ABSTRACT
Recently there has been a surge in emergent SARS-CoV-2 lineages that are able to evade both vaccine induced immunity as well as prior infection from the founding Omicron BA.1 and BA.2 lineages. These highly transmissible and evasive lineages are on the rise and include Omicron variants BA.2.12.1, BA.4, and BA.5. Aotearoa New Zealand recently reopened its borders to many travellers, without their need to enter quarantine. By generating 10,403 complete SARS-CoV-2 genomes classified as Omicron, we show that New Zealand is observing an influx of these immune-evasive variants through the border. Specifically, there has been a recent surge of BA.5 and BA.2.12.1 introductions into the community and these can be explained by the gradual return to pre-pandemic levels of international traveller arrival rates. We estimate there is one Omicron transmission event from the border to the community for every ~5,000 passenger arrivals into the country, or around one introduction event per day at the current levels of travel. Given the waning levels of population immunity, this rate of importation presents the risk of a large wave in New Zealand during the second half of 2022. Genomic surveillance, coupled with modelling the rate at which new variants cross the border into the community, provides a lens on the rate at which new variants might gain a foothold and trigger new waves of infection.
ABSTRACT
New Zealand's COVID-19 elimination strategy heavily relied on the use of genomics to inform contact tracing, linking cases to the border and to clusters during community outbreaks. In August 2021, New Zealand entered its second nationwide lockdown after the detection of a single community case with no immediately apparent epidemiological link to the border. This incursion resulted in the largest outbreak seen in New Zealand caused by the Delta Variant of Concern. Here we generated 3806 high quality SARS-CoV-2 genomes from cases reported in New Zealand between 17 August and 1 December 2021, representing 43% of reported cases. We detected wide geographical spread coupled with undetected community transmission, characterised by the apparent extinction and reappearance of genomically linked clusters. We also identified the emergence, and near replacement, of genomes possessing a 10-nucleotide frameshift deletion that caused the likely truncation of accessory protein ORF7a. By early October, New Zealand moved from elimination to suppression and the role of genomics changed markedly from being used to track and trace, towards population-level surveillance.
Subject(s)
COVID-19ABSTRACT
There have been thirteen known COVID-19 community outbreaks in Aotearoa New Zealand since the virus was first eliminated in May 2020, two of which led to stay-at-home orders being issued by health officials. These outbreaks originated at the border; via isolating returnees, airline workers, and cargo vessels. With a public health system informed by real-time viral genomic sequencing which typically had complete genomes within 12 hours after a community-based positive COVID-19 test, every outbreak was well-contained with a total of 225 community cases, resulting in three deaths. Real-time genomics were essential for establishing links between cases when epidemiological data could not, and for identifying when concurrent outbreaks had different origins. By reconstructing the viral transmission history from genomic sequences, here we recount all thirteen community outbreaks and demonstrate how genomics played a vital role in containing them.
Subject(s)
COVID-19ABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged from a zoonotic spill-over event and has led to a global pandemic. The public health response has been predominantly informed by surveillance of symptomatic individuals and contact tracing, with quarantine, and other preventive measures have then been applied to mitigate further spread. Non-traditional methods of surveillance such as genomic epidemiology and wastewater-based epidemiology (WBE) have also been leveraged during this pandemic. Genomic epidemiology uses high-throughput sequencing of SARS-CoV-2 genomes to inform local and international transmission events, as well as the diversity of circulating variants. WBE uses wastewater to analyse community spread, as it is known that SARS-CoV-2 is shed through bodily excretions. Since both symptomatic and asymptomatic individuals contribute to wastewater inputs, we hypothesized that the resultant pooled sample of population-wide excreta can provide a more comprehensive picture of SARS-CoV-2 genomic diversity circulating in a community than clinical testing and sequencing alone. In this study, we analysed 91 wastewater samples from 11 states in the USA, where the majority of samples represent Maricopa County, Arizona (USA). With the objective of assessing the viral diversity at a population scale, we undertook a single-nucleotide variant (SNV) analysis on data from 52 samples with >90% SARS-CoV-2 genome coverage of sequence reads, and compared these SNVs with those detected in genomes sequenced from clinical patients. We identified 7973 SNVs, of which 5680 were "novel" SNVs that had not yet been identified in the global clinical-derived data as of 17th June 2020 (the day after our last wastewater sampling date). However, between 17th of June 2020 and 20th November 2020, almost half of the SNVs have since been detected in clinical-derived data. Using the combination of SNVs present in each sample, we identified the more probable lineages present in that sample and compared them to lineages observed in North America prior to our sampling dates. The wastewater-derived SARS-CoV-2 sequence data indicates there were more lineages circulating across the sampled communities than represented in the clinical-derived data. Principal coordinate analyses identified patterns in population structure based on genetic variation within the sequenced samples, with clear trends associated with increased diversity likely due to a higher number of infected individuals relative to the sampling dates. We demonstrate that genetic correlation analysis combined with SNVs analysis using wastewater sampling can provide a comprehensive snapshot of the SARS-CoV-2 genetic population structure circulating within a community, which might not be observed if relying solely on clinical cases.
ABSTRACT
Background. Real-time genomic sequencing has played a major role in tracking the global spread and local transmission of SARS-CoV-2, contributing greatly to disease mitigation strategies. After effectively eliminating the virus, New Zealand experienced a second outbreak of SARS-CoV-2 in August 2020. During this August outbreak, New Zealand utilised genomic sequencing in a primary role to support its track and trace efforts for the first time, leading to a second successful elimination of the virus. Methods. We generated the genomes of 80% of the laboratory-confirmed samples of SARS-CoV-2 from New Zealand's August 2020 outbreak and compared these genomes to the available global genomic data. Findings. Genomic sequencing was able to rapidly identify that the new COVID-19 cases in New Zealand belonged to a single cluster and hence resulted from a single introduction. However, successful identification of the origin of this outbreak was impeded by substantial biases and gaps in global sequencing data. Interpretation. Access to a broader and more heterogenous sample of global genomic data would strengthen efforts to locate the source of any new outbreaks.
Subject(s)
COVID-19ABSTRACT
In October 2020, an outbreak of at least 50 COVID-19 cases was reported surrounding individuals employed at or visiting the White House. Here, we applied genomic epidemiology to investigate the origins of this outbreak. We enrolled two individuals with exposures linked to the White House COVID-19 outbreak into an IRB-approved research study and sequenced their SARS-CoV-2 infections. We find these viral sequences are highly genetically similar to each other, but are distinct from over 160,000 publicly available SARS-CoV-2 genomes, possessing 5 nucleotide mutations that differentiate this lineage from all other circulating lineages sequenced to date. We estimate this lineage has a common ancestor in the USA in April or May 2020, but its whereabouts for the past 5 to 6 months are not clear. Looking forwards, sequencing of additional community SARS-CoV-2 infections collected in the USA prior to October 2020 may reveal linked infections and shed light on its geographic ancestry. In sequencing of SARS-CoV-2 infections collected after October 2020, the relative rarity of this constellation of mutations may make it possible to identify infections that likely descend from the White House COVID-19 outbreak.
Subject(s)
COVID-19 , Severe Acute Respiratory Syndrome , InfectionsABSTRACT
BackgroundNew Zealand, Australia, Iceland, and Taiwan all saw success at controlling the first wave of the COVID-19 pandemic. As islands, they make excellent case studies for exploring the effects of international travel and human movement on the spread of COVID-19. MethodsWe employed a range of robust phylodynamic methods and genome subsampling strategies to infer the epidemiological history of SARS-CoV-2 in these four countries. We compared these results to transmission clusters identified by the New Zealand Ministry of Health by contract tracing strategies. FindingsWe estimated the effective reproduction number of COVID-19 as 1-1.4 during early stages of the pandemic, and show that it declined below 1 as human movement was restricted. We also showed that this disease was introduced many times into each country, and that introductions slowed down markedly following the reduction of international travel in mid March 2020. Finally, we confirmed that New Zealand transmission clusters identified via standard health surveillance strategies largely agree with those defined by genomic data. InterpretationWe have demonstrated how the use of genomic data and computational biology methods can assist health officials in characterising the epidemiology of viral epidemics, and for contact tracing. FundingThis research was funded by the Health Research Council of New Zealand, the Ministry of Business, Innovation, and Employment, the Royal Society of New Zealand, and the New Zealand Ministry of Health. Research in ContextO_ST_ABSEvidence before this studyC_ST_ABSOur study looks at the early months of the COVID-19 pandemic, a period in which the first wave was controlled in four "island" nations - New Zealand, Australia, Taiwan, and Iceland. All prior data used in this study was collected from late 2019 until the end of April 2020. This includes over 3000 SARS-CoV-2 genomic sequences which were collected in this period (and subsequently deposited into GISAID), as well as arrival and departure information (provided by official statistics from each country), human mobility data collected from mobile phones (by Apple), and COVID-19 case data (released by the World Health Organisation). Even early on during the COVID-19 pandemic, the properties of SARS-CoV-2 - including the reproduction number and mutation rate - were well characterised, and a range of these estimates have been covered in our article. Our Bayesian phylodynamic models, including their prior distributions, are informed by all of the above sources of information. Finally, we have incorporated all of the available information on COVID-19 transmission clusters identified by the New Zealand Ministry of Health during this period. Added value of this studyWe quantified the decline in the reproduction number of SARS-CoV-2, following the decline in human mobility, in four "island" countries. We also demonstrated how importation events of SARS-CoV-2 into each considered country declined markedly following the reduction of international travel. Our results shed a different light on these patterns because of (i) our locations of choice - the four countries had success in dealing with the first pandemic wave, with their geographic isolation contributing to cleaner signals of human mobility, and (ii) our novel and empirically driven phylodynamic model, which we built from explicitly modelling mobile phone data in the four islands. Furthermore, by crossing epidemiological against ge3nomic data, our paper quantitatively assesses the ability of contact tracing, as implemented by the New Zealand Ministry of Health (NZMH), in identifying COVID-19 transmission clusters. We find evidence for a high efficacy of the specific measures taken - and when they were taken - by the NZMH in identifying transmission clusters, considered worldwide to have been successful in its response to the pandemic. Our analyses also illustrate the power of viral genomic data in assisting contact tracing. Implications of all the available evidenceThe conclusions drawn from this research inform effective policy for locations pursuing an elimination strategy. We confirm the accuracy of standard contact tracing methods at identifying clusters and show how these methods are improved using genomic data. We demonstrate how the overseas introduction rates and domestic transmission rates of an infectious viral agent can be surveilled using genomic data, and the important role each plays in overall transmission. Specifically, we have quantified these processes for four countries and have shown that they did decline significantly following declines in human travel and mobility. The phylodynamic methods used in this work is shown to be robust and applicable to a range of scenarios where appropriate subsampling is used.
Subject(s)
COVID-19ABSTRACT
New Zealand, a geographically remote Pacific island with easily sealable borders, implemented a nation-wide lockdown of all non-essential services to curb the spread of COVID-19. New Zealand has now effectively eliminated the virus, with low numbers of new cases limited to new arrivals in managed quarantine facilities at the border. Here, we generated 649 SARS-CoV-2 genome sequences from infected patients in New Zealand with samples collected between 26 February and 22 May 2020, representing 56% of all confirmed cases in this time period. Despite its remoteness, the viruses imported into New Zealand represented nearly all of the genomic diversity sequenced from the global virus population. The proportion of D614G variants in the virus spike protein increased over time due to an increase in their importation frequency, rather than selection within New Zealand. These data also helped to quantify the effectiveness of public health interventions. For example, the effective reproductive number, Re, of New Zealands largest cluster decreased from 7 to 0.2 within the first week of lockdown. Similarly, only 19% of virus introductions into New Zealand resulted in a transmission lineage of more than one additional case. Most of the cases that resulted in a transmission lineage originated from North America, rather than from Asia where the virus first emerged or from the nearest geographical neighbour, Australia. Genomic data also helped link more infections to a major transmission cluster than through epidemiological data alone, providing probable sources of infections for cases in which the source was unclear. Overall, these results demonstrate the utility of genomic pathogen surveillance to inform public health and disease mitigation.
Subject(s)
COVID-19ABSTRACT
Since the start of the COVID-19 pandemic, an unprecedented number of genomic sequences of the causative virus (SARS-CoV-2) have been generated and shared with the scientific community. The unparalleled volume of available genetic data presents a unique opportunity to gain real-time insights into the virus transmission during the pandemic, but also a daunting computational hurdle if analysed with gold-standard phylogeographic approaches. We here describe and apply an analytical pipeline that is a compromise between fast and rigorous analytical steps. As a proof of concept, we focus on the Belgium epidemic, with one of the highest spatial density of available SARS-CoV-2 genomes. At the global scale, our analyses confirm the importance of external introduction events in establishing multiple transmission chains in the country. At the country scale, our spatially-explicit phylogeographic analyses highlight that the national lockdown had a relatively low impact on both the lineage dispersal velocity and the long-distance dispersal events within Belgium. Our pipeline has the potential to be quickly applied to other countries or regions, with key benefits in complementing epidemiological analyses in assessing the impact of intervention measures or their progressive easement.
Subject(s)
COVID-19ABSTRACT
Infecting large portions of the global population, seasonal influenza is a major burden on societies around the globe. While the global source sink dynamics of the different seasonal influenza viruses have been studied intensively, it’s local spread remains less clear. In order to improve our understanding of how influenza is transmitted on a city scale, we collected an extremely densely sampled set of influenza sequences alongside patient metadata. To do so, we sequenced influenza viruses isolated from patients of two different hospitals, as well as private practitioners in Basel, Switzerland during the 2016/2017 influenza season. The genetic sequences reveal that repeated introductions into the city drove the influenza season. We then reconstruct how the effective reproduction number changed over the course of the season. We find trends in transmission dynamics correlated positively with trends in temperature, but not relative humidity nor school holidays. Alongside the genetic sequence data that allows us to see how individual cases are connected, we gathered patient information, such as the age or household status. Zooming into the local transmission outbreaks suggests that the elderly were to a large extent infected within their own transmission network, while school children likely drove the spread within the remaining transmission network. These patterns will be valuable to plan interventions combating the spread of respiratory diseases within cities given that similar patterns are observed for other influenza seasons and cities. Author summary As shown with the current SARS-CoV-2 pandemic, respiratory diseases can quickly spread around the globe. While it can be hugely important to understand how diseases spread around the globe, local spread is most often the main driver of novel infections of respiratory diseases such as SARS-CoV-2 or influenza. We here use genetic sequence data alongside patient information to better understand what the drives the local spread of influenza by looking at the 2016/2017 influenza season in Basel, Switzerland as an example. The genetic sequence data allows us to reconstruct the how the transmission dynamics changed over the course of the season, which we correlate to changes, but not humidity or school holidays. Additionally, the genetic sequence data allows us to see how individual cases are connected. Using patient information, such as age and household status our analyses suggest that the elderly mainly transmit within their own transmission network. Additionally, they suggest that school aged children, but not pre-school aged children are important drivers of the local spread of influenza.
ABSTRACT
Following its emergence in Wuhan, China, in late November or early December 2019, the SARS-CoV-2 virus has rapidly spread throughout the world. On March 11, 2020, the World Health Organization declared Coronavirus Disease 2019 (COVID-19) a pandemic. Genome sequencing of SARS-CoV-2 strains allows for the reconstruction of transmission history connecting these infections. Here, we analyze 346 SARS-CoV-2 genomes from samples collected between 20 February and 15 March 2020 from infected patients in Washington State, USA. We found that the large majority of SARS-CoV-2 infections sampled during this time frame appeared to have derived from a single introduction event into the state in late January or early February 2020 and subsequent local spread, strongly suggesting cryptic spread of COVID-19 during the months of January and February 2020, before active community surveillance was implemented. We estimate a common ancestor of this outbreak clade as occurring between 18 January and 9 February 2020. From genomic data, we estimate an exponential doubling between 2.4 and 5.1 days. These results highlight the need for large-scale community surveillance for SARS-CoV-2 introductions and spread and the power of pathogen genomics to inform epidemiological understanding.
Subject(s)
Coronavirus Infections , Severe Acute Respiratory Syndrome , COVID-19 , InfectionsABSTRACT
The SARS-CoV-2 epidemic has rapidly spread outside China with major outbreaks occurring in Italy, South Korea and Iran. Phylogenetic analyses of whole genome sequencing data identified a distinct SARS-CoV-2 clade linked to travellers returning from Iran to Australia and New Zealand. This study highlights potential viral diversity driving the epidemic in Iran, and underscores the power of rapid genome sequencing and public data sharing to improve the detection and management of emerging infectious diseases.