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1. Attenuated humoral responses in HIV after SARS-CoV-2 vaccination linked to B cell defects and altered immune profiles

Author

Touizer, Emma, Alrubayyi, Aljawharah, Ford, Rosemarie, Hussain, Noshin, Gerber, Pehuén Pereyra, Shum, Hiu-Long, Rees-Spear, Chloe, Muir, Luke, Gea-Mallorquí, Ester, Kopycinski, Jakub, Jankovic, Dylan, Jeffery-Smith, Anna, Pinder, Christopher L., Fox, Thomas A., Williams, Ian, Mullender, Claire, Maan, Irfaan, Waters, Laura, Johnson, Margaret, Madge, Sara, Youle, Michael, Barber, Tristan J., Burns, Fiona, Kinloch, Sabine, Rowland-Jones, Sarah, Gilson, Richard, Matheson, Nicholas J., Morris, Emma, Peppa, Dimitra, and McCoy, Laura E.

Published
2023
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2. Pre-existing polymerase-specific T cells expand in abortive seronegative SARS-CoV-2

Author

Swadling, Leo, Diniz, Mariana O., Schmidt, Nathalie M., Amin, Oliver E., Chandran, Aneesh, Shaw, Emily, Pade, Corinna, Gibbons, Joseph M., Le Bert, Nina, Tan, Anthony T., Jeffery-Smith, Anna, Tan, Cedric C. S., Tham, Christine Y. L., Kucykowicz, Stephanie, Aidoo-Micah, Gloryanne, Rosenheim, Joshua, Davies, Jessica, Johnson, Marina, Jensen, Melanie P., Joy, George, McCoy, Laura E., Valdes, Ana M., Chain, Benjamin M., Goldblatt, David, Altmann, Daniel M., Boyton, Rosemary J., Manisty, Charlotte, Treibel, Thomas A., Moon, James C., van Dorp, Lucy, Balloux, Francois, McKnight, Áine, Noursadeghi, Mahdad, Bertoletti, Antonio, and Maini, Mala K.

Published
2022
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3. Antibody persistence and neutralising activity in primary school students and staff: Prospective active surveillance, June to December 2020, England

Author

Ireland, Georgina, Jeffery-Smith, Anna, Zambon, Maria, Hoschler, Katja, Harris, Ross, Poh, John, Baawuah, Frances, Beckmann, Joanne, Okike, Ifeanyichukwu O, Ahmad, Shazaad, Garstang, Joanna, Brent, Andrew J, Brent, Bernadette, Aiano, Felicity, Amin-Chowdhury, Zahin, Letley, Louise, Jones, Samuel E I, Kall, Meaghan, Patel, Monika, Gopal, Robin, Borrow, Ray, Linley, Ezra, Amirthalingam, Gayatri, Brown, Kevin E, Ramsay, Mary E, and Ladhani, Shamez N

Published
2021
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4. High prevalence of SARS-CoV-2 antibodies in care homes affected by COVID-19: Prospective cohort study, England

Author

Ladhani, Shamez N, Jeffery-Smith, Anna, Patel, Monika, Janarthanan, Roshni, Fok, Jonathan, Crawley-Boevey, Emma, Vusirikala, Amoolya, Fernandez Ruiz De Olano, Elena, Perez, Marina Sanchez, Tang, Suzanne, Dun-Campbell, Kate, Evans, Edward Wynne, Bell, Anita, Patel, Bharat, Amin-Chowdhury, Zahin, Aiano, Felicity, Paranthaman, Karthik, Ma, Thomas, Saavedra-Campos, Maria, Ellis, Joanna, Chand, Meera, Brown, Kevin, Ramsay, Mary E., Hopkins, Susan, Shetty, Nandini, Chow, J. Yimmy, Gopal, Robin, and Zambon, Maria

Published
2020
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6. Targeting human Acyl-CoA:cholesterol acyltransferase as a dual viral and T cell metabolic checkpoint

Author

Schmidt, Nathalie M., Wing, Peter A. C., Diniz, Mariana O., Pallett, Laura J., Swadling, Leo, Harris, James M., Burton, Alice R., Jeffery-Smith, Anna, Zakeri, Nekisa, Amin, Oliver E., Kucykowicz, Stephanie, Heemskerk, Mirjam H., Davidson, Brian, Meyer, Tim, Grove, Joe, Stauss, Hans J., Pineda-Torra, Ines, Jolly, Clare, Jury, Elizabeth C., McKeating, Jane A., and Maini, Mala K.

Published
2021
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7. SARS-CoV-2-specific memory B cells can persist in the elderly who have lost detectable neutralizing antibodies

Author

Jeffery-Smith, Anna, Burton, Alice R., Lens, Sabela, Rees-Spear, Chloe, Davies, Jessica, Patel, Monika, Gopal, Robin, Muir, Luke, Aiano, Felicity, Doores, Katie J., Chow, J. Yimmy, Ladhani, Shamez N., Zambon, Maria, McCoy, Laura E., and Maini, Mala K.

Subjects
Aged -- Health aspects -- Physiological aspects, Immunologic memory -- Research, Immunological research, Viral antibodies -- Health aspects -- Physiological aspects, B cells -- Health aspects -- Physiological aspects, Antibodies -- Health aspects -- Physiological aspects, Health care industry
Abstract

Memory B cells (MBCs) can provide a recall response able to supplement waning antibodies (Abs) with an affinity-matured response better able to neutralize variant viruses. We studied a cohort of elderly care home residents and younger staff (median age of 87 years and 56 years, respectively), who had survived COVID-19 outbreaks with only mild or asymptomatic infection. The cohort was selected because of its high proportion of individuals who had lost neutralizing antibodies (nAbs), thus allowing us to specifically investigate the reserve immunity from SARS-CoV-2-specific MBCs in this setting. Classswitched spike and receptor-binding domain (RBD) tetramer-binding MBCs persisted 5 months after mild or asymptomatic SARS-CoV-2 infection, irrespective of age. The majority of spike- and RBD-specific MBCs had a classical phenotype, but we found that activated MBCs, indicating possible ongoing antigenic stimulation or inflammation, were expanded in the elderly group. Spike- and RBD-specific MBCs remained detectable in the majority of individuals who had lost nAbs, although at lower frequencies and with a reduced IgG/IgA isotype ratio. Functional spike-, S1 subunit of the spike protein- (S1-), and RBDspecific recall was also detectable by enzyme-linked immune absorbent spot (ELISPOT) assay in some individuals who had lost nAbs, but was significantly impaired in the elderly. Our findings demonstrate that a reserve of SARS-CoV-2- specific MBCs persists beyond the loss of nAbs but highlight the need for careful monitoring of functional defects in spike- and RBD- specific B cell immunity in the elderly., Introduction The human coronavirus SARS-CoV-2 has had a particularly devastating impact on the elderly, who are at much greater risk of morbidity and mortality (1, 2). Understanding the nature of [...]

Published
2022
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10. Differential changes in global and antigen-specific B cell frequencies and function associate with the outcome of HBV nucleos (t)ide analog treatment withdrawal

Author

Lens, Sabela, primary, Burton, Alice, additional, Davies, Jessica, additional, García-López, Mireia, additional, Jeffery-Smith, Anna, additional, Novikov, Nikolai, additional, Fletcher, Simon, additional, Pérez-del-Pulgar, Sofía, additional, Forns, Xavier, additional, and Maini, Mala, additional

Published
2022
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11. Isolation of human intrahepatic leukocytes for phenotypic and functional characterization by flow cytometry

Author

Kucykowicz, Stephanie, primary, Amin, Oliver E., additional, Burton, Alice R., additional, Swadling, Leo, additional, Schmidt, Nathalie M., additional, Zakeri, Nekisa, additional, Davies, Jessica, additional, Aidoo-Micah, Gloryanne, additional, Stegmann, Kerstin A., additional, Easom, Nicholas J., additional, Jeffery-Smith, Anna, additional, Maini, Mala K., additional, and Pallett, Laura J., additional

Published
2022
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12. Pre-existing polymerase-specific T cells expand in abortive seronegative SARS-CoV-2

Author

Swadling, Leo, Diniz, Mariana O., Schmidt, Nathalie M., Amin, Oliver E., Chandran, Aneesh, Shaw, Emily, Pade, Corinna, Gibbons, Joseph M., Le Bert, Nina, Tan, Anthony T., Jeffery-Smith, Anna, Tan, Cedric C. S., Tham, Christine Y. L., Kucykowicz, Stephanie, Aidoo-Micah, Gloryanne, Rosenheim, Joshua, Davies, Jessica, Johnson, Marina, Jensen, Melanie P., Joy, George, McCoy, Laura E., Valdes, Ana M., Chain, Benjamin M., Goldblatt, David, Altmann, Daniel M., Boyton, Rosemary J., Manisty, Charlotte, Treibel, Thomas A., Moon, James C., Abbass, Hakam, Abiodun, Aderonke, Alfarih, Mashael, Alldis, Zoe, Andiapen, Mervyn, Artico, Jessica, Augusto, João B., Baca, Georgina L., Bailey, Sasha N. L., Bhuva, Anish N., Boulter, Alex, Bowles, Ruth, Bracken, Olivia V., O’Brien, Ben, Brooks, Tim, Bullock, Natalie, Butler, David K., Captur, Gabriella, Champion, Nicola, Chan, Carmen, Collier, David, de Sousa, Jorge Couto, Couto-Parada, Xose, Cutino-Moguel, Teresa, Davies, Rhodri H., Douglas, Brooke, Di Genova, Cecilia, Dieobi-Anene, Keenan, Ellis, Anaya, Feehan, Karen, Finlay, Malcolm, Fontana, Marianna, Forooghi, Nasim, Gaier, Celia, Gilroy, Derek, Hamblin, Matt, Harker, Gabrielle, Hewson, Jacqueline, Hickling, Lauren M., Hingorani, Aroon D., Howes, Lee, Hughes, Alun, Hughes, Gemma, Hughes, Rebecca, Itua, Ivie, Jardim, Victor, Lee, Wing-Yiu Jason, Jensen, Melanie petra, Jones, Jessica, Jones, Meleri, Kapil, Vikas, Kurdi, Hibba, Lambourne, Jonathan, Lin, Kai-Min, Louth, Sarah, Mandadapu, Vineela, McKnight, Áine, Menacho, Katia, Mfuko, Celina, Mitchelmore, Oliver, Moon, Christopher, Murray, Sam M., Noursadeghi, Mahdad, Otter, Ashley, Palma, Susana, Parker, Ruth, Patel, Kush, Pawarova, Babita, Petersen, Steffen E., Piniera, Brian, Pieper, Franziska P., Pope, Daniel, Prossora, Mary, Rannigan, Lisa, Rapala, Alicja, Reynolds, Catherine J., Richards, Amy, Robathan, Matthew, Sambile, Genine, Semper, Amanda, Seraphim, Andreas, Simion, Mihaela, Smit, Angelique, Sugimoto, Michelle, Taylor, Stephen, Temperton, Nigel J., Thomas, Stephen, Thornton, George D., Tucker, Art, Veerapen, Jessry, Vijayakumar, Mohit, Welch, Sophie, Wodehouse, Theresa, Wynne, Lucinda, Zahedi, Dan, Dorp, Lucy van, Balloux, Francois, McKnight, Áine, Bertoletti, Antonio, Maini, Mala K., Swadling, Leo [0000-0002-0537-6715], Schmidt, Nathalie M [0000-0002-9841-8418], Gibbons, Joseph M [0000-0002-7238-2381], Le Bert, Nina [0000-0003-0502-2527], Tham, Christine YL [0000-0002-2913-7591], Kucykowicz, Stephanie [0000-0002-8849-218X], Rosenheim, Joshua [0000-0003-0171-2053], McCoy, Laura E [0000-0001-9503-7946], Valdes, Ana M [0000-0003-1141-4471], Chain, Benjamin M [0000-0002-7417-3970], Goldblatt, David [0000-0002-0769-5242], Boyton, Rosemary J [0000-0002-5608-0797], van Dorp, Lucy [0000-0002-6211-2310], Balloux, Francois [0000-0003-1978-7715], Noursadeghi, Mahdad [0000-0002-4774-0853], Bertoletti, Antonio [0000-0002-2942-0485], Maini, Mala K [0000-0001-6384-1462], Apollo - University of Cambridge Repository, Medical Research Council (MRC), and Multiple Sclerosis Society

Subjects
Male, Transcription, Genetic, 631/250/1619/554, medicine.disease_cause, DISEASE, Neutralization, Cohort Studies, 13/1, 631/250/2152/1566/1571, INFECTION, Coronaviridae, Asymptomatic Infections, Polymerase, Coronavirus, Multidisciplinary, biology, article, virus diseases, DNA-Directed RNA Polymerases, Multidisciplinary Sciences, 13/31, Seroconversion, Cohort, Science & Technology - Other Topics, VIRUS, Female, 82/75, HEALTH-CARE WORKERS, Antibody, ANTIBODY-RESPONSES, General Science & Technology, Health Personnel, 13/106, IMMUNITY, Evolution, Molecular, Memory T Cells, In vivo, Multienzyme Complexes, medicine, Humans, EXPOSURE, 631/326/596/4130, COVIDsortium Investigators, Cell Proliferation, PATHOGENS, Science & Technology, SARS-CoV-2, MEMORY, CORONAVIRUSES, COVID-19, Membrane Proteins, 631/250/254, biology.organism_classification, Virology, biology.protein
Abstract

Individuals with potential exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) do not necessarily develop PCR or antibody positivity, suggesting that some individuals may clear subclinical infection before seroconversion. T cells can contribute to the rapid clearance of SARS-CoV-2 and other coronavirus infections1–3. Here we hypothesize that pre-existing memory T cell responses, with cross-protective potential against SARS-CoV-2 (refs. 4–11), would expand in vivo to support rapid viral control, aborting infection. We measured SARS-CoV-2-reactive T cells, including those against the early transcribed replication–transcription complex (RTC)12,13, in intensively monitored healthcare workers (HCWs) who tested repeatedly negative according to PCR, antibody binding and neutralization assays (seronegative HCWs (SN-HCWs)). SN-HCWs had stronger, more multispecific memory T cells compared with a cohort of unexposed individuals from before the pandemic (prepandemic cohort), and these cells were more frequently directed against the RTC than the structural-protein-dominated responses observed after detectable infection (matched concurrent cohort). SN-HCWs with the strongest RTC-specific T cells had an increase in IFI27, a robust early innate signature of SARS-CoV-2 (ref. 14), suggesting abortive infection. RNA polymerase within RTC was the largest region of high sequence conservation across human seasonal coronaviruses (HCoV) and SARS-CoV-2 clades. RNA polymerase was preferentially targeted (among the regions tested) by T cells from prepandemic cohorts and SN-HCWs. RTC-epitope-specific T cells that cross-recognized HCoV variants were identified in SN-HCWs. Enriched pre-existing RNA-polymerase-specific T cells expanded in vivo to preferentially accumulate in the memory response after putative abortive compared to overt SARS-CoV-2 infection. Our data highlight RTC-specific T cells as targets for vaccines against endemic and emerging Coronaviridae.

Published
2021

13. Reinfection with new variants of SARS-CoV-2 after natural infection: a prospective observational cohort in 13 care homes in England

Author

Jeffery-Smith, Anna, primary, Rowland, Thomas A J, additional, Patel, Monika, additional, Whitaker, Heather, additional, Iyanger, Nalini, additional, Williams, Sarah V, additional, Giddings, Rebecca, additional, Thompson, Leah, additional, Zavala, Maria, additional, Aiano, Felicity, additional, Ellis, Joanna, additional, Lackenby, Angie, additional, Höschler, Katja, additional, Brown, Kevin, additional, Ramsay, Mary E, additional, Gopal, Robin, additional, Chow, J Yimmy, additional, Ladhani, Shamez N, additional, and Zambon, Maria, additional

Published
2021
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15. Antibody persistence and neutralising activity in primary school students and staff: prospective active surveillance, June to December 2020, England

Author

Ireland, Georgina, primary, Jeffery-Smith, Anna, additional, Zambon, Maria, additional, Hoschler, Katja, additional, Harris, Ross, additional, Poh, John, additional, Baawuah, Frances, additional, Beckmann, Joanne, additional, Okike, Ifeanyichukwu O, additional, Ahmad, Shazaad, additional, Garstang, Joanna, additional, Brent, Andrew J, additional, Brent, Bernadette, additional, Aiano, Felicity, additional, Amin-Chowdhury, Zahin, additional, Letley, Louise, additional, Jones, Samuel E I, additional, Kall, Meaghan, additional, Patel, Monika, additional, Gopal, Robin, additional, Borrow, Ray, additional, Linley, Ezra, additional, Amirthalingam, Gayatri, additional, Brown, Kevin E, additional, Ramsay, Mary E, additional, and Ladhani, Shamez N, additional

Published
2021
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16. SARS-CoV-2-specific memory B cells can persist in the elderly despite loss of neutralising antibodies

Author

Jeffery-Smith, Anna, primary, Burton, Alice R, additional, Lens, Sabela, additional, Rees-Spear, Chloe, additional, Patel, Monika, additional, Gopal, Robin, additional, Muir, Luke, additional, Aiano, Felicity, additional, Doores, Katie J, additional, Chow, J. Yimmy, additional, Ladhani, Shamez N, additional, Zambon, Maria, additional, McCoy, Laura E, additional, and Maini, Mala K, additional

Published
2021
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18. Infection and transmission of SARS-CoV-2 in London care homes reporting no cases or outbreaks of COVID-19: Prospective observational cohort study, England 2020

Author

Jeffery-Smith, Anna, primary, Dun-Campbell, Kate, additional, Janarthanan, Roshni, additional, Fok, Jonathan, additional, Crawley-Boevey, Emma, additional, Vusirikala, Amoolya, additional, Fernandez Ruiz De Olano, Elena, additional, Sanchez Perez, Marina, additional, Tang, Suzanne, additional, Rowland, Thomas AJ, additional, Wynne-Evans, Edward, additional, Bell, Anita, additional, Patel, Bharat, additional, Amin-Chowdhury, Zahin, additional, Aiano, Felicity, additional, Paranthaman, Karthik, additional, Ma, Thomas, additional, Saavedra-Campos, Maria, additional, Ellis, Joanna, additional, Lackenby, Angie, additional, Whitaker, Heather, additional, Myers, Richard, additional, Höschler, Katja, additional, Brown, Kevin, additional, Ramsay, Mary E, additional, Shetty, Nandini, additional, Chow, J. Yimmy, additional, Ladhani, Shamez, additional, and Zambon, Maria, additional

Published
2021
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19. Antibodies to SARS-CoV-2 protect against re-infection during outbreaks in care homes, September and October 2020

Author

Jeffery-Smith, Anna, primary, Iyanger, Nalini, additional, Williams, Sarah V, additional, Chow, J Yimmy, additional, Aiano, Felicity, additional, Hoschler, Katja, additional, Lackenby, Angie, additional, Ellis, Joanna, additional, Platt, Steven, additional, Miah, Shahjahan, additional, Brown, Kevin, additional, Amirthalingam, Gayatri, additional, Patel, Monika, additional, Ramsay, Mary E, additional, Gopal, Robin, additional, Charlett, Andre, additional, Ladhani, Shamez N, additional, and Zambon, Maria, additional

Published
2021
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20. High prevalence of SARS-CoV-2 antibodies in care homes affected by COVID-19; prospective cohort study, England

Author

Ladhani, Shamez N, primary, Jeffery-Smith, Anna, additional, Patel, Monika, additional, Janarthanan, Roshni, additional, Fok, Jonathan, additional, Crawley-Boevey, Emma, additional, Vusirikala, Amoolya, additional, Fernandez, Elena, additional, Perez, Marina Sanchez, additional, Tang, Suzanne, additional, Dun-Campbell, Kate, additional, Wynne-Evans, Edward, additional, Bell, Anita, additional, Patel, Bharat, additional, Amin-Chowdhury, Zahin, additional, Aiano, Felicity, additional, Paranthaman, Karthik, additional, Ma, Thomas, additional, Saavedra-Campos, Maria, additional, Ellis, Joanna, additional, Chand, Meera, additional, Brown, Kevin, additional, Ramsay, Mary E, additional, Hopkins, Susan, additional, Shetty, Nandini, additional, Chow, J. Yimmy, additional, Gopal, Robin, additional, and Zambon, Maria, additional

Published
2020
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21. Longevity and replenishment of human liver-resident memory T cells and mononuclear phagocytes

Author

Pallett, Laura J., primary, Burton, Alice R., additional, Amin, Oliver E., additional, Rodriguez-Tajes, Sergio, additional, Patel, Amit A., additional, Zakeri, Nekisa, additional, Jeffery-Smith, Anna, additional, Swadling, Leo, additional, Schmidt, Nathalie M., additional, Baiges, Anna, additional, Gander, Amir, additional, Yu, Dominic, additional, Nasralla, David, additional, Froghi, Farid, additional, Iype, Satheesh, additional, Davidson, Brian R., additional, Thorburn, Douglas, additional, Yona, Simon, additional, Forns, Xavier, additional, and Maini, Mala K., additional

Published
2020
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22. High Prevalence of SARS-CoV-2 Antibodies in Care Homes Affected by COVID-19; Prospective Cohort Study, England

Author

Ladhani, Shamez N., primary, Jeffery-Smith, Anna, additional, Patel, Monika, additional, Janarthanan, Roshni, additional, Fok, Jonathan, additional, Crawley-Boevey, Emma, additional, Vusirikala, Amoolya, additional, Fernandez, Elena, additional, Sanchez Perez, Marina, additional, Tang, Suzanne, additional, Dun-Campbell, Kate, additional, Wynne-Evans, Edward, additional, Bell, Anita, additional, Patel, Bharat, additional, Amin-Chowdhury, Zahin, additional, Aiano, Felicity, additional, Paranthaman, Karthik, additional, Ma, Thomas, additional, Saavedra-Campos, Maria, additional, Ellis, Joanna, additional, Chand, Meera, additional, Brown, Kevin, additional, Ramsay, Mary E., additional, Hopkins, Susan, additional, Shetty, Nandini, additional, Chow, J. Yimmy, additional, Gopal, Robin, additional, and Zambon, Maria, additional

Published
2020
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23. Human Liver Memory CD8+ T Cells Use Autophagy for Tissue Residence

Author

Swadling, Leo, primary, Pallett, Laura J., additional, Diniz, Mariana O., additional, Baker, Josephine M., additional, Amin, Oliver E., additional, Stegmann, Kerstin A., additional, Burton, Alice R., additional, Schmidt, Nathalie M., additional, Jeffery-Smith, Anna, additional, Zakeri, Nekisa, additional, Suveizdyte, Kornelija, additional, Froghi, Farid, additional, Fusai, Giuseppe, additional, Rosenberg, William M., additional, Davidson, Brian R., additional, Schurich, Anna, additional, Simon, A. Katharina, additional, and Maini, Mala K., additional

Published
2020
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26. Herpesviruses

Author

Riddell, Anna, primary, Jeffery-Smith, Anna, additional, and Tong, Cheuk Yan William, additional

Published
2017
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31. Is the Presence of Actinomycesspp. in Blood Culture Always Significant?

Author

Jeffery-Smith, Anna, Nic-Fhogartaigh, Caoimhe, and Millar, Michael

Abstract

ABSTRACTThe isolation of Actinomycesspp. from sterile clinical samples is traditionally regarded as significant. We reviewed the demographic characteristics, clinical risk factors, and outcomes of patients with Actinomycesspp. isolated from blood cultures in our NHS Trust and found that this is not necessarily the case.

Published
2016
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32. Human Liver Memory CD8+T Cells Use Autophagy for Tissue Residence

Author

Swadling, Leo, Pallett, Laura J., Diniz, Mariana O., Baker, Josephine M., Amin, Oliver E., Stegmann, Kerstin A., Burton, Alice R., Schmidt, Nathalie M., Jeffery-Smith, Anna, Zakeri, Nekisa, Suveizdyte, Kornelija, Froghi, Farid, Fusai, Giuseppe, Rosenberg, William M., Davidson, Brian R., Schurich, Anna, Simon, A. Katharina, and Maini, Mala K.

Abstract

Tissue-resident memory T cells have critical roles in long-term pathogen and tumor immune surveillance in the liver. We investigate the role of autophagy in equipping human memory T cells to acquire tissue residence and maintain functionality in the immunosuppressive liver environment. By performing ex vivostaining of freshly isolated cells from human liver tissue, we find that an increased rate of basal autophagy is a hallmark of intrahepatic lymphocytes, particularly liver-resident CD8+T cells. CD8+T cells with increased autophagy are those best able to proliferate and mediate cytotoxicity and cytokine production. Conversely, blocking autophagy induction results in the accumulation of depolarized mitochondria, a feature of exhausted T cells. Primary hepatic stellate cells or the prototypic hepatic cytokine interleukin (IL)-15 induce autophagy in parallel with tissue-homing/retention markers. Inhibition of T cell autophagy abrogates tissue-residence programming. Thus, upregulation of autophagy adapts CD8+T cells to combat mitochondrial depolarization, optimize functionality, and acquire tissue residence.

Published
2020
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33. Candida auris: a Review of the Literature

Author

Jeffery-Smith, Anna, Taori, Surabhi K., Schelenz, Silke, Jeffery, Katie, Johnson, Elizabeth M., Borman, Andrew, Manuel, Rohini, and Brown, Colin S.

Abstract

SUMMARYThe emerging pathogen Candida aurishas been associated with nosocomial outbreaks on five continents. Genetic analysis indicates the simultaneous emergence of separate clades of this organism in different geographical locations. Invasive infection and colonization have been detected predominantly in patients in high-dependency settings and have garnered attention due to variable antifungal resistance profiles and transmission within units instituting a range of infection prevention and control measures. Issues with the identification of C. aurisusing both phenotypic and molecular techniques have raised concerns about detecting the true scale of the problem. This review considers the literature available on C. aurisand highlights the key unknowns, which will provide direction for further work in this field.

Published
2017
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34. Infection and transmission of SARS-CoV-2 in London care homes reporting no cases or outbreaks of COVID-19: Prospective observational cohort study, England 2020.

Author

Jeffery-Smith A, Dun-Campbell K, Janarthanan R, Fok J, Crawley-Boevey E, Vusirikala A, Fernandez Ruiz De Olano E, Sanchez Perez M, Tang S, Rowland TA, Wynne-Evans E, Bell A, Patel B, Amin-Chowdhury Z, Aiano F, Paranthaman K, Ma T, Saavedra-Campos M, Ellis J, Lackenby A, Whitaker H, Myers R, Höschler K, Brown K, Ramsay ME, Shetty N, Chow JY, Ladhani S, and Zambon M

Abstract

Background: Care homes have been disproportionately affected by the COVID-19 pandemic. We investigated the potential role of asymptomatic infection and silent transmission in London care homes that reported no cases of COVID-19 during the first wave of the pandemic., Methods: Five care homes with no cases and two care homes reporting a single case of COVID-19 (non-outbreak homes) were investigated with nasal swabbing for SARS-CoV-2 RT-PCR and serology for SARS-CoV-2 antibodies five weeks later. Whole genome sequencing (WGS) was performed on RT-PCR positive samples. Serology results were compared with those of six care homes with recognised outbreaks., Findings: Across seven non-outbreak homes, 718 (387 staff, 331 residents) individuals had a nasal swab and 651 (386 staff, 265 residents) had follow-up serology. Sixteen individuals (13 residents, 3 staff) in five care homes with no reported cases were RT-PCR positive (care home positivity rates, 0 to 7.6%) compared to 13 individuals (3.0 and 10.8% positivity) in two homes reporting a single case.Seropositivity across these seven homes varied between 10.7-56.5%, with four exceeding community seroprevalence in London (14.8%). Seropositivity rates for staff and residents correlated significantly (r s 0.84, [95% CI 0.51-0.95] p <0.001) across the 13 homes. WGS identified multiple introductions into some homes and silent transmission of a single lineage between staff and residents in one home., Interpretation: We found high rates of asymptomatic infection and transmission even in care homes with no COVID-19 cases. The higher seropositivity rates compared to RT-PCR positivity highlights the true extent of the silent outbreak., Funding: PHE., Competing Interests: The authors have nothing to disclose., (Crown Copyright © 2021 Published by Elsevier Ltd.)

Published
2021
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35. Human Liver Memory CD8 + T Cells Use Autophagy for Tissue Residence.

Author

Swadling L, Pallett LJ, Diniz MO, Baker JM, Amin OE, Stegmann KA, Burton AR, Schmidt NM, Jeffery-Smith A, Zakeri N, Suveizdyte K, Froghi F, Fusai G, Rosenberg WM, Davidson BR, Schurich A, Simon AK, and Maini MK

Subjects
Cell Differentiation, Cell Proliferation, Humans, Mitochondria metabolism, Autophagy, CD8-Positive T-Lymphocytes cytology, Immunologic Memory, Liver cytology, Liver immunology
Abstract

Tissue-resident memory T cells have critical roles in long-term pathogen and tumor immune surveillance in the liver. We investigate the role of autophagy in equipping human memory T cells to acquire tissue residence and maintain functionality in the immunosuppressive liver environment. By performing ex vivo staining of freshly isolated cells from human liver tissue, we find that an increased rate of basal autophagy is a hallmark of intrahepatic lymphocytes, particularly liver-resident CD8 + T cells. CD8 + T cells with increased autophagy are those best able to proliferate and mediate cytotoxicity and cytokine production. Conversely, blocking autophagy induction results in the accumulation of depolarized mitochondria, a feature of exhausted T cells. Primary hepatic stellate cells or the prototypic hepatic cytokine interleukin (IL)-15 induce autophagy in parallel with tissue-homing/retention markers. Inhibition of T cell autophagy abrogates tissue-residence programming. Thus, upregulation of autophagy adapts CD8 + T cells to combat mitochondrial depolarization, optimize functionality, and acquire tissue residence., Competing Interests: Declaration of Interests Authors declare no competing interests. The Maini Laboratory has received unrestricted research grants from Gilead Science Inc, Roche, and Immunocore., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

Published
2020
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