San Francisco, CA, USA.
Jack AlbrightDepartment of Critical Care Medicine, Western University, London, Ontario, Canada.
Aartik SarmaDepartment of Medicine, Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California San Francisco, San Francisco, CA, USA.ORCID 0000-0002-7508-7345
Alexandra TsitsiklisDepartment of Medicine, Division of Infectious Diseases, University of California San Francisco, San Francisco, CA, USA.ORCID 0000-0003-3467-1171
Aleksandra LeligdowiczDepartment of Critical Care Medicine, Western University, London, Ontario, Canada.ORCID 0000-0001-6055-4644
Stephanie A ChristensonDepartment of Medicine, Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California San Francisco, San Francisco, CA, USA.
Kathleen LiuDepartment of Medicine, Division of Nephrology, University of California San Francisco, San Francisco, CA, USA.
Kirsten N KangelarisDepartment of Medicine, University of California San Francisco, San Francisco, CA, USA.
Carolyn HendricksonDepartment of Medicine, Division of Infectious Diseases, University of California San Francisco, San Francisco, CA, USA.
Pratik SinhaWashington University, St Louis, St. Louis, MO, USA.
Antonio GomezDepartment of Medicine, Zuckerberg San Francisco General Hospital, San Francisco, CA, USA.
Norma NeffChan Zuckerberg Biohub, San Francisco, CA, USA.ORCID 0000-0001-7141-5420
Angela PiscoChan Zuckerberg Biohub, San Francisco, CA, USA.ORCID 0000-0003-0142-2355
Sarah B DoernbergDepartment of Medicine, Division of Infectious Diseases, University of California San Francisco, San Francisco, CA, USA.
Joseph L DerisiChan Zuckerberg Biohub, San Francisco, CA, USA.
Michael A MatthayDepartment of Medicine, Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California San Francisco, San Francisco, CA, USA.ORCID 0000-0003-3039-8155
Carolyn S Calfee *Department of Medicine, Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California San Francisco, San Francisco, CA, USA.
Charles R Langelier *Department of Medicine, Division of Infectious Diseases, University of California San Francisco, San Francisco, CA, USA. chaz.langelier@ucsf.edu.ORCID 0000-0002-6708-4646

Funding

Precision Medicine in the Acute Respiratory Distress SyndromeR35HL140026 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CALFEE, CAROLYN · 2018 to 2024
$6.8M
Precision Medicine in Sepsis with Critical IllnessR35GM142992 · NIGMS · WASHINGTON UNIVERSITY · PI Pratik Sinha · 2021 to 2026
$2.4M
Integrated Host/Microbe Metagenomics to Improve Lower Respiratory Tract Infection Diagnosis in Critically Ill ChildrenR01HL155418 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LANGELIER, CHARLES · 2021 to 2024
$1.6M
Profiling the Lung Transcriptome for Precision Diagnosis of Respiratory Infections using Host/Pathogen Metagenomic SequencingK23HL138461 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LANGELIER, CHARLES · 2018 to 2021
$718k
Transcriptomic signatures of airway inflammation in acute respiratory diseasesF32HL151117 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SARMA, AARTIK · 2020 to 2022
$206k
NHLBI NIH HHS F32 HL151117NHLBI NIH HHS K23 HL138461NHLBI NIH HHS R01 HL155418NHLBI NIH HHS R35 HL140026NIGMS NIH HHS R35 GM142992
6 · The paper itself

Abstract

We carried out integrated host and pathogen metagenomic RNA and DNA next generation sequencing (mNGS) of whole blood (n = 221) and plasma (n = 138) from critically ill patients following hospital admission. We assigned patients into sepsis groups on the basis of clinical and microbiological criteria. From whole-blood gene expression data, we distinguished patients with sepsis from patients with non-infectious systemic inflammatory conditions using a trained bagged support vector machine (bSVM) classifier (area under the receiver operating characteristic curve (AUC) = 0.81 in the training set; AUC = 0.82 in a held-out validation set). Plasma RNA also yielded a transcriptional signature of sepsis with several genes previously reported as sepsis biomarkers, and a bSVM sepsis diagnostic classifier (AUC = 0.97 training set; AUC = 0.77 validation set). Pathogen detection performance of plasma mNGS varied on the basis of pathogen and site of infection. To improve detection of virus, we developed a secondary transcriptomic classifier (AUC = 0.94 training set; AUC = 0.96 validation set). We combined host and microbial features to develop an integrated sepsis diagnostic model that identified 99% of microbiologically confirmed sepsis cases, and predicted sepsis in 74% of suspected and 89% of indeterminate sepsis cases. In summary, we suggest that integrating host transcriptional profiling and broad-range metagenomic pathogen detection from nucleic acid is a promising tool for sepsis diagnosis.

Indexed as

Critical IllnessSepsisAdultCohort StudiesHumansProspective StudiesRNARNA

Identifiers

PMID36266337
PMCPMC9613463

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Registered trials

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.