Large scale sequencing of SARS-CoV-2 genomes from one region allows detailed epidemiology and enables local outbreak management

Page, Andrew J.; Mather, Alison E.; Viet, Thanh Le; Meader, Emma; Alikhan, Nabil-Fareed; Kay, Gemma L.; Martins, Leonardo de Oliveira; Aydin, Alp; Baker, Dave; Trotter, Alexander J.; Rudder, Steven; Tedim, Ana P.; Kolyva, Anastasia; Stanley, Rachael; Díaz, María; Potter, Will; Stuart, Claire; Meadows, Lizzie; Bell, Andrew; Gutiérrez, Ana Victoria; Thomson, Nicholas M.; Adriaenssens, Evelien M.; Swingler, T.E.; Gilroy, Rachel; Griffith, Luke; Sethi, Dheeraj K; Davidson, Rose K.; Kingsley, Robert A.; Bedford, Luke; Coupland, Lindsay; Charles, Ian G.; Elumogo, Ngozi; Wain, John; Prakash, Reenesh; Webber, Mark A.; Smith, S. J. Louise; Chand, Meera; Dervisevic, Samir; O’Grady, Justin

doi:10.1101/2020.09.28.20201475

Cited by 22 publications

(19 citation statements)

References 37 publications

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“…The presence of lineage A viruses from lethal and community cases throughout Uganda indicates that this lineage is circulating in Uganda and capable of producing a severe infection. Several variant lineages were observed at low frequencies and only briefly and may have undergone apparent extinction, similar to patterns observed in the UK (12) and Scotland (13).…”

Section: Main Textsupporting

confidence: 70%

“…A number of A and B variant lineages were observed briefly at low frequencies and may have undergone extinction, similar to patterns observed in the UK (11) and Scotland (12). Genomes identified from a truck driver are often observed basal to community clusters (Figure 2), suggesting the importance of this route in the introduction and spread of the virus into Uganda.…”

Section: Main Textsupporting

confidence: 68%

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A SARS-CoV-2 lineage A variant (A.23.1) with altered spike has emerged and is dominating the current Uganda epidemic

Phan

Ssewanyana³

et al. 2021

Preprint

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The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) was first detected in March 2020 in Uganda. Recently the epidemic showed a shift of SARS-CoV-2 variant distribution and we report here newly emerging A sub-lineages, A.23 and A.23.1, encoding replacements in the spike protein, nsp6, ORF8 and ORF9, with A.23.1 the major virus lineage now observed in Kampala. Although the clinical impact of the A.23.1 variant is not yet clear it is essential to continue careful monitoring of this variant, as well as rapid assessment of the consequences of the spike protein changes for vaccine efficacy.

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Section: Main Textsupporting

confidence: 70%

Section: Main Textsupporting

confidence: 68%

A SARS-CoV-2 lineage A variant (A.23.1) with altered spike has emerged and is dominating the current Uganda epidemic

Phan

Ssewanyana³

et al. 2021

Preprint

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“…2,3 Since the first full SARS-CoV-2 genome was published in January 2020 4 , sequencing of specimens from COVID-19 patients has allowed tracking of viral spread and identification of novel strains. [5][6][7][8][9][10][11] Seminal work early in the pandemic demonstrated how SARS-CoV-2 had entered Washington state in the US 2 , with most early infections linked to a single introduction in late January or early February. In Northern California, analysis of 36 early samples demonstrated that there were multiple points of entry.…”

Section: Introductionmentioning

confidence: 99%

Genomic surveillance at scale is required to detect newly emerging strains at an early timepoint

Vavrek

Speroni

Curnow

et al. 2021

Preprint

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Genomic surveillance in the setting of the coronavirus disease 2019 (COVID-19) pandemic has the potential to identify emerging SARS-CoV-2 strains that may be more transmissible, virulent, evade detection by standard diagnostic tests, or vaccine escapes. The rapid spread of the SARS-CoV-2 B.1.1.7 strain from southern England to other parts of the country and globe is a clear example of the impact of such strains. Early discovery of the B.1.1.7 strain was enabled through the proactive COVID-19 Genomics UK (COG-UK) program and the UK’s commitment to genomic surveillance, sequencing about 10% of positive samples.1 In order to enact more aggressive public health measures to minimize the spread of such strains, genomic surveillance needs to be of sufficient scale to detect early emergence and expansion in the broader virus population. By modeling common performance characteristics of available diagnostic and sequencing tests, we developed a model that assesses the sampling required to detect emerging strains when they are less than 1% of all strains in a population. This model demonstrates that 5% sampling of all positive tests allows the detection of emerging strains when they are a prevalence of 0.1% to 1.0%. While each country will determine their risk tolerance for the emergence of novel strains, as vaccines are distributed and we work to end the pandemic and prevent future SARS-CoV-2 outbreaks, genomic surveillance will be an integral part of success.

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“…A concentrated, ongoing, local approach to genomic surveillance is critical for the identification of variants and establishing epidemiological links with the trend of the outbreak 5,7,12,22 . This has also proved critical for local outbreak management and informed policy decisions across the world 5,7,37,38 .…”

Section: Introductionmentioning

confidence: 99%

Importation, circulation, and emergence of variants of SARS-CoV-2 in the South Indian State of Karnataka

Pattabiraman

Prasad

George

et al. 2021

Preprint

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As the pandemic of COVID-19 caused by the coronavirus SARS-CoV-2 continues, the selection of genomic variants which can influence how the pandemic progresses is of growing concern. Of particular concern, are those variants that carry mutations/amino acid changes conferring higher transmission, more severe disease, re-infection, and immune escape. These can broadly be classified as Variants of Concern (VOCs). VOCs have been reported from several parts of the world- UK (lineage B.1.1.7), South Africa (lineage B.1.351) and, Brazil (lineage P.1/B.1.1.28). The conditions that contribute to the emergence of VOCs are not well understood. International travel remains an important means of spread. To track importation, spread, and the emergence of variants locally; we sequenced whole genomes of SARS-CoV-2 from international travellers (n=75) entering Karnataka, a state in South India, between Dec 22, 2020- Jan 31, 2021, and from positive cases in the city of Bengaluru (n=108), between Nov 22, 2020- Jan 22, 2021. The resulting 176 SARS-CoV-2 genomes could be classified into 34 lineages, that were either imported (73/176) or circulating (103/176) in this time period. The lineage B.1.1.7 (a.k.a the UK variant) was the major lineage imported into the state (24/73, 32.9%), followed by B.1.36 (20/73, 27.4%) and B.1 (14/73, 19.2%). We identified B.1.36 (45/103; 43.7%), B.1 (26/103; 25.2%), B.1.1.74 (5/103; 4.9%) and B.1.468 (4/103; 3.9%) as the major variants circulating in Bengaluru city. A distinct clade within the B.1.36 lineage was associated with a local outbreak. Analysis of the complete genomes predicted multiple amino acid replacements in the Spike protein. In total, we identified nine amino acid changes (singly or in pairs) in the Receptor Binding Domain of the Spike protein. Of these, the amino acid replacement N440K was found in 37/65 (56.92%) sequences in the B.1.36 lineage. The E484K amino acid change which is present in both VOCs, B.1.351 and P.1/B.1.1.28, was found in a single circulating virus in the B.1.36 lineage. This study highlights the introduction of VOCs by travel and the local circulation of viruses with amino acid replacements in the Spike protein. These were spread across lineages, suggesting that multiple paths can lead to the emergence of VOCs, this, in turn, highlights the need to sequence and limit outbreaks of SARS-CoV-2 locally. Our data support the use of concentrated and continued genomic surveillance of SARS-CoV-2 to direct public health measures, suggest revisions to vaccines, and serve as an early warning system to prepare for a surge in COVID-19 cases.

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Large scale sequencing of SARS-CoV-2 genomes from one region allows detailed epidemiology and enables local outbreak management

Cited by 22 publications

References 37 publications

A SARS-CoV-2 lineage A variant (A.23.1) with altered spike has emerged and is dominating the current Uganda epidemic

A SARS-CoV-2 lineage A variant (A.23.1) with altered spike has emerged and is dominating the current Uganda epidemic

Genomic surveillance at scale is required to detect newly emerging strains at an early timepoint

Importation, circulation, and emergence of variants of SARS-CoV-2 in the South Indian State of Karnataka

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