Genomics-informed responses in the elimination of COVID-19 in Victoria, Australia: an observational, genomic epidemiological study

Abstract

Background: A cornerstone of Australia's ability to control COVID-19 has been effective border control with an extensive supervised quarantine programme. However, a rapid recrudescence of COVID-19 was observed in the state of Victoria in June, 2020. We aim to describe the genomic findings that located the source of this second wave and show the role of genomic epidemiology in the successful elimination of COVID-19 for a second time in Australia.

Methods: In this observational, genomic epidemiological study, we did genomic sequencing of all laboratory-confirmed cases of COVID-19 diagnosed in Victoria, Australia between Jan 25, 2020, and Jan 31, 2021. We did phylogenetic analyses, genomic cluster discovery, and integrated results with epidemiological data (detailed information on demographics, risk factors, and exposure) collected via interview by the Victorian Government Department of Health. Genomic transmission networks were used to group multiple genomic clusters when epidemiological and genomic data suggested they arose from a single importation event and diversified within Victoria. To identify transmission of emergent lineages between Victoria and other states or territories in Australia, all publicly available SARS-CoV-2 sequences uploaded before Feb 11, 2021, were obtained from the national sequence sharing programme AusTrakka, and epidemiological data were obtained from the submitting laboratories. We did phylodynamic analyses to estimate the growth rate, doubling time, and number of days from the first local infection to the collection of the first sequenced genome for the dominant local cluster, and compared our growth estimates to previously published estimates from a similar growth phase of lineage B.1.1.7 (also known as the Alpha variant) in the UK.

Findings: Between Jan 25, 2020, and Jan 31, 2021, there were 20 451 laboratory-confirmed cases of COVID-19 in Victoria, Australia, of which 15 431 were submitted for sequencing, and 11 711 met all quality control metrics and were included in our analysis. We identified 595 genomic clusters, with a median of five cases per cluster (IQR 2-11). Overall, samples from 11 503 (98·2%) of 11 711 cases clustered with another sample in Victoria, either within a genomic cluster or transmission network. Genomic analysis revealed that 10 426 cases, including 10 416 (98·4%) of 10 584 locally acquired cases, diagnosed during the second wave (between June and October, 2020) were derived from a single incursion from hotel quarantine, with the outbreak lineage (transmission network G, lineage D.2) rapidly detected in other Australian states and territories. Phylodynamic analyses indicated that the epidemic growth rate of the outbreak lineage in Victoria during the initial growth phase (samples collected between June 4 and July 9, 2020; 47·4 putative transmission events, per branch, per year [1/years; 95% credible interval 26·0-85·0]), was similar to that of other reported variants, such as B.1.1.7 in the UK (mean approximately 71·5 1/years). Strict interventions were implemented, and the outbreak lineage has not been detected in Australia since Oct 29, 2020. Subsequent cases represented independent international or interstate introductions, with limited local spread.

Interpretation: Our study highlights how rapid escalation of clonal outbreaks can occur from a single incursion. However, strict quarantine measures and decisive public health responses to emergent cases are effective, even with high epidemic growth rates. Real-time genomic surveillance can alter the way in which public health agencies view and respond to COVID-19 outbreaks.

Funding: The Victorian Government, the National Health and Medical Research Council Australia, and the Medical Research Future Fund.

Figure 1

Epidemic curve of COVID-19 in Victoria, Australia between Jan 25, 2020, and Jan 31, 2021 Cases of COVID-19 are plotted by reported date of COVID-19 diagnosis and coloured according to availability of sequence data for inclusion in our analysis. Cases will not have included sequence data if a sample collected from the case was not received at the sequencing laboratory, or the sample was unable to be sequenced due to insufficient volume, or failure of presequencing DNA extraction or library preparation steps, or both.

Figure 2

Timeline of SARS-CoV-2 genomic clusters in Victoria, Australia between Jan 25, 2020 and Jan 31, 2021 Cases of COVID-19 in Victoria diagnosed between Jan 25, 2020, and Jan 31, 2021, are included. Cases are plotted by diagnosis date and genomic cluster or transmission network. Mode of acquisition was categorised as: travel overseas if the individual reported travel in the 14 days before symptom onset; contact with a confirmed case if no overseas travel was reported and case contact had occurred within the same time period; or source unknown. The size of the circles corresponds to the number of cases diagnosed per day within a genomic cluster or transmission network and with the same mode of acquisition, with larger circle sizes indicating a greater number of cases. Genomic clusters or transmission networks of interest during periods 2, 3, and 4, as discussed in the main text, are labelled on the y-axis (see appendix 1 p 7 for details of all genomic clusters and transmission networks).

Figure 3

Maximum likelihood phylogenetic trees of Australian SARS-CoV-2 samples Samples from COVID-19 cases in Victoria diagnosed between Jan 25, 2020, and Jan 31, 2021, and interstate samples from cases uploaded to AusTrakka before Feb 11, 2021, are included. (A) Sequences from Victorian cases diagnosed during period 3 (May 31, 2020, to Dec 6, 2021) identified as within local transmission networks or genomic clusters indicated. Travel-only clusters and unclustered sequences have not been indicated. Further information on genomic clusters 661 and 203 are provided in appendix 1 (p 7). (B) Sequences from Victorian cases diagnosed during period 4 (Dec 7, 2020, to Jan 31, 2021) identified as within local genomic clusters or variants of concern are indicated. Regions of the phylogenetic tree containing B.1.1.7 and B.1.351 variants of concern are also labelled. Travel-only clusters and unclustered sequences have not been indicated. (C) Sequences from interstate samples (excluding Victoria) identified within transmission network G.

Figure 4

Growth rate and genome detection lag of transmission network G (A) Posterior distribution of the growth rate (as putative transmission events, per branch, per year) for the exponential phase of transmission network G generated with a birth-death model. The sequences were collected from June 4 to July 9, 2020. To compare the growth rate of transmission network G with that of lineage B.1.1.7, a previous estimate of the growth rate of B.1.1.7 is represented by a red dashed line, with the 95% credible interval represented by black dashed lines. (B) The genome detection lag, defined as the number of days from the first local infection to the collection of the first sequenced genome, for transmission network G.