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Researchers have revealed the fine-scale genetic lineage structure of the coronavirus disease 2019 (COVID-19) epidemic in the UK earlier this year, when severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ) swept the country for the first time.
By analyzing 50,887 SARS-CoV-2 genomes, the team has provided insights into the microepidemiological patterns underlying the characteristics of one of the largest national COVID-19 epidemics in the world.
Researchers from the UK and Canada say the exceptional size of their genomic study enabled them to quantify the abundance, size distribution and spatial range of SARS-CoV-2 transmission lineages in the UK during the first half of the year. 2020.
Such information can provide a new context for planning and evaluating future public health interventions, whether at the regional, national or international level.
A pre-printed version of the paper is available on the server. medRxiv *, while the article undergoes peer review.
Structure and dynamics of the UK transmission lineages. (A) Collection dates of the 50,887 genomes analyzed here (left axis). Genomes are colored based on sampling location (England = red, Scotland = dark blue, Wales = yellow, Northern Ireland = light blue, elsewhere = gray). The solid line shows the cumulative number of UK virus genomes (right axis). The dashed and dotted lines show, respectively, the cumulative number of UK laboratory confirmed cases (by sample date) and the estimated number of infections in the UK (17; gray shading = 95% CI; axis right). Due to retrospective screening, the cumulative number of genomes at the beginning of the epidemic exceeds that of confirmed cases. (B) UK transmission lineage size distribution. The blue bars show the number of transmission lineages of each size (red bars = 95% HPD of these sizes in the posterior tree distribution). Inset: the corresponding cumulative frequency distribution of the lineage size (blue line), on double logarithmic axes (red shading = 95% HPD of this distribution across the posterior tree distribution). The values on both sides of the vertical dashed line show coefficients of power law distributions (P[X ³ x] ~ xa) matched to lineages containing ≤50 (a 1) and> 50 (a 2) virus genomes, respectively. (C) Partition of 26,181 UK genomes into UK transmission lineages and singletons, colored by (i) lineage, for the 8 largest lineages, or (ii) duration of lineage detection (time between genomes most older and more recent lineage) for the rest. (D) Lineage size breakdown of UK genomes collected each week. The colors of the 8 largest lineages are those shown in (C). (E) Trends over time in the detection of UK transmission lineages. For each day, all lineages detected up to that day are colored by the time elapsed since the transmission lineage was last sampled. The isoclines correspond to weeks. Shaded area = transmission lineages that were first sampled <1 week ago. The red arrow indicates the start of the UK lockdown. (F) Red line=daily rate of detecting new transmission lineages. Blue line=rate at which lineages have not been observed for >4 weeks.
Viruses can be tracked by large-scale genome sequencing
Infectious disease epidemics are made up of multiple transmission chains, but very little is known about how co-circulating transmission lineages differ in size, persistence, and distribution. Similarly, little is known about how the combined actions of these lineages contribute to important factors such as the size and duration of an epidemic.
However, recent studies of some viruses, including Ebola, Zika, and influenza, have shown that the emergence and spread of viruses can be tracked by large-scale genome sequencing.
These studies have shown how highly dynamic regional epidemics can be at the genetic level, with recurrent importation and extinction of transmission chains that coexist within a given location, say Oliver Pybus (University of Oxford) and his team.
“In addition to measuring genetic diversity, understanding pathogen lineage dynamics can help target interventions effectively, track variants with potentially different phenotypes, and improve interpretation of incidence data,” they add.
The COVID-19 epidemic experienced in the UK in early 2020 was one of the most extensive and best represented through genomic sampling.
The number of new SARS-CoV-2 infections increased during March, peaked in April, and by June 26, 40,453 people had died from COVID-19.
What did the researchers do?
Pybus and his colleagues combined an analysis of 50,887 SARS-CoV-2 genomes (including 26,181 from the UK during the first wave of infection) with epidemiological and travel data to characterize the genetic makeup and lineage dynamics of the UK epidemic. United.
Before the lockdown at home, high travel volumes and little restriction on overseas arrivals had resulted in the establishment and co-circulation of over 1,000 identifiable transmission lineages in the UK.
The lineages introduced before the closure were larger and more dispersed.
The eight largest lineages were first detected before the March 23 shutdown.rd, and these larger lineages persisted longer.
The detection of UK transmission lineages changed significantly over time. In early March, the epidemic was characterized by lineages that had been observed for the first time during the previous week. By June 1S tOn the other hand, more than 73% had not been detected for more than 4 weeks, indicating that they were rare or had become extinct.
These results suggest that the first epidemic wave was due to the simultaneous growth of many transmission lineages that had been introduced into the UK independently, the team says. They also suggest that the implementation of non-pharmaceutical interventions was followed by lineage extinction in a size-dependent manner.
Spatial distribution of the UK transmission lineages
The study revealed that larger lineages were seen in more places, indicating that they were more spread out geographically. With every 100 additional genomes in a transmission lineage, their range increased from 6 to 7 regions.
“These observations indicate a substantial spread of a subset of lineages in the UK and suggest that many regions experienced a number of introductions of new lineages from elsewhere, which could hamper the impact of local interventions,” say Pybus and colleagues. .
Investigating the introduction of lineages
To investigate how transmission lineages were introduced into the UK, the team estimated the rate and origin of SARS-CoV-2 imports into the country.
The researchers say that the import was surprisingly dynamic, rising and falling dramatically over the course of just 4 weeks. Eighty percent of the imports that resulted in detectable transmissions occurred between February 27 and March 30.
Analysis of country-specific contributions to virus imports showed that the relative contributions of international arrivals were also very dynamic.
The dominant font locations changed rapidly during February and March, and the font locations became more diverse in mid-March.
“The first imports were probably from China or elsewhere in Asia, but they were rare compared to Europe,” say the researchers.
What are the implications of the study?
The team says that older lineages, which are larger, more dispersed and more difficult to eliminate, emphasize the importance of prompt or preventive interventions to reduce transmission.
Although the UK blockade coincided with import restrictions and a reduced diversity of regional lineages, any resulting extinctions of the transmission lineages were dependent on size.
The overly dispersed nature of SARS-CoV-2 transmission likely exacerbated this effect, say Pybus and his colleagues, thus favoring longer survival of the largest and most widespread lineages and faster elimination of locals in low-lying regions. prevalence.
“The extent to which the surviving lineages contributed to the UK’s second ongoing epidemic is currently under investigation,” the researchers write.
“The structure and dynamics of transmission measured here provide a new context in which future public health actions must be planned and evaluated at a regional, national and international scale,” they add.
*Important news
medRxiv publishes preliminary scientific reports that are not peer-reviewed and therefore should not be considered conclusive, guide clinical practice / health-related behavior, or be treated as established information.
