Metagenomic Analysis Reveals Clinical SARS-CoV-2 Infection and Bacterial or Viral Superinfection and Colonization.


Journal

Clinical chemistry
ISSN: 1530-8561
Titre abrégé: Clin Chem
Pays: England
ID NLM: 9421549

Informations de publication

Date de publication:
01 07 2020
Historique:
received: 28 03 2020
accepted: 23 04 2020
pubmed: 8 5 2020
medline: 16 7 2020
entrez: 8 5 2020
Statut: ppublish

Résumé

More than 2 months separated the initial description of SARS-CoV-2 and discovery of its widespread dissemination in the United States. Despite this lengthy interval, implementation of specific quantitative reverse transcription (qRT)-PCR-based SARS-CoV-2 tests in the US has been slow, and testing is still not widely available. Metagenomic sequencing offers the promise of unbiased detection of emerging pathogens, without requiring prior knowledge of the identity of the responsible agent or its genomic sequence. To evaluate metagenomic approaches in the context of the current SARS-CoV-2 epidemic, laboratory-confirmed positive and negative samples from Seattle, WA were evaluated by metagenomic sequencing, with comparison to a 2019 reference genomic database created before the emergence of SARS-CoV-2. Within 36 h our results showed clear identification of a novel human Betacoronavirus, closely related to known Betacoronaviruses of bats, in laboratory-proven cases of SARS-CoV-2. A subset of samples also showed superinfection or colonization with human parainfluenza virus 3 or Moraxella species, highlighting the need to test directly for SARS-CoV-2 as opposed to ruling out an infection using a viral respiratory panel. Samples negative for SARS-CoV-2 by RT-PCR were also negative by metagenomic analysis, and positive for Rhinovirus A and C. Unlike targeted SARS-CoV-2 qRT-PCR testing, metagenomic analysis of these SARS-CoV-2 negative samples identified candidate etiological agents for the patients' respiratory symptoms. Taken together, these results demonstrate the value of metagenomic analysis in the monitoring and response to this and future viral pandemics.

Sections du résumé

BACKGROUND
More than 2 months separated the initial description of SARS-CoV-2 and discovery of its widespread dissemination in the United States. Despite this lengthy interval, implementation of specific quantitative reverse transcription (qRT)-PCR-based SARS-CoV-2 tests in the US has been slow, and testing is still not widely available. Metagenomic sequencing offers the promise of unbiased detection of emerging pathogens, without requiring prior knowledge of the identity of the responsible agent or its genomic sequence.
METHODS
To evaluate metagenomic approaches in the context of the current SARS-CoV-2 epidemic, laboratory-confirmed positive and negative samples from Seattle, WA were evaluated by metagenomic sequencing, with comparison to a 2019 reference genomic database created before the emergence of SARS-CoV-2.
RESULTS
Within 36 h our results showed clear identification of a novel human Betacoronavirus, closely related to known Betacoronaviruses of bats, in laboratory-proven cases of SARS-CoV-2. A subset of samples also showed superinfection or colonization with human parainfluenza virus 3 or Moraxella species, highlighting the need to test directly for SARS-CoV-2 as opposed to ruling out an infection using a viral respiratory panel. Samples negative for SARS-CoV-2 by RT-PCR were also negative by metagenomic analysis, and positive for Rhinovirus A and C. Unlike targeted SARS-CoV-2 qRT-PCR testing, metagenomic analysis of these SARS-CoV-2 negative samples identified candidate etiological agents for the patients' respiratory symptoms.
CONCLUSION
Taken together, these results demonstrate the value of metagenomic analysis in the monitoring and response to this and future viral pandemics.

Identifiants

pubmed: 32379863
pii: 5831830
doi: 10.1093/clinchem/hvaa106
pmc: PMC7239240
doi:

Substances chimiques

RNA, Viral 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

966-972

Informations de copyright

© American Association for Clinical Chemistry 2020. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Auteurs

Vikas Peddu (V)

Department of Laboratory Medicine, University of Washington, Seattle, WA.

Ryan C Shean (RC)

Department of Laboratory Medicine, University of Washington, Seattle, WA.

Hong Xie (H)

Department of Laboratory Medicine, University of Washington, Seattle, WA.

Lasata Shrestha (L)

Department of Laboratory Medicine, University of Washington, Seattle, WA.

Garrett A Perchetti (GA)

Department of Laboratory Medicine, University of Washington, Seattle, WA.

Samuel S Minot (SS)

Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA.

Pavitra Roychoudhury (P)

Department of Laboratory Medicine, University of Washington, Seattle, WA.
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA.

Meei-Li Huang (ML)

Department of Laboratory Medicine, University of Washington, Seattle, WA.

Arun Nalla (A)

Department of Laboratory Medicine, University of Washington, Seattle, WA.

Shriya B Reddy (SB)

Department of Medicine, Boston University School of Medicine, Boston, MA.

Quynh Phung (Q)

Department of Laboratory Medicine, University of Washington, Seattle, WA.

Adam Reinhardt (A)

Department of Laboratory Medicine, University of Washington, Seattle, WA.

Keith R Jerome (KR)

Department of Laboratory Medicine, University of Washington, Seattle, WA.
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA.

Alexander L Greninger (AL)

Department of Laboratory Medicine, University of Washington, Seattle, WA.
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA.

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Classifications MeSH