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2. SARS-CoV-2 evolution during treatment of chronic infection

Author

Kemp, S. A., Collier, D. A., Datir, R. P., Ferreira, I. A. T. M., Gayed, S., Jahun, A., Hosmillo, M., Rees-Spear, C., Mlcochova, P., Lumb, I. U., Roberts, D. J., Chandra, A., Temperton, N., Baker, S., Dougan, G., Hess, C., Kingston, N., Lehner, P. J., Lyons, P. A., Matheson, N. J., Owehand, W. H., Saunders, C., Summers, C., Thaventhiran, J. E. D., Toshner, M., Weekes, M. P., Bucke, A., Calder, J., Canna, L., Domingo, J., Elmer, A., Fuller, S., Harris, J., Hewitt, S., Kennet, J., Jose, S., Kourampa, J., Meadows, A., O'Brien, C., Price, J., Publico, C., Rastall, R., Ribeiro, C., Rowlands, J., Ruffolo, V., Tordesillas, H., Bullman, B., Dunmore, B. J., Fawke, S., Graf, S., Hodgson, J., Huang, C., Hunter, K., Jones, E., Legchenko, E., Matara, C., Martin, J., Mescia, F., O'Donnell, C., Pointon, L., Pond, N., Shih, J., Sutcliffe, R., Tilly, T., Treacy, C., Tong, Z., Wood, J., Wylot, M., Bergamaschi, L., Betancourt, A., Bower, G., Cossetti, C., De Sa, A., Epping, M., Gleadall, N., Grenfell, R., Hinch, A., Huhn, O., Jackson, S., Jarvis, I., Lewis, D., Marsden, J., Nice, F., Okecha, G., Omarjee, O., Perera, M., Richoz, N., Romashova, V., Yarkoni, N. S., Sharma, R., Stefanucci, L., Stephens, J., Strezlecki, M., Turner, L., De Bie, E. M. D. D., Bunclark, K., Josipovic, M., Mackay, M., Rossi, S., Selvan, M., Spencer, S., Yong, C., Ansaripour, A., Michael, A., Mwaura, L., Patterson, C., Polwarth, G., Polgarova, P., di Stefano, G., Fahey, C., Michel, R., Bong, S. -H., Coudert, J. D., Holmes, E., Allison, J., Butcher, H., Caputo, D., Clapham-Riley, D., Dewhurst, E., Furlong, A., Graves, B., Gray, J., Ivers, T., Kasanicki, M., Le Gresley, E., Linger, R., Meloy, S., Muldoon, F., Ovington, N., Papadia, S., Phelan, I., Stark, H., Stirrups, K. E., Townsend, P., Walker, N., Webster, J., Robson, S. C., Loman, N. J., Connor, T. R., Golubchik, T., Martinez Nunez, R. T., Ludden, C., Corden, S., Johnston, I., Bonsall, D., Smith, C. P., Awan, A. R., Bucca, G., Estee Torok, M., Saeed, K., Prieto, J. A., Jackson, D. K., Hamilton, W. L., Snell, L. B., Moore, C., Harrison, E. M., Goncalves, S., Fairley, D. J., Loose, M. W., Watkins, J., Livett, R., Moses, S., Amato, R., Nicholls, S., Bull, M., Smith, D. L., Barrett, J., Aanensen, D. M., Curran, M. D., Parmar, S., Aggarwal, D., Shepherd, J. G., Parker, M. D., Glaysher, S., Bashton, M., Underwood, A. P., Pacchiarini, N., Loveson, K. F., Carabelli, A. M., Templeton, K. E., Langford, C. F., Sillitoe, J., de Silva, T. I., Wang, D., Kwiatkowski, D., Rambaut, A., O'Grady, J., Cottrell, S., Holden, M. T. G., Thomson, E. C., Osman, H., Andersson, M., Chauhan, A. J., Hassan-Ibrahim, M. O., Lawniczak, M., Alderton, A., Chand, M., Constantinidou, C., Unnikrishnan, M., Darby, A. C., Hiscox, J. A., Paterson, S., Martincorena, I., Robertson, D. L., Volz, E. M., Page, A. J., Pybus, O. G., Bassett, A. R., Ariani, C. V., Spencer Chapman, M. H., K. K., Li, Shah, R. N., Jesudason, N. G., Taha, Y., Mchugh, M. P., Dewar, R., Jahun, A. S., Mcmurray, C., Pandey, S., Mckenna, J. P., Nelson, A., Young, G. R., Mccann, C. M., Elliott, S., Lowe, H., Temperton, B., Roy, S., Price, A., Rey, S., Wyles, M., Rooke, S., Shaaban, S., de Cesare, M., Letchford, L., Silveira, S., Pelosi, E., Wilson-Davies, E., O'Toole, A., Hesketh, A. R., Stark, R., du Plessis, L., Ruis, C., Adams, H., Bourgeois, Y., Michell, S. L., Gramatopoulos, D., Edgeworth, J., Breuer, J., Todd, J. A., Fraser, C., Buck, D., John, M., Kay, G. L., Palmer, S., Peacock, S. J., Heyburn, D., Weldon, D., Robinson, E., Mcnally, A., Muir, P., Vipond, I. B., Boyes, J., Sivaprakasam, V., Salluja, T., Dervisevic, S., Meader, E. J., Park, N. R., Oliver, K., Jeffries, A. R., Ott, S., da Silva Filipe, A., Simpson, D. A., Williams, C., Masoli, J. A. H., Knight, B. A., Jones, C. R., Koshy, C., Ash, A., Casey, A., Bosworth, A., Ratcliffe, L., Xu-McCrae, L., Pymont, H. M., Hutchings, S., Berry, L., Jones, K., Halstead, F., Davis, T., Holmes, C., Iturriza-Gomara, M., Lucaci, A. O., Randell, P. A., Cox, A., Madona, P., Harris, K. A., Brown, J. R., Mahungu, T. W., Irish-Tavares, D., Haque, T., Hart, J., Witele, E., Fenton, M. L., Liggett, S., Graham, C., Swindells, E., Collins, J., Eltringham, G., Campbell, S., Mcclure, P. C., Clark, G., Sloan, T. J., Jones, C., Lynch, J., Warne, B., Leonard, S., Durham, J., Williams, T., Haldenby, S. T., Storey, N., Alikhan, N. -F., Holmes, N., Carlile, M., Perry, M., Craine, N., Lyons, R. A., Beckett, A. H., Goudarzi, S., Fearn, C., Cook, K., Dent, H., Paul, H., Davies, R., Blane, B., Girgis, S. T., Beale, M. A., Bellis, K. L., Dorman, M. J., Drury, E., Kane, L., Kay, S., Mcguigan, S., Nelson, R., Prestwood, L., Rajatileka, S., Batra, R., Williams, R. J., Kristiansen, M., Green, A., Justice, A., Mahanama, A. I. K., Samaraweera, B., Hadjirin, N. F., Quick, J., Poplawski, R., Kermack, L. M., Reynolds, N., Hall, G., Chaudhry, Y., Pinckert, M. L., Georgana, I., Moll, R. J., Thornton, A., Myers, R., Stockton, J., Williams, C. A., Yew, W. C., Trotter, A. J., Trebes, A., MacIntyre-Cockett, G., Birchley, A., Adams, A., Plimmer, A., Gatica-Wilcox, B., Mckerr, C., Hilvers, E., Jones, H., Asad, H., Coombes, J., Evans, J. M., Fina, L., Gilbert, L., Graham, L., Cronin, M., Kumziene-Summerhayes, S., Taylor, S., Jones, S., Groves, D. C., Zhang, P., Gallis, M., Louka, S. F., Starinskij, I., Jackson, C., Gourtovaia, M., Tonkin-Hill, G., Lewis, K., Tovar-Corona, J. M., James, K., Baxter, L., Alam, M. T., Orton, R. J., Hughes, J., Vattipally, S., Ragonnet-Cronin, M., Nascimento, F. F., Jorgensen, D., Boyd, O., Geidelberg, L., Zarebski, A. E., Raghwani, J., Kraemer, M. U. G., Southgate, J., Lindsey, B. B., Freeman, T. M., Keatley, J. -P., Singer, J. B., de Oliveira Martins, L., Yeats, C. A., Abudahab, K., Taylor, B. E. W., Menegazzo, M., Danesh, J., Hogsden, W., Eldirdiri, S., Kenyon, A., Mason, J., Robinson, T. I., Holmes, A., Hartley, J. A., Curran, T., Mather, A. E., Shankar, G., Jones, R., Howe, R., Morgan, S., Wastenge, E., Chapman, M. R., Mookerjee, S., Stanley, R., Smith, W., Peto, T., Eyre, D., Crook, D., Vernet, G., Kitchen, C., Gulliver, H., Merrick, I., Guest, M., Munn, R., Bradley, D. T., Wyatt, T., Beaver, C., Foulser, L., Churcher, C. M., Brooks, E., Smith, K. S., Galai, K., Mcmanus, G. M., Bolt, F., Coll, F., Meadows, L., Attwood, S. W., Davies, A., De Lacy, E., Downing, F., Edwards, S., Scarlett, G. P., Jeremiah, S., Smith, N., Leek, D., Sridhar, S., Forrest, S., Cormie, C., Gill, H. K., Dias, J., Higginson, E. E., Maes, M., Young, J., Wantoch, M., Jamrozy, D., Lo, S., Patel, M., Hill, V., Bewshea, C. M., Ellard, S., Auckland, C., Harrison, I., Bishop, C., Chalker, V., Richter, A., Beggs, A., Best, A., Percival, B., Mirza, J., Megram, O., Mayhew, M., Crawford, L., Ashcroft, F., Moles-Garcia, E., Cumley, N., Hopes, R., Asamaphan, P., Niebel, M. O., Gunson, R. N., Bradley, A., Maclean, A., Mollett, G., Blacow, R., Bird, P., Helmer, T., Fallon, K., Tang, J., Hale, A. D., Macfarlane-Smith, L. R., Harper, K. L., Carden, H., Machin, N. W., Jackson, K. A., Ahmad, S. S. Y., George, R. P., Turtle, L., O'Toole, E., Watts, J., Breen, C., Cowell, A., Alcolea-Medina, A., Charalampous, T., Patel, A., Levett, L. J., Heaney, J., Rowan, A., Taylor, G. P., Shah, D., Atkinson, L., Lee, J. C. D., Westhorpe, A. P., Jannoo, R., Lowe, H. L., Karamani, A., Ensell, L., Chatterton, W., Pusok, M., Dadrah, A., Symmonds, A., Sluga, G., Molnar, Z., Baker, P., Bonner, S., Essex, S., Barton, E., Padgett, D., Scott, G., Greenaway, J., Payne, B. A. I., Burton-Fanning, S., Waugh, S., Raviprakash, V., Sheriff, N., Blakey, V., Williams, L. -A., Moore, J., Stonehouse, S., Smith, L., Davidson, R. K., Bedford, L., Coupland, L., Wright, V., Chappell, J. G., Tsoleridis, T., Ball, J., Khakh, M., Fleming, V. M., Lister, M. M., Howson-Wells, H. C., Boswell, T., Joseph, A., Willingham, I., Duckworth, N., Walsh, S., Wise, E., Moore, N., Mori, M., Cortes, N., Kidd, S., Williams, R., Gifford, L., Bicknell, K., Wyllie, S., Lloyd, A., Impey, R., Malone, C. S., Cogger, B. J., Levene, N., Monaghan, L., Keeley, A. J., Partridge, D. G., Raza, M., Evans, C., Johnson, K., Abnizova, I., Aigrain, L., Ali, M., Allen, L., Anderson, R., Ariani, C., Austin-Guest, S., Bala, S., Bassett, A., Battleday, K., Beal, J., Beale, M., Bellany, S., Bellerby, T., Bellis, K., Berger, D., Berriman, M., Betteridge, E., Bevan, P., Binley, S., Bishop, J., Blackburn, K., Bonfield, J., Boughton, N., Bowker, S., Brendler-Spaeth, T., Bronner, I., Brooklyn, T., Buddenborg, S. K., Bush, R., Caetano, C., Cagan, A., Carter, N., Cartwright, J., Monteiro, T. C., Chapman, L., Chillingworth, T. -J., Clapham, P., Clark, R., Clarke, A., Clarke, C., Cole, D., Cook, E., Coppola, M., Cornell, L., Cornwell, C., Corton, C., Crackett, A., Cranage, A., Craven, H., Craw, S., Crawford, M., Cutts, T., Dabrowska, M., Davies, M., Dawson, J., Day, C., Densem, A., Dibling, T., Dockree, C., Dodd, D., Dogga, S., Dougherty, M., Dove, A., Drummond, L., Dudek, M., Durrant, L., Easthope, E., Eckert, S., Ellis, P., Farr, B., Fenton, M., Ferrero, M., Flack, N., Fordham, H., Forsythe, G., Francis, M., Fraser, A., Freeman, A., Galvin, A., Garcia-Casado, M., Gedny, A., Girgis, S., Glover, J., Goodwin, S., Gould, O., Gray, A., Gray, E., Griffiths, C., Gu, Y., Guerin, F., Hamilton, W., Hanks, H., Harrison, E., Harrott, A., Harry, E., Harvison, J., Heath, P., Hernandez-Koutoucheva, A., Hobbs, R., Holland, D., Holmes, S., Hornett, G., Hough, N., Huckle, L., Hughes-Hallet, L., Hunter, A., Inglis, S., Iqbal, S., Jackson, A., Jackson, D., Verdejo, C. J., Jones, M., Kallepally, K., Kay, K., Keatley, J., Keith, A., King, A., Kitchin, L., Kleanthous, M., Klimekova, M., Korlevic, P., Krasheninnkova, K., Lane, G., Langford, C., Laverack, A., Law, K., Lensing, S., Lewis-Wade, A., Liddle, J., Lin, Q., Lindsay, S., Linsdell, S., Long, R., Lovell, J., Mack, J., Maddison, M., Makunin, A., Mamun, I., Mansfield, J., Marriott, N., Martin, M., Mayho, M., Mccarthy, S., Mcclintock, J., Mchugh, S., Mcminn, L., Meadows, C., Mobley, E., Moll, R., Morra, M., Morrow, L., Murie, K., Nash, S., Nathwani, C., Naydenova, P., Neaverson, A., Nerou, E., Nicholson, J., Nimz, T., Noell, G. G., O'Meara, S., Ohan, V., Olney, C., Ormond, D., Oszlanczi, A., Pang, Y. F., Pardubska, B., Park, N., Parmar, A., Patel, G., Payne, M., Peacock, S., Petersen, A., Plowman, D., Preston, T., Puethe, C., Quail, M., Rajan, D., Rance, R., Rawlings, S., Redshaw, N., Reynolds, J., Reynolds, M., Rice, S., Richardson, M., Roberts, C., Robinson, K., Robinson, M., Robinson, D., Rogers, H., Rojo, E. M., Roopra, D., Rose, M., Rudd, L., Sadri, R., Salmon, N., Saul, D., Schwach, F., Scott, C., Seekings, P., Shirley, L., Simms, A., Sinnott, M., Sivadasan, S., Siwek, B., Sizer, D., Skeldon, K., Skelton, J., Slater-Tunstill, J., Sloper, L., Smerdon, N., Smith, C., Smith, J., Smith, K., Smith, M., Smith, S., Smith, T., Sneade, L., Soria, C. D., Sousa, C., Souster, E., Sparkes, A., Spencer-Chapman, M., Squares, J., Steed, C., Stickland, T., Still, I., Stratton, M., Strickland, M., Swann, A., Swiatkowska, A., Sycamore, N., Swift, E., Symons, E., Szluha, S., Taluy, E., Tao, N., Taylor, K., Thompson, S., Thompson, M., Thomson, M., Thomson, N., Thurston, S., Toombs, D., Topping, B., Tovar-Corona, J., Ungureanu, D., Uphill, J., Urbanova, J., Jansen Van, P., Vancollie, V., Voak, P., Walker, D., Walker, M., Waller, M., Ward, G., Weatherhogg, C., Webb, N., Wells, A., Wells, E., Westwood, L., Whipp, T., Whiteley, T., Whitton, G., Whitwham, A., Widaa, S., Williams, M., Wilson, M., Wright, S., Farr, B. W., Quail, M. A., Thurston, S. A. J., Bronner, I. F., Redshaw, N. M., Lensing, S. V., Balcazar, C. E., Gallagher, M. D., Williamson, K. A., Stanton, T. D., Michelsen, M. L., Warwick-Dugdale, J., Manley, R., Farbos, A., Harrison, J. W., Sambles, C. M., Studholme, D. J., Lackenby, A., Mbisa, T., Platt, S., Miah, S., Bibby, D., Manso, C., Hubb, J., Dabrera, G., Ramsay, M., Bradshaw, D., Schaefer, U., Groves, N., Gallagher, E., Lee, D., Williams, D., Ellaby, N., Hartman, H., Manesis, N., Patel, V., Ledesma, J., Twohig, K. A., Allara, E., Pearson, C., Cheng, J. K. J., Bridgewater, H. E., Frost, L. R., Taylor-Joyce, G., Brown, P. E., Tong, L., Broos, A., Mair, D., Nichols, J., Carmichael, S. N., Smollett, K. L., Nomikou, K., Aranday-Cortes, E., Johnson, N., Nickbakhsh, S., Vamos, E. E., Hughes, M., Rainbow, L., Eccles, R., Nelson, C., Whitehead, M., Gregory, R., Gemmell, M., Wierzbicki, C., Webster, H. J., Fisher, C. L., Signell, A. W., Betancor, G., Wilson, H. D., Nebbia, G., Flaviani, F., Cerda, A. C., Merrill, T. V., Wilson, R. E., Cotic, M., Bayzid, N., Thompson, T., Acheson, E., Rushton, S., O'Brien, S., Baker, D. J., Rudder, S., Aydin, A., Sang, F., Debebe, J., Francois, S., Vasylyeva, T. I., Zamudio, M. E., Gutierrez, B., Marchbank, A., Maksimovic, J., Spellman, K., Mccluggage, K., Morgan, M., Beer, R., Afifi, S., Workman, T., Fuller, W., Bresner, C., Angyal, A., Green, L. R., Parsons, P. J., Tucker, R. M., Brown, R., Whiteley, M., Rowe, W., Siveroni, I., Le-Viet, T., Gaskin, A., Johnson, R., Sharrocks, K., Blane, E., Modis, Y., Leigh, K. E., Briggs, J. A. G., van Gils, M. J., Smith, K. G. C., Bradley, J. R., Doffinger, R., Ceron-Gutierrez, L., Barcenas-Morales, G., Pollock, D. D., Goldstein, R. A., Smielewska, A., Skittrall, J. P., Gouliouris, T., Goodfellow, I. G., Gkrania-Klotsas, E., Illingworth, C. J. R., Mccoy, L. E., Gupta, R. K., Medical Microbiology and Infection Prevention, AII - Infectious diseases, Collier, Dami A [0000-0001-5446-4423], Jahun, Aminu [0000-0002-4585-1701], Temperton, Nigel [0000-0002-7978-3815], Modis, Yorgo [0000-0002-6084-0429], Briggs, John AG [0000-0003-3990-6910], Goldstein, Richard A [0000-0001-5148-4672], Skittrall, Jordan P [0000-0002-8228-3758], Gkrania-Klotsas, Effrossyni [0000-0002-0930-8330], McCoy, Laura E [0000-0001-9503-7946], Gupta, Ravindra K [0000-0001-9751-1808], and Apollo - University of Cambridge Repository

Subjects
0301 basic medicine, Male, Time Factors, viruses, Passive, Antibodies, Viral, CITIID-NIHR BioResource COVID-19 Collaboration, 2.1 Biological and endogenous factors, Viral, Aetiology, Neutralizing, Lung, Phylogeny, neutralising antibodies, Infectivity, education.field_of_study, Genome, Multidisciplinary, Alanine, biology, High-Throughput Nucleotide Sequencing, Viral Load, Spike Glycoprotein, Virus Shedding, Adenosine Monophosphate, Aged, Antibodies, Neutralizing, COVID-19, Chronic Disease, Genome, Viral, Humans, Immune Evasion, Immune Tolerance, Immunization, Passive, Immunosuppression Therapy, Mutagenesis, Mutant Proteins, Mutation, SARS-CoV-2, Spike Glycoprotein, Coronavirus, Evolution, Molecular, Infectious Diseases, Pneumonia & Influenza, Antibody, Infection, Viral load, Biotechnology, Evolution, General Science & Technology, antibody escape, Convalescent plasma, 030106 microbiology, Population, evasion, Antibodies, Virus, Article, Vaccine Related, resistance, 03 medical and health sciences, Immune system, COVID-19 Genomics UK (COG-UK) Consortium, Biodefense, Genetics, Viral shedding, education, COVID-19 Serotherapy, QR355, Prevention, Wild type, Molecular, Pneumonia, Virology, COVID-19 Drug Treatment, Coronavirus, Emerging Infectious Diseases, Good Health and Well Being, 030104 developmental biology, biology.protein, Immunization, immune suppression, mutation
Abstract

The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical for virus infection through the engagement of the human ACE2 protein1 and is a major antibody target. Here we show that chronic infection with SARS-CoV-2 leads to viral evolution and reduced sensitivity to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma, by generating whole-genome ultra-deep sequences for 23 time points that span 101 days and using in vitro techniques to characterize the mutations revealed by sequencing. There was little change in the overall structure of the viral population after two courses of remdesivir during the first 57 days. However, after convalescent plasma therapy, we observed large, dynamic shifts in the viral population, with the emergence of a dominant viral strain that contained a substitution (D796H) in the S2 subunit and a deletion (ΔH69/ΔV70) in the S1 N-terminal domain of the spike protein. As passively transferred serum antibodies diminished, viruses with the escape genotype were reduced in frequency, before returning during a final, unsuccessful course of convalescent plasma treatment. In vitro, the spike double mutant bearing both ΔH69/ΔV70 and D796H conferred modestly decreased sensitivity to convalescent plasma, while maintaining infectivity levels that were similar to the wild-type virus.The spike substitution mutant D796H appeared to be the main contributor to the decreased susceptibility to neutralizing antibodies, but this mutation resulted in an infectivity defect. The spike deletion mutant ΔH69/ΔV70 had a twofold higher level of infectivity than wild-type SARS-CoV-2, possibly compensating for the reduced infectivity of the D796H mutation. These data reveal strong selection on SARS-CoV-2 during convalescent plasma therapy, which is associated with the emergence of viral variants that show evidence of reduced susceptibility to neutralizing antibodies in immunosuppressed individuals.

Published
2021

3. Circulation of respiratory viruses during the COVID-19 pandemic in The Gambia

Author

Jarju, S., primary, Senghore, E., additional, Brotherton, H., additional, Saidykhan, A., additional, Jallow, S., additional, Krubally, E., additional, Sinjanka, E., additional, Ndene, M.N., additional, Bajo, F., additional, Sanyang, M., additional, Saidy, B., additional, Bah, A, additional, Forrest, K., additional, Clarke, E., additional, D’Alessandro, U., additional, Usuf, E., additional, Cerami, C., additional, Roca, A., additional, Kampmann, B., additional, and de Silva, T. I., additional

Published
2022
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4. Intrahost evolution of the HIV-2 capsid correlates with progression to AIDS

Author

Boswell, M T, primary, Nazziwa, J, additional, Kuroki, K, additional, Palm, A, additional, Karlson, S, additional, Månsson, F, additional, Biague, A, additional, da Silva, Z J, additional, Onyango, C O, additional, de Silva, T I, additional, Jaye, A, additional, Norrgren, H, additional, Medstrand, P, additional, Jansson, M, additional, Maenaka, K, additional, Rowland-Jones, S L, additional, and Esbjörnsson, J, additional

Published
2022
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5. Joint consensus statement on the vaccination of adult and paediatric haematopoietic stem cell transplant recipients: Prepared on behalf of the British society of blood and marrow transplantation and cellular therapy (BSBMTCT), the Children's cancer...

Author

Miller, PDE, Patel, SR, Skinner, R, Dignan, F, Richter, A, Jeffery, K, Khan, A, Heath, PT, Clark, A, Orchard, K, Snowden, JA, de Silva, TI, Patel, S R, Heath, P T, Snowden, J A, and de Silva, T I

Abstract

Haematopoietic stem cell transplant (HSCT) recipients have deficiencies in their adaptive immunity against vaccine preventable diseases. National and International guidance recommends that HSCT recipients are considered 'never vaccinated' and offered a comprehensive course of revaccination. This position statement aims to draw upon the current evidence base and existing guidelines, and align this with national vaccine availability and licensing considerations in order to recommend a pragmatic and standardised re-vaccination schedule for adult and paediatric HSCT recipients in the UK. [ABSTRACT FROM AUTHOR]

Published
2023
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6. Sensitivity of SARS-CoV-2 B.1.1.7 to mRNA vaccine-elicited antibodies

Author

Collier, D. A., De Marco, A., Ferreira, I. A. T. M., Meng, B., Datir, R. P., Walls, A. C., Kemp, S. A., Bassi, J., Pinto, D., Silacci-Fregni, C., Bianchi, S., Tortorici, M. A., Bowen, J., Culap, K., Jaconi, S., Cameroni, E., Snell, G., Pizzuto, M. S., Pellanda, A. F., Garzoni, C., Riva, A., Baker, S., Dougan, G., Hess, C., Kingston, N., Lehner, P. J., Lyons, P. A., Matheson, N. J., Owehand, W. H., Saunders, C., Summers, C., Thaventhiran, J. E. D., Toshner, M., Weekes, M. P., Bucke, A., Calder, J., Canna, L., Domingo, J., Elmer, A., Fuller, S., Harris, J., Hewitt, S., Kennet, J., Jose, S., Kourampa, J., Meadows, A., O'Brien, C., Price, J., Publico, C., Rastall, R., Ribeiro, C., Rowlands, J., Ruffolo, V., Tordesillas, H., Bullman, B., Dunmore, B. J., Fawke, S., Graf, S., Hodgson, J., Huang, C., Hunter, K., Jones, E., Legchenko, E., Matara, C., Martin, J., Mescia, F., O'Donnell, C., Pointon, L., Pond, N., Shih, J., Sutcliffe, R., Tilly, T., Treacy, C., Tong, Z., Wood, J., Wylot, M., Bergamaschi, L., Betancourt, A., Bower, G., Cossetti, C., De Sa, A., Epping, M., Grenfell, R., Hinch, A., Huhn, O., Jackson, S., Jarvis, I., Lewis, D., Marsden, J., Nice, F., Okecha, G., Omarjee, O., Perera, M., Richoz, N., Romashova, V., Yarkoni, N. S., Sharma, R., Stefanucci, L., Stephens, J., Strezlecki, M., Turner, L., De Bie, E. M. D. D., Bunclark, K., Josipovic, M., Mackay, M., Rossi, S., Selvan, M., Spencer, S., Yong, C., Ansaripour, A., Michael, A., Mwaura, L., Patterson, C., Polwarth, G., Polgarova, P., di Stefano, G., Fahey, C., Michel, R., Bong, S. -H., Coudert, J. 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P., Pacchiarini, N., Loveson, K. F., Carabelli, A. M., Templeton, K. E., Langford, C. F., Sillitoe, J., de Silva, T. I., Wang, D., Kwiatkowski, D., Rambaut, A., O'Grady, J., Cottrell, S., Holden, M. T. G., Thomson, E. C., Osman, H., Andersson, M., Chauhan, A. J., Hassan-Ibrahim, M. O., Lawniczak, M., Alderton, A., Chand, M., Constantinidou, C., Unnikrishnan, M., Darby, A. C., Hiscox, J. A., Paterson, S., Martincorena, I., Robertson, D. L., Volz, E. M., Page, A. J., Pybus, O. G., Bassett, A. R., Ariani, C. V., Spencer Chapman, M. H., K. K., Li, Shah, R. N., Jesudason, N. G., Taha, Y., Mchugh, M. P., Dewar, R., Jahun, A. S., Mcmurray, C., Pandey, S., Mckenna, J. P., Nelson, A., Young, G. R., Mccann, C. M., Elliott, S., Lowe, H., Temperton, B., Roy, S., Price, A., Rey, S., Wyles, M., Rooke, S., Shaaban, S., de Cesare, M., Letchford, L., Silveira, S., Pelosi, E., Wilson-Davies, E., Hosmillo, M., O'Toole, A., Hesketh, A. R., Stark, R., du Plessis, L., Ruis, C., Adams, H., Bourgeois, Y., Michell, S. L., Gramatopoulos, D., Edgeworth, J., Breuer, J., Todd, J. A., Fraser, C., Buck, D., John, M., Kay, G. L., Palmer, S., Peacock, S. J., Heyburn, D., Weldon, D., Robinson, E., Mcnally, A., Muir, P., Vipond, I. B., Boyes, J., Sivaprakasam, V., Salluja, T., Dervisevic, S., Meader, E. J., Park, N. R., Oliver, K., Jeffries, A. R., Ott, S., da Silva Filipe, A., Simpson, D. A., Williams, C., Masoli, J. A. H., Knight, B. A., Jones, C. R., Koshy, C., Ash, A., Casey, A., Bosworth, A., Ratcliffe, L., Xu-McCrae, L., Pymont, H. M., Hutchings, S., Berry, L., Jones, K., Halstead, F., Davis, T., Holmes, C., Iturriza-Gomara, M., Lucaci, A. O., Randell, P. A., Cox, A., Madona, P., Harris, K. A., Brown, J. R., Mahungu, T. W., Irish-Tavares, D., Haque, T., Hart, J., Witele, E., Fenton, M. L., Liggett, S., Graham, C., Swindells, E., Collins, J., Eltringham, G., Campbell, S., Mcclure, P. C., Clark, G., Sloan, T. J., Jones, C., Lynch, J., Warne, B., Leonard, S., Durham, J., Williams, T., Haldenby, S. T., Storey, N., Alikhan, N. -F., Holmes, N., Carlile, M., Perry, M., Craine, N., Lyons, R. A., Beckett, A. H., Goudarzi, S., Fearn, C., Cook, K., Dent, H., Paul, H., Davies, R., Blane, B., Girgis, S. T., Beale, M. A., Bellis, K. L., Dorman, M. J., Drury, E., Kane, L., Kay, S., Mcguigan, S., Nelson, R., Prestwood, L., Rajatileka, S., Batra, R., Williams, R. J., Kristiansen, M., Green, A., Justice, A., Mahanama, A. I. K., Samaraweera, B., Hadjirin, N. F., Quick, J., Poplawski, R., Kermack, L. M., Reynolds, N., Hall, G., Chaudhry, Y., Pinckert, M. L., Georgana, I., Moll, R. J., Thornton, A., Myers, R., Stockton, J., Williams, C. A., Yew, W. C., Trotter, A. J., Trebes, A., MacIntyre-Cockett, G., Birchley, A., Adams, A., Plimmer, A., Gatica-Wilcox, B., Mckerr, C., Hilvers, E., Jones, H., Asad, H., Coombes, J., Evans, J. M., Fina, L., Gilbert, L., Graham, L., Cronin, M., Kumziene-Summerhayes, S., Taylor, S., Jones, S., Groves, D. C., Zhang, P., Gallis, M., Louka, S. F., Starinskij, I., Jackson, C., Gourtovaia, M., Tonkin-Hill, G., Lewis, K., Tovar-Corona, J. M., James, K., Baxter, L., Alam, M. T., Orton, R. J., Hughes, J., Vattipally, S., Ragonnet-Cronin, M., Nascimento, F. F., Jorgensen, D., Boyd, O., Geidelberg, L., Zarebski, A. E., Raghwani, J., Kraemer, M. U. G., Southgate, J., Lindsey, B. B., Freeman, T. M., Keatley, J. -P., Singer, J. B., de Oliveira Martins, L., Yeats, C. A., Abudahab, K., Taylor, B. E. W., Menegazzo, M., Danesh, J., Hogsden, W., Eldirdiri, S., Kenyon, A., Mason, J., Robinson, T. I., Holmes, A., Hartley, J. A., Curran, T., Mather, A. E., Shankar, G., Jones, R., Howe, R., Morgan, S., Wastenge, E., Chapman, M. R., Mookerjee, S., Stanley, R., Smith, W., Peto, T., Eyre, D., Crook, D., Vernet, G., Kitchen, C., Gulliver, H., Merrick, I., Guest, M., Munn, R., Bradley, D. T., Wyatt, T., Beaver, C., Foulser, L., Churcher, C. M., Brooks, E., Smith, K. S., Galai, K., Mcmanus, G. M., Bolt, F., Coll, F., Meadows, L., Attwood, S. W., Davies, A., De Lacy, E., Downing, F., Edwards, S., Scarlett, G. P., Jeremiah, S., Smith, N., Leek, D., Sridhar, S., Forrest, S., Cormie, C., Gill, H. K., Dias, J., Higginson, E. E., Maes, M., Young, J., Wantoch, M., Jamrozy, D., Lo, S., Patel, M., Hill, V., Bewshea, C. M., Ellard, S., Auckland, C., Harrison, I., Bishop, C., Chalker, V., Richter, A., Beggs, A., Best, A., Percival, B., Mirza, J., Megram, O., Mayhew, M., Crawford, L., Ashcroft, F., Moles-Garcia, E., Cumley, N., Hopes, R., Asamaphan, P., Niebel, M. O., Gunson, R. N., Bradley, A., Maclean, A., Mollett, G., Blacow, R., Bird, P., Helmer, T., Fallon, K., Tang, J., Hale, A. D., Macfarlane-Smith, L. R., Harper, K. L., Carden, H., Machin, N. W., Jackson, K. A., Ahmad, S. S. Y., George, R. P., Turtle, L., O'Toole, E., Watts, J., Breen, C., Cowell, A., Alcolea-Medina, A., Charalampous, T., Patel, A., Levett, L. J., Heaney, J., Rowan, A., Taylor, G. P., Shah, D., Atkinson, L., Lee, J. C. D., Westhorpe, A. P., Jannoo, R., Lowe, H. L., Karamani, A., Ensell, L., Chatterton, W., Pusok, M., Dadrah, A., Symmonds, A., Sluga, G., Molnar, Z., Baker, P., Bonner, S., Essex, S., Barton, E., Padgett, D., Scott, G., Greenaway, J., Payne, B. A. I., Burton-Fanning, S., Waugh, S., Raviprakash, V., Sheriff, N., Blakey, V., Williams, L. -A., Moore, J., Stonehouse, S., Smith, L., Davidson, R. K., Bedford, L., Coupland, L., Wright, V., Chappell, J. G., Tsoleridis, T., Ball, J., Khakh, M., Fleming, V. M., Lister, M. M., Howson-Wells, H. C., Boswell, T., Joseph, A., Willingham, I., Duckworth, N., Walsh, S., Wise, E., Moore, N., Mori, M., Cortes, N., Kidd, S., Williams, R., Gifford, L., Bicknell, K., Wyllie, S., Lloyd, A., Impey, R., Malone, C. S., Cogger, B. J., Levene, N., Monaghan, L., Keeley, A. J., Partridge, D. G., Raza, M., Evans, C., Johnson, K., Betteridge, E., Farr, B. W., Goodwin, S., Quail, M. A., Scott, C., Shirley, L., Thurston, S. A. J., Rajan, D., Bronner, I. F., Aigrain, L., Redshaw, N. M., Lensing, S. V., Mccarthy, S., Makunin, A., Balcazar, C. E., Gallagher, M. D., Williamson, K. A., Stanton, T. D., Michelsen, M. L., Warwick-Dugdale, J., Manley, R., Farbos, A., Harrison, J. W., Sambles, C. M., Studholme, D. J., Lackenby, A., Mbisa, T., Platt, S., Miah, S., Bibby, D., Manso, C., Hubb, J., Dabrera, G., Ramsay, M., Bradshaw, D., Schaefer, U., Groves, N., Gallagher, E., Lee, D., Williams, D., Ellaby, N., Hartman, H., Manesis, N., Patel, V., Ledesma, J., Twohig, K. A., Allara, E., Pearson, C., Cheng, J. K. J., Bridgewater, H. E., Frost, L. R., Taylor-Joyce, G., Brown, P. E., Tong, L., Broos, A., Mair, D., Nichols, J., Carmichael, S. N., Smollett, K. L., Nomikou, K., Aranday-Cortes, E., Johnson, N., Nickbakhsh, S., Vamos, E. E., Hughes, M., Rainbow, L., Eccles, R., Nelson, C., Whitehead, M., Gregory, R., Gemmell, M., Wierzbicki, C., Webster, H. J., Fisher, C. L., Signell, A. W., Betancor, G., Wilson, H. D., Nebbia, G., Flaviani, F., Cerda, A. C., Merrill, T. V., Wilson, R. E., Cotic, M., Bayzid, N., Thompson, T., Acheson, E., Rushton, S., O'Brien, S., Baker, D. J., Rudder, S., Aydin, A., Sang, F., Debebe, J., Francois, S., Vasylyeva, T. I., Zamudio, M. E., Gutierrez, B., Marchbank, A., Maksimovic, J., Spellman, K., Mccluggage, K., Morgan, M., Beer, R., Afifi, S., Workman, T., Fuller, W., Bresner, C., Angyal, A., Green, L. R., Parsons, P. J., Tucker, R. M., Brown, R., Whiteley, M., Bonfield, J., Puethe, C., Whitwham, A., Liddle, J., Rowe, W., Siveroni, I., Le-Viet, T., Gaskin, A., Johnson, R., Abnizova, I., Ali, M., Allen, L., Anderson, R., Ariani, C., Austin-Guest, S., Bala, S., Bassett, A., Battleday, K., Beal, J., Beale, M., Bellany, S., Bellerby, T., Bellis, K., Berger, D., Berriman, M., Bevan, P., Binley, S., Bishop, J., Blackburn, K., Boughton, N., Bowker, S., Brendler-Spaeth, T., Bronner, I., Brooklyn, T., Buddenborg, S. K., Bush, R., Caetano, C., Cagan, A., Carter, N., Cartwright, J., Monteiro, T. C., Chapman, L., Chillingworth, T. -J., Clapham, P., Clark, R., Clarke, A., Clarke, C., Cole, D., Cook, E., Coppola, M., Cornell, L., Cornwell, C., Corton, C., Crackett, A., Cranage, A., Craven, H., Craw, S., Crawford, M., Cutts, T., Dabrowska, M., Davies, M., Dawson, J., Day, C., Densem, A., Dibling, T., Dockree, C., Dodd, D., Dogga, S., Dougherty, M., Dove, A., Drummond, L., Dudek, M., Durrant, L., Easthope, E., Eckert, S., Ellis, P., Farr, B., Fenton, M., Ferrero, M., Flack, N., Fordham, H., Forsythe, G., Francis, M., Fraser, A., Freeman, A., Galvin, A., Garcia-Casado, M., Gedny, A., Girgis, S., Glover, J., Gould, O., Gray, A., Gray, E., Griffiths, C., Gu, Y., Guerin, F., Hamilton, W., Hanks, H., Harrison, E., Harrott, A., Harry, E., Harvison, J., Heath, P., Hernandez-Koutoucheva, A., Hobbs, R., Holland, D., Holmes, S., Hornett, G., Hough, N., Huckle, L., Hughes-Hallet, L., Hunter, A., Inglis, S., Iqbal, S., Jackson, A., Jackson, D., Verdejo, C. J., Jones, M., Kallepally, K., Kay, K., Keatley, J., Keith, A., King, A., Kitchin, L., Kleanthous, M., Klimekova, M., Korlevic, P., Krasheninnkova, K., Lane, G., Langford, C., Laverack, A., Law, K., Lensing, S., Lewis-Wade, A., Lin, Q., Lindsay, S., Linsdell, S., Long, R., Lovell, J., Mack, J., Maddison, M., Mamun, I., Mansfield, J., Marriott, N., Martin, M., Mayho, M., Mcclintock, J., Mchugh, S., Mcminn, L., Meadows, C., Mobley, E., Moll, R., Morra, M., Morrow, L., Murie, K., Nash, S., Nathwani, C., Naydenova, P., Neaverson, A., Nerou, E., Nicholson, J., Nimz, T., Noell, G. G., O'Meara, S., Ohan, V., Olney, C., Ormond, D., Oszlanczi, A., Pang, Y. F., Pardubska, B., Park, N., Parmar, A., Patel, G., Payne, M., Peacock, S., Petersen, A., Plowman, D., Preston, T., Quail, M., Rance, R., Rawlings, S., Redshaw, N., Reynolds, J., Reynolds, M., Rice, S., Richardson, M., Roberts, C., Robinson, K., Robinson, M., Robinson, D., Rogers, H., Rojo, E. M., Roopra, D., Rose, M., Rudd, L., Sadri, R., Salmon, N., Saul, D., Schwach, F., Seekings, P., Simms, A., Sinnott, M., Sivadasan, S., Siwek, B., Sizer, D., Skeldon, K., Skelton, J., Slater-Tunstill, J., Sloper, L., Smerdon, N., Smith, C., Smith, J., Smith, K., Smith, M., Smith, S., Smith, T., Sneade, L., Soria, C. D., Sousa, C., Souster, E., Sparkes, A., Spencer-Chapman, M., Squares, J., Steed, C., Stickland, T., Still, I., Stratton, M., Strickland, M., Swann, A., Swiatkowska, A., Sycamore, N., Swift, E., Symons, E., Szluha, S., Taluy, E., Tao, N., Taylor, K., Thompson, S., Thompson, M., Thomson, M., Thomson, N., Thurston, S., Toombs, D., Topping, B., Tovar-Corona, J., Ungureanu, D., Uphill, J., Urbanova, J., Van, P. J., Vancollie, V., Voak, P., Walker, D., Walker, M., Waller, M., Ward, G., Weatherhogg, C., Webb, N., Wells, A., Wells, E., Westwood, L., Whipp, T., Whiteley, T., Whitton, G., Widaa, S., Williams, M., Wilson, M., Wright, S., Harvey, W., Virgin, H. W., Lanzavecchia, A., Piccoli, L., Doffinger, R., Wills, M., Veesler, D., Corti, D., and Gupta, R. K.

Subjects
0301 basic medicine, Male, Models, Molecular, Passive, Antibodies, Viral, Neutralization, 0302 clinical medicine, Models, Monoclonal, 80 and over, Viral, Neutralizing antibody, Neutralizing, Aged, 80 and over, Vaccines, Vaccines, Synthetic, Multidisciplinary, biology, Antibodies, Monoclonal, C500, Middle Aged, C700, Spike Glycoprotein, Vaccination, Spike Glycoprotein, Coronavirus, Female, Angiotensin-Converting Enzyme 2, Antibody, Aged, Antibodies, Neutralizing, COVID-19, COVID-19 Vaccines, HEK293 Cells, Humans, Immune Evasion, Immunization, Passive, Mutation, Neutralization Tests, SARS-CoV-2, medicine.drug_class, B100, Monoclonal antibody, Antibodies, Virus, 03 medical and health sciences, Immune system, medicine, COVID-19 Serotherapy, QR355, Synthetic, Molecular, Virology, Coronavirus, 030104 developmental biology, Immunization, biology.protein, 030217 neurology & neurosurgery
Abstract

Transmission of SARS-CoV-2 is uncontrolled in many parts of the world; control is compounded in some areas by the higher transmission potential of the B.1.1.7 variant1, which has now been reported in 94 countries. It is unclear whether the response of the virus to vaccines against SARS-CoV-2 on the basis of the prototypic strain will be affected by the mutations found in B.1.1.7. Here we assess the immune responses of individuals after vaccination with the mRNA-based vaccine BNT162b22. We measured neutralizing antibody responses after the first and second immunizations using pseudoviruses that expressed the wild-type spike protein or a mutated spike protein that contained the eight amino acid changes found in the B.1.1.7 variant. The sera from individuals who received the vaccine exhibited a broad range of neutralizing titres against the wild-type pseudoviruses that were modestly reduced against the B.1.1.7 variant. This reduction was also evident in sera from some patients who had recovered from COVID-19. Decreased neutralization of the B.1.1.7 variant was also observed for monoclonal antibodies that target the N-terminal domain (9 out of 10) and the receptor-binding motif (5 out of 31), but not for monoclonal antibodies that recognize the receptor-binding domain that bind outside the receptor-binding motif. Introduction of the mutation that encodes the E484K substitution in the B.1.1.7 background to reflect a newly emerged variant of concern (VOC 202102/02) led to a more-substantial loss of neutralizing activity by vaccine-elicited antibodies and monoclonal antibodies (19 out of 31) compared with the loss of neutralizing activity conferred by the mutations in B.1.1.7 alone. The emergence of the E484K substitution in a B.1.1.7 background represents a threat to the efficacy of the BNT162b2 vaccine.

Published
2021

24. The impact of viral mutations on recognition by SARS-CoV-2 specific T cells

Author

de Silva, T. I., Liu, G., Lindsey, B. B., Dong, D., Moore, S. C., Hsu, N. S., Shah, D., Wellington, D., Mentzer, A. J., Angyal, A., Brown, R., Parker, M. D., Ying, Z., Yao, X., Turtle, L., Dunachie, S., COVID-19 Genomics UK (COG-UK) Consortium, Maini, M. K., Ogg, G., Knight, J. C., ISARIC4C Investigators, Peng, Y., Rowland-Jones, S. L., Dong, T., de Silva, T. I., Liu, G., Lindsey, B. B., Dong, D., Moore, S. C., Hsu, N. S., Shah, D., Wellington, D., Mentzer, A. J., Angyal, A., Brown, R., Parker, M. D., Ying, Z., Yao, X., Turtle, L., Dunachie, S., COVID-19 Genomics UK (COG-UK) Consortium, Maini, M. K., Ogg, G., Knight, J. C., ISARIC4C Investigators, Peng, Y., Rowland-Jones, S. L., and Dong, T.

25. Recurrent SARS-CoV-2 mutations in immunodeficient patients

Author

Wilkinson, S. A. J., Sparks, N., Kele, B., Peacock, T. P., 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., 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., 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., 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., 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. 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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., Nicodemi, R., Podplomyk, O., Somassa, T., Beggs, A., Richter, A., Cormie, C., Dias, J., Forrest, S., Higginson, E. E., Maes, M., Young, J., Davidson, R. K., Jackson, K. A., Turtle, L., Keeley, A. J., Ball, J., Byaruhanga, T., Chappell, J. G., Dey, J., Hill, J. D., Park, E. J., Fanaie, A., Hilson, R. A., Yaze, G., Lo, S., Afifi, S., Beer, R., Maksimovic, J., McCluggage, K., Spellman, K., Bresner, C., Fuller, W., Marchbank, A., Workman, T., Shelest, E., Debebe, J., Sang, F., Zamudio, M. E., Francois, S., Gutierrez, B., Vasylyeva, T. I., Flaviani, F., Ragonnet-Cronin, M, Smollett, K. 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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., 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., 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., 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., 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., 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., Nicodemi, R., Podplomyk, O., Somassa, T., Beggs, A., Richter, A., Cormie, C., Dias, J., Forrest, S., Higginson, E. E., Maes, M., Young, J., Davidson, R. K., Jackson, K. A., Turtle, L., Keeley, A. J., Ball, J., Byaruhanga, T., Chappell, J. G., Dey, J., Hill, J. D., Park, E. J., Fanaie, A., Hilson, R. A., Yaze, G., Lo, S., Afifi, S., Beer, R., Maksimovic, J., McCluggage, K., Spellman, K., Bresner, C., Fuller, W., Marchbank, A., Workman, T., Shelest, E., Debebe, J., Sang, F., Zamudio, M. E., Francois, S., Gutierrez, B., Vasylyeva, T. I., Flaviani, F., Ragonnet-Cronin, M, Smollett, K. L., Broos, A., Mair, D., Nichols, J., Nomikou, K., Tong, L., Tsatsani, I., O’Brien, S., Rushton, S., Sanderson, R., Perkins, J., Cotton, S., Gallagher, A., Allara, E., Pearson, C., Bibby, D., Dabrera, G., Ellaby, N., Gallagher, E., Hubb, J., Lackenby, A., Lee, D., Manesis, N., Mbisa, T., Platt, S., Twohig, K. A., Morgan, M., Aydin, A., Baker, D. J., Foster-Nyarko, E., Prosolek, S. J., Rudder, S., Baxter, C., Carvalho, S. F., Lavin, D., Mariappan, A., Radulescu, C., Singh, A., Tang, M., Morcrette, H., Bayzid, N., Cotic, M., Balcazar, C. E, Gallagher, M. D., Maloney, D., Stanton, T. D., Williamson, K. A., Manley, R., Michelsen, M. L., Sambles, C. M., Studholme, D. J., Warwick-Dugdale, J., Eccles, R., Gemmell, M., Gregory, R., Hughes, M., Nelson, C., Rainbow, L., Vamos, E. E., Webster, H. J., Whitehead, M., Wierzbicki, C., Angyal, A., Green, L. R., Whiteley, M., Betteridge, E., Bronner, I. F., Farr, B. W., Goodwin, S., Lensing, S. V., McCarthy, S. A., Quail, M. A., Rajan, D., Redshaw, N. M., Scott, C., Shirley, L., Thurston, S. A. J., Rowe, W., Gaskin, A., Le-Viet, T., Bonfield, J., Liddle, J., and Whitwham, A.

Abstract

Long-term severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in immunodeficient patients are an important source of variation for the virus but are understudied. Many case studies have been published which describe one or a small number of long-term infected individuals but no study has combined these sequences into a cohesive dataset. This work aims to rectify this and study the genomics of this patient group through a combination of literature searches as well as identifying new case series directly from the COVID-19 Genomics UK (COG-UK) dataset. The spike gene receptor-binding domain and N-terminal domain (NTD) were identified as mutation hotspots. Numerous mutations associated with variants of concern were observed to emerge recurrently. Additionally a mutation in the envelope gene, T30I was determined to be the second most frequent recurrently occurring mutation arising in persistent infections. A high proportion of recurrent mutations in immunodeficient individuals are associated with ACE2 affinity, immune escape, or viral packaging optimisation.There is an apparent selective pressure for mutations that aid cell–cell transmission within the host or persistence which are often different from mutations that aid inter-host transmission, although the fact that multiple recurrent de novo mutations are considered defining for variants of concern strongly indicates that this potential source of novel variants should not be discounted. © The Author(s) 2022. Published by Oxford University Press.

26. COVID-19 due to the B.1.617.2 (Delta) variant compared to B.1.1.7 (Alpha) variant of SARS-CoV-2: a prospective observational cohort study

Author

Kläser, K., Molteni, E., Graham, M., Canas, L. S., Österdahl, M. F., Antonelli, M., Chen, L., Deng, J., Murray, B., Kerfoot, E., Wolf, J., May, A., Fox, B., Capdevila, J., Aanensen, D. M., Abudahab, K., Adams, H., Adams, A., Afifi, S., Aggarwal, D., Ahmad, S. S. Y., Aigrain, L., Alcolea-Medina, A., Alikhan, N-F, Allara, E., Amato, R., Angyal, A., Annett, T., Aplin, S., Ariani, C. V., Asad, H., Ash, A., Ashfield, P., Ashford, F., Atkinson, L., Attwood, S. W., Auckland, C., Aydin, A., Baker, D. J., Baker, P., Balcazar, C. E., Ball, J., Barrett, J. C., Barrow, M., Barton, E., Bashton, M., Bassett, A. R., Batra, R., Baxter, C., Bayzid, N., Beaver, C., Beckett, A. H., Beckwith, S. M., Bedford, L., Beer, R., Beggs, A., Bellis, K. L., Berry, L., Bertolusso, B., Best, A., Betteridge, E., Bibby, D., Bicknell, K., Binns, D., Birchley, A., Bird, P. W., Bishop, C., Blacow, R., Blakey, V., Blane, B., Bolt, F., Bonfield, J., Bonner, S., Bonsall, D., Boswell, T., Bosworth, A., Bourgeois, Y., Boyd, O., Bradley, D. T., Breen, C., Bresner, C., Breuer, J., Bridgett, S., Bronner, I. F., Brooks, E., Broos, A., Brown, J. R., Bucca, G., Buchan, S. L., Buck, D., Bull, M., Burns, P. J., Burton-Fanning, S., Byaruhanga, T., Byott, M., Campbell, S., Carabelli, A. M., Cargill, J. S., Carlile, M., Carvalho, S. F., Casey, A., Castigador, A., Catalan, J., Chalker, V., Chaloner, N. J., Chand, M., Chappell, J. G., Charalampous, T., Chatterton, W., Chaudhry, Y., Churcher, C. M., Clark, G., Clarke, P., Cogger, B. J., Cole, K., Collins, J., Colquhoun, R., Connor, T. R., Cook, K. F., Coombes, J., Corden, S., Cormie, C., Cortes, N., Cotic, M., Cotton, S., Cottrell, S., Coupland, L., Cox, M. G., Cox, A., Craine, N., Crawford, L., Cross, A., Crown, M. R., Crudgington, D., Cumley, N., Curran, T., Curran, M. D., da Silva Filipe, A., Dabrera, G., Darby, A. C., Davidson, R. K., Davies, A., Davies, R. M., Davis, T., de Angelis, D., De Lacy, E., de Oliveira Martins, L., de Silva, T. I., Debebe, J., Denton-Smith, R., Dervisevic, S., Dewar, R., Dey, J., Dias, J., Dobie, D., Dorman, M. J., Downing, F., Driscoll, M., du Plessis, L., Duckworth, N., Durham, J., Eastick, K., Easton, L. J., Eccles, R., Edgeworth, J., Edwards, S., Bouzidi, K. E., Eldirdiri, S., Ellaby, N., Elliott, S., Eltringham, G., Ensell, L., Erkiert, M. J., Zamudio, M. E., Essex, S., Evans, J. M., Evans, C., Everson, W., Fairley, D. J., Fallon, K., Fanaie, A., Farr, B. W., Fearn, C., Feltwell, T., Ferguson, L., Fina, L., Flaviani, F., Fleming, V. M., Forrest, S., Foster-Nyarko, E., Foulkes, B. H., Foulser, L., Fragakis, M., Frampton, D., Francois, S., Fraser, C., Freeman, T. M., Fryer, H., Fuchs, M., Fuller, W., Gajee, K., Galai, K., Gallagher, A., Gallagher, E., Gallagher, M. D., Gallis, M., Gaskin, A., Gatica-Wilcox, B., Geidelberg, L., Gemmell, M., Georgana, I., George, R. P., Gifford, L., Gilbert, L., Girgis, S. T., Glaysher, S., Goldstein, E. J., Golubchik, T., Gomes, A. N., Gonçalves, S., Goodfellow, I. G., Goodwin, S., Goudarzi, S., Gourtovaia, M., Graham, C. A., Graham, L., Grant, P. R., Green, L. R., Green, A., Greenaway, J., Gregory, R., Guest, M., Gunson, R. N., Gupta, R. K., Gutierrez, B., Haldenby, S. T., Hamilton, W. L., Hansford, S. E., Haque, T., Harris, K. A., Harrison, I., Harrison, E. M., Hart, J., Hartley, .J. A., Harvey, W. T., Harvey, M., Hassan-Ibrahim, M. O., Heaney, J., Helmer, T., Henderson, J. H., Hesketh, A. R., Hey, J., Heyburn, D., Higginson, E. E., Hill, V., Hill, J. D., Hilson, R. A., Hilvers, E., Holden, M. T. G., Hollis, A., Holmes, C. W., Holmes, N., Holmes, A. H., Hopes, R., Hornsby, H. R., Hosmillo, M., Houlihan, C., Howson-Wells, H. C., Hsu, S. N., Hubb, J., Huckson, H., Hughes, W., Hughes, J., Hughes, M., Hutchings, S., Idle, G, Illingworth, CJ, Impey, R, Irish-Tavares, D, Iturriza-Gomara, M, Izuagbe, R, Jackson, C, Jackson, B, Jackson, LM, Jackson, KA, Jackson, DK, Jahun, AS, James, V, James, K, Jeanes, C, Jeffries, AR, Jeremiah, S, Jermy, A, John, M, Johnson, R, Johnson, K, Johnston, I, Jones, O, Jones, S, Jones, H, Jones, CR, Jones, N, Joseph, A, Judges, S, Kay, GL, Kay, S, Keatley, J - P, Keeley, AJ, Kenyon, A, Kermack, LM, Khakh, M, Kidd, SP, Kimuli, M, Kirk, S, Kitchen, C, Kitchman, K, Knight, BA, Koshy, C, Kraemer, MUG, Kumziene-Summerhayes, S, Kwiatkowski, D, Lackenby, A, Laing, KG, Lampejo, T, Langford, CF, Lavin, D, Lawton, AI, Lee, JCD, Lee, D, Lensing, SV, Leonard, S, Levett, LJ, Le-Viet, T, Lewis, J, Lewis, K, Liddle, J, Liggett, S, Lillie, PJ, Lindsey, BB, Lister, MM, Livett, R, Lo, S, Loman, NJ, Loose, MW, Louka, SF, Loveson, KF, Lowdon, S, Lowe, H, Lowe, HL, Lucaci, AO, Ludden, C, Lynch, J, Lyons, RA, Lythgoe, K, Machin, NW, MacIntyre-Cockett, G, Mack, A, Macklin, B, Maclean, A, Macnaughton, E, Madona, P, Maes, M, Maftei, L, Mahanama, AIK, Mahungu, TW, Mair, D, Maksimovic, J, Malone, CS, Maloney, D, Manesis, N, Manley, R, Mantzouratou, A, Marchbank, A, Mariappan, A, Martincorena, I, Nunez, RTM, Mather, AE, Maxwell, P, Mayhew, M, Mbisa, T, McCann, CM, McCarthy, SA, McCluggage, K, McClure, PC, McCrone, JT, McHugh, MP, McKenna, JP, McKerr, C, McManus, GM, McMurray, CL, McMurray, C, McNally, A, Meadows, L, Medd, N, Megram, O, Menegazzo, M, Merrick, I, Michell, SL, Michelsen, ML, Mirfenderesky, M, Mirza, J, Miskelly, J, Moles-Garcia, E, Moll, RJ, Molnar, Z, Monahan, IM, Mondani, M, Mookerjee, S, Moore, C, Moore, J, Moore, N, Morcrette, H, Morgan, S, Morgan, M, Mori, M, Morriss, A, Moses, S, Mower, C, Muir, P, Mukaddas, A, Munemo, F, Munn, R, Murray, A, Murray, LJ, Murray, DR, Mutingwende, M, Myers, R, Nastouli, E, Nebbia, G, Nelson, A, Nelson, C, Nicholls, S, Nichols, J, Nicodemi, R, Nomikou, K, O’Grady, J, O’Brien, S, Odedra, M, Ohemeng-Kumi, N, Oliver, K, Orton, RJ, Osman, H, O’Toole, Á, Pacchiarini, N, Padgett, D, Page, AJ, Park, EJ, Park, NR, Parker, MD, Parmar, S, Partridge, DG, Pascall, D, Patel, A, Patel, B, Paterson, S, Payne, BAI, Peacock, SJ, Pearson, C, Pelosi, E, Percival, B, Perkins, J, Perry, M, Pinckert, ML, Platt, S, Podplomyk, O, Pohare, M, Pond, M, Pope, CF, Poplawski, R, Powell, J, Poyner, J, Prestwood, L, Price, A, Price, JR, Prieto, JA, Pritchard, DT, Prosolek, SJ, Pugh, G, Pusok, M, Pybus, OG, Pymont, HM, Quail, MA, Quick, J, Radulescu, C, Raghwani, J, Ragonnet-Cronin, M, Rainbow, L, Rajan, D, Rajatileka, S, Ramadan, NA, Rambaut, A, Ramble, J, Randell, PA, Randell, P, Ratcliffe, L, Raviprakash, V, Raza, M, Redshaw, NM, Rey, S, Reynolds, N, Richter, A, Robertson, DL, Robinson, E, Robson, SC, Rogan, F, Rooke, S, Rowe, W, Roy, S, Rudder, S, Ruis, C, Rushton, S, Ryan, F, Saeed, K, Samaraweera, B, Sambles, CM, Sanderson, R, Sanderson, T, Sang, F, Sass, T, Scher, E, Scott, G, Scott, C, Sehmi, J, Shaaban, S, Shah, D, Shaw, J, Shelest, E, Shepherd, JG, Sheridan, LA, Sheriff, N, Shirley, L, Sillitoe, J, Silviera, S, Simpson, DA, Singh, A, Singleton, D, Skvortsov, T, Sloan, TJ, Sluga, G, Smith, K, Smith, KS, Smith, P, Smith, DL, Smith, L, Smith, CP, Smith, N, Smollett, KL, Snell, LB, Somassa, T, Southgate, J, Spellman, K, Chapman, MHS, Spurgin, LG, Spyer, MJ, Stanley, R, Stanley, W, Stanton, TD, Starinskij, I, Stockton, J, Stonehouse, S, Storey, N, Studholme, DJ, Sudhanva, M, Swindells, E, Taha, Y, Tan, NK, Tang, JW, Tang, M, Taylor, BEW, Taylor, JF, Taylor, S, Temperton, B, Templeton, KE, Thomas, C, Thomson, L, Thomson, EC, Thornton, A, Thurston, SAJ, Todd, JA, Tomb, R, Tong, L, Tonkin-Hill, G, Torok, ME, Tovar-Corona, JM, Trebes, A, Trotter, AJ, Tsatsani, I, Turnbull, R, Turtle, L, Twohig, KA, Umpleby, H, Underwood, AP, Vamos, EE, Vasylyeva, TI, Vattipally, S, Vernet, G, Vipond, BB, Volz, EM, Walsh, S, Wang, D, Warne, B, Warwick-Dugdale, J, Wastnedge, E, Watkins, J, Watson, LK, Waugh, S, Webster, HJ, Weldon, D, Westwick, E, Whalley, T, Wheeler, H, Whitehead, M, Whiteley, M, Whitwham, A, Wierzbicki, C, Willford, NJ, Williams, L-A, Williams, R, Williams, C, Williams, CA, Williams, RJ, Williams, T, Williamson, KA, Wilson-Davies, E, Witele, E, Withell, KT, Witney, AA, Wolverson, P, Wong, N, Workman, T, Wright, V, Wright, DW, Wyatt, T, Wyllie, S, Xu-McCrae, L., Yavus, M., Yaze, G., Yeats, C. A., Yebra, G., Yew, W. C., Young, G. R., Young, J., Zarebski, A. E., Zhang, P., Modat, M., Hammers, A., Spector, T. D., Steves, C. J., Sudre, C. H., Ourselin, S., Duncan, E. L., Kläser, K., Molteni, E., Graham, M., Canas, L. S., Österdahl, M. F., Antonelli, M., Chen, L., Deng, J., Murray, B., Kerfoot, E., Wolf, J., May, A., Fox, B., Capdevila, J., Aanensen, D. M., Abudahab, K., Adams, H., Adams, A., Afifi, S., Aggarwal, D., Ahmad, S. S. Y., Aigrain, L., Alcolea-Medina, A., Alikhan, N-F, Allara, E., Amato, R., Angyal, A., Annett, T., Aplin, S., Ariani, C. V., Asad, H., Ash, A., Ashfield, P., Ashford, F., Atkinson, L., Attwood, S. W., Auckland, C., Aydin, A., Baker, D. J., Baker, P., Balcazar, C. E., Ball, J., Barrett, J. C., Barrow, M., Barton, E., Bashton, M., Bassett, A. R., Batra, R., Baxter, C., Bayzid, N., Beaver, C., Beckett, A. H., Beckwith, S. M., Bedford, L., Beer, R., Beggs, A., Bellis, K. L., Berry, L., Bertolusso, B., Best, A., Betteridge, E., Bibby, D., Bicknell, K., Binns, D., Birchley, A., Bird, P. W., Bishop, C., Blacow, R., Blakey, V., Blane, B., Bolt, F., Bonfield, J., Bonner, S., Bonsall, D., Boswell, T., Bosworth, A., Bourgeois, Y., Boyd, O., Bradley, D. T., Breen, C., Bresner, C., Breuer, J., Bridgett, S., Bronner, I. F., Brooks, E., Broos, A., Brown, J. R., Bucca, G., Buchan, S. L., Buck, D., Bull, M., Burns, P. J., Burton-Fanning, S., Byaruhanga, T., Byott, M., Campbell, S., Carabelli, A. M., Cargill, J. S., Carlile, M., Carvalho, S. F., Casey, A., Castigador, A., Catalan, J., Chalker, V., Chaloner, N. J., Chand, M., Chappell, J. G., Charalampous, T., Chatterton, W., Chaudhry, Y., Churcher, C. M., Clark, G., Clarke, P., Cogger, B. J., Cole, K., Collins, J., Colquhoun, R., Connor, T. R., Cook, K. F., Coombes, J., Corden, S., Cormie, C., Cortes, N., Cotic, M., Cotton, S., Cottrell, S., Coupland, L., Cox, M. G., Cox, A., Craine, N., Crawford, L., Cross, A., Crown, M. R., Crudgington, D., Cumley, N., Curran, T., Curran, M. D., da Silva Filipe, A., Dabrera, G., Darby, A. C., Davidson, R. K., Davies, A., Davies, R. M., Davis, T., de Angelis, D., De Lacy, E., de Oliveira Martins, L., de Silva, T. I., Debebe, J., Denton-Smith, R., Dervisevic, S., Dewar, R., Dey, J., Dias, J., Dobie, D., Dorman, M. J., Downing, F., Driscoll, M., du Plessis, L., Duckworth, N., Durham, J., Eastick, K., Easton, L. J., Eccles, R., Edgeworth, J., Edwards, S., Bouzidi, K. E., Eldirdiri, S., Ellaby, N., Elliott, S., Eltringham, G., Ensell, L., Erkiert, M. J., Zamudio, M. E., Essex, S., Evans, J. M., Evans, C., Everson, W., Fairley, D. J., Fallon, K., Fanaie, A., Farr, B. W., Fearn, C., Feltwell, T., Ferguson, L., Fina, L., Flaviani, F., Fleming, V. M., Forrest, S., Foster-Nyarko, E., Foulkes, B. H., Foulser, L., Fragakis, M., Frampton, D., Francois, S., Fraser, C., Freeman, T. M., Fryer, H., Fuchs, M., Fuller, W., Gajee, K., Galai, K., Gallagher, A., Gallagher, E., Gallagher, M. D., Gallis, M., Gaskin, A., Gatica-Wilcox, B., Geidelberg, L., Gemmell, M., Georgana, I., George, R. P., Gifford, L., Gilbert, L., Girgis, S. T., Glaysher, S., Goldstein, E. J., Golubchik, T., Gomes, A. N., Gonçalves, S., Goodfellow, I. G., Goodwin, S., Goudarzi, S., Gourtovaia, M., Graham, C. A., Graham, L., Grant, P. R., Green, L. R., Green, A., Greenaway, J., Gregory, R., Guest, M., Gunson, R. N., Gupta, R. K., Gutierrez, B., Haldenby, S. T., Hamilton, W. L., Hansford, S. E., Haque, T., Harris, K. A., Harrison, I., Harrison, E. M., Hart, J., Hartley, .J. A., Harvey, W. T., Harvey, M., Hassan-Ibrahim, M. O., Heaney, J., Helmer, T., Henderson, J. H., Hesketh, A. R., Hey, J., Heyburn, D., Higginson, E. E., Hill, V., Hill, J. D., Hilson, R. A., Hilvers, E., Holden, M. T. G., Hollis, A., Holmes, C. W., Holmes, N., Holmes, A. H., Hopes, R., Hornsby, H. R., Hosmillo, M., Houlihan, C., Howson-Wells, H. C., Hsu, S. N., Hubb, J., Huckson, H., Hughes, W., Hughes, J., Hughes, M., Hutchings, S., Idle, G, Illingworth, CJ, Impey, R, Irish-Tavares, D, Iturriza-Gomara, M, Izuagbe, R, Jackson, C, Jackson, B, Jackson, LM, Jackson, KA, Jackson, DK, Jahun, AS, James, V, James, K, Jeanes, C, Jeffries, AR, Jeremiah, S, Jermy, A, John, M, Johnson, R, Johnson, K, Johnston, I, Jones, O, Jones, S, Jones, H, Jones, CR, Jones, N, Joseph, A, Judges, S, Kay, GL, Kay, S, Keatley, J - P, Keeley, AJ, Kenyon, A, Kermack, LM, Khakh, M, Kidd, SP, Kimuli, M, Kirk, S, Kitchen, C, Kitchman, K, Knight, BA, Koshy, C, Kraemer, MUG, Kumziene-Summerhayes, S, Kwiatkowski, D, Lackenby, A, Laing, KG, Lampejo, T, Langford, CF, Lavin, D, Lawton, AI, Lee, JCD, Lee, D, Lensing, SV, Leonard, S, Levett, LJ, Le-Viet, T, Lewis, J, Lewis, K, Liddle, J, Liggett, S, Lillie, PJ, Lindsey, BB, Lister, MM, Livett, R, Lo, S, Loman, NJ, Loose, MW, Louka, SF, Loveson, KF, Lowdon, S, Lowe, H, Lowe, HL, Lucaci, AO, Ludden, C, Lynch, J, Lyons, RA, Lythgoe, K, Machin, NW, MacIntyre-Cockett, G, Mack, A, Macklin, B, Maclean, A, Macnaughton, E, Madona, P, Maes, M, Maftei, L, Mahanama, AIK, Mahungu, TW, Mair, D, Maksimovic, J, Malone, CS, Maloney, D, Manesis, N, Manley, R, Mantzouratou, A, Marchbank, A, Mariappan, A, Martincorena, I, Nunez, RTM, Mather, AE, Maxwell, P, Mayhew, M, Mbisa, T, McCann, CM, McCarthy, SA, McCluggage, K, McClure, PC, McCrone, JT, McHugh, MP, McKenna, JP, McKerr, C, McManus, GM, McMurray, CL, McMurray, C, McNally, A, Meadows, L, Medd, N, Megram, O, Menegazzo, M, Merrick, I, Michell, SL, Michelsen, ML, Mirfenderesky, M, Mirza, J, Miskelly, J, Moles-Garcia, E, Moll, RJ, Molnar, Z, Monahan, IM, Mondani, M, Mookerjee, S, Moore, C, Moore, J, Moore, N, Morcrette, H, Morgan, S, Morgan, M, Mori, M, Morriss, A, Moses, S, Mower, C, Muir, P, Mukaddas, A, Munemo, F, Munn, R, Murray, A, Murray, LJ, Murray, DR, Mutingwende, M, Myers, R, Nastouli, E, Nebbia, G, Nelson, A, Nelson, C, Nicholls, S, Nichols, J, Nicodemi, R, Nomikou, K, O’Grady, J, O’Brien, S, Odedra, M, Ohemeng-Kumi, N, Oliver, K, Orton, RJ, Osman, H, O’Toole, Á, Pacchiarini, N, Padgett, D, Page, AJ, Park, EJ, Park, NR, Parker, MD, Parmar, S, Partridge, DG, Pascall, D, Patel, A, Patel, B, Paterson, S, Payne, BAI, Peacock, SJ, Pearson, C, Pelosi, E, Percival, B, Perkins, J, Perry, M, Pinckert, ML, Platt, S, Podplomyk, O, Pohare, M, Pond, M, Pope, CF, Poplawski, R, Powell, J, Poyner, J, Prestwood, L, Price, A, Price, JR, Prieto, JA, Pritchard, DT, Prosolek, SJ, Pugh, G, Pusok, M, Pybus, OG, Pymont, HM, Quail, MA, Quick, J, Radulescu, C, Raghwani, J, Ragonnet-Cronin, M, Rainbow, L, Rajan, D, Rajatileka, S, Ramadan, NA, Rambaut, A, Ramble, J, Randell, PA, Randell, P, Ratcliffe, L, Raviprakash, V, Raza, M, Redshaw, NM, Rey, S, Reynolds, N, Richter, A, Robertson, DL, Robinson, E, Robson, SC, Rogan, F, Rooke, S, Rowe, W, Roy, S, Rudder, S, Ruis, C, Rushton, S, Ryan, F, Saeed, K, Samaraweera, B, Sambles, CM, Sanderson, R, Sanderson, T, Sang, F, Sass, T, Scher, E, Scott, G, Scott, C, Sehmi, J, Shaaban, S, Shah, D, Shaw, J, Shelest, E, Shepherd, JG, Sheridan, LA, Sheriff, N, Shirley, L, Sillitoe, J, Silviera, S, Simpson, DA, Singh, A, Singleton, D, Skvortsov, T, Sloan, TJ, Sluga, G, Smith, K, Smith, KS, Smith, P, Smith, DL, Smith, L, Smith, CP, Smith, N, Smollett, KL, Snell, LB, Somassa, T, Southgate, J, Spellman, K, Chapman, MHS, Spurgin, LG, Spyer, MJ, Stanley, R, Stanley, W, Stanton, TD, Starinskij, I, Stockton, J, Stonehouse, S, Storey, N, Studholme, DJ, Sudhanva, M, Swindells, E, Taha, Y, Tan, NK, Tang, JW, Tang, M, Taylor, BEW, Taylor, JF, Taylor, S, Temperton, B, Templeton, KE, Thomas, C, Thomson, L, Thomson, EC, Thornton, A, Thurston, SAJ, Todd, JA, Tomb, R, Tong, L, Tonkin-Hill, G, Torok, ME, Tovar-Corona, JM, Trebes, A, Trotter, AJ, Tsatsani, I, Turnbull, R, Turtle, L, Twohig, KA, Umpleby, H, Underwood, AP, Vamos, EE, Vasylyeva, TI, Vattipally, S, Vernet, G, Vipond, BB, Volz, EM, Walsh, S, Wang, D, Warne, B, Warwick-Dugdale, J, Wastnedge, E, Watkins, J, Watson, LK, Waugh, S, Webster, HJ, Weldon, D, Westwick, E, Whalley, T, Wheeler, H, Whitehead, M, Whiteley, M, Whitwham, A, Wierzbicki, C, Willford, NJ, Williams, L-A, Williams, R, Williams, C, Williams, CA, Williams, RJ, Williams, T, Williamson, KA, Wilson-Davies, E, Witele, E, Withell, KT, Witney, AA, Wolverson, P, Wong, N, Workman, T, Wright, V, Wright, DW, Wyatt, T, Wyllie, S, Xu-McCrae, L., Yavus, M., Yaze, G., Yeats, C. A., Yebra, G., Yew, W. C., Young, G. R., Young, J., Zarebski, A. E., Zhang, P., Modat, M., Hammers, A., Spector, T. D., Steves, C. J., Sudre, C. H., Ourselin, S., and Duncan, E. L.

Abstract

The Delta (B.1.617.2) variant was the predominant UK circulating SARS-CoV-2 strain between May and December 2021. How Delta infection compares with previous variants is unknown. This prospective observational cohort study assessed symptomatic adults participating in the app-based COVID Symptom Study who tested positive for SARS-CoV-2 from May 26 to July 1, 2021 (Delta overwhelmingly the predominant circulating UK variant), compared (1:1, age- and sex-matched) with individuals presenting from December 28, 2020 to May 6, 2021 (Alpha (B.1.1.7) the predominant variant). We assessed illness (symptoms, duration, presentation to hospital) during Alpha- and Delta-predominant timeframes; and transmission, reinfection, and vaccine effectiveness during the Delta-predominant period. 3581 individuals (aged 18 to 100 years) from each timeframe were assessed. The seven most frequent symptoms were common to both variants. Within the first 28 days of illness, some symptoms were more common with Delta versus Alpha infection (including fever, sore throat, and headache) and some vice versa (dyspnoea). Symptom burden in the first week was higher with Delta versus Alpha infection; however, the odds of any given symptom lasting ≥ 7 days was either lower or unchanged. Illness duration ≥ 28 days was lower with Delta versus Alpha infection, though unchanged in unvaccinated individuals. Hospitalisation for COVID-19 was unchanged. The Delta variant appeared more (1.49) transmissible than Alpha. Re-infections were low in all UK regions. Vaccination markedly reduced the risk of Delta infection (by 69-84%). We conclude that COVID-19 from Delta or Alpha infections is similar. The Delta variant is more transmissible than Alpha; however, current vaccines showed good efficacy against disease. This research framework can be useful for future comparisons with new emerging variants. © 2022, The Author(s).

30. Full-length KIR3DL1*022 detected in an African donor.

Author

Yindom, L.‐M., James, K., de Silva, T. I., and Rowland‐Jones, S. L.

Subjects
ALLELES, HUMAN genetics, NUCLEOTIDE sequencing, PUBLIC health, GENETIC polymorphisms, DELETION mutation
Abstract

KIR3DL1*022 is significantly different from the most common West African allele - KIR3DL1*01501. [ABSTRACT FROM AUTHOR]

Published
2014
Full Text
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32. A prospective cohort study to investigate the transmission and burden of Staphylococcus aureus in Sri Lanka.

Author

Locke T, Siribaddana S, Jayaweera JAAS, Suligoy CM, de Silva TI, Corrigan RM, and Darton TC

Subjects
Humans, Sri Lanka epidemiology, Prospective Studies, Male, Female, Adult, Middle Aged, Whole Genome Sequencing, Longitudinal Studies, Adolescent, Staphylococcus aureus genetics, Staphylococcus aureus isolation & purification, Staphylococcus aureus classification, Young Adult, Child, Aged, Prevalence, Family Characteristics, Staphylococcal Infections epidemiology, Staphylococcal Infections transmission, Staphylococcal Infections microbiology, Methicillin-Resistant Staphylococcus aureus genetics, Methicillin-Resistant Staphylococcus aureus isolation & purification, Methicillin-Resistant Staphylococcus aureus classification
Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of infection in both community and healthcare settings, and the household may be a central component linking these two environments. Strategies to prevent S. aureus transmission and thereby reduce the risk of infection must be informed by a detailed understanding of local epidemiology. These data are typically lacking in many low- and middle-income countries. Therefore, we aimed to investigate the circulation of infecting S. aureus strains in Sri Lanka, with a focus on the community and healthcare interface. A prospective longitudinal cohort study was performed between July and December 2021. Index patients with S. aureus infection and up to four of their household contacts were enrolled in the study. Colonization was assessed by sampling participants' nose and axilla at two time points over 3 months of follow-up. Whole-genome sequencing (WGS) was used to characterize isolates and assess strain similarity to identify transmission episodes and environmental clusters. A total of 153 participants were recruited, including 42  S . aureus -positive index patients and 111 household contacts. The baseline prevalence of S. aureus colonization amongst household contacts was 11.7% (13/111), of which 30.8% (4/13) were methicillin-resistant. A total of 88  S . aureus isolates underwent WGS and three multilocus sequence types predominated: ST672, ST5 and ST6. Each type had unique virulence characteristics but was identified in both community and healthcare environments. Colonization of household members with the index's infecting strain was not detected. S. aureus is a major cause of morbidity and mortality in low-resource settings such as Sri Lanka, yet little is known about risk factors and transmission networks. In this descriptive study, we have identified a small number of strains that appear to be well established and capable of causing both severe infection and asymptomatic colonization. Transmission of S. aureus did not appear to be occurring frequently in the household, and, therefore, preventative strategies that target high-risk groups may be more successful than universal community-based measures.

Published
2024
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33. Evaluating the cost implications of integrating SARS-CoV-2 genome sequencing for infection prevention and control investigation of nosocomial transmission within hospitals.

Author

Panca M, Blackstone J, Stirrup O, Cutino-Moguel MT, Thomson E, Peters C, Snell LB, Nebbia G, Holmes A, Chawla A, Machin N, Taha Y, Mahungu T, Saluja T, de Silva TI, Saeed K, Pope C, Shin GY, Williams R, Darby A, Smith DL, Loose M, Robson SC, Laing K, Partridge DG, Price JR, and Breuer J

Subjects
Humans, SARS-CoV-2 genetics, Infection Control, Hospitals, Cross Infection epidemiology, Cross Infection prevention & control, COVID-19 epidemiology, COVID-19 prevention & control
Abstract

Background: The COG-UK hospital-onset COVID-19 infection (HOCI) trial evaluated the impact of SARS-CoV-2 whole-genome sequencing (WGS) on acute infection, prevention, and control (IPC) investigation of nosocomial transmission within hospitals., Aim: To estimate the cost implications of using the information from the sequencing reporting tool (SRT), used to determine likelihood of nosocomial infection in IPC practice., Methods: A micro-costing approach for SARS-CoV-2 WGS was conducted. Data on IPC management resource use and costs were collected from interviews with IPC teams from 14 participating sites and used to assign cost estimates for IPC activities as collected in the trial. Activities included IPC-specific actions following a suspicion of healthcare-associated infection (HAI) or outbreak, as well as changes to practice following the return of data via SRT., Findings: The mean per-sample costs of SARS-CoV-2 sequencing were estimated at £77.10 for rapid and £66.94 for longer turnaround phases. Over the three-month interventional phases, the total management costs of IPC-defined HAIs and outbreak events across the sites were estimated at £225,070 and £416,447, respectively. The main cost drivers were bed-days lost due to ward closures because of outbreaks, followed by outbreak meetings and bed-days lost due to cohorting contacts. Actioning SRTs, the cost of HAIs increased by £5,178 due to unidentified cases and the cost of outbreaks decreased by £11,246 as SRTs excluded hospital outbreaks., Conclusion: Although SARS-CoV-2 WGS adds to the total IPC management cost, additional information provided could balance out the additional cost, depending on identified design improvements and effective deployment., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Published
2023
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34. Factors affecting turnaround time of SARS-CoV-2 sequencing for inpatient infection prevention and control decision making: analysis of data from the COG-UK HOCI study.

Author

Colton H, Parker MD, Stirrup O, Blackstone J, Loose M, McClure CP, Roy S, Williams C, McLeod J, Smith D, Taha Y, Zhang P, Hsu SN, Kele B, Harris K, Mapp F, Williams R, Flowers P, Breuer J, Partridge DG, and de Silva TI

Subjects
Humans, Inpatients, Decision Making, United Kingdom, SARS-CoV-2 genetics, COVID-19 diagnosis, COVID-19 prevention & control
Abstract

Background: Barriers to rapid return of sequencing results can affect the utility of sequence data for infection prevention and control decisions., Aim: To undertake a mixed-methods analysis to identify challenges that sites faced in achieving a rapid turnaround time (TAT) in the COVID-19 Genomics UK Hospital-Onset COVID-19 Infection (COG-UK HOCI) study., Methods: For the quantitative analysis, timepoints relating to different stages of the sequencing process were extracted from both the COG-UK HOCI study dataset and surveys of study sites. Qualitative data relating to the barriers and facilitators to achieving rapid TATs were included from thematic analysis., Findings: The overall TAT, from sample collection to receipt of sequence report by infection control teams, varied between sites (median 5.1 days, range 3.0-29.0 days). Most variation was seen between reporting of a positive COVID-19 polymerase chain reaction (PCR) result to sequence report generation (median 4.0 days, range 2.3-27.0 days). On deeper analysis, most of this variability was accounted for by differences in the delay between the COVID-19 PCR result and arrival of the sample at the sequencing laboratory (median 20.8 h, range 16.0-88.7 h). Qualitative analyses suggest that closer proximity of sequencing laboratories to diagnostic laboratories, increased staff flexibility and regular transport times facilitated a shorter TAT., Conclusion: Integration of pathogen sequencing into diagnostic laboratories may help to improve sequencing TAT to allow sequence data to be of tangible value to infection control practice. Adding a quality control step upstream to increase capacity further down the workflow may also optimize TAT if lower quality samples are removed at an earlier stage., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Published
2023
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35. A bundle of infection control measures reduces postoperative sternal wound infection due to Staphylococcus aureus but not Gram-negative bacteria: a retrospective analysis of 6903 patient episodes.

Author

Locke T, Parsons H, Briffa N, Stott M, de Silva TI, and Darton TC

Subjects
Gram-Negative Bacteria, Humans, Infection Control, Retrospective Studies, Surgical Wound Infection epidemiology, Surgical Wound Infection etiology, Surgical Wound Infection prevention & control, Staphylococcal Infections epidemiology, Staphylococcal Infections prevention & control, Staphylococcus aureus
Abstract

Background: Prevention of cardiac surgical site infection has largely focused on reducing infection due to Staphylococcus aureus, although other bacteria also play an important role in this complication., Aim: To assess the impact of an evolving infection control programme on the incidence of sternal wound infection (SWI), and the changing incidence of non-staphylococcal infections., Methods: A retrospective cohort study of all patients who underwent primary sternotomy at a single UK centre between September 2010 and May 2018 was undertaken. Data were collated from the 2 years preceding the stepwise introduction of a broad-ranging infection control programme, including S. aureus decolonization., Findings: In total, 6903 primary sternotomies were performed, of which 2.6% (N=178) were complicated by SWI. Gram-negative bacteria (GNB) and S. aureus were most commonly identified as causative pathogens (45.5% and 30.3%, respectively). Following programme introduction, there was a reduction in the rate of SWI from 3.9 to 1.8 cases/100 patients/month. This was mainly due to a sustained reduction in cases of S. aureus infection, with no discernible impact on GNB. Multi-variable logistic regression analysis identified coronary artery bypass grafting, procedural urgency, and procedures performed in the third quarter of the calendar year (July to September) as independent risk factors for postoperative infection., Conclusion: A multi-faceted infection control programme was successful at reducing the rate of SWI, primarily due to a reduction in S. aureus infections. GNB also play an important role in SWI, and traditional preventative measures fail to address these. Future intervention and impact assessments should consider GNB infections when measuring effectiveness., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Published
2022
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36. Evaluation of procalcitonin as a contribution to antimicrobial stewardship in SARS-CoV-2 infection: a retrospective cohort study.

Author

Williams EJ, Mair L, de Silva TI, Green DJ, House P, Cawthron K, Gillies C, Wigfull J, Parsons H, and Partridge DG

Subjects
Adolescent, Adult, Aged, Aged, 80 and over, Antimicrobial Stewardship methods, Bacterial Infections blood, Biomarkers blood, Cohort Studies, Coinfection blood, Coinfection drug therapy, Female, Humans, Male, Middle Aged, Practice Guidelines as Topic, Retrospective Studies, Young Adult, Anti-Bacterial Agents standards, Anti-Bacterial Agents therapeutic use, Antiviral Agents standards, Antiviral Agents therapeutic use, Bacterial Infections drug therapy, Procalcitonin blood, COVID-19 Drug Treatment
Abstract

It can be a diagnostic challenge to identify patients with coronavirus disease 2019 in whom antibiotics can be safely withheld. This study evaluated the effectiveness of a guideline implemented at Sheffield Teaching Hospitals NHS Foundation Trust that recommends withholding antibiotics in patients with low serum procalcitonin (PCT), defined as ≤0.25 ng/mL. Results showed reduced antibiotic consumption in patients with PCT ≤0.25 ng/mL with no increase in mortality, alongside a reduction in subsequent carbapenem prescriptions during admission. The results support the effectiveness of this guideline, and further research is recommended to identify the optimal cut-off value for PCT in this setting., (Crown Copyright © 2021. Published by Elsevier Ltd. All rights reserved.)

Published
2021
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37. The use of adjuvant granulocyte-macrophage colony-stimulating factor in HIV-related disseminated atypical mycobacterial infection.

Author

de Silva TI, Cope A, Goepel J, and Greig JM

Subjects
AIDS-Related Opportunistic Infections immunology, AIDS-Related Opportunistic Infections microbiology, Adjuvants, Immunologic pharmacology, Granulocyte-Macrophage Colony-Stimulating Factor pharmacology, HIV Infections immunology, HIV-1, Humans, Macrophages drug effects, Macrophages microbiology, Male, Middle Aged, Mycobacterium avium-intracellulare Infection immunology, Mycobacterium avium-intracellulare Infection microbiology, Treatment Outcome, AIDS-Related Opportunistic Infections therapy, Adjuvants, Immunologic therapeutic use, Granulocyte-Macrophage Colony-Stimulating Factor therapeutic use, HIV Infections complications, Mycobacterium avium Complex drug effects, Mycobacterium avium-intracellulare Infection therapy
Abstract

Mycobacterium avium complex (MAC) continues to be a challenging problem in some patients with advanced human immunodeficiency virus (HIV) infection despite the availability of potent chemotherapeutic agents. The use of adjunctive immunomodulatory therapy has shown promise in vitro, but there is currently limited supportive clinical evidence [Kemper CA, Bermudez LE, Derenski SC. Immunomodulatory treatment of Mycobacterium avium complex bacteraemia in patients with AIDS by use of recombinant granulocyte-macrophage colony-stimulating factor. J Infect Dis 1998;177:914-20; Kedzierska K, Johnson M, Mijch A, Cooke I, Rainbird M, Roberts S, et al. Granulocyte-macrophage colony-stimulating factor augments phagocytosis of Mycobacterium avium complex by human immunodeficiency virus type-1 infected monocytes/macrophages in vitro and in vivo. J Infect Dis 2000;181:390-94]. We report the resolution of MAC disease resistant to traditional therapy, in an HIV-infected individual, following the addition of granulocyte-macrophage colony-stimulating factor (GM-CSF).

Published
2007
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