The origin and early spread of SARS-CoV-2 in Europe
TL;DR: A view on the early state of the epidemic in Europe and on migration patterns of the virus before border closures is offered, including inferences of the geographic location of ancestral lineages and the number of migration events into and between European regions.
Abstract: The investigation of migratory patterns of the SARS-CoV-2 pandemic before border closures in Europe is a crucial first step towards an in-depth evaluation of border closure policies. Here we analyze viral genome sequences using a phylodynamic model with geographic structure to estimate the origin and spread of SARS-CoV-2 in Europe prior to border closures. Based on SARS-CoV-2 genomes, we reconstruct a partial transmission tree of the early pandemic, including inferences of the geographic location of ancestral lineages and the number of migration events into and between European regions. We find that the predominant lineage spreading in Europe has a most recent common ancestor in Italy and was probably seeded by a transmission event in either Hubei or Germany. We do not find evidence for preferential migration paths from Hubei into different European regions or from each European region to the others. Sustained local transmission is first evident in Italy and then shortly thereafter in the other European regions considered. Before the first border closures in Europe, we estimate that the rate of occurrence of new cases from within-country transmission was within the bounds of the estimated rate of new cases from migration. In summary, our analysis offers a view on the early state of the epidemic in Europe and on migration patterns of the virus before border closures. This information will enable further study of the necessity and timeliness of border closures. Significance Statement We estimate the origin and spread of SARS-CoV-2 in Europe prior to border closures based on viral genome sequences using a phylodynamic model with geographic structure. We confirm that the predominant European outbreak most likely started in Italy and spread from there. This outbreak was probably seeded by a transmission event in either Hubei or Germany. In particular, we find that before the first border closures in Europe, the rate of new cases occurring from within-country transmission was within the estimated bounds on the rate of new migration cases.
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TL;DR: The United Kingdom's COVID-19 epidemic during early 2020 was one of world's largest and was unusually well represented by virus genomic sampling as mentioned in this paper, which determined the fine-scale genetic lineage structure of this epidemic through analysis of 50,887 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes, including 26,181 from the UK sampled throughout the country's first wave of infection.
Abstract: The United Kingdom’s COVID-19 epidemic during early 2020 was one of world’s largest and was unusually well represented by virus genomic sampling. We determined the fine-scale genetic lineage structure of this epidemic through analysis of 50,887 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes, including 26,181 from the UK sampled throughout the country’s first wave of infection. Using large-scale phylogenetic analyses combined with epidemiological and travel data, we quantified the size, spatiotemporal origins, and persistence of genetically distinct UK transmission lineages. Rapid fluctuations in virus importation rates resulted in >1000 lineages; those introduced prior to national lockdown tended to be larger and more dispersed. Lineage importation and regional lineage diversity declined after lockdown, whereas lineage elimination was size-dependent. We discuss the implications of our genetic perspective on transmission dynamics for COVID-19 epidemiology and control.
285 citations
TL;DR: The winners will be announced at a special ceremony in New York later this month.
135 citations
TL;DR: The fine-scale genetic lineage structure of this epidemic is revealed through analysis of 50,887 SARS-CoV-2 genomes, including 26,181 from the UK sampled throughout the country's first wave of infection.
Abstract: The UK’s COVID-19 epidemic during early 2020 was one of world’s largest and unusually well represented by virus genomic sampling. Here we reveal the fine-scale genetic lineage structure of this epidemic through analysis of 50,887 SARS-CoV-2 genomes, including 26,181 from the UK sampled throughout the country’s first wave of infection. Using large-scale phylogenetic analyses, combined with epidemiological and travel data, we quantify the size, spatio-temporal origins and persistence of genetically-distinct UK transmission lineages. Rapid fluctuations in virus importation rates resulted in >1000 lineages; those introduced prior to national lockdown were larger and more dispersed. Lineage importation and regional lineage diversity declined after lockdown, whilst lineage elimination was size-dependent. We discuss the implications of our genetic perspective on transmission dynamics for COVID-19 epidemiology and control.
133 citations
TL;DR: In this paper , the authors describe how phylogenetic and phylodynamic methods provide insight into viral evolution, focusing on the SARS-CoV-2 pandemic, and summarize their contributions to our understanding of SARS transmission and control.
Abstract: Determining the transmissibility, prevalence and patterns of movement of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections is central to our understanding of the impact of the pandemic and to the design of effective control strategies. Phylogenies (evolutionary trees) have provided key insights into the international spread of SARS-CoV-2 and enabled investigation of individual outbreaks and transmission chains in specific settings. Phylodynamic approaches combine evolutionary, demographic and epidemiological concepts and have helped track virus genetic changes, identify emerging variants and inform public health strategy. Here, we review and synthesize studies that illustrate how phylogenetic and phylodynamic techniques were applied during the first year of the pandemic, and summarize their contributions to our understanding of SARS-CoV-2 transmission and control. In this Review, the authors describe how phylogenetic and phylodynamic methods provide insight into viral evolution, focusing on the SARS-CoV-2 pandemic. The approaches reveal routes and timings of transmission events, and they can assess the effectiveness of various intervention measures aimed at controlling the virus.
52 citations
TL;DR: It is estimated that the sampled viral diversity has originated from 67 closely timed introductions into Russia, mostly in late February to early March, suggesting that border closure with China has helped delay establishment of SARS-CoV-2 in Russia.
Abstract: The ongoing pandemic of SARS-CoV-2 presents novel challenges and opportunities for the use of phylogenetics to understand and control its spread. Here, we analyze the emergence of SARS-CoV-2 in Russia in March and April 2020. Combining phylogeographic analysis with travel history data, we estimate that the sampled viral diversity has originated from 67 closely timed introductions into Russia, mostly in late February to early March. All but one of these introductions came from non-Chinese sources, suggesting that border closure with China has helped delay establishment of SARS-CoV-2 in Russia. These introductions resulted in at least 9 distinct Russian lineages corresponding to domestic transmission. A notable transmission cluster corresponded to a nosocomial outbreak at the Vreden hospital in Saint Petersburg; phylodynamic analysis of this cluster reveals multiple (2-4) introductions each giving rise to a large number of cases, with a high initial effective reproduction number of 3.7 (2.5-5.0).
36 citations
References
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TL;DR: Phylogenetic and metagenomic analyses of the complete viral genome of a new coronavirus from the family Coronaviridae reveal that the virus is closely related to a group of SARS-like coronaviruses found in bats in China.
Abstract: Emerging infectious diseases, such as severe acute respiratory syndrome (SARS) and Zika virus disease, present a major threat to public health1–3. Despite intense research efforts, how, when and where new diseases appear are still a source of considerable uncertainty. A severe respiratory disease was recently reported in Wuhan, Hubei province, China. As of 25 January 2020, at least 1,975 cases had been reported since the first patient was hospitalized on 12 December 2019. Epidemiological investigations have suggested that the outbreak was associated with a seafood market in Wuhan. Here we study a single patient who was a worker at the market and who was admitted to the Central Hospital of Wuhan on 26 December 2019 while experiencing a severe respiratory syndrome that included fever, dizziness and a cough. Metagenomic RNA sequencing4 of a sample of bronchoalveolar lavage fluid from the patient identified a new RNA virus strain from the family Coronaviridae, which is designated here ‘WH-Human 1’ coronavirus (and has also been referred to as ‘2019-nCoV’). Phylogenetic analysis of the complete viral genome (29,903 nucleotides) revealed that the virus was most closely related (89.1% nucleotide similarity) to a group of SARS-like coronaviruses (genus Betacoronavirus, subgenus Sarbecovirus) that had previously been found in bats in China5. This outbreak highlights the ongoing ability of viral spill-over from animals to cause severe disease in humans. Phylogenetic and metagenomic analyses of the complete viral genome of a new coronavirus from the family Coronaviridae reveal that the virus is closely related to a group of SARS-like coronaviruses found in bats in China.
9,231 citations
"The origin and early spread of SARS..." refers background in this paper
...Its characteristic ORF1b mutation was found in some of the earliest confirmed COVID-19 cases in Italy, Switzerland, Germany, Finland, Mexico, and Brazil in late February (14, 15)....
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...The SARS-CoV-2 virus was identified as the cause of an epidemic in Wuhan, China in late 2019 (3)....
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...The origin and early spread of SARS-CoV-2 in Europe Sarah A. Nadeau1,2, Timothy G. Vaughan1,2, Jérémie Sciré1,2, Jana S. Huisman1,2,3, Tanja Stadler1,2* 1 Department of Biosystems Science and Engineering, ETH Zürich, Mattenstrasse 26, 4058 Basel, Switzerland 2 Swiss Institute of Bioinformatics 3 Department of Environmental Systems Science, ETH Zürich, Universitätstrasse 16, 8092 Zürich, Switzerland * Corresponding Author Tanja Stadler tanja.stadler@bsse.ethz.ch +41 61 387 34 10...
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...Other European 41 Spain (18), Netherlands (4), United Kingdom (4), Switzerland (3), Belgium (1), Czech Republic (1), Denmark (1), Finland (1), Iceland (1), Ireland (1), Luxembourg (1), Norway (1), Poland (1), Portugal (1), Slovakia (1), Sweden (1) 07....
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...Italy 13 Italy 29.01.2020 04.03.2020 Other European 41 Spain (18), Netherlands (4), United Kingdom (4), Switzerland (3), Belgium (1), Czech Republic (1), Denmark (1), Finland (1), Iceland (1), Ireland (1), Luxembourg (1), Norway (1), Poland (1), Portugal (1), Slovakia (1), Sweden (1) 07.02.2020 08.03.2020...
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TL;DR: The software package Tracer is presented, for visualizing and analyzing the MCMC trace files generated through Bayesian phylogenetic inference, which provides kernel density estimation, multivariate visualization, demographic trajectory reconstruction, conditional posterior distribution summary, and more.
Abstract: Bayesian inference of phylogeny using Markov chain Monte Carlo (MCMC) plays a central role in understanding evolutionary history from molecular sequence data. Visualizing and analyzing the MCMC-generated samples from the posterior distribution is a key step in any non-trivial Bayesian inference. We present the software package Tracer (version 1.7) for visualizing and analyzing the MCMC trace files generated through Bayesian phylogenetic inference. Tracer provides kernel density estimation, multivariate visualization, demographic trajectory reconstruction, conditional posterior distribution summary, and more. Tracer is open-source and available at http://beast.community/tracer.
5,492 citations
"The origin and early spread of SARS..." refers methods in this paper
...We used Tracer (22) to assess the convergence and confirm that ESS was > 200 for all parameters....
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TL;DR: The results suggest that early detection, hand washing, self-isolation, and household quarantine will likely be more effective than travel restrictions at mitigating this pandemic, and sustained 90% travel restrictions to and from mainland China only modestly affect the epidemic trajectory unless combined with a 50% or higher reduction of transmission in the community.
Abstract: Motivated by the rapid spread of coronavirus disease 2019 (COVID-19) in mainland China, we use a global metapopulation disease transmission model to project the impact of travel limitations on the national and international spread of the epidemic. The model is calibrated on the basis of internationally reported cases and shows that, at the start of the travel ban from Wuhan on 23 January 2020, most Chinese cities had already received many infected travelers. The travel quarantine of Wuhan delayed the overall epidemic progression by only 3 to 5 days in mainland China but had a more marked effect on the international scale, where case importations were reduced by nearly 80% until mid-February. Modeling results also indicate that sustained 90% travel restrictions to and from mainland China only modestly affect the epidemic trajectory unless combined with a 50% or higher reduction of transmission in the community.
2,949 citations
TL;DR: The authors' review found the average R0 for 2019-nCoV to be 3.28, which exceeds WHO estimates of 1.4 to 2.5, and is higher than expected.
Abstract: Teaser: Our review found the average R0 for 2019-nCoV to be 3.28, which exceeds WHO estimates of 1.4 to 2.5.
2,664 citations
TL;DR: On 5 February 2020, in Yokohama, Japan, a cruise ship hosting 3,711 people underwent a 2-week quarantine after a former passenger was found with COVID-19 post-disembarking, and the delay-adjusted asymptomatic proportion of infections, along with the infections’ timeline were derived.
Abstract: On 5 February 2020, in Yokohama, Japan, a cruise ship hosting 3,711 people underwent a 2-week quarantine after a former passenger was found with COVID-19 post-disembarking. As at 20 February, 634 persons on board tested positive for the causative virus. We conducted statistical modelling to derive the delay-adjusted asymptomatic proportion of infections, along with the infections' timeline. The estimated asymptomatic proportion was 17.9% (95% credible interval (CrI): 15.5-20.2%). Most infections occurred before the quarantine start.
2,195 citations