11 results on '"Flaviani, F."'
Search Results
2. SARS-CoV-2 evolution during treatment of chronic infection
- Author
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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. Genomic reconstruction of the SARS-CoV-2 epidemic in England
- Author
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Vöhringer, HS, Sanderson, T, Sinnott, M, De Maio, N, Nguyen, T, Goater, R, Schwach, F, Harrison, I, Hellewell, J, Ariani, CV, Gonçalves, S, Jackson, DK, Johnston, I, Jung, AW, Saint, C, Sillitoe, J, Suciu, M, Goldman, N, Panovska-Griffiths, J, Abnizova, I, Aigrain, L, Alderton, A, Ali, M, Allen, L, Amato, R, Anderson, R, Ariani, C, Austin-Guest, S, Bala, S, Barrett, J, Bassett, A, Battleday, K, Beal, J, Beale, M, Beaver, C, 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, SK, Bush, R, Caetano, C, Cagan, A, Carter, N, Cartwright, J, Monteiro, TC, 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, Davies, R, Dawson, J, Day, C, Densem, A, Dibling, T, Dockree, C, Dodd, D, Dogga, S, Dorman, M, Dougan, G, Dougherty, M, Dove, A, Drummond, L, Drury, E, Dudek, M, Durham, J, Durrant, L, Easthope, E, Eckert, S, Ellis, P, Farr, B, Fenton, M, Ferrero, M, Flack, N, Fordham, H, Forsythe, G, Foulser, L, Francis, M, Fraser, A, Freeman, A, Galvin, A, Garcia-Casado, M, Gedny, A, Girgis, S, Glover, J, Goncalves, S, Goodwin, S, Gould, O, Gourtovaia, M, 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, James, K, Jamrozy, D, Verdejo, CJ, Jones, M, Kallepally, K, Kane, L, Kay, K, Kay, S, Keatley, J, Keith, A, King, A, Kitchin, L, Kleanthous, M, Klimekova, M, Korlevic, P, Krasheninnkova, K, Lane, G, Langford, C, Laverack, A, Law, K, Lawniczak, M, Lensing, S, Leonard, S, Letchford, L, Lewis, K, Lewis-Wade, A, Liddle, J, Lin, Q, Lindsay, S, Linsdell, S, Livett, R, Lo, S, Long, R, Lovell, J, Ludden, C, Mack, J, Maddison, M, Makunin, A, Mamun, I, Mansfield, J, Marriott, N, Martin, M, Mayho, M, McCarthy, S, McClintock, J, McGuigan, S, McHugh, S, McMinn, L, Meadows, C, Mobley, E, Moll, R, Morra, M, Morrow, L, Murie, K, Nash, S, Nathwani, C, Naydenova, P, Neaverson, A, Nelson, R, Nerou, E, Nicholson, J, Nimz, T, Noell, GG, O’Meara, S, Ohan, V, Oliver, K, Olney, C, Ormond, D, Oszlanczi, A, Palmer, S, Pang, YF, Pardubska, B, Park, N, Parmar, A, Patel, G, Patel, M, Payne, M, Peacock, S, Petersen, A, Plowman, D, Preston, T, Prestwood, L, Puethe, C, Quail, M, Rajan, D, Rajatileka, S, 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, EM, Roopra, D, Rose, M, Rudd, L, Sadri, R, Salmon, N, Saul, D, Scott, C, Seekings, P, Shirley, L, Simms, A, 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, CD, Sousa, C, Souster, E, Sparkes, A, Spencer-Chapman, M, Squares, J, Stanley, R, Steed, C, Stickland, T, Still, I, Stratton, MR, Strickland, M, Swann, A, Swiatkowska, A, Sycamore, N, Swift, E, Symons, E, Szluha, S, Taluy, E, Tao, N, Taylor, K, Taylor, S, Thompson, S, Thompson, M, Thomson, M, Thomson, N, Thurston, S, Tonkin-Hill, G, Toombs, D, Topping, B, Tovar-Corona, J, Ungureanu, D, Uphill, J, Urbanova, J, Van Vuuren, PJ, Vancollie, V, Voak, P, Walker, D, Walker, M, Waller, M, Ward, G, Weatherhogg, C, Webb, N, Weldon, D, Wells, A, Wells, E, Westwood, L, Whipp, T, Whiteley, T, Whitton, G, Whitwham, A, Widaa, S, Williams, M, Wilson, M, Wright, S, Robson, SC, Connor, TR, Loman, NJ, Golubchik, T, Martinez Nunez, RT, Bonsall, D, Rambaut, A, Snell, LB, Corden, S, Nastouli, E, Nebbia, G, Lythgoe, K, Torok, ME, Goodfellow, IG, Prieto, JA, Saeed, K, Houlihan, C, Frampton, D, Hamilton, WL, Witney, AA, Bucca, G, Pope, CF, Moore, C, Thomson, EC, Harrison, EM, Smith, CP, Rogan, F, Beckwith, SM, Murray, A, Singleton, D, Eastick, K, Sheridan, LA, Randell, P, Jackson, LM, Fairley, DJ, Loose, MW, Watkins, J, Moses, S, Nicholls, S, Bull, M, Smith, DL, Aanensen, DM, Aggarwal, D, Shepherd, JG, Curran, MD, Parmar, S, Parker, MD, Williams, C, Glaysher, S, Underwood, AP, Bashton, M, Pacchiarini, N, Loveson, KF, Byott, M, Carabelli, AM, Templeton, KE, de Silva, TI, Wang, D, Langford, CF, Gunson, RN, Cottrell, S, O’Grady, J, Kwiatkowski, D, Lillie, PJ, Cortes, N, Moore, N, Thomas, C, Burns, PJ, Mahungu, TW, Liggett, S, Beckett, AH, Holden, MTG, Levett, LJ, Osman, H, Hassan-Ibrahim, MO, Simpson, DA, Chand, M, Gupta, RK, Darby, AC, Paterson, S, Pybus, OG, Volz, EM, de Angelis, D, Robertson, DL, Page, AJ, Bassett, AR, Wong, N, Taha, Y, Erkiert, MJ, Spencer Chapman, MH, Dewar, R, McHugh, MP, Mookerjee, S, Aplin, S, Harvey, M, Sass, T, Umpleby, H, Wheeler, H, McKenna, JP, Warne, B, Taylor, JF, Chaudhry, Y, Izuagbe, R, Jahun, AS, Young, GR, McMurray, C, McCann, CM, Nelson, A, Elliott, S, Lowe, H, Price, A, Crown, MR, Rey, S, Roy, S, Temperton, B, Shaaban, S, Hesketh, AR, Laing, KG, Monahan, IM, Heaney, J, Pelosi, E, Silviera, S, Wilson-Davies, E, Fryer, H, Adams, H, du Plessis, L, Johnson, R, Harvey, WT, Hughes, J, Orton, RJ, Spurgin, LG, Bourgeois, Y, Ruis, C, O’Toole, Á, Fraser, C, Edgeworth, J, Breuer, J, Michell, SL, Todd, JA, John, M, Buck, D, Gajee, K, Kay, GL, Peacock, SJ, Heyburn, D, Kitchman, K, McNally, A, Pritchard, DT, Dervisevic, S, Muir, P, Robinson, E, Vipond, BB, Ramadan, NA, Jeanes, C, Catalan, J, Jones, N, da Silva Filipe, A, Fuchs, M, Miskelly, J, Jeffries, AR, Park, NR, Ash, A, Koshy, C, Barrow, M, Buchan, SL, Mantzouratou, A, Clark, G, Holmes, CW, Campbell, S, Davis, T, Tan, NK, Brown, JR, Harris, KA, Kidd, SP, Grant, PR, Xu-McCrae, L, Cox, A, Madona, P, Pond, M, Randell, PA, Withell, KT, Graham, C, Denton-Smith, R, Swindells, E, Turnbull, R, Sloan, TJ, Bosworth, A, Hutchings, S, Pymont, HM, Casey, A, Ratcliffe, L, Jones, CR, Knight, BA, Haque, T, Hart, J, Irish-Tavares, D, Witele, E, Mower, C, Watson, LK, Collins, J, Eltringham, G, Crudgington, D, Macklin, B, Iturriza-Gomara, M, Lucaci, AO, McClure, PC, Carlile, M, Holmes, N, Storey, N, Rooke, S, Yebra, G, Craine, N, Perry, M, Alikhan, N-F, Bridgett, S, Cook, KF, Fearn, C, Goudarzi, S, Lyons, RA, Williams, T, Haldenby, ST, Davies, RM, Batra, R, Blane, B, Spyer, MJ, Smith, P, Yavus, M, Williams, RJ, Mahanama, AIK, Samaraweera, B, Girgis, ST, Hansford, SE, Green, A, Bellis, KL, Dorman, MJ, Quick, J, Poplawski, R, Reynolds, N, Mack, A, Morriss, A, Whalley, T, Patel, B, Georgana, I, Hosmillo, M, Pinckert, ML, Stockton, J, Henderson, JH, Hollis, A, Stanley, W, Yew, WC, Myers, R, Thornton, A, Adams, A, Annett, T, Asad, H, Birchley, A, Coombes, J, Evans, JM, 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, Trotter, AJ, Williams, CA, Kermack, LM, Foulkes, BH, Gallis, M, Hornsby, HR, Louka, SF, Pohare, M, Wolverson, P, Zhang, P, MacIntyre-Cockett, G, Trebes, A, Moll, RJ, Ferguson, L, Goldstein, EJ, Maclean, A, Tomb, R, Starinskij, I, Thomson, L, Southgate, J, Kraemer, MUG, Raghwani, J, Zarebski, AE, Boyd, O, Geidelberg, L, Illingworth, CJ, Jackson, C, Pascall, D, Vattipally, S, Freeman, TM, Hsu, SN, Lindsey, BB, Tovar-Corona, JM, Cox, M, Abudahab, K, Menegazzo, M, Taylor, BEW, Yeats, CA, Mukaddas, A, Wright, DW, de Oliveira Martins, L, Colquhoun, R, Hill, V, Jackson, B, McCrone, JT, Medd, N, Scher, E, Keatley, J-P, Curran, T, Morgan, S, Maxwell, P, Eldirdiri, S, Kenyon, A, Holmes, AH, Price, JR, Wyatt, T, Mather, AE, Skvortsov, T, Hartley, JA, Guest, M, Kitchen, C, Merrick, I, Munn, R, Bertolusso, B, Lynch, J, Vernet, G, Kirk, S, Wastnedge, E, Idle, G, Bradley, DT, Poyner, J, Mori, M, Jones, O, Wright, V, Brooks, E, Churcher, CM, Fragakis, M, Galai, K, Jermy, A, Judges, S, McManus, GM, Smith, KS, Westwick, E, Attwood, SW, Bolt, F, Davies, A, De Lacy, E, Downing, F, Edwards, S, Meadows, L, Jeremiah, S, Smith, N, Charalampous, T, Patel, A, Berry, L, Boswell, T, Fleming, VM, Howson-Wells, HC, Joseph, A, Khakh, M, Lister, MM, Bird, PW, Fallon, K, Helmer, T, McMurray, CL, Odedra, M, Shaw, J, Tang, JW, Willford, NJ, Blakey, V, Raviprakash, V, Sheriff, N, Williams, L-A, Feltwell, T, Bedford, L, Cargill, JS, Hughes, W, Moore, J, Stonehouse, S, Atkinson, L, Lee, JCD, Shah, D, Alcolea, 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, SSY, George, RP, Machin, NW, 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, Gifford, L, Molnar, Z, Auckland, C, Evans, C, Johnson, K, Partridge, DG, Raza, M, Baker, P, Bonner, S, Essex, S, Murray, LJ, Lawton, AI, Burton-Fanning, S, Payne, BAI, Waugh, S, Gomes, AN, Kimuli, M, Murray, DR, Ashfield, P, Dobie, D, Ashford, F, Best, A, Crawford, L, Cumley, N, Mayhew, M, Megram, O, Mirza, J, Moles-Garcia, E, Percival, B, Ensell, L, Lowe, HL, Maftei, L, Mondani, M, Chaloner, NJ, Cogger, BJ, Easton, LJ, Huckson, H, Lewis, J, Lowdon, S, Malone, CS, Munemo, F, Mutingwende, M, Nicodemi, R, Podplomyk, O, Somassa, T, Beggs, A, Richter, A, Cormie, C, Dias, J, Forrest, S, Higginson, EE, Maes, M, Young, J, Davidson, RK, Jackson, KA, Turtle, L, Keeley, AJ, Ball, J, Byaruhanga, T, Chappell, JG, Dey, J, Hill, JD, Park, EJ, Fanaie, A, Hilson, RA, Yaze, G, Afifi, S, Beer, R, Maksimovic, J, Masters, KM, Spellman, K, Bresner, C, Fuller, W, Marchbank, A, Workman, T, Shelest, E, Debebe, J, Sang, F, Zamudio, ME, Francois, S, Gutierrez, B, Vasylyeva, TI, Flaviani, F, Ragonnet-Cronin, M, Smollett, KL, 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, KA, Morgan, M, Aydin, A, Baker, DJ, Foster-Nyarko, E, Prosolek, SJ, Rudder, S, Baxter, C, Carvalho, SF, Lavin, D, Mariappan, A, Radulescu, C, Singh, A, Tang, M, Morcrette, H, Bayzid, N, Cotic, M, Balcazar, CE, Gallagher, MD, Maloney, D, Stanton, TD, Williamson, KA, Manley, R, Michelsen, ML, Sambles, CM, Studholme, DJ, Warwick-Dugdale, J, Eccles, R, Gemmell, M, Gregory, R, Hughes, M, Nelson, C, Rainbow, L, Vamos, EE, Webster, HJ, Whitehead, M, Wierzbicki, C, Angyal, A, Green, LR, Whiteley, M, Bronner, IF, Farr, BW, Lensing, SV, McCarthy, SA, Quail, MA, Redshaw, NM, Thurston, SAJ, Rowe, W, Gaskin, A, Le-Viet, T, Birney, E, Volz, E, Funk, S, Martincorena, I, Barrett, JC, and Gerstung, M
- Abstract
The evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus leads to new variants that warrant timely epidemiological characterization. Here we use the dense genomic surveillance data generated by the COVID-19 Genomics UK Consortium to reconstruct the dynamics of 71 different lineages in each of 315 English local authorities between September 2020 and June 2021. This analysis reveals a series of subepidemics that peaked in early autumn 2020, followed by a jump in transmissibility of the B.1.1.7/Alpha lineage. The Alpha variant grew when other lineages declined during the second national lockdown and regionally tiered restrictions between November and December 2020. A third more stringent national lockdown suppressed the Alpha variant and eliminated nearly all other lineages in early 2021. Yet a series of variants (most of which contained the spike E484K mutation) defied these trends and persisted at moderately increasing proportions. However, by accounting for sustained introductions, we found that the transmissibility of these variants is unlikely to have exceeded the transmissibility of the Alpha variant. Finally, B.1.617.2/Delta was repeatedly introduced in England and grew rapidly in early summer 2021, constituting approximately 98% of sampled SARS-CoV-2 genomes on 26 June 2021.
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- 2021
4. Real-Time Whole Genome Sequencing to Guide Patient-Tailored Therapy of Severe Acute Respiratory Syndrome Coronavirus 2 Infection.
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Snell LB, Alcolea-Medina A, Charalampous T, Alder C, Williams TGS, Flaviani F, Batra R, Bakrania P, Thangarajah R, Neil SJD, van Nispen Tot Pannerden C, Botgros A, Aarons E, Douthwaite ST, Edgeworth JD, and Nebbia G
- Subjects
- Humans, SARS-CoV-2 genetics, Whole Genome Sequencing, Mutation, COVID-19
- Abstract
The management of coronavirus disease 2019 has become more complex due to the expansion of available therapies. The presence of severe acute respiratory syndrome coronavirus 2 variants and mutations further complicates treatment due to their differing susceptibilities to therapies. Here we outline the use of real-time whole genome sequencing to detect persistent infection, evaluate for mutations confering resistance to treatments, and guide treatment decisions., Competing Interests: Potential conflicts of interest. J. D. E. has received speaking honoraria, consultancy fees, in-kind contributions, or research funding from Oxford Nanopore Technologies (ONT); reports grants or contracts from ONT (Guy's & St Thomas’ Hospital signed collaboration agreement with ONT that commenced after completion of this work); and has a part-time employment contract with ONT that commenced in October 2022 after completion of this work. G. N. and J. D. E. report support from the Guy’s & St. Thomas’ Charity (https://www.gsttcharity.org.uk/; grant number TR130505). R. T. reports honoraria as invited speaker on one occasion from Gilead. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
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- 2023
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5. Effectiveness of rapid SARS-CoV-2 genome sequencing in supporting infection control for hospital-onset COVID-19 infection: Multicentre, prospective study.
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Stirrup O, Blackstone J, Mapp F, MacNeil A, Panca M, Holmes A, Machin N, Shin GY, Mahungu T, Saeed K, Saluja T, Taha Y, Mahida N, Pope C, Chawla A, Cutino-Moguel MT, Tamuri A, Williams R, Darby A, Robertson DL, Flaviani F, Nastouli E, Robson S, Smith D, Loose M, Laing K, Monahan I, Kele B, Haldenby S, George R, Bashton M, Witney AA, Byott M, Coll F, Chapman M, Peacock SJ, Hughes J, Nebbia G, Partridge DG, Parker M, Price JR, Peters C, Roy S, Snell LB, de Silva TI, Thomson E, Flowers P, Copas A, and Breuer J
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- Humans, SARS-CoV-2 genetics, Prospective Studies, Infection Control methods, Hospitals, COVID-19 epidemiology, COVID-19 prevention & control, Cross Infection epidemiology, Cross Infection prevention & control
- 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' (<48 hr) and 4 weeks of 'longer-turnaround' (5-10 days) sequencing using a sequence reporting tool (SRT). Data were collected on all hospital-onset COVID-19 infections (HOCIs; detected ≥48 hr from admission). The impact of the sequencing intervention on IPC knowledge and actions, and on the incidence of probable/definite hospital-acquired infections (HAIs), was evaluated., Results: A total of 2170 HOCI cases were recorded from October 2020 to 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., Conclusions: 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: NCT04405934., Competing Interests: OS, JB, FM, AM, MP, AH, NM, TM, KS, TS, YT, NM, CP, AC, AT, RW, AD, DR, FF, SR, ML, KL, IM, BK, SH, RG, MB, AW, MB, MC, JH, GN, DP, MP, JP, CP, SR, LS, Td, ET, AC, JB No competing interests declared, GS has an unpaid role as Deputy Chair, British Medical Association London Regional Council. The author has no other competing interests to declare, MC received payment for anonymous interview conducted by Adkins Research Group. The author has no other competing interests to declare, EN holds grants by NIHR, EPSRC, MRC-UKRI , H2020, ViiV Healthcare, Pfizer and Amfar, and has received grants to attend meetings from H2020 and ViiV Healthcare, DS holds the following grants that are not specifically for the present work: COG-UK, PHE test and trace funded the sequencing aspect. HOCI funded a technician to support sequencing during study period. The author has no other competing interests to declare, FC received consulting fees from Next Gen Diagnostics LLC (during 2018/2019), received payment or honoria for lectures from University of Cambridge and Wellcome Genome Campus Advanced Courses, and received support for attending meeting and/or travel to meetings from European Congress of Clinical Microbiology & Infectious Diseases (ECCMID), The American Society for Microbiology (ASM), Microbiology Society, European Congress of Clinical Microbiology & Infectious Diseases (ECCMID), and the British Infection Association (BIA). The author has no other competing interests to declare, SP received consultancy fees from Pfizer (Coronavirus External Advisory Board) and Melinta Therapeutics, received payment from SVB Leerink for a round table meeting and for Mary Strauss Distinguished Public Lecture from the Fralin Biomedical Research Institute, US, and support for attending ICPIC conference, Geneva and World Health Summit, Berlin in 2021, and hold stocks or stock options in Specific Technologies (European Union Scientific Advisory Board) and Next Gen Diagnostics (Scientific Advisory Board). SP also serves as Chair, Medical Advisory Committee, Sir Jules Thorn Charitable Trust, Board member of the Wellcome SEDRIC (Surveillance and Epidemiology of Drug Resistant Consortium), and Non-Executive Director of Cambridge University Hospitals NHS Foundation Trust. The author has no other competing interests to declare, PF is a member of the SAGE hospital onset covid working group 2020-2022. The author has no other competing interests to declare, (© 2022, Stirrup et al.)
- Published
- 2022
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6. Neutrophils Dominate the Cervical Immune Cell Population in Pregnancy and Their Transcriptome Correlates With the Microbial Vaginal Environment.
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Mohd Zaki A, Hadingham A, Flaviani F, Haque Y, Mi JD, Finucane D, Dalla Valle G, Mason AJ, Saqi M, Gibbons DL, and Tribe RM
- Abstract
The cervicovaginal environment in pregnancy is proposed to influence risk of spontaneous preterm birth. The environment is shaped both by the resident microbiota and local inflammation driven by the host response (epithelia, immune cells and mucous). The contributions of the microbiota, metabolome and host defence peptides have been investigated, but less is known about the immune cell populations and how they may respond to the vaginal environment. Here we investigated the maternal immune cell populations at the cervicovaginal interface in early to mid-pregnancy (10-24 weeks of gestation, samples from N = 46 women), we confirmed neutrophils as the predominant cell type and characterised associations between the cervical neutrophil transcriptome and the cervicovaginal metagenome ( N = 9 women). In this exploratory study, the neutrophil cell proportion was affected by gestation at sampling but not by birth outcome or ethnicity. Following RNA sequencing (RNA-seq) of a subset of neutrophil enriched cells, principal component analysis of the transcriptome profiles indicated that cells from seven women clustered closely together these women had a less diverse cervicovaginal microbiota than the remaining three women. Expression of genes involved in neutrophil mediated immunity, activation, degranulation, and other immune functions correlated negatively with Gardnerella vaginalis abundance and positively with Lactobacillus iners abundance; microbes previously associated with birth outcome. The finding that neutrophils are the dominant immune cell type in the cervix during pregnancy and that the cervical neutrophil transcriptome of pregnant women may be modified in response to the microbial cervicovaginal environment, or vice versa, establishes the rationale for investigating associations between the innate immune response, cervical shortening and spontaneous preterm birth and the underlying mechanisms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Mohd Zaki, Hadingham, Flaviani, Haque, Mi, Finucane, Dalla Valle, Mason, Saqi, Gibbons and Tribe.)
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- 2022
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7. Rapid genome sequencing in hospitals to identify potential vaccine-escape SARS-CoV-2 variants.
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Snell LB, Cliff PR, Charalampous T, Alcolea-Medina A, Ebie SART, Sehmi JK, Flaviani F, Batra R, Douthwaite ST, Edgeworth JD, and Nebbia G
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- Humans, Mutation, COVID-19 diagnosis, COVID-19 epidemiology, COVID-19 virology, COVID-19 Vaccines, Genome, Viral, SARS-CoV-2 isolation & purification
- Abstract
Competing Interests: We declare no competing interests. This work was funded by the National Institute for Health Research Biomedical Research Centre programme of infection and immunity (RJ112/N027) based at Guy's and St Thomas' National Health Service (NHS) Foundation Trust and King's College London, Guy's and St Thomas' NHS Foundation Trust, and The Guy's and St Thomas' Charity.
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- 2021
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8. Cervicovaginal microbiota and metabolome predict preterm birth risk in an ethnically diverse cohort.
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Flaviani F, Hezelgrave NL, Kanno T, Prosdocimi EM, Chin-Smith E, Ridout AE, von Maydell DK, Mistry V, Wade WG, Shennan AH, Dimitrakopoulou K, Seed PT, Mason AJ, and Tribe RM
- Subjects
- Adult, Aspartic Acid metabolism, Calcium metabolism, Case-Control Studies, Female, Glucose metabolism, Humans, Infant, Newborn, Lactobacillus acidophilus immunology, Lactobacillus acidophilus metabolism, Lactobacillus crispatus immunology, Lactobacillus crispatus metabolism, Longitudinal Studies, Maternal Age, Metabolomics, Pregnancy, Premature Birth immunology, Premature Birth microbiology, Prospective Studies, Risk Assessment methods, Risk Assessment statistics & numerical data, United Kingdom epidemiology, Cervix Uteri microbiology, Microbiota immunology, Premature Birth epidemiology, Vagina microbiology
- Abstract
The syndrome of spontaneous preterm birth (sPTB) presents a challenge to mechanistic understanding, effective risk stratification, and clinical management. Individual associations between sPTB, self-reported ethnic ancestry, vaginal microbiota, metabolome, and innate immune response are known but not fully understood, and knowledge has yet to impact clinical practice. Here, we used multi-data type integration and composite statistical models to gain insight into sPTB risk by exploring the cervicovaginal environment of an ethnically heterogenous pregnant population (n = 346 women; n = 60 sPTB < 37 weeks' gestation, including n = 27 sPTB < 34 weeks). Analysis of cervicovaginal samples (10-15+6 weeks) identified potentially novel interactions between risk of sPTB and microbiota, metabolite, and maternal host defense molecules. Statistical modeling identified a composite of metabolites (leucine, tyrosine, aspartate, lactate, betaine, acetate, and Ca2+) associated with risk of sPTB < 37 weeks (AUC 0.752). A combination of glucose, aspartate, Ca2+, Lactobacillus crispatus, and L. acidophilus relative abundance identified risk of early sPTB < 34 weeks (AUC 0.758), improved by stratification by ethnicity (AUC 0.835). Increased relative abundance of L. acidophilus appeared protective against sPTB < 34 weeks. By using cervicovaginal fluid samples, we demonstrate the potential of multi-data type integration for developing composite models toward understanding the contribution of the vaginal environment to risk of sPTB.
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- 2021
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9. Ursodeoxycholic acid improves feto-placental and offspring metabolic outcomes in hypercholanemic pregnancy.
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Borges Manna L, Papacleovoulou G, Flaviani F, Pataia V, Qadri A, Abu-Hayyeh S, McIlvride S, Jansen E, Dixon P, Chambers J, Vazquez-Lopez M, Wahlström A, Kitaba N, Marschall HU, Godfrey KM, Lillycrop K, and Williamson C
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- Adult, Animals, Cholestasis, Intrahepatic metabolism, Cholestasis, Intrahepatic pathology, Dyslipidemias epidemiology, Dyslipidemias metabolism, Female, Fetus metabolism, Fetus pathology, Humans, Male, Mice, Mice, Inbred C57BL, Placenta metabolism, Placenta pathology, Pregnancy, Pregnancy Complications metabolism, Pregnancy Complications pathology, Bile Acids and Salts metabolism, Cholestasis, Intrahepatic drug therapy, Dyslipidemias prevention & control, Epigenome drug effects, Fetus drug effects, Placenta drug effects, Pregnancy Complications drug therapy, Ursodeoxycholic Acid pharmacology
- Abstract
Perturbations in the intrauterine environment can result in lifelong consequences for metabolic health during postnatal life. Intrahepatic cholestasis of pregnancy (ICP) can predispose offspring to metabolic disease in adulthood, likely due to a combination of the effects of increased bile acids, maternal dyslipidemia and deranged maternal and fetal lipid homeostasis. Whereas ursodeoxycholic acid (UDCA) is a commonly used treatment for ICP, no studies have yet addressed whether it can also prevent the metabolic effects of ICP in the offspring and fetoplacental unit. We therefore analyzed the lipid profile of fetal serum from untreated ICP, UDCA-treated ICP and uncomplicated pregnancies and found that UDCA ameliorates ICP-associated fetal dyslipidemia. We then investigated the effects of UDCA in a mouse model of hypercholanemic pregnancy and showed that it induces hepatoprotective mechanisms in the fetal liver, reduces hepatic fatty acid synthase (Fas) expression and improves glucose tolerance in the adult offspring. Finally, we showed that ICP leads to epigenetic changes in pathways of relevance to the offspring phenotype. We therefore conclude that UDCA can be used as an intervention in pregnancy to reduce features of metabolic disease in the offspring of hypercholanemic mothers.
- Published
- 2020
- Full Text
- View/download PDF
10. Distinct Oceanic Microbiomes From Viruses to Protists Located Near the Antarctic Circumpolar Current.
- Author
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Flaviani F, Schroeder DC, Lebret K, Balestreri C, Highfield AC, Schroeder JL, Thorpe SE, Moore K, Pasckiewicz K, Pfaff MC, and Rybicki EP
- Abstract
Microbes occupy diverse ecological niches and only through recent advances in next generation sequencing technologies have the true microbial diversity been revealed. Furthermore, lack of perceivable marine barriers to genetic dispersal (i.e., mountains or islands) has allowed the speculation that organisms that can be easily transported by currents and therefore proliferate everywhere. That said, ocean currents are now commonly being recognized as barriers for microbial dispersal. Here we analyzed samples collected from a total of six stations, four located in the Indian Ocean, and two in the Southern Ocean. Amplicon sequencing was used to characterize both prokaryotic and eukaryotic plankton communities, while shotgun sequencing was used for the combined environmental DNA (eDNA), microbial eDNA (meDNA), and viral fractions. We found that Cyanobacteria dominated the prokaryotic component in the South-West Indian Ocean, while γ-Proteobacteria dominated the South-East Indian Ocean. A combination of γ- and α-Proteobacteria dominated the Southern Ocean. Alveolates dominated almost exclusively the eukaryotic component, with variation in the ratio of Protoalveolata and Dinoflagellata depending on station. However, an increase in haptophyte relative abundance was observed in the Southern Ocean. Similarly, the viral fraction was dominated by members of the order Caudovirales across all stations; however, a higher presence of nucleocytoplasmic large DNA viruses (mainly chloroviruses and mimiviruses) was observed in the Southern Ocean. To our knowledge, this is the first that a statistical difference in the microbiome (from viruses to protists) between the subtropical Indian and Southern Oceans. We also show that not all phylotypes can be found everywhere, and that meDNA is not a suitable resource for monitoring aquatic microbial diversity.
- Published
- 2018
- Full Text
- View/download PDF
11. A Pelagic Microbiome (Viruses to Protists) from a Small Cup of Seawater.
- Author
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Flaviani F, Schroeder DC, Balestreri C, Schroeder JL, Moore K, Paszkiewicz K, Pfaff MC, and Rybicki EP
- Subjects
- Bacteria genetics, Eukaryota genetics, Viruses genetics, Bacteria classification, Eukaryota classification, Microbiota, Seawater microbiology, Viruses classification
- Abstract
The aquatic microbiome is composed of a multi-phylotype community of microbes, ranging from the numerically dominant viruses to the phylogenetically diverse unicellular phytoplankton. They influence key biogeochemical processes and form the base of marine food webs, becoming food for secondary consumers. Due to recent advances in next-generation sequencing, this previously overlooked component of our hydrosphere is starting to reveal its true diversity and biological complexity. We report here that 250 mL of seawater is sufficient to provide a comprehensive description of the microbial diversity in an oceanic environment. We found that there was a dominance of the order Caudovirales (59%), with the family Myoviridae being the most prevalent. The families Phycodnaviridae and Mimiviridae made up the remainder of pelagic double-stranded DNA (dsDNA) virome. Consistent with this analysis, the Cyanobacteria dominate (52%) the prokaryotic diversity. While the dinoflagellates and their endosymbionts, the superphylum Alveolata dominates (92%) the microbial eukaryotic diversity. A total of 834 prokaryotic, 346 eukaryotic and 254 unique virus phylotypes were recorded in this relatively small sample of water. We also provide evidence, through a metagenomic-barcoding comparative analysis, that viruses are the likely source of microbial environmental DNA (meDNA). This study opens the door to a more integrated approach to oceanographic sampling and data analysis.
- Published
- 2017
- Full Text
- View/download PDF
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