Noninvasive diagnosis of secondary infections in COVID-19 by sequencing of plasma microbial cell-free DNA
© 2023 The Authors..
Secondary infection (SI) diagnosis in severe COVID-19 remains challenging. We correlated metagenomic sequencing of plasma microbial cell-free DNA (mcfDNA-Seq) with clinical SI assessment, immune response, and outcomes. We classified 42 COVID-19 inpatients as microbiologically confirmed-SI (Micro-SI, n = 8), clinically diagnosed-SI (Clinical-SI, n = 13, i.e., empiric antimicrobials), or no-clinical-suspicion-for-SI (No-Suspected-SI, n = 21). McfDNA-Seq was successful in 73% of samples. McfDNA detection was higher in Micro-SI (94%) compared to Clinical-SI (57%, p = 0.03), and unexpectedly high in No-Suspected-SI (83%), similar to Micro-SI. We detected culture-concordant mcfDNA species in 81% of Micro-SI samples. McfDNA correlated with LRT 16S rRNA bacterial burden (r = 0.74, p = 0.02), and biomarkers (white blood cell count, IL-6, IL-8, SPD, all p < 0.05). McfDNA levels were predictive of worse 90-day survival (hazard ratio 1.30 [1.02-1.64] for each log10 mcfDNA, p = 0.03). High mcfDNA levels in COVID-19 patients without clinical SI suspicion may suggest SI under-diagnosis. McfDNA-Seq offers a non-invasive diagnostic tool for pathogen identification, with prognostic value on clinical outcomes.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:26 |
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| Enthalten in: |
iScience - 26(2023), 11 vom: 17. Nov., Seite 108093 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Lisius, Grace [VerfasserIn] |
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| Links: |
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| Themen: |
Classification description immunology |
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| Anmerkungen: |
Date Revised 10.02.2024 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1016/j.isci.2023.108093 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM36456752X |
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| 520 | |a Secondary infection (SI) diagnosis in severe COVID-19 remains challenging. We correlated metagenomic sequencing of plasma microbial cell-free DNA (mcfDNA-Seq) with clinical SI assessment, immune response, and outcomes. We classified 42 COVID-19 inpatients as microbiologically confirmed-SI (Micro-SI, n = 8), clinically diagnosed-SI (Clinical-SI, n = 13, i.e., empiric antimicrobials), or no-clinical-suspicion-for-SI (No-Suspected-SI, n = 21). McfDNA-Seq was successful in 73% of samples. McfDNA detection was higher in Micro-SI (94%) compared to Clinical-SI (57%, p = 0.03), and unexpectedly high in No-Suspected-SI (83%), similar to Micro-SI. We detected culture-concordant mcfDNA species in 81% of Micro-SI samples. McfDNA correlated with LRT 16S rRNA bacterial burden (r = 0.74, p = 0.02), and biomarkers (white blood cell count, IL-6, IL-8, SPD, all p < 0.05). McfDNA levels were predictive of worse 90-day survival (hazard ratio 1.30 [1.02-1.64] for each log10 mcfDNA, p = 0.03). High mcfDNA levels in COVID-19 patients without clinical SI suspicion may suggest SI under-diagnosis. McfDNA-Seq offers a non-invasive diagnostic tool for pathogen identification, with prognostic value on clinical outcomes | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Classification description immunology | |
| 650 | 4 | |a Sequence analysis | |
| 650 | 4 | |a Virology | |
| 700 | 1 | |a Duttagupta, Radha |e verfasserin |4 aut | |
| 700 | 1 | |a Ahmed, Asim A |e verfasserin |4 aut | |
| 700 | 1 | |a Hensley, Matthew |e verfasserin |4 aut | |
| 700 | 1 | |a Al-Yousif, Nameer |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Michael |e verfasserin |4 aut | |
| 700 | 1 | |a Bain, William |e verfasserin |4 aut | |
| 700 | 1 | |a Shah, Faraaz |e verfasserin |4 aut | |
| 700 | 1 | |a Blauwkamp, Timothy A |e verfasserin |4 aut | |
| 700 | 1 | |a Bercovici, Sivan |e verfasserin |4 aut | |
| 700 | 1 | |a Schaefer, Caitlin |e verfasserin |4 aut | |
| 700 | 1 | |a Qin, Shulin |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Xiaohong |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Yingze |e verfasserin |4 aut | |
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| 700 | 1 | |a Kitsios, Georgios D |e verfasserin |4 aut | |
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