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

Background: A cornerstone of Australia’s ability to control COVID-19 has been effective border control with anextensive supervised quarantine programme. However, a rapid recrudescence of COVID-19 was observed in thestate of Victoria in June, 2020. We aim to describe the genomic findings that located the source of this second waveand show the role of genomic epidemiology in the successful elimination of COVID-19 for a second time inAustralia.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 didphylogenetic analyses, genomic cluster discovery, and integrated results with epidemiological data (detailedinformation on demographics, risk factors, and exposure) collected via interview by the Victorian GovernmentDepartment of Health. Genomic transmission networks were used to group multiple genomic clusters whenepidemiological and genomic data suggested they arose from a single importation event and diversified withinVictoria. 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 nationalsequence 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 localinfection to the collection of the first sequenced genome for the dominant local cluster, and compared our growthestimates to previously published estimates from a similar growth phase of lineage B.1.1.7 (also known as theAlpha variant) in the UK.Findings: Between Jan 25, 2020, and Jan 31, 2021, there were 20 451 laboratory-confirmed cases of COVID-19 inVictoria, Australia, of which 15 431 were submitted for sequencing, and 11 711 met all quality control metrics andwere 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 agenomic cluster or transmission network. Genomic analysis revealed that 10 426 cases, including 10 416 (98·4%) of10 584 locally acquired cases, diagnosed during the second wave (between June and October, 2020) were derivedfrom 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 epidemicgrowth rate of the outbreak lineage in Victoria during the initial growth phase (samples collected between June 4and 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). Strictinterventions 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 withhigh epidemic growth rates. Real-time genomic surveillance can alter the way in which public health agencies viewand respond to COVID-19 outbreaks