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1.
Virus Evolution ; 8(2), 2022.
Article in English | Web of Science | ID: covidwho-1997080

ABSTRACT

The emergence and global dissemination of Severe Acute Respiratory Syndrome virus 2 (SARS-CoV-2) variants of concern (VOCs) have been described as the main factor driving the Coronavirus Disease 2019 pandemic. In Brazil, the Gamma variant dominated the epidemiological scenario during the first period of 2021. Many Brazilian regions detected the Delta variant after its first description and documented its spread. To monitor the introduction and spread of VOC Delta, we performed Polymerase Chain Reaction (PCR) genotyping and genome sequencing in ten regional sentinel units from June to October 2021 in the State of Minas Gerais (MG). We documented the introduction and spread of Delta, comprising 70 per cent of the cases 8 weeks later. Comparing the viral loads of the Gamma and Delta dominance periods, we provide additional evidence that the latter is more transmissible. The spread and dominance of Delta did not culminate in the increase in cases and deaths, suggesting that the vaccination may have restrained the epidemic growth. Analysis of 224 novel Delta genomes revealed that Rio de Janeiro state was the primary source for disseminating this variant in the state of MG. We present the establishment of Delta, providing evidence of its enhanced transmissibility and showing that this variant shift did not aggravate the epidemiological scenario in a high immunity setting.

2.
PubMed; 2021.
Preprint in English | PubMed | ID: ppcovidwho-334727

ABSTRACT

The SARS-CoV-2 Gamma variant spread rapidly across Brazil, causing substantial infection and death waves. We use individual-level patient records following hospitalisation with suspected or confirmed COVID-19 to document the extensive shocks in hospital fatality rates that followed Gamma's spread across 14 state capitals, and in which more than half of hospitalised patients died over sustained time periods. We show that extensive fluctuations in COVID-19 in-hospital fatality rates also existed prior to Gamma's detection, and were largely transient after Gamma's detection, subsiding with hospital demand. Using a Bayesian fatality rate model, we find that the geographic and temporal fluctuations in Brazil's COVID-19 in-hospital fatality rates are primarily associated with geographic inequities and shortages in healthcare capacity. We project that approximately half of Brazil's COVID-19 deaths in hospitals could have been avoided without pre-pandemic geographic inequities and without pandemic healthcare pressure. Our results suggest that investments in healthcare resources, healthcare optimization, and pandemic preparedness are critical to minimize population wide mortality and morbidity caused by highly transmissible and deadly pathogens such as SARS-CoV-2, especially in low- and middle-income countries. NOTE: The following manuscript has appeared as 'Report 46 - Factors driving extensive spatial and temporal fluctuations in COVID-19 fatality rates in Brazilian hospitals' at https://spiral.imperial.ac.uk:8443/handle/10044/1/91875 . ONE SENTENCE SUMMARY: COVID-19 in-hospital fatality rates fluctuate dramatically in Brazil, and these fluctuations are primarily associated with geographic inequities and shortages in healthcare capacity.

3.
PubMed; 2021.
Preprint in English | PubMed | ID: ppcovidwho-330706

ABSTRACT

With the emergence of SARS-CoV-2 variants that may increase transmissibility and/or cause escape from immune responses 1-3 , there is an urgent need for the targeted surveillance of circulating lineages. It was found that the B.1.1.7 (also 501Y.V1) variant first detected in the UK 4,5 could be serendipitously detected by the ThermoFisher TaqPath COVID-19 PCR assay because a key deletion in these viruses, spike DELTA69-70, would cause a "spike gene target failure" (SGTF) result. However, a SGTF result is not definitive for B.1.1.7, and this assay cannot detect other variants of concern that lack spike DELTA69-70, such as B.1.351 (also 501Y.V2) detected in South Africa 6 and P.1 (also 501Y.V3) recently detected in Brazil 7 . We identified a deletion in the ORF1a gene (ORF1a DELTA3675-3677) in all three variants, which has not yet been widely detected in other SARS-CoV-2 lineages. Using ORF1a DELTA3675-3677 as the primary target and spike DELTA69-70 to differentiate, we designed and validated an open source PCR assay to detect SARS-CoV-2 variants of concern 8 . Our assay can be rapidly deployed in laboratories around the world to enhance surveillance for the local emergence spread of B.1.1.7, B.1.351, and P.1.

4.
Science ; 372(6544):815-821, 2021.
Article in English | EMBASE | ID: covidwho-1735994

ABSTRACT

Cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Manaus, Brazil, resurged in late 2020 despite previously high levels of infection. Genome sequencing of viruses sampled in Manaus between November 2020 and January 2021 revealed the emergence and circulation of a novel SARS-CoV-2 variant of concern. Lineage P.1 acquired 17 mutations, including a trio in the spike protein (K417T, E484K, and N501Y) associated with increased binding to the human ACE2 (angiotensin-converting enzyme 2) receptor. Molecular clock analysis shows that P.1 emergence occurred around mid-November 2020 and was preceded by a period of faster molecular evolution. Using a two-category dynamical model that integrates genomic and mortality data, we estimate that P.1 may be 1.7- to 2.4-fold more transmissible and that previous (non-P.1) infection provides 54 to 79% of the protection against infection with P.1 that it provides against non-P.1 lineages. Enhanced global genomic surveillance of variants of concern, which may exhibit increased transmissibility and/or immune evasion, is critical to accelerate pandemic responsiveness.

5.
McCrone, J. T.; Hill, V.; Bajaj, S.; Pena, R. E.; Lambert, B. C.; Inward, R.; Bhatt, S.; Volz, E.; Ruis, C.; Dellicour, S.; Baele, G.; Zarebski, A. E.; Sadilek, A.; Wu, N.; Schneider, A.; Ji, X.; Raghwani, J.; Jackson, B.; Colquhoun, R.; O'Toole, Á, Peacock, T. P.; Twohig, K.; Thelwall, S.; Dabrera, G.; Myers, R.; Faria, N. R.; Huber, C.; Bogoch, I. I.; Khan, K.; du Plessis, L.; Barrett, J. C.; Aanensen, D. M.; Barclay, W. S.; Chand, M.; Connor, T.; Loman, N. J.; Suchard, M. A.; Pybus, O. G.; Rambaut, A.; Kraemer, M. U. G.; Robson, S. C.; Connor, T. R.; Loman, N. J.; Golubchik, T.; Martinez Nunez, R. T.; Bonsall, D.; Rambaut, A.; Snell, L. B.; Livett, R.; Ludden, C.; Corden, S.; Nastouli, E.; Nebbia, G.; Johnston, I.; Lythgoe, K.; Estee Torok, M.; Goodfellow, I. G.; Prieto, J. A.; Saeed, K.; Jackson, D. K.; Houlihan, C.; Frampton, D.; Hamilton, W. L.; Witney, A. A.; Bucca, G.; Pope, C. F.; Moore, C.; Thomson, E. C.; Harrison, E. M.; Smith, C. P.; Rogan, F.; Beckwith, S. M.; Murray, A.; Singleton, D.; Eastick, K.; Sheridan, L. A.; Randell, P.; Jackson, L. M.; Ariani, C. V.; Gonçalves, S.; Fairley, D. J.; Loose, M. W.; Watkins, J.; Moses, S.; Nicholls, S.; Bull, M.; Amato, R.; Smith, D. L.; Aanensen, D. M.; Barrett, J. C.; Aggarwal, D.; Shepherd, J. G.; Curran, M. D.; Parmar, S.; Parker, M. D.; Williams, C.; Glaysher, S.; Underwood, A. P.; Bashton, M.; Pacchiarini, N.; Loveson, K. F.; Byott, M.; Carabelli, A. M.; Templeton, K. E.; de Silva, T. I.; Wang, D.; Langford, C. F.; Sillitoe, J.; Gunson, R. N.; Cottrell, S.; O'Grady, J.; Kwiatkowski, D.; Lillie, P. J.; Cortes, N.; Moore, N.; Thomas, C.; Burns, P. J.; Mahungu, T. W.; Liggett, S.; Beckett, A. H.; Holden, M. T. G.; Levett, L. J.; Osman, H.; Hassan-Ibrahim, M. O.; Simpson, D. A.; Chand, M.; Gupta, R. K.; Darby, A. C.; Paterson, S.; Pybus, O. G.; Volz, E. M.; de Angelis, D.; Robertson, D. L.; Page, A. J.; Martincorena, I.; Aigrain, L.; Bassett, A. R.; Wong, N.; Taha, Y.; Erkiert, M. J.; Spencer Chapman, M. H.; Dewar, R.; McHugh, M. P.; Mookerjee, S.; Aplin, S.; Harvey, M.; Sass, T.; Umpleby, H.; Wheeler, H.; McKenna, J. P.; Warne, B.; Taylor, J. F.; Chaudhry, Y.; Izuagbe, R.; Jahun, A. S.; Young, G. R.; McMurray, C.; McCann, C. M.; Nelson, A.; Elliott, S.; Lowe, H.; Price, A.; Crown, M. R.; Rey, S.; Roy, S.; Temperton, B.; Shaaban, S.; Hesketh, A. R.; Laing, K. G.; Monahan, I. M.; Heaney, J.; Pelosi, E.; Silviera, S.; Wilson-Davies, E.; Fryer, H.; Adams, H.; du Plessis, L.; Johnson, R.; Harvey, W. T.; Hughes, J.; Orton, R. J.; Spurgin, L. G.; Bourgeois, Y.; Ruis, C.; O'Toole, Á, Gourtovaia, M.; Sanderson, T.; Fraser, C.; Edgeworth, J.; Breuer, J.; Michell, S. L.; Todd, J. A.; John, M.; Buck, D.; Gajee, K.; Kay, G. L.; Peacock, S. J.; Heyburn, D.; Kitchman, K.; McNally, A.; Pritchard, D. T.; Dervisevic, S.; Muir, P.; Robinson, E.; Vipond, B. B.; Ramadan, N. A.; Jeanes, C.; Weldon, D.; Catalan, J.; Jones, N.; da Silva Filipe, A.; Williams, C.; Fuchs, M.; Miskelly, J.; Jeffries, A. R.; Oliver, K.; Park, N. R.; Ash, A.; Koshy, C.; Barrow, M.; Buchan, S. L.; Mantzouratou, A.; Clark, G.; Holmes, C. W.; Campbell, S.; Davis, T.; Tan, N. K.; Brown, J. R.; Harris, K. A.; Kidd, S. P.; Grant, P. R.; Xu-McCrae, L.; Cox, A.; Madona, P.; Pond, M.; Randell, P. A.; Withell, K. T.; Williams, C.; Graham, C.; Denton-Smith, R.; Swindells, E.; Turnbull, R.; Sloan, T. J.; Bosworth, A.; Hutchings, S.; Pymont, H. M.; Casey, A.; Ratcliffe, L.; Jones, C. R.; Knight, B. A.; Haque, T.; Hart, J.; Irish-Tavares, D.; Witele, E.; Mower, C.; Watson, L. K.; Collins, J.; Eltringham, G.; Crudgington, D.; Macklin, B.; Iturriza-Gomara, M.; Lucaci, A. O.; McClure, P. C.; Carlile, M.; Holmes, N.; Moore, C.; Storey, N.; Rooke, S.; Yebra, G.; Craine, N.; Perry, M.; Alikhan, N. F.; Bridgett, S.; Cook, K. F.; Fearn, C.; Goudarzi, S.; Lyons, R. A.; Williams, T.; Haldenby, S. T.; Durham, J.; Leonard, S.; Davies, R. M.; Batra, R.; Blane, B.; Spyer, M. J.; Smith, P.; Yavus, M.; Williams, R. J.; Mahanama, A. I. K.; Samaraweera, B.; Girgis, S. T.; Hansford, S. E.; Green, A.; Beaver, C.; Bellis, K. L.; Dorman, M. J.; Kay, S.; Prestwood, L.; Rajatileka, S.; Quick, J.; Poplawski, R.; Reynolds, N.; Mack, A.; Morriss, A.; Whalley, T.; Patel, B.; Georgana, I.; Hosmillo, M.; Pinckert, M. L.; Stockton, J.; Henderson, J. H.; Hollis, A.; Stanley, W.; Yew, W. C.; Myers, R.; Thornton, A.; Adams, A.; Annett, T.; Asad, H.; Birchley, A.; Coombes, J.; Evans, J. M.; Fina, L.; Gatica-Wilcox, B.; Gilbert, L.; Graham, L.; Hey, J.; Hilvers, E.; Jones, S.; Jones, H.; Kumziene-Summerhayes, S.; McKerr, C.; Powell, J.; Pugh, G.; Taylor, S.; Trotter, A. J.; Williams, C. A.; Kermack, L. M.; Foulkes, B. H.; Gallis, M.; Hornsby, H. R.; Louka, S. F.; Pohare, M.; Wolverson, P.; Zhang, P.; MacIntyre-Cockett, G.; Trebes, A.; Moll, R. J.; Ferguson, L.; Goldstein, E. J.; Maclean, A.; Tomb, R.; Starinskij, I.; Thomson, L.; Southgate, J.; Kraemer, M. U. G.; Raghwani, J.; Zarebski, A. E.; Boyd, O.; Geidelberg, L.; Illingworth, C. J.; Jackson, C.; Pascall, D.; Vattipally, S.; Freeman, T. M.; Hsu, S. N.; Lindsey, B. B.; James, K.; Lewis, K.; Tonkin-Hill, G.; Tovar-Corona, J. M.; Cox, M.; Abudahab, K.; Menegazzo, M.; Taylor, B. E. W.; Yeats, C. A.; Mukaddas, A.; Wright, D. W.; de Oliveira Martins, L.; Colquhoun, R.; Hill, V.; Jackson, B.; McCrone, J. T.; Medd, N.; Scher, E.; Keatley, J. P.; Curran, T.; Morgan, S.; Maxwell, P.; Smith, K.; Eldirdiri, S.; Kenyon, A.; Holmes, A. H.; Price, J. R.; Wyatt, T.; Mather, A. E.; Skvortsov, T.; Hartley, J. A.; Guest, M.; Kitchen, C.; Merrick, I.; Munn, R.; Bertolusso, B.; Lynch, J.; Vernet, G.; Kirk, S.; Wastnedge, E.; Stanley, R.; Idle, G.; Bradley, D. T.; Poyner, J.; Mori, M.; Jones, O.; Wright, V.; Brooks, E.; Churcher, C. M.; Fragakis, M.; Galai, K.; Jermy, A.; Judges, S.; McManus, G. M.; Smith, K. S.; Westwick, E.; Attwood, S. W.; Bolt, F.; Davies, A.; De Lacy, E.; Downing, F.; Edwards, S.; Meadows, L.; Jeremiah, S.; Smith, N.; Foulser, L.; Charalampous, T.; Patel, A.; Berry, L.; Boswell, T.; Fleming, V. M.; Howson-Wells, H. C.; Joseph, A.; Khakh, M.; Lister, M. M.; Bird, P. W.; Fallon, K.; Helmer, T.; McMurray, C. L.; Odedra, M.; Shaw, J.; Tang, J. W.; Willford, N. J.; Blakey, V.; Raviprakash, V.; Sheriff, N.; Williams, L. A.; Feltwell, T.; Bedford, L.; Cargill, J. S.; Hughes, W.; Moore, J.; Stonehouse, S.; Atkinson, L.; Lee, J. C. D.; Shah, D.; Alcolea-Medina, A.; Ohemeng-Kumi, N.; Ramble, J.; Sehmi, J.; Williams, R.; Chatterton, W.; Pusok, M.; Everson, W.; Castigador, A.; Macnaughton, E.; El Bouzidi, K.; Lampejo, T.; Sudhanva, M.; Breen, C.; Sluga, G.; Ahmad, S. S. Y.; George, R. P.; Machin, N. W.; Binns, D.; James, V.; Blacow, R.; Coupland, L.; Smith, L.; Barton, E.; Padgett, D.; Scott, G.; Cross, A.; Mirfenderesky, M.; Greenaway, J.; Cole, K.; Clarke, P.; Duckworth, N.; Walsh, S.; Bicknell, K.; Impey, R.; Wyllie, S.; Hopes, R.; Bishop, C.; Chalker, V.; et al..
Embase;
Preprint in English | EMBASE | ID: ppcovidwho-326827

ABSTRACT

The Delta variant of concern of SARS-CoV-2 has spread globally causing large outbreaks and resurgences of COVID-19 cases1-3. The emergence of Delta in the UK occurred on the background of a heterogeneous landscape of immunity and relaxation of non-pharmaceutical interventions4,5. Here we analyse 52,992 Delta genomes from England in combination with 93,649 global genomes to reconstruct the emergence of Delta, and quantify its introduction to and regional dissemination across England, in the context of changing travel and social restrictions. Through analysis of human movement, contact tracing, and virus genomic data, we find that the focus of geographic expansion of Delta shifted from India to a more global pattern in early May 2021. In England, Delta lineages were introduced >1,000 times and spread nationally as non-pharmaceutical interventions were relaxed. We find that hotel quarantine for travellers from India reduced onward transmission from importations;however the transmission chains that later dominated the Delta wave in England had been already seeded before restrictions were introduced. In England, increasing inter-regional travel drove Delta's nationwide dissemination, with some cities receiving >2,000 observable lineage introductions from other regions. Subsequently, increased levels of local population mixing, not the number of importations, was associated with faster relative growth of Delta. Among US states, we find that regions that previously experienced large waves also had faster Delta growth rates, and a model including interactions between immunity and human behaviour could accurately predict the rise of Delta there. Delta's invasion dynamics depended on fine scale spatial heterogeneity in immunity and contact patterns and our findings will inform optimal spatial interventions to reduce transmission of current and future VOCs such as Omicron.

6.
MEDLINE;
Preprint in English | MEDLINE | ID: ppcovidwho-326624

ABSTRACT

Cases of SARS-CoV-2 infection in Manaus, Brazil, resurged in late 2020, despite high levels of previous infection there. Through genome sequencing of viruses sampled in Manaus between November 2020 and January 2021, we identified the emergence and circulation of a novel SARS-CoV-2 variant of concern, lineage P.1, that acquired 17 mutations, including a trio in the spike protein (K417T, E484K and N501Y) associated with increased binding to the human ACE2 receptor. Molecular clock analysis shows that P.1 emergence occurred around early November 2020 and was preceded by a period of faster molecular evolution. Using a two-category dynamical model that integrates genomic and mortality data, we estimate that P.1 may be 1.4-2.2 times more transmissible and 25-61% more likely to evade protective immunity elicited by previous infection with non-P.1 lineages. Enhanced global genomic surveillance of variants of concern, which may exhibit increased transmissibility and/or immune evasion, is critical to accelerate pandemic responsiveness. One-Sentence Summary: We report the evolution and emergence of a SARS-CoV-2 lineage of concern associated with rapid transmission in Manaus.

7.
PubMed; 2021.
Preprint in English | PubMed | ID: ppcovidwho-296567

ABSTRACT

The COVID-19 pandemic has revealed the importance of virus genome sequencing to guide public health interventions to control virus transmission and understand SARS-CoV-2 evolution. As of July 20th, 2021, >2 million SARS-CoV-2 genomes have been submitted to GISAID, 94% from high income and 6% from low and middle income countries. Here, we analyse the spatial and temporal heterogeneity in SARS-CoV-2 global genomic surveillance efforts. We report a comprehensive analysis of virus lineage diversity and genomic surveillance strategies adopted globally, and investigate their impact on the detection of known SARS-CoV-2 virus lineages and variants of concern. Our study provides a perspective on the global disparities surrounding SARS-CoV-2 genomic surveillance, their causes and consequences, and possible solutions to maximize the impact of pathogen genome sequencing for efforts on public health.

8.
PUBMED; 2021.
Preprint in English | PUBMED | ID: ppcovidwho-292866

ABSTRACT

The SARS-CoV-2 Gamma variant spread rapidly across Brazil, causing substantial infection and death waves. We use individual-level patient records following hospitalisation with suspected or confirmed COVID-19 to document the extensive shocks in hospital fatality rates that followed Gamma's spread across 14 state capitals, and in which more than half of hospitalised patients died over sustained time periods. We show that extensive fluctuations in COVID-19 in-hospital fatality rates also existed prior to Gamma's detection, and were largely transient after Gamma's detection, subsiding with hospital demand. Using a Bayesian fatality rate model, we find that the geographic and temporal fluctuations in Brazil's COVID-19 in-hospital fatality rates are primarily associated with geographic inequities and shortages in healthcare capacity. We project that approximately half of Brazil's COVID-19 deaths in hospitals could have been avoided without pre-pandemic geographic inequities and without pandemic healthcare pressure. Our results suggest that investments in healthcare resources, healthcare optimization, and pandemic preparedness are critical to minimize population wide mortality and morbidity caused by highly transmissible and deadly pathogens such as SARS-CoV-2, especially in low- and middle-income countries. Note: The following manuscript has appeared as 'Report 46 - Factors driving extensive spatial and temporal fluctuations in COVID-19 fatality rates in Brazilian hospitals' at https://spiral.imperial.ac.uk:8443/handle/10044/1/91875 . One sentence summary: COVID-19 in-hospital fatality rates fluctuate dramatically in Brazil, and these fluctuations are primarily associated with geographic inequities and shortages in healthcare capacity.

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