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Genomic epidemiological analysis of SARS-CoV-2 household transmission.

ABSTRACT: Family clusters have contributed significantly to the onward spread of SARS-CoV-2. However, the dynamics of viral transmission in this setting remain incompletely understood. We describe the clinical and viral-phylogenetic characteristics of a family cluster of SARS-CoV-2 infections with a high attack rate, and explore how whole-genome sequencing (WGS) can inform outbreak investigations in this context. In this cluster, the first symptomatic case was a 22-month-old infant who developed rhinorrhoea and sneezing 2 days prior to attending a family gathering. Subsequently, seven family members in attendance at this event were diagnosed with SARS-CoV-2 infections, including the infant described. WGS revealed indistinguishable SARS-CoV-2 genomes recovered from the adults at the gathering, which were closely related genetically to B.1 lineage viruses circulating in the local community. However, a divergent viral sub-lineage was recovered from the infant and another child, each harbouring a distinguishing spike substitution (N30S). This suggested that the infant was unlikely to be the primary case, despite displaying symptoms first, and additional analysis of her nasopharyngeal swab revealed a picornavirus co-infection to account for her early symptoms. Our findings demonstrate how WGS can elucidate the transmission dynamics of SARS-CoV-2 infections within household clusters and provide useful information to support outbreak investigations. Additionally, our description of SARS-CoV-2 viral lineages and notable variants circulating in Ireland to date provides an important genomic-epidemiological baseline in the context of vaccine introduction.

SUBMITTER: Hare D

PROVIDER: S-EPMC8479960 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:A detailed understanding of how and when severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission occurs is crucial for designing effective prevention measures. Other than contact tracing, genome sequencing provides information to help infer who infected whom. However, the effectiveness of the genomic approach in this context depends on both (high enough) mutation and (low enough) transmission rates. Today, the level of resolution that we can obtain when describing SARS-CoV-2 outbreaks using just genomic information alone remains unclear. In order to answer this question, we sequenced forty-nine SARS-CoV-2 patient samples from ten local clusters in NW Spain for which partial epidemiological information was available and inferred transmission history using genomic variants. Importantly, we obtained high-quality genomic data, sequencing each sample twice and using unique barcodes to exclude cross-sample contamination. Phylogenetic and cluster analyses showed that consensus genomes were generally sufficient to discriminate among independent transmission clusters. However, levels of intrahost variation were low, which prevented in most cases the unambiguous identification of direct transmission events. After filtering out recurrent variants across clusters, the genomic data were generally compatible with the epidemiological information but did not support specific transmission events over possible alternatives. We estimated the effective transmission bottleneck size to be one to two viral particles for sample pairs whose donor-recipient relationship was likely. Our analyses suggest that intrahost genomic variation in SARS-CoV-2 might be generally limited and that homoplasy and recurrent errors complicate identifying shared intrahost variants. Reliable reconstruction of direct SARS-CoV-2 transmission based solely on genomic data seems hindered by a slow mutation rate, potential convergent events, and technical artifacts. Detailed contact tracing seems essential in most cases to study SARS-CoV-2 transmission at high resolution.

Project description:ImportanceCrowded indoor environments, such as households, are high-risk settings for the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).ObjectivesTo examine evidence for household transmission of SARS-CoV-2, disaggregated by several covariates, and to compare it with other coronaviruses.Data sourcePubMed, searched through October 19, 2020. Search terms included SARS-CoV-2 or COVID-19 with secondary attack rate, household, close contacts, contact transmission, contact attack rate, or family transmission.Study selectionAll articles with original data for estimating household secondary attack rate were included. Case reports focusing on individual households and studies of close contacts that did not report secondary attack rates for household members were excluded.Data extraction and synthesisMeta-analyses were done using a restricted maximum-likelihood estimator model to yield a point estimate and 95% CI for secondary attack rate for each subgroup analyzed, with a random effect for each study. To make comparisons across exposure types, study was treated as a random effect, and exposure type was a fixed moderator. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline was followed.Main outcomes and measuresSecondary attack rate for SARS-CoV-2, disaggregated by covariates (ie, household or family contact, index case symptom status, adult or child contacts, contact sex, relationship to index case, adult or child index cases, index case sex, number of contacts in household) and for other coronaviruses.ResultsA total of 54 relevant studies with 77 758 participants reporting household secondary transmission were identified. Estimated household secondary attack rate was 16.6% (95% CI, 14.0%-19.3%), higher than secondary attack rates for SARS-CoV (7.5%; 95% CI, 4.8%-10.7%) and MERS-CoV (4.7%; 95% CI, 0.9%-10.7%). Household secondary attack rates were increased from symptomatic index cases (18.0%; 95% CI, 14.2%-22.1%) than from asymptomatic index cases (0.7%; 95% CI, 0%-4.9%), to adult contacts (28.3%; 95% CI, 20.2%-37.1%) than to child contacts (16.8%; 95% CI, 12.3%-21.7%), to spouses (37.8%; 95% CI, 25.8%-50.5%) than to other family contacts (17.8%; 95% CI, 11.7%-24.8%), and in households with 1 contact (41.5%; 95% CI, 31.7%-51.7%) than in households with 3 or more contacts (22.8%; 95% CI, 13.6%-33.5%).Conclusions and relevanceThe findings of this study suggest that given that individuals with suspected or confirmed infections are being referred to isolate at home, households will continue to be a significant venue for transmission of SARS-CoV-2.

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Genomic epidemiological analysis of SARS-CoV-2 household transmission.

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