Literature detail

Tracking cryptic SARS-CoV-2 lineages detected in NYC wastewater.

Davida S Smyth1 Monica Trujillo2 Devon A Gregory3 Kristen Cheung4 Anna Gao4 Maddie Graham3 Yue Guan3 Caitlyn Guldenpfennig3 Irene Hoxie4 Sherin Kannoly4 Nanami Kubota4 Terri D Lyddon3 Michelle Markman4 Clayton Rushford3 Kaung Myat San4 Geena Sompanya1 Fabrizio Spagnolo5 Reinier Suarez3 Emma Teixeiro3 Mark Daniels3 Marc C Johnson6 John J Dennehy7
Affiliations 7 institutions
  1. Department of Life Sciences, Texas A&M University-San Antonio, San Antonio, TX, 78224, USA.
  2. Department of Biological Sciences and Geology, Queensborough Community College of The City University of New York, Queens, NY, 11364, USA.
  3. Department of Molecular Microbiology and Immunology, University of Missouri-School of Medicine, Columbia, MO, 65212, USA.
  4. Biology Department, Queens College and The Graduate Center of The City University of New York, Queens, NY, 11367, USA.
  5. Department of Biological & Environmental Sciences, Long Island University-Post, Greenvale, New York, 11548, USA.
  6. Department of Molecular Microbiology and Immunology, University of Missouri-School of Medicine, Columbia, MO, 65212, USA. [email protected].
  7. Biology Department, Queens College and The Graduate Center of The City University of New York, Queens, NY, 11367, USA. [email protected].
PMID 35115523 2022 Nat Commun eng epublish
PubMed DOI Browse context

Article

Publication summary

Tracking SARS-CoV-2 genetic diversity is strongly indicated because diversifying selection may lead to the emergence of novel variants resistant to naturally acquired or vaccine-induced immunity. To monitor New York City (NYC) for the presence of novel variants, we deep sequence most of the receptor binding domain coding sequence of the S protein of SARS-CoV-2 isolated from the New York City wastewater. Here we report detecting increasing frequencies of novel cryptic SARS-CoV-2 lineages not recognized in GISAID's EpiCoV database. These lineages contain mutations that had been rarely observed in clinical samples, including Q493K, Q498Y, E484A, and T572N and share many mutations with the Omicron variant of concern. Some of these mutations expand the tropism of SARS-CoV-2 pseudoviruses by allowing infection of cells expressing the human, mouse, or rat ACE2 receptor. Finally, pseudoviruses containing the spike amino acid sequence of these lineages were resistant to different classes of receptor binding domain neutralizing monoclonal antibodies. We offer several hypotheses for the anomalous presence of these lineages, including the possibility that these lineages are derived from unsampled human COVID-19 infections or that they indicate the presence of a non-human animal reservoir.

Water Microbiology Adult Aged Animals Antibodies, Monoclonal Antibodies, Neutralizing Antibodies, Viral COVID-19 Female Genetic Variation High-Throughput Nucleotide Sequencing Humans Male Mice Middle Aged Mutation New York City Protein Binding

Structured evidence records

Evidence records

6 total
3 records
Extraction confidence 0.95
Key finding

Cryptic SARS-CoV-2 lineages from New York City wastewater possess spike mutations that permit infection of cells expressing human, mouse, or rat ACE2, showing altered receptor usage.

Virus
Location
Not specified
Supporting text

Some of these mutations expand the tropism of SARS-CoV-2 pseudoviruses by allowing infection of cells expressing the human, mouse, or rat ACE2 receptor.

Method
pseudovirus assay
Receptors
ACE2
Extraction confidence 0.95
Key finding

Cryptic SARS-CoV-2 lineages from New York City wastewater possess spike mutations that permit infection of cells expressing mouse ACE2, showing altered receptor usage.

Virus
Location
Not specified
Supporting text

Some of these mutations expand the tropism of SARS-CoV-2 pseudoviruses by allowing infection of cells expressing the human, mouse, or rat ACE2 receptor.

Method
pseudovirus assay
Receptors
ACE2
Extraction confidence 0.95
Key finding

Cryptic SARS-CoV-2 lineages from New York City wastewater possess spike mutations that permit infection of cells expressing rat ACE2, showing altered receptor usage.

Virus
Host
Location
Not specified
Supporting text

Some of these mutations expand the tropism of SARS-CoV-2 pseudoviruses by allowing infection of cells expressing the human, mouse, or rat ACE2 receptor.

Method
pseudovirus assay
Receptors
ACE2
1 records
Extraction confidence 0.80
Key finding

Sequencing of SARS-CoV-2 from NYC wastewater revealed new cryptic lineages with distinct spike mutations, indicating ongoing viral genomic evolution outside known sampled populations.

Virus
Host
Not specified
Location
Not specified
Supporting text

We deep sequence most of the receptor binding domain coding sequence of the S protein of SARS-CoV-2 isolated from the New York City wastewater. Here we report detecting increasing frequencies of novel cryptic SARS-CoV-2 lineages not recognized in GISAID's EpiCoV database. These lineages contain mutations that had been rarely observed in clinical samples, including Q493K, Q498Y, E484A, and T572N and share many mutations with the Omicron variant of concern.

Genes or proteins
Spike protein; receptor binding domain
Analysis methods
deep sequencing; comparative genomic analysis
1 records
Extraction confidence 0.90
Key finding

SARS-CoV-2 lineages from NYC wastewater carried spike mutations Q493K, Q498Y, E484A, and T572N that enabled infection via human, mouse, and rat ACE2 receptors and conferred resistance to neutralizing antibodies.

Virus
Host
Not specified
Location
Not specified
Supporting text

These lineages contain mutations that had been rarely observed in clinical samples, including Q493K, Q498Y, E484A, and T572N and share many mutations with the Omicron variant of concern. Some of these mutations expand the tropism of SARS-CoV-2 pseudoviruses by allowing infection of cells expressing the human, mouse, or rat ACE2 receptor. Finally, pseudoviruses containing the spike amino acid sequence of these lineages were resistant to different classes of receptor binding domain neutralizing monoclonal antibodies.

Genes or proteins
spike
Receptors
ACE2
Mutations
Q493K; Q498Y; E484A; T572N
Mechanism types
receptor_binding; tropism; immune_escape
1 records
Extraction confidence 0.85
Key finding

SARS-CoV-2 variants were monitored by deep sequencing of New York City wastewater, revealing previously unrecognized cryptic lineages possibly linked to unsampled infections or a non-human reservoir.

Virus
Host
Not specified
Location
Supporting text

To monitor New York City (NYC) for the presence of novel variants, we deep sequence most of the receptor binding domain coding sequence of the S protein of SARS-CoV-2 isolated from the New York City wastewater.

Method
deep sequencing; genomic surveillance
Sample type
wastewater
Geographic raw
New York City
Country inferred
United States