Dataset Information

Hidden genomic diversity of SARS-CoV-2: implications for qRT-PCR diagnostics and transmission.

ABSTRACT: The COVID-19 pandemic has sparked an urgent need to uncover the underlying biology of this devastating disease. Though RNA viruses mutate more rapidly than DNA viruses, there are a relatively small number of single nucleotide polymorphisms (SNPs) that differentiate the main SARS-CoV-2 clades that have spread throughout the world. In this study, we investigated over 7,000 SARS-CoV-2 datasets to unveil both intrahost and interhost diversity. Our intrahost and interhost diversity analyses yielded three major observations. First, the mutational profile of SARS-CoV-2 highlights iSNV and SNP similarity, albeit with high variability in C>T changes. Second, iSNV and SNP patterns in SARS-CoV-2 are more similar to MERS-CoV than SARS-CoV-1. Third, a significant fraction of small indels fuel the genetic diversity of SARS-CoV-2. Altogether, our findings provide insight into SARS-CoV-2 genomic diversity, inform the design of detection tests, and highlight the potential of iSNVs for tracking the transmission of SARS-CoV-2.

SUBMITTER: Sapoval N

PROVIDER: S-EPMC7337385 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Hidden genomic diversity of SARS-CoV-2: implications for qRT-PCR diagnostics and transmission.

Sapoval Nicolae N Mahmoud Medhat M Jochum Michael D MD Liu Yunxi Y Elworth R A Leo RAL Wang Qi Q Albin Dreycey D Ogilvie Huw H Lee Michael D MD Villapol Sonia S Hernandez Kyle M KM Berry Irina Maljkovic IM Foox Jonathan J Beheshti Afshin A Ternus Krista K Aagaard Kjersti M KM Posada David D Mason Christopher E CE Sedlazeck Fritz F Treangen Todd J TJ

bioRxiv : the preprint server for biology 20200702

The COVID-19 pandemic has sparked an urgent need to uncover the underlying biology of this devastating disease. Though RNA viruses mutate more rapidly than DNA viruses, there are a relatively small number of single nucleotide polymorphisms (SNPs) that differentiate the main SARS-CoV-2 clades that have spread throughout the world. In this study, we investigated over 7,000 SARS-CoV-2 datasets to unveil both intrahost and interhost diversity. Our intrahost and interhost diversity analyses yielded t ...[more]

PMID: 32637955

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Project description:The reliability of sequence-based inference of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission is not clear. Sequence data from infections among household members can define the expected genomic diversity of a virus along a defined transmission chain. SARS-CoV-2 cases were identified prospectively among 2,369 participants in 706 households. Specimens with a reverse transcription-PCR cycle threshold of ≤30 underwent whole-genome sequencing. Intrahost single-nucleotide variants (iSNV) were identified at a ≥5% frequency. Phylogenetic trees were used to evaluate the relationship of household and community sequences. There were 178 SARS-CoV-2 cases in 706 households. Among 147 specimens sequenced, 106 yielded a whole-genome consensus with coverage suitable for identifying iSNV. Twenty-six households had sequences from multiple cases within 14 days. Consensus sequences were indistinguishable among cases in 15 households, while 11 had ≥1 consensus sequence that differed by 1 to 2 mutations. Sequences from households and the community were often interspersed on phylogenetic trees. Identification of iSNV improved inference in 2 of 15 households with indistinguishable consensus sequences and in 6 of 11 with distinct ones. In multiple-infection households, whole-genome consensus sequences differed by 0 to 1 mutations. Identification of shared iSNV occasionally resolved linkage, but the low genomic diversity of SARS-CoV-2 limits the utility of "sequence-only" transmission inference. IMPORTANCE We performed whole-genome sequencing of SARS-CoV-2 from prospectively identified cases in three longitudinal household cohorts. In a majority of multi-infection households, SARS-CoV-2 consensus sequences were indistinguishable, and they differed by 1 to 2 mutations in the rest. Importantly, even with modest genomic surveillance of the community (3 to 5% of cases sequenced), it was not uncommon to find community sequences interspersed with household sequences on phylogenetic trees. Identification of shared minority variants only occasionally resolved these ambiguities in transmission linkage. Overall, the low genomic diversity of SARS-CoV-2 limits the utility of "sequence-only" transmission inference. Our work highlights the need to carefully consider both epidemiologic linkage and sequence data to define transmission chains in households, hospitals, and other transmission settings.

Dataset Information

Hidden genomic diversity of SARS-CoV-2: implications for qRT-PCR diagnostics and transmission.

Publications

Hidden genomic diversity of SARS-CoV-2: implications for qRT-PCR diagnostics and transmission.

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