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Researchers in New Zealand, the United States and Australia have demonstrated the effectiveness of real-time genomic sequencing in monitoring the reappearance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in New Zealand in August this year. .
SARS-CoV-2 is the agent responsible for the current 2019 coronavirus pandemic (COVID-19) that continues to plague the globe by posing a threat to public health and the economy.
Jemma Geoghegan of the University of Otago in Dunedin, New Zealand, and colleagues say that real-time genomic sequencing quickly identified that the new cases belonged to a single genomic lineage and were, therefore, the result of a single introduction.
Sequencing was used to inform blocking measures and to monitor and track the efforts needed to control the outbreak and allow the virus to be cleared from the community for a second time.
However, the team also says that biases and substantial gaps in global sequencing data have limited the power of genomics to successfully identify the precise origin of the August outbreak.
The researchers advise that potential sampling errors and gaps in these sequencing data should always be carefully considered when trying to identify the source of a specific SARS-CoV-2 outbreak.
They also say that access to a larger and more diverse sample of global genomic data would enhance future efforts to identify sources of new outbreaks.
A pre-printed version of the document is available on the server medRxiv*, while the article is under peer review.
a. Maximum credibility phylogenetic tree of the clade of 2,000 subsampled global genomes (1996 B.1.1.1 most recently sampled plus four non-B.1.1.1 used as outgroups) with an outer ring colored by the sampling region; b. Probability of genomes within the twin clade posterior to the August outbreak in New Zealand, color-coded based on sampling location; c. Proportion of genomes within the lineage B.1.1.1. in the global dataset over time, color-coded by sampling location.
SARS-CoV-2 Genomic Sequencing “Happened So Quickly”
Just twelve days after the first identification of SARS-CoV-2, a genome of the virus was published and by September 25th this year, more than 110,000 SARS-CoV-2 genomes have been made available to the public.
“Sequencing of the underlying genome occurred so rapidly that, for the first time during an infectious disease outbreak, it enabled real-time integration of virological and epidemiological data,” say Geoghegan and colleagues.
Real-time genomic sequencing of this data has been instrumental in informing the response to the pandemic by monitoring the global transmission and evolution of SARS-CoV-2, including identifying the number, source, and timing of introductions in different countries.
However, according to the researchers, there was significant variation between countries in the number and proportion of sequenced positive cases and published genomes.
Geoghegan and colleagues say these disparities in sequencing efforts can have important implications for data interpretation and need to be addressed with careful consideration.
The reappearance of SARS-CoV-2 in New Zealand
‘Real-time sequencing of SARS-CoV-2 genomes, however, had particular utility in monitoring the re-emergence of the virus in New Zealand,’ the team says.
After the initial outbreak in late February, SARS-CoV-2 had effectively been eliminated in the country by June, with any positive cases limited to those related to border quarantine facilities.
However, after more than 100 days of no detectable community transmission, four new cases emerged on August 12, none of which could be epidemiologically linked to any known cases.
During this second outbreak, genomic sequencing was used to support tracking and tracing efforts in the country for the first time.
Geoghegan and colleagues generated the genomes of 80% of the laboratory-confirmed SARS-CoV-2 positive samples from the new outbreak. They then compared these cases with the sequenced cases of the first outbreak and with those of the quarantine facilities.
However, no link was identified, and the team continued to compare the genomes of the new community outbreak with the global dataset.
What did they find?
Initial genomic sequencing was able to quickly identify that the new COVID-19 cases and subclusters were linked to the unique B.1.1.1 genomic lineage, thus demonstrating that the outbreak was the result of a single introduction.
However, of the countries that have so far provided SARS-CoV-2 genomic data, 40% had genomes originating from this lineage.
Phylogenetic analysis of the last B.1.1.1 championships. genomes found that those identified in Switzerland, South Africa and England in August were the closest relatives of the viruses associated with the new outbreak in New Zealand.
However, the genomic epidemiological analysis of the possible origins of the new outbreak proved inconclusive, which, according to the team, is “likely due to the lack of genomic data within the quarantine boundary structures and in the global dataset.” .
For example, twelve SARS-CoV-2 genomes of people returning to New Zealand from India who had all arrived on the same flight covered at least four genomic lineages, with sequence divergences of up to 34 genomic mutations.
‘Such a high level of diversity in only a small sample of positive cases from India suggests that the genomic data currently available fails to understand the true diversity that existed locally, let alone globally,’ say the researchers.
Real-time genomic sequencing helped New Zealand eliminate the virus a second time
However, real-time genomic sequencing following the re-emergence of the virus helped quickly inform the tracking and tracing efforts and blocking measures needed to control the outbreak, putting New Zealand on track to eliminate the virus for the second time, they add.
However, the partial nature of global sampling clearly limited the power of genomics to identify the geographic origin of the August 2020 outbreak in New Zealand, the team says.
“Therefore, we argue that careful consideration of potential sampling errors and gaps in available genomic data is made whenever attempting to determine the geographic origins of a specific SARS-CoV-2 outbreak,” write Geoghegan and colleagues. “The analysis should consider all available evidence, including genomic and epidemiological sources.”
*Important Notice
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be considered conclusive, guide clinical practice / health-related behaviors, or treated as consolidated information.
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