Metagenomic analysis reveals clinical SARS-CoV-2 infection and bacterial or viral superinfection and colonization.
Open accessAbstract
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.
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A recent study revealed coinfection with Moraxella catarrhalis in laboratory-proven cases of SARS-CoV-2, and quantified increased bacterial burden in some patients over others.
“A recent study revealed coinfection with Moraxella catarrhalis in laboratory-proven cases of SARS-CoV-2, and quantified increased bacterial burden in some patients over others (Peddu et al., 2020).”
From Oral Microbiome and SARS-CoV-2: Beware of Lung Co-infection (2020) · cites this paper as Peddu et al., 2020
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Tan, L. V., Hong, N. T. T., Ngoc, N. M., Thanh, T. T., Lam, V. T., Nguyet, L. A., Nhu, L. N. T., Ny, N. T. H., Minh, N. N. Q., Man, D. N. H., et al. (2020) · medRxiv · doi:10.1101/2020.05.24.20110205 · Cited by 1 · see citing works
Computing informative k-mers for phylogenetic placement
Romashchenko, N. (2021) · doi:10.70675/e9f35f8fz2d75z4febza504z6c6de6857242 · Cited by 1 · see citing works
Metagenomics and Pandemic Viruses
Simas, P. V. M., & Arns, C. W. (2020) · IntechOpen eBooks · doi:10.5772/intechopen.93687
Zhao, L. P., Roychoudhury, P., Jerome, K. R., Gilbert, P. B., Schiffer, J. T., Lybrand, T. P., Payne, T. H., Randhawa, A. K., Thiebaud, S. E., Mills, M. G., et al. (2021) · Research Square · doi:10.21203/rs.3.rs-888049/v1
Hoque, M. N., Akter, S., Mishu, I. D., Islam, M., Rahman, M. M., Akther, M., Islam, I., Hasan, M. M., Rahaman, M. M., Sultana, M., et al. (2022) · doi:10.22541/au.164864574.45709246/v1
Zhao, L. P., Roychoudhury, P., Jerome, K. R., Gilbert, P. B., Schiffer, J. T., Lybrand, T. P., Payne, T. H., Randhawa, A. K., Thiebaud, S. E., Mills, M. G., et al. (2021) · Research Square · doi:10.21203/rs.3.rs-888049/v2
Zhao, J., Wang, H., zhang, J., Ou, F., Wang, J., Liu, T., & Wu, J. (2022) · Research Square · doi:10.21203/rs.3.rs-1905481/v1
Additional file 3 of Genomic epidemiology of SARS-CoV-2 in Esteio, Rio Grande do Sul, Brazil
Franceschi, V. B., Caldana, G. D., de Menezes Mayer, A., Cybis, G. B., Neves, C. A. M., Ferrareze, P. A. G., Demoliner, M., de Almeida, P. R., Gularte, J. S., Hansen, A. W., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14633687
Additional file 2 of Genomic epidemiology of SARS-CoV-2 in Esteio, Rio Grande do Sul, Brazil
Franceschi, V. B., Caldana, G. D., de Menezes Mayer, A., Cybis, G. B., Neves, C. A. M., Ferrareze, P. A. G., Demoliner, M., de Almeida, P. R., Gularte, J. S., Hansen, A. W., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14633684
Additional file 4 of Genomic epidemiology of SARS-CoV-2 in Esteio, Rio Grande do Sul, Brazil
Franceschi, V. B., Caldana, G. D., de Menezes Mayer, A., Cybis, G. B., Neves, C. A. M., Ferrareze, P. A. G., Demoliner, M., de Almeida, P. R., Gularte, J. S., Hansen, A. W., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14633690
Zhao, J., Wang, H., zhang, J., Ou, F., Wang, J., Liu, T., & Wu, J. (2022) · Figshare · doi:10.6084/m9.figshare.21376371
Additional file 1 of Genomic epidemiology of SARS-CoV-2 in Esteio, Rio Grande do Sul, Brazil
Franceschi, V. B., Caldana, G. D., de Menezes Mayer, A., Cybis, G. B., Neves, C. A. M., Ferrareze, P. A. G., Demoliner, M., de Almeida, P. R., Gularte, J. S., Hansen, A. W., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14633681
- Authors
- Peddu, V., Shean, R. C., Xie, H., Shrestha, L., Perchetti, G. A., Minot, S. S., Roychoudhury, P., Huang, M.-L., Nalla, A., Reddy, S. B., Phung, Q., Reinhardt, A., Jerome, K. R., & Greninger, A. L.
- Affiliations
- University of Washington (US)
- Fred Hutch Cancer Center (US)
- Boston University (US)
- ORCID
- Venue
- Clinical Chemistry
- Publisher
- Oxford University Press (OUP)
- Published
- 2020-06-12
- Volume
- 66
- Issue
- 7
- Pages
- 966-972
- ISSN
- 0009-9147 (ISSN-L)
- 1530-8561
- PMC
- PMC7239240
- OpenAlex
- W3022902999
- Cited by
- 73
- References
- 15
- Citations by year
- 2025: 2 · 2024: 7 · 2023: 6 · 2022: 18 · 2021: 28 · 2020: 12
- FWCI
- 2.10
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Clinical Chemistry (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 detection and testing
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Keywords
- SARS-CoV-2, metagenomic sequencing, superinfection, bacterial colonization, viral superinfection, parainfluenza virus type 3, Moraxella, rhinovirus A, rhinovirus C, respiratory viral panel, COVID-19 diagnosis
- MeSH terms
- Betacoronavirus, COVID-19, SARS-CoV-2, Enterovirus, Humans, Nasopharynx, Phylogeny, Pneumonia, Viral, RNA, Viral, Superinfection, Sequence Analysis, RNA, Coronavirus Infections, Metagenomics, Pandemics, Real-Time Polymerase Chain Reaction
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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