SARS-CoV-2 Genomic Diversity in Households Highlights the Challenges of Sequence-Based Transmission Inference
ABSTRACT 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 ca...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2022-12-01
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| Series: | mSphere |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/msphere.00400-22 |
| _version_ | 1798003817236660224 |
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| author | Emily E. Bendall Gabriela Paz-Bailey Gilberto A. Santiago Christina A. Porucznik Joseph B. Stanford Melissa S. Stockwell Jazmin Duque Zuha Jeddy Vic Veguilla Chelsea Major Vanessa Rivera-Amill Melissa A. Rolfes Fatimah S. Dawood Adam S. Lauring |
| author_facet | Emily E. Bendall Gabriela Paz-Bailey Gilberto A. Santiago Christina A. Porucznik Joseph B. Stanford Melissa S. Stockwell Jazmin Duque Zuha Jeddy Vic Veguilla Chelsea Major Vanessa Rivera-Amill Melissa A. Rolfes Fatimah S. Dawood Adam S. Lauring |
| author_sort | Emily E. Bendall |
| collection | DOAJ |
| description | ABSTRACT 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. |
| first_indexed | 2024-04-11T12:13:45Z |
| format | Article |
| id | doaj.art-3cd98a9abc9646459c082df9171b6e39 |
| institution | Directory Open Access Journal |
| issn | 2379-5042 |
| language | English |
| last_indexed | 2024-04-11T12:13:45Z |
| publishDate | 2022-12-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mSphere |
| spelling | doaj.art-3cd98a9abc9646459c082df9171b6e392022-12-22T04:24:26ZengAmerican Society for MicrobiologymSphere2379-50422022-12-017610.1128/msphere.00400-22SARS-CoV-2 Genomic Diversity in Households Highlights the Challenges of Sequence-Based Transmission InferenceEmily E. Bendall0Gabriela Paz-Bailey1Gilberto A. Santiago2Christina A. Porucznik3Joseph B. Stanford4Melissa S. Stockwell5Jazmin Duque6Zuha Jeddy7Vic Veguilla8Chelsea Major9Vanessa Rivera-Amill10Melissa A. Rolfes11Fatimah S. Dawood12Adam S. Lauring13Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, USACenters for Disease Control and Prevention, Atlanta, Georgia, USACenters for Disease Control and Prevention, Atlanta, Georgia, USADivision of Public Health, Department of Family and Preventive Medicine, University of Utah School of Medicine, Salt Lake City, Utah, USADivision of Public Health, Department of Family and Preventive Medicine, University of Utah School of Medicine, Salt Lake City, Utah, USADivision of Child and Adolescent Health, Department of Pediatrics, Columbia University Vagelos College of Physicians and Surgeons, Columbia University, New York, New York, USAAbt Associates, Rockville, Maryland, USAAbt Associates, Rockville, Maryland, USACenters for Disease Control and Prevention, Atlanta, Georgia, USACenters for Disease Control and Prevention, Atlanta, Georgia, USAPonce Research Institute, Ponce Health Sciences University, Ponce, Puerto Rico, USACenters for Disease Control and Prevention, Atlanta, Georgia, USACenters for Disease Control and Prevention, Atlanta, Georgia, USADepartment of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, USAABSTRACT 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.https://journals.asm.org/doi/10.1128/msphere.00400-22SARS-CoV-2genomic epidemiologytransmissionhousehold |
| spellingShingle | Emily E. Bendall Gabriela Paz-Bailey Gilberto A. Santiago Christina A. Porucznik Joseph B. Stanford Melissa S. Stockwell Jazmin Duque Zuha Jeddy Vic Veguilla Chelsea Major Vanessa Rivera-Amill Melissa A. Rolfes Fatimah S. Dawood Adam S. Lauring SARS-CoV-2 Genomic Diversity in Households Highlights the Challenges of Sequence-Based Transmission Inference mSphere SARS-CoV-2 genomic epidemiology transmission household |
| title | SARS-CoV-2 Genomic Diversity in Households Highlights the Challenges of Sequence-Based Transmission Inference |
| title_full | SARS-CoV-2 Genomic Diversity in Households Highlights the Challenges of Sequence-Based Transmission Inference |
| title_fullStr | SARS-CoV-2 Genomic Diversity in Households Highlights the Challenges of Sequence-Based Transmission Inference |
| title_full_unstemmed | SARS-CoV-2 Genomic Diversity in Households Highlights the Challenges of Sequence-Based Transmission Inference |
| title_short | SARS-CoV-2 Genomic Diversity in Households Highlights the Challenges of Sequence-Based Transmission Inference |
| title_sort | sars cov 2 genomic diversity in households highlights the challenges of sequence based transmission inference |
| topic | SARS-CoV-2 genomic epidemiology transmission household |
| url | https://journals.asm.org/doi/10.1128/msphere.00400-22 |
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