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1.
eLife ; 11:13, 2022.
Article in English | MEDLINE | ID: covidwho-2030290

ABSTRACT

Background: Viral sequencing of SARS-CoV-2 has been used for outbreak investigation, but there is limited evidence supporting routine use for infection prevention and control (IPC) within hospital settings. Methods: We conducted a prospective non-randomised trial of sequencing at 14 acute UK hospital trusts. Sites each had a 4-week baseline data-collection period, followed by intervention periods comprising 8 weeks of 'rapid' (<48h) and 4 weeks of 'longer-turnaround' (5-10 day) sequencing using a sequence reporting tool (SRT). Data were collected on all hospital onset COVID-19 infections (HOCIs;detected >=48h from admission). The impact of the sequencing intervention on IPC knowledge and actions, and on incidence of probable/definite hospital-acquired infections (HAIs) was evaluated. Results: A total of 2170 HOCI cases were recorded from October 2020-April 2021, corresponding to a period of extreme strain on the health service, with sequence reports returned for 650/1320 (49.2%) during intervention phases. We did not detect a statistically significant change in weekly incidence of HAIs in longer-turnaround (incidence rate ratio 1.60, 95%CI 0.85-3.01;P=0.14) or rapid (0.85, 0.48-1.50;P=0.54) intervention phases compared to baseline phase. However, IPC practice was changed in 7.8% and 7.4% of all HOCI cases in rapid and longer-turnaround phases, respectively, and 17.2% and 11.6% of cases where the report was returned. In a 'per-protocol' sensitivity analysis there was an impact on IPC actions in 20.7% of HOCI cases when the SRT report was returned within 5 days. Capacity to respond effectively to insights from sequencing was breached in most sites by the volume of cases and limited resources. Conclusion: While we did not demonstrate a direct impact of sequencing on the incidence of nosocomial transmission, our results suggest that sequencing can inform IPC response to HOCIs, particularly when returned within 5 days. Funding: COG-UK is supported by funding from the Medical Research Council (MRC) part of UK Research & Innovation (UKRI), the National Institute of Health Research (NIHR) [grant code: MC_PC_19027], and Genome Research Limited, operating as the Wellcome Sanger Institute. Clinical trial number: ClinicalTrials.gov Identifier: NCT04405934.

2.
Acta Crystallographica a-Foundation and Advances ; 77:C197-C197, 2021.
Article in English | Web of Science | ID: covidwho-1762485
4.
2021 ASEE Virtual Annual Conference, ASEE 2021 ; 2021.
Article in English | Scopus | ID: covidwho-1696190
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.
Robson, S. C.; Connor, T. R.; Loman, N. J.; Golubchik, T.; Nunez, R. T. M.; Bonsall, D.; Rambaut, A.; Snell, L. B.; Livett, R.; Ludden, C.; Corden, S.; Nastouli, E.; Nebbia, G.; Johnston, I.; Lythgoe, K.; Torok, M. E.; 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.; Loveson, K. F.; Byott, M.; Pacchiarini, N.; 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.; Chapman, M. H. S.; 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.; 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.; Fearn, N. 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.; Bouzidi, K. El, 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.; Harrison, I.; Gifford, L.; Molnar, Z.; Auckland, C.; Evans, C.; Johnson, K.; Partridge, D. G.; Raza, M.; Baker, P.; Bonner, S.; Essex, S.; Murray, L. J.; Lawton, A. I.; Burton-Fanning, S.; Payne, B. A. I.; Waugh, S.; Gomes, A. N.; Kimuli, M.; Murray, D. R.; Ashfield, P.; Dobie, D.; Ashford, F.; Best, A.; Crawford, L.; Cumley, N.; Mayhew, M.; Megram, O.; Mirza, J.; Moles-Garcia, E.; Percival, B.; Driscoll, M.; Ensell, L.; Lowe, H. L.; Maftei, L.; Mondani, M.; Chaloner, N. J.; Cogger, B. J.; Easton, L. J.; Huckson, H.; Lewis, J.; Lowdon, S.; Malone, C. S.; Munemo, F.; Mutingwende, M.; et al..
Embase;
Preprint in English | EMBASE | ID: ppcovidwho-326811

ABSTRACT

The scale of data produced during the SARS-CoV-2 pandemic has been unprecedented, with more than 5 million sequences shared publicly at the time of writing. This wealth of sequence data provides important context for interpreting local outbreaks. However, placing sequences of interest into national and international context is difficult given the size of the global dataset. Often outbreak investigations and genomic surveillance efforts require running similar analyses again and again on the latest dataset and producing reports. We developed civet (cluster investigation and virus epidemiology tool) to aid these routine analyses and facilitate virus outbreak investigation and surveillance. Civet can place sequences of interest in the local context of background diversity, resolving the query into different 'catchments' and presenting the phylogenetic results alongside metadata in an interactive, distributable report. Civet can be used on a fine scale for clinical outbreak investigation, for local surveillance and cluster discovery, and to routinely summarise the virus diversity circulating on a national level. Civet reports have helped researchers and public health bodies feedback genomic information in the appropriate context within a timeframe that is useful for public health.

7.
Anaesthesia ; 77(SUPPL 2):44, 2022.
Article in English | EMBASE | ID: covidwho-1666279

ABSTRACT

Allergy to excipients used in drug formulations is an often overlooked issue, recently highlighted by cases of severe reaction to the Pfizer-Biontech COVID-19 vaccination. Sulphites, including metabisulphites, are antioxidant preservatives found in many foods but also in certain drugs used by anaesthetists, including metaraminol, catecholamines, metoclopramide and some forms of propofol. Patients may present with a variety of intolerances to sulphites. Anaesthetists need to know how to counsel them, which drugs to avoid, and whether to administer sulphite-containing adrenaline in an emergency scenario. Description A patient with reported sulphite allergy following previous reactions to metabisulphite-containing local anaesthetic presented for an elective operation. The hospital pharmacist took several weeks to confirm the sulphite content of key anaesthetic drugs and to find alternatives. In particular, sulphite-free adrenaline had to be sourced from France. General anaesthesia proceeded uneventfully, and a 'green bag' of safe emergency drugs stayed with the patient until her discharge. The patient was referred for further allergy testing, but as the allergy centre could not provide sulphite-free adrenaline, she declined challenge with metabisulphites and with preparations of adrenaline available in the UK. This will clearly pose a challenge in the future should she present with anaphylaxis or for emergency surgery or critical care. Discussion Documented reactions to parenteral sulphites are uncommon, varied and cover a variety of suggested pathophysiologies, of which IgE-mediated allergy is rare [1]. Additionally, asthmatics may report bronchospasm related to sulphite containing foodstuffs, but this results from direct irritation from sulphur dioxide and is not immune mediated. Establishing the diagnosis is difficult, requiring challenge testing in specialist allergy centres;skin prick testing can be unreliable. Challenge with sulphite-containing adrenaline, thus establishing safety of use in case of anaphylaxis, is one pragmatic option. Sensible precautions include close liaison with the hospital pharmacist, an easily accessible list of sulphite-free alternatives and a policy on adrenaline use in anaphylaxis. Although evidence is scant, expert opinion suggests that in anaphylaxis the benefit of administering sulphite-containing adrenaline outweighs the risks [2].

8.
Allergy: European Journal of Allergy and Clinical Immunology ; 76(SUPPL 110):482-483, 2021.
Article in English | EMBASE | ID: covidwho-1570417

ABSTRACT

Background: A simple, accurate and rapid whole blood-based T cell test was previously developed to determine SARS-CoV-2-specific T cell immunity. The test was established by comparing cytokine production from naturally infected convalescent donors with covid-19 negative donors. The data revealed IL-2 production to be the most indicative of prior SARS-CoV-2 infection. However, accurately identifying vaccine-induced SARS-CoV-2-specific T cell immunity via this method was still to be confirmed. Herein, we sort to address if this was possible. Method: A cohort of unvaccinated healthy individuals was recruited to donate a single blood sample for an overnight in vitro stimulation with peptides spanning immunodominant regions specific for SARS-CoV-2. Blood plasma samples were harvested and analysed for a broad panel of cytokines using ELISA for IFN-g and Luminex xMAP cytokine arrays for IL-2 and other TH1/TH2 cytokines. The same cohort were then asked to donate a second blood sample following SARS-CoV-2 vaccinations, and the same stimulations and analyses were performed. In addition, plasma anti-SARS-CoV-2 IgG levels were assessed in both pre-and post-vaccination samples by direct ELISA against the whole spike protein. Results: A multiplex cytokine array revealed IL-2 to be the most reliable biomarker in indicating a vaccine-induced SARS-CoV-2-specific T cell response, with 100% of post-vaccinated donors mounting a significant IL-2 response above a pre-determined cut off level for positivity of 19.91pg/ml. All donors demonstrated a considerable increase in magnitude of IL-2 responses from pre-vaccination to post-vaccination, with results ranging from ∼125% change to >36,000% change. In addition, IFN-g and plasma IgG ELISAs revealed both to be reliable biomarkers, with post-vaccination levels of each being significantly raised above pre-vaccination levels. However, the magnitude of these responses was not as greatly increased as those observed with IL-2, nor did they achieve an increase in 100% of donors assessed. Conclusion: This standardisable, rapid, and accurate T cell test approach can be utilised to make accurate and comparable assessments of vaccine-induced T cell immunity across multiple population cohorts. This could provide valuable insight into the extremely important question of how long vaccine-induced immunity may last, and aid decision making around if and when vaccine boosters should be administered.

9.
Clinical Lymphoma, Myeloma and Leukemia ; 21:S2-S3, 2021.
Article in English | EMBASE | ID: covidwho-1517533

ABSTRACT

Background: The role of upfront ASCT for NDTE MM remains under evaluation with high MRD rates following novel induction and consolidation (cons) strategies. K maintenance represents an alternative strategy to lenalidomide maintenance. The CARDAMON trial investigated K maintenance following KCd induction plus either ASCT or KCd cons. Methods: NDTE pts received 4 x KCd induction (K 20/56 mg/m2 biweekly, C 500 mg D 1,8,15, d 40mg weekly) before 1:1 randomisation to ASCT or 4 x KCd cons followed by 18 cycles K maintenance (56mg/m2 D1,8,15). Flow cytometric MRD (10-5) was assessed post induction, pre-maintenance and at 6 months maintenance. Primary endpoints were ≥VGPR post induction and 2-year PFS from randomisation. Secondary endpoints included improvements in disease response and MRD conversion following ASCT/ cons and maintenance. Results: 281 patients were registered, with 218 randomised to either ASCT or cons. The median PFS for ASCT was not yet reached vs 3.4 years for cons, with cons failing to show non-inferiority (difference in 2-year PFS 6.5%, 70% CI 1.0% to 11.1%). 196 patients received K maintenance (99 ASCT, 97 cons), 17 remain on treatment. A median of 16 cycles (1-18) were given over a median of 15.9 months (0-21.5). COVID-19 led to maintenance treatment interruptions in 41 (8 ASCT, 6 Cons) and treatment discontinuation in 15 (9 ASCT, 6 Cons). The median K dose given was 50.6mg/m2 and was similar across both arms (51.2 vs 49.4mg/m2, p=0.03). K maintenance was discontinued for PD in 14.1% (ASCT) vs 22.7% (cons), and for adverse events (AEs) in 7.1% (ASCT) vs 4.1% (cons). Most common AEs were hypertension and infections and more ≥G3 AEs were noted in ASCT vs cons (p=0.01). Patient/ clinician withdrawals from maintenance were low but occurred more in the ASCT arm (9.1% vs 1%). MRD neg patients post ASCT/ Cons had a longer PFS than MRD pos (p=0.002);with a higher MRD neg rate in the ASCT arm (53.6% vs 35.1% in Cons, p=0.01). MRD neg patients at 6 months post maintenance also had longer PFS (p=0.004 cf MRD pos patients);again with higher MRD neg rates in the ASCT arm (58.1% ASCT vs 40.5% Cons, p=0.02). There was no difference in PFS for MRD neg patients according to treatment arm from PBSCH, post-ASCT/ Cons or 6 months maintenance timepoints. Overall, 27.8% of MRD pos patients converted to MRD neg post ASCT/ Cons with more converting with ASCT (39.1% ASCT vs 16.1%, p=0.004). 23.5% of MRD pos patients converted to neg during maintenance (30.6% ASCT, 17.8%: p=0.2). Maintenance of MRD negativity over the first 6 months was similar between ASCT and Cons arms (p=0.3). There was no evidence that the timing of achievement of MRD negativity impacted PFS. Conclusions: K maintenance at 56mg/m2 weekly was deliverable and tolerable, with continued higher MRD neg rates at 6 months post-ASCT compared to post-Cons. However more ≥G3 AEs and discontinuations for AEs/ patient choice were noted for K maintenance after ASCT.

10.
AMIA ... Annual Symposium Proceedings/AMIA Symposium ; 2021:142-151, 2021.
Article in English | MEDLINE | ID: covidwho-1377209

ABSTRACT

Phenotyping is an effective way to identify cohorts of patients with particular characteristics within a population. In order to enhance the portability of a phenotype definition across institutions, it is often defined abstractly, with implementers expected to realise the phenotype computationally before executing it against a dataset. However, un-clear definitions, with little information about how best to implement the definition in practice, hinder this process. To address this issue, we propose a new multi-layer, workflow-based model for defining phenotypes, and a novel authoring architecture, Phenoflow, that supports the development of these structured definitions and their realisation as computable phenotypes. To evaluate our model, we determine its impact on the portability of both code-based (COVID-19) and logic-based (diabetes) definitions, in the context of key datasets, including 26,406 patients at North-western University. Our approach is shown to ensure the portability of phenotype definitions and thus contributes to the transparency of resulting studies.

11.
8th and 9th International Provenance and Annotation Workshop, IPAW 2020 and IPAW 2021 held as part of ProvenanceWeek in 2020 and 2021 ; 12839 LNCS:256-262, 2021.
Article in English | Scopus | ID: covidwho-1361249

ABSTRACT

Whilst the need to record and understand the evolution of data, together with the processes and users associated with those changes, is now widely appreciated, the uptake of solutions to these issues remains slow. Data provenance techniques have the potential to provide such an understanding, but their use is often considered a specialist activity, requiring detailed knowledge of standards such as W3C PROV. In this work, we introduce ProvIt, a suite of tools designed to lower the barriers to entry for the use of provenance technology. We demonstrate the utility of ProvIt by using it to add provenance capabilities to the Jupyter IDE, in order to provide insight into the tools used by a group of researchers analysing a COVID-19 dataset. © 2021, Springer Nature Switzerland AG.

12.
Journal of Allergy and Clinical Immunology ; 147(2):AB152-AB152, 2021.
Article in English | Web of Science | ID: covidwho-1148653
13.
Journal of Allergy and Clinical Immunology ; 147(2):AB67-AB67, 2021.
Article in English | Web of Science | ID: covidwho-1148444
14.
Clin Immunol ; 221: 108614, 2020 12.
Article in English | MEDLINE | ID: covidwho-912100

ABSTRACT

The heterogeneous disease course of COVID-19 is unpredictable, ranging from mild self-limiting symptoms to cytokine storms, acute respiratory distress syndrome (ARDS), multi-organ failure and death. Identification of high-risk cases will enable appropriate intervention and escalation. This study investigates the routine laboratory tests and cytokines implicated in COVID-19 for their potential application as biomarkers of disease severity, respiratory failure and need of higher-level care. From analysis of 203 samples, CRP, IL-6, IL-10 and LDH were most strongly correlated with the WHO ordinal scale of illness severity, the fraction of inspired oxygen delivery, radiological evidence of ARDS and level of respiratory support (p ≤ 0.001). IL-6 levels of ≥3.27 pg/ml provide a sensitivity of 0.87 and specificity of 0.64 for a requirement of ventilation, and a CRP of ≥37 mg/l of 0.91 and 0.66. Reliable stratification of high-risk cases has significant implications on patient triage, resource management and potentially the initiation of novel therapies in severe patients.


Subject(s)
C-Reactive Protein/metabolism , COVID-19/diagnosis , Cytokine Release Syndrome/diagnosis , Interleukin-6/blood , Respiratory Distress Syndrome/diagnosis , SARS-CoV-2/pathogenicity , Adult , Aged , Aged, 80 and over , Biomarkers/blood , COVID-19/blood , COVID-19/therapy , COVID-19/virology , Cytokine Release Syndrome/blood , Cytokine Release Syndrome/therapy , Cytokine Release Syndrome/virology , Female , Hospitalization , Humans , Interleukin-10/blood , L-Lactate Dehydrogenase/blood , Male , Middle Aged , Respiration, Artificial , Respiratory Distress Syndrome/blood , Respiratory Distress Syndrome/therapy , Respiratory Distress Syndrome/virology , Risk Factors , Severity of Illness Index
15.
Stroke ; 51(6):1891-1895, 2020.
Article in English | GIM | ID: covidwho-827076

ABSTRACT

Background and Purpose- Hyperacute assessment and management of patients with stroke, termed code stroke, is a time-sensitive and high-stakes clinical scenario. In the context of the current coronavirus disease 2019 (COVID-19) pandemic caused by the SARS-CoV-2 virus, the ability to deliver timely and efficacious care must be balanced with the risk of infectious exposure to the clinical team. Furthermore, rapid and effective stroke care remains paramount to achieve maximal functional recovery for those needing admission and to triage care appropriately for those who may be presenting with neurological symptoms but have an alternative diagnosis. Methods- Available resources, COVID-19-specific infection prevention and control recommendations, and expert consensus were used to identify clinical screening criteria for patients and provide the required nuanced considerations for the healthcare team, thereby modifying the conventional code stroke processes to achieve a protected designation. Results- A protected code stroke algorithm was developed. Features specific to prenotification and clinical status of the patient were used to define precode screening. These include primary infectious symptoms, clinical, and examination features. A focused framework was then developed with regard to a protected code stroke. We outline the specifics of personal protective equipment use and considerations thereof including aspects of crisis resource management impacting team role designation and human performance factors during a protected code stroke. Conclusions- We introduce the concept of a protected code stroke during a pandemic, as in the case of COVID-19, and provide a framework for key considerations including screening, personal protective equipment, and crisis resource management. These considerations and suggested algorithms can be utilized and adapted for local practice.

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