Noninvasive diagnosis of secondary infections in COVID-19 by sequencing of plasma microbial cell-free DNA.
Classification description immunology
Sequence analysis
Virology
Journal
iScience
ISSN: 2589-0042
Titre abrégé: iScience
Pays: United States
ID NLM: 101724038
Informations de publication
Date de publication:
17 Nov 2023
17 Nov 2023
Historique:
received:
25
02
2023
revised:
04
07
2023
accepted:
26
09
2023
medline:
15
11
2023
pubmed:
15
11
2023
entrez:
15
11
2023
Statut:
epublish
Résumé
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 log
Identifiants
pubmed: 37965142
doi: 10.1016/j.isci.2023.108093
pii: S2589-0042(23)02170-3
pmc: PMC10641743
doi:
Types de publication
Journal Article
Langues
eng
Pagination
108093Informations de copyright
© 2023 The Authors.
Déclaration de conflit d'intérêts
Drs. Duttagupta and Ahmed were employed by Karius, Inc at the time of the study but are no longer employed by Karius, Inc. Drs. Kitsios and Haidar have received research funding from Karius, Inc. Drs. Kitsios and Morris have received research funding from Pfizer, Inc. Dr. Haidar serves on the Karius, Inc scientific advisory board. Dr. Mellors is a consultant to AlloVir, Infectious Disease Connect, Inc., and Gilead Sciences, Inc., has received research funding from Gilead Sciences, Inc. to the University of Pittsburgh, receives compensation from Abound Bio, Inc. (unrelated to the current work) and holds shares options in Galapogos, Infectious Disease Connect, Inc., and MingMed Biotechnology Co. Ltd. (unrelated to the current work). Dr. McVerry has received research funding from Bayer Pharmaceuticals, Inc. and consulting fees from Boehringer Ingelheim, both unrelated to this work.
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