SARS-CoV-2 Genomic Diversity in Households Highlights the Challenges of Sequence-Based Transmission Inference.
SARS-CoV-2 Genomic Diversity in Households Highlights the Challenges of Sequence-Based Transmission Inference.
复制标题
作者：
基于序列推断严重急性呼吸综合征冠状病毒2 （SARS-CoV-2）传播的可靠性尚不清楚。来自家庭成员之间感染的序列数据可以确定沿确定的传播链的病毒的预期基因组多样性。在706个家庭的2369名参与者中前瞻性地发现了SARS-CoV-2病例。逆转录- pcr周期阈值≤30的标本进行全基因组测序。宿主内单核苷酸变异（iSNV）的鉴定频率≥5%。系统发育树分析了家系序列与群落序列的关系。706户出现178例新冠肺炎病例。在147个测序标本中，106个获得了全基因组共识，覆盖范围适合鉴定iSNV。26个家庭在14天内出现了多例病例的序列。共识序列在15个家庭病例中无法区分，而11个家庭有≥1个共识序列，差异为1到2个突变。来自家庭和社区的序列经常穿插在系统发育树上。iSNV的识别改善了15个共识序列不可区分的家庭中的2个和11个共识序列不同的家庭中的6个的推理。在多次感染的家庭中，全基因组共识序列的差异为0到1个突变。共享iSNV的鉴定偶尔会解决连锁问题，但SARS-CoV-2的低基因组多样性限制了“仅序列”传播推断的实用性。我们从三个纵向家庭队列中前瞻性鉴定的病例中对SARS-CoV-2进行了全基因组测序。在大多数多重感染家庭中，SARS-CoV-2共识序列无法区分，其余家庭的共识序列差异为1至2个突变。重要的是，即使对社区进行适度的基因组监测（3 - 5%的病例测序），在系统发育树上发现社区序列与家庭序列穿插的情况并不罕见。对共享的少数变异的识别只能偶尔解决这些传播联系中的模糊性。总体而言，SARS-CoV-2的低基因组多样性限制了“仅序列”传播推断的实用性。我们的工作强调需要仔细考虑流行病学联系和序列数据，以确定家庭、医院和其他传播环境中的传播链。
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.
登录
查看更多内容
DOI：
10.1093/cid/ciab281
发表时间：
2021-09-15
期刊：
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
影响因子：
--
作者：
Braun KM;Moreno GK;Buys A;Somsen ED;Bobholz M;Accola MA;Anderson L;Rehrauer WM;Baker DA;Safdar N;Lepak AJ;O'Connor DH;Friedrich TC
通讯作者：
Friedrich TC
影响因子：
15.9
作者：
Kao RR;Haydon DT;Lycett SJ;Murcia PR
通讯作者：
Murcia PR
影响因子：
9.4
作者：
Addetia A;Crawford KHD;Dingens A;Zhu H;Roychoudhury P;Huang ML;Jerome KR;Bloom JD;Greninger AL
通讯作者：
Greninger AL
影响因子：
16.6
作者：
Aggarwal D;Warne B;Jahun AS;Hamilton WL;Fieldman T;du Plessis L;Hill V;Blane B;Watkins E;Wright E;Hall G;Ludden C;Myers R;Hosmillo M;Chaudhry Y;Pinckert ML;Georgana I;Izuagbe R;Leek D;Nsonwu O;Hughes GJ;Packer S;Page AJ;Metaxaki M;Fuller S;Weale G;Holgate J;Brown CA;Cambridge Covid-19 testing Centre;University of Cambridge Asymptomatic COVID-19 Screening Programme Consortium;COVID-19 Genomics UK (COG-UK) Consortium;Howes R;McFarlane D;Dougan G;Pybus OG;Angelis D;Maxwell PH;Peacock SJ;Weekes MP;Illingworth C;Harrison EM;Matheson NJ;Goodfellow IG
通讯作者：
Goodfellow IG
影响因子：
16.6
作者：
Lindsey BB;Villabona-Arenas CJ;Campbell F;Keeley AJ;Parker MD;Shah DR;Parsons H;Zhang P;Kakkar N;Gallis M;Foulkes BH;Wolverson P;Louka SF;Christou S;State A;Johnson K;Raza M;Hsu S;Jombart T;Cori A;Sheffield COVID-19 Genomics Group;COVID-19 Genomics UK (COG-UK) consortium;CMMID COVID-19 working group;Evans CM;Partridge DG;Atkins KE;Hué S;de Silva TI
通讯作者：
de Silva TI