Revealing COVID-19 transmission in Australia by SARS-CoV-2 genome sequencing and agent-based modeling

Rockett, Rebecca; Arnott, Alicia; Lam, Connie; Sadsad, Rosemarie; Timms, Verlaine J.; Gray, Karen-Ann; Eden, John‐Sebastian; Chang, Sheryl L.; Gall, Mailie; Draper, Jenny; E, Sim; Bachmann, Nathan L.; Carter, Ian; Basile, Kerri; Byun, Roy; O’Sullivan, Matthew V. N.; Chen, Sharon C‐A; Maddocks, Susan; Sorrell, Tania C.; Dwyer, Dominic E.; Holmes, Edward C.; Kok, Jen; Prokopenko, Mikhail; Sintchenko, Vitali

doi:10.1038/s41591-020-1000-7

Cited by 322 publications

(274 citation statements)

References 36 publications

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“…Viral genome sequencing could potentially have helped in some cases, such as for the patient exposed to both a COVID-positive staff member and spouse; however, this was not readily available to us. 21 , 22 Even if that case and every other late-onset or postdischarge case were truly hospital acquired, this would represent a low rate of nosocomial infection. Second, despite the implementation of aggressive testing practices, there may have been additional undetected nosocomial cases related to false-negative RT-PCR test results or from patients who might have acquired asymptomatic infection in the hospital but were never tested.…”

Section: Discussionmentioning

confidence: 99%

Incidence of Nosocomial COVID-19 in Patients Hospitalized at a Large US Academic Medical Center

et al. 2020

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Section: Discussionmentioning

confidence: 99%

Incidence of Nosocomial COVID-19 in Patients Hospitalized at a Large US Academic Medical Center

et al. 2020

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“…Stringent QC to ensure only high-quality consensus sequences entered the final alignment was particularly important when considering the minimal diversity in SARS-CoV-2 sequence data used to infer genomic clusters 11,12 . While the use of a predefined Ct value to select samples for SARS-CoV-2 genomic sequencing could be considered 21 , our use of QC parameters, rather than a Ct value, enabled the inclusion of additional samples for genomic analysis, with some samples with Ct values up to 40 being successfully included.…”

Section: Discussionmentioning

confidence: 99%

Tracking the COVID-19 pandemic in Australia using genomics

et al. 2020

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Genomic sequencing has significant potential to inform public health management for SARS-CoV-2. Here we report high-throughput genomics for SARS-CoV-2, sequencing 80% of cases in Victoria, Australia (population 6.24 million) between 6 January and 14 April 2020 (total 1,333 COVID-19 cases). We integrate epidemiological, genomic and phylodynamic data to identify clusters and impact of interventions. The global diversity of SARS-CoV-2 is represented, consistent with multiple importations. Seventy-six distinct genomic clusters were identified, including large clusters associated with social venues, healthcare and cruise ships. Sequencing sequential samples from 98 patients reveals minimal intra-patient SARS-CoV-2 genomic diversity. Phylodynamic modelling indicates a significant reduction in the effective viral reproductive number (R e) from 1.63 to 0.48 after implementing travel restrictions and physical distancing. Our data provide a concrete framework for the use of SARS-CoV-2 genomics in public health responses, including its use to rapidly identify SARS-CoV-2 transmission chains, increasingly important as social restrictions ease globally.

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“…SARS-CoV-2 genome sequencing from original patient material was performed using a previously described targeted, tiled-amplicon, sequencing approach (48, 49). Briefly, total nucleic acids were extracted followed by reverse transcription with random hexamers and oligo-dT priming (ratio 3:1) using SuperScript IV Reverse Transcriptase (Thermo Fisher Scientific).…”

Section: Methodsmentioning

confidence: 99%

SARS-CoV-2 Variants Reveal Features Critical for Replication in Primary Human Cells

Pohl

Busnadiego

Kufner

et al. 2020

Preprint

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Since entering the human population, SARS-CoV-2 (the causative agent of COVID-19) has spread across the world, causing >40 million infections and >1 million deaths. While large-scale sequencing efforts have identified numerous genetic mutations in SARS-CoV-2 during its circulation, it remains largely unclear whether these changes impact adaptation, replication or transmission of the virus in its new host. Here, we characterized 14 different low-passage replication-competent human SARS-CoV-2 isolates representing all the major European clades observed during the first pandemic wave in early 2020. By integrating viral sequencing data from patient material, viral stocks and passaging experiments, with kinetic virus replication data from non-human Vero-CCL81 cells and primary differentiated human bronchial epithelial cells (BEpCs), we observed several SARS-CoV-2 sequence features that associate with distinct phenotypes. Notably, naturally-occurring substitutions in Orf3a (Q57H) and nsp2 (T85I) were associated with poor replication in Vero-CCL81 cells but not in BEpCs, while SARS-CoV-2 isolates expressing the Spike D614G substitution generally exhibited enhanced replication abilities in BEpCs. Strikingly, low-passage Vero-derived stock preparation of 3 SARS-CoV-2 isolates selected for substitutions at positions 5/6 of E, and were highly attenuated in BEpCs, revealing a key cell-specific function to this region. Rare isolate-specific deletions were also observed in the Spike furin-cleavage site during Vero-CCL81 passage, but these were rapidly selected against in BEpCs, underscoring the importance of this site for SARS-CoV-2 replication in primary human respiratory cells. Overall, our study uncovers natural sequence features in the SARS-CoV-2 genome that determine efficient virus replication and tropism for the human respiratory epithelium.

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Revealing COVID-19 transmission in Australia by SARS-CoV-2 genome sequencing and agent-based modeling

Cited by 322 publications

References 36 publications

Incidence of Nosocomial COVID-19 in Patients Hospitalized at a Large US Academic Medical Center

Incidence of Nosocomial COVID-19 in Patients Hospitalized at a Large US Academic Medical Center

Tracking the COVID-19 pandemic in Australia using genomics

SARS-CoV-2 Variants Reveal Features Critical for Replication in Primary Human Cells

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