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1. Bayesian Uncertainty Estimation by Hamiltonian Monte Carlo: Applications to Cardiac MRI Segmentation

Author: Zhao, Yidong, Tourais, Joao, Pierce, Iain, Nitsche, Christian, Treibel, Thomas A., Weingärtner, Sebastian, Schweidtmann, Artur M., Tao, Qian, Zhao, Yidong, Tourais, Joao, Pierce, Iain, Nitsche, Christian, Treibel, Thomas A., Weingärtner, Sebastian, Schweidtmann, Artur M., and Tao, Qian
Abstract: Deep learning (DL)-based methods have achieved state-of-the-art performance for a wide range of medical image segmentation tasks. Nevertheless, recent studies show that deep neural networks (DNNs) can be miscalibrated and overconfident, leading to "silent failures" that are risky} for clinical applications. Bayesian statistics provide an intuitive approach to DL failure detection, based on posterior probability estimation. However, Bayesian DL, and in particular the posterior estimation, is intractable for large medical image segmentation DNNs. To tackle this challenge, we propose a Bayesian learning framework by Hamiltonian Monte Carlo (HMC), tempered by cold posterior (CP) to accommodate medical data augmentation, named HMC-CP. For HMC computation, we further propose a cyclical annealing strategy, which captures both local and global geometries of the posterior distribution, enabling highly efficient Bayesian DNN training with the same computational budget requirements as training a single DNN. The resulting Bayesian DNN outputs an ensemble segmentation along with the segmentation uncertainty. We evaluate the proposed HMC-CP extensively on cardiac magnetic resonance image (MRI) segmentation, using in-domain steady-state free precession (SSFP) cine images as well as out-of-domain datasets of quantitative $T_1$ and $T_2$ mapping.
Published: 2024

2. Quantitative, multiplexed, targeted proteomics for ascertaining variant specific SARS-CoV-2 antibody response

Author: Doykov, Ivan, Baldwin, Tomas, Spiewak, Justyna, Gilmour, Kimberly C., Gibbons, Joseph M., Pade, Corinna, Reynolds, Catherine J., McKnight, Áine, Noursadeghi, Mahdad, Maini, Mala K., Manisty, Charlotte, Treibel, Thomas, Captur, Gabriella, Fontana, Marianna, Boyton, Rosemary J., Altmann, Daniel M., Brooks, Tim, Semper, Amanda, Moon, James C., Mills, Kevin, Heywood, Wendy E., Abbass, Hakam, Abiodun, Aderonke, Alfarih, Mashael, Alldis, Zoe, Amin, Oliver E., 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, Bullock, Natalie, Butler, David K., Carr, Olivia, Champion, Nicola, Chan, Carmen, Chandran, Aneesh, Coleman, Tom, Couto de Sousa, Jorge, Couto-Parada, Xose, Cross, Eleanor, Cutino-Moguel, Teresa, D’Arcangelo, Silvia, Davies, Rhodri H., Douglas, Brooke, Di Genova, Cecilia, Dieobi-Anene, Keenan, Diniz, Mariana O., Ellis, Anaya, Feehan, Karen, Finlay, Malcolm, Forooghi, Nasim, Francis, Sasha, Gillespie, David, Gilroy, Derek, Hamblin, Matt, Harker, Gabrielle, Hemingway, Georgia, Hewson, Jacqueline, Heywood, Wendy, Hickling, Lauren M., Hicks, Bethany, Hingorani, Aroon D., Howes, Lee, Itua, Ivie, Jardim, Victor, Lee, Wing-Yiu Jason, Jensen, Melaniepetra, Jones, Jessica, Jones, Meleri, Joy, George, Kapil, Vikas, Kelly, Caoimhe, Kurdi, Hibba, Lambourne, Jonathan, Lin, Kai-Min, Liu, Siyi, Lloyd, Aaron, Louth, Sarah, Mandadapu, Vineela, Menacho, Katia, Mfuko, Celina, Millward, Sebastian, Mitchelmore, Oliver, Moon, Christopher, Moon, James, Sandoval, Diana Muñoz, Murray, Sam M., Otter, Ashley, Palma, Susana, Parker, Ruth, Patel, Kush, Pawarova, Mihaela, Petersen, Steffen E., Piniera, Brian, Pieper, Franziska P., Rannigan, Lisa, Rapala, Alicja, Richards, Amy, Robathan, Matthew, Rosenheim, Joshua, Rowe, Cathy, Royds, Matthew, West, Jane Sackville, Sambile, Genine, Schmidt, Nathalie M., Selman, Hannah, Seraphim, Andreas, Simion, Mihaela, Smit, Angelique, Sugimoto, Michelle, Swadling, Leo, Taylor, Stephen, Temperton, Nigel J., Thomas, Stephen, Thornton, George D., Treibel, Thomas A., Tucker, Art, Varghese, Ann, Veerapen, Jessry, Vijayakumar, Mohit, Warner, Tim, Welch, Sophie, White, Hannah, Wodehouse, Theresa, Wynne, Lucinda, Zahedi, Dan, Doykov, Ivan, Baldwin, Tomas, Spiewak, Justyna, Gilmour, Kimberly C., Gibbons, Joseph M., Pade, Corinna, Reynolds, Catherine J., McKnight, Áine, Noursadeghi, Mahdad, Maini, Mala K., Manisty, Charlotte, Treibel, Thomas, Captur, Gabriella, Fontana, Marianna, Boyton, Rosemary J., Altmann, Daniel M., Brooks, Tim, Semper, Amanda, Moon, James C., Mills, Kevin, Heywood, Wendy E., Abbass, Hakam, Abiodun, Aderonke, Alfarih, Mashael, Alldis, Zoe, Amin, Oliver E., 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, Bullock, Natalie, Butler, David K., Carr, Olivia, Champion, Nicola, Chan, Carmen, Chandran, Aneesh, Coleman, Tom, Couto de Sousa, Jorge, Couto-Parada, Xose, Cross, Eleanor, Cutino-Moguel, Teresa, D’Arcangelo, Silvia, Davies, Rhodri H., Douglas, Brooke, Di Genova, Cecilia, Dieobi-Anene, Keenan, Diniz, Mariana O., Ellis, Anaya, Feehan, Karen, Finlay, Malcolm, Forooghi, Nasim, Francis, Sasha, Gillespie, David, Gilroy, Derek, Hamblin, Matt, Harker, Gabrielle, Hemingway, Georgia, Hewson, Jacqueline, Heywood, Wendy, Hickling, Lauren M., Hicks, Bethany, Hingorani, Aroon D., Howes, Lee, Itua, Ivie, Jardim, Victor, Lee, Wing-Yiu Jason, Jensen, Melaniepetra, Jones, Jessica, Jones, Meleri, Joy, George, Kapil, Vikas, Kelly, Caoimhe, Kurdi, Hibba, Lambourne, Jonathan, Lin, Kai-Min, Liu, Siyi, Lloyd, Aaron, Louth, Sarah, Mandadapu, Vineela, Menacho, Katia, Mfuko, Celina, Millward, Sebastian, Mitchelmore, Oliver, Moon, Christopher, Moon, James, Sandoval, Diana Muñoz, Murray, Sam M., Otter, Ashley, Palma, Susana, Parker, Ruth, Patel, Kush, Pawarova, Mihaela, Petersen, Steffen E., Piniera, Brian, Pieper, Franziska P., Rannigan, Lisa, Rapala, Alicja, Richards, Amy, Robathan, Matthew, Rosenheim, Joshua, Rowe, Cathy, Royds, Matthew, West, Jane Sackville, Sambile, Genine, Schmidt, Nathalie M., Selman, Hannah, Seraphim, Andreas, Simion, Mihaela, Smit, Angelique, Sugimoto, Michelle, Swadling, Leo, Taylor, Stephen, Temperton, Nigel J., Thomas, Stephen, Thornton, George D., Treibel, Thomas A., Tucker, Art, Varghese, Ann, Veerapen, Jessry, Vijayakumar, Mohit, Warner, Tim, Welch, Sophie, White, Hannah, Wodehouse, Theresa, Wynne, Lucinda, and Zahedi, Dan
Abstract: Determining the protection an individual has to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants of concern (VoCs) is crucial for future immune surveillance, vaccine development, and understanding of the changing immune response. We devised an informative assay to current ELISA-based serology using multiplexed, baited, targeted proteomics for direct detection of multiple proteins in the SARS-CoV-2 anti-spike antibody immunocomplex. Serum from individuals collected after infection or first- and second-dose vaccination demonstrates this approach and shows concordance with existing serology and neutralization. Our assays show altered responses of both immunoglobulins and complement to the Alpha (B.1.1.7), Beta (B.1.351), and Delta (B.1.617.1) VoCs and a reduced response to Omicron (B1.1.1529). We were able to identify individuals who had prior infection, and observed that C1q is closely associated with IgG1 (r > 0.82) and may better reflect neutralization to VoCs. Analyzing additional immunoproteins beyond immunoglobulin (Ig) G, provides important information about our understanding of the response to infection and vaccination.
Published: 2022

3. Quantitative, multiplexed, targeted proteomics for ascertaining variant specific SARS-CoV-2 antibody response

Author: Doykov, Ivan, Baldwin, Tomas, Spiewak, Justyna, Gilmour, Kimberly C., Gibbons, Joseph M., Pade, Corinna, Reynolds, Catherine J., McKnight, Áine, Noursadeghi, Mahdad, Maini, Mala K., Manisty, Charlotte, Treibel, Thomas, Captur, Gabriella, Fontana, Marianna, Boyton, Rosemary J., Altmann, Daniel M., Brooks, Tim, Semper, Amanda, Moon, James C., Mills, Kevin, Heywood, Wendy E., Abbass, Hakam, Abiodun, Aderonke, Alfarih, Mashael, Alldis, Zoe, Amin, Oliver E., 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, Bullock, Natalie, Butler, David K., Carr, Olivia, Champion, Nicola, Chan, Carmen, Chandran, Aneesh, Coleman, Tom, Couto de Sousa, Jorge, Couto-Parada, Xose, Cross, Eleanor, Cutino-Moguel, Teresa, D’Arcangelo, Silvia, Davies, Rhodri H., Douglas, Brooke, Di Genova, Cecilia, Dieobi-Anene, Keenan, Diniz, Mariana O., Ellis, Anaya, Feehan, Karen, Finlay, Malcolm, Forooghi, Nasim, Francis, Sasha, Gillespie, David, Gilroy, Derek, Hamblin, Matt, Harker, Gabrielle, Hemingway, Georgia, Hewson, Jacqueline, Heywood, Wendy, Hickling, Lauren M., Hicks, Bethany, Hingorani, Aroon D., Howes, Lee, Itua, Ivie, Jardim, Victor, Lee, Wing-Yiu Jason, Jensen, Melaniepetra, Jones, Jessica, Jones, Meleri, Joy, George, Kapil, Vikas, Kelly, Caoimhe, Kurdi, Hibba, Lambourne, Jonathan, Lin, Kai-Min, Liu, Siyi, Lloyd, Aaron, Louth, Sarah, Mandadapu, Vineela, Menacho, Katia, Mfuko, Celina, Millward, Sebastian, Mitchelmore, Oliver, Moon, Christopher, Moon, James, Sandoval, Diana Muñoz, Murray, Sam M., Otter, Ashley, Palma, Susana, Parker, Ruth, Patel, Kush, Pawarova, Mihaela, Petersen, Steffen E., Piniera, Brian, Pieper, Franziska P., Rannigan, Lisa, Rapala, Alicja, Richards, Amy, Robathan, Matthew, Rosenheim, Joshua, Rowe, Cathy, Royds, Matthew, West, Jane Sackville, Sambile, Genine, Schmidt, Nathalie M., Selman, Hannah, Seraphim, Andreas, Simion, Mihaela, Smit, Angelique, Sugimoto, Michelle, Swadling, Leo, Taylor, Stephen, Temperton, Nigel J., Thomas, Stephen, Thornton, George D., Treibel, Thomas A., Tucker, Art, Varghese, Ann, Veerapen, Jessry, Vijayakumar, Mohit, Warner, Tim, Welch, Sophie, White, Hannah, Wodehouse, Theresa, Wynne, Lucinda, Zahedi, Dan, Doykov, Ivan, Baldwin, Tomas, Spiewak, Justyna, Gilmour, Kimberly C., Gibbons, Joseph M., Pade, Corinna, Reynolds, Catherine J., McKnight, Áine, Noursadeghi, Mahdad, Maini, Mala K., Manisty, Charlotte, Treibel, Thomas, Captur, Gabriella, Fontana, Marianna, Boyton, Rosemary J., Altmann, Daniel M., Brooks, Tim, Semper, Amanda, Moon, James C., Mills, Kevin, Heywood, Wendy E., Abbass, Hakam, Abiodun, Aderonke, Alfarih, Mashael, Alldis, Zoe, Amin, Oliver E., 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, Bullock, Natalie, Butler, David K., Carr, Olivia, Champion, Nicola, Chan, Carmen, Chandran, Aneesh, Coleman, Tom, Couto de Sousa, Jorge, Couto-Parada, Xose, Cross, Eleanor, Cutino-Moguel, Teresa, D’Arcangelo, Silvia, Davies, Rhodri H., Douglas, Brooke, Di Genova, Cecilia, Dieobi-Anene, Keenan, Diniz, Mariana O., Ellis, Anaya, Feehan, Karen, Finlay, Malcolm, Forooghi, Nasim, Francis, Sasha, Gillespie, David, Gilroy, Derek, Hamblin, Matt, Harker, Gabrielle, Hemingway, Georgia, Hewson, Jacqueline, Heywood, Wendy, Hickling, Lauren M., Hicks, Bethany, Hingorani, Aroon D., Howes, Lee, Itua, Ivie, Jardim, Victor, Lee, Wing-Yiu Jason, Jensen, Melaniepetra, Jones, Jessica, Jones, Meleri, Joy, George, Kapil, Vikas, Kelly, Caoimhe, Kurdi, Hibba, Lambourne, Jonathan, Lin, Kai-Min, Liu, Siyi, Lloyd, Aaron, Louth, Sarah, Mandadapu, Vineela, Menacho, Katia, Mfuko, Celina, Millward, Sebastian, Mitchelmore, Oliver, Moon, Christopher, Moon, James, Sandoval, Diana Muñoz, Murray, Sam M., Otter, Ashley, Palma, Susana, Parker, Ruth, Patel, Kush, Pawarova, Mihaela, Petersen, Steffen E., Piniera, Brian, Pieper, Franziska P., Rannigan, Lisa, Rapala, Alicja, Richards, Amy, Robathan, Matthew, Rosenheim, Joshua, Rowe, Cathy, Royds, Matthew, West, Jane Sackville, Sambile, Genine, Schmidt, Nathalie M., Selman, Hannah, Seraphim, Andreas, Simion, Mihaela, Smit, Angelique, Sugimoto, Michelle, Swadling, Leo, Taylor, Stephen, Temperton, Nigel J., Thomas, Stephen, Thornton, George D., Treibel, Thomas A., Tucker, Art, Varghese, Ann, Veerapen, Jessry, Vijayakumar, Mohit, Warner, Tim, Welch, Sophie, White, Hannah, Wodehouse, Theresa, Wynne, Lucinda, and Zahedi, Dan
Abstract: Determining the protection an individual has to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants of concern (VoCs) is crucial for future immune surveillance, vaccine development, and understanding of the changing immune response. We devised an informative assay to current ELISA-based serology using multiplexed, baited, targeted proteomics for direct detection of multiple proteins in the SARS-CoV-2 anti-spike antibody immunocomplex. Serum from individuals collected after infection or first- and second-dose vaccination demonstrates this approach and shows concordance with existing serology and neutralization. Our assays show altered responses of both immunoglobulins and complement to the Alpha (B.1.1.7), Beta (B.1.351), and Delta (B.1.617.1) VoCs and a reduced response to Omicron (B1.1.1529). We were able to identify individuals who had prior infection, and observed that C1q is closely associated with IgG1 (r > 0.82) and may better reflect neutralization to VoCs. Analyzing additional immunoproteins beyond immunoglobulin (Ig) G, provides important information about our understanding of the response to infection and vaccination.
Published: 2022

4. Improved reproducibility for myocardial ASL: Impact of physiological and acquisition parameters

Author: Bozic, M. (author), Rapacchi, Stanislas (author), Tao, Q. (author), Pierce, Iain (author), Thornton, George (author), Nitsche, Christian (author), Treibel, Thomas A. (author), Schad, Lothar R. (author), Weingärtner, S.D. (author), Bozic, M. (author), Rapacchi, Stanislas (author), Tao, Q. (author), Pierce, Iain (author), Thornton, George (author), Nitsche, Christian (author), Treibel, Thomas A. (author), Schad, Lothar R. (author), and Weingärtner, S.D. (author)
Abstract: Purpose: To investigate and mitigate the influence of physiological and acquisition-related parameters on myocardial blood flow (MBF) measurements obtained with myocardial Arterial Spin Labeling (myoASL). Methods: A Flow-sensitive Alternating Inversion Recovery (FAIR) myoASL sequence with bSSFP and spoiled GRE (spGRE) readout is investigated for MBF quantification. Bloch-equation simulations and phantom experiments were performed to evaluate how variations in acquisition flip angle (FA), acquisition matrix size (AMS), heart rate (HR) and blood (Formula presented.) relaxation time ((Formula presented.)) affect quantification of myoASL-MBF. In vivo myoASL-images were acquired in nine healthy subjects. A corrected MBF quantification approach was proposed based on subject-specific (Formula presented.) values and, for spGRE imaging, subtracting an additional saturation-prepared baseline from the original baseline signal. Results: Simulated and phantom experiments showed a strong dependence on AMS and FA ((Formula presented.) >0.73), which was eliminated in simulations and alleviated in phantom experiments using the proposed saturation-baseline correction in spGRE. Only a very mild HR dependence ((Formula presented.) >0.59) was observed which was reduced when calculating MBF with individual (Formula presented.). For corrected spGRE, in vivo mean global spGRE-MBF ranged from 0.54 to 2.59 mL/g/min and was in agreement with previously reported values. Compared to uncorrected spGRE, the intra-subject variability within a measurement (0.60 mL/g/min), between measurements (0.45 mL/g/min), as well as the inter-subject variability (1.29 mL/g/min) were improved by up to 40% and were comparable with conventional bSSFP. Conclusion: Our results show that physiological and acquisition-related factors can lead to spurious changes in myoASL-MBF if not accounted for. Using individual (Formula presented.) and a saturation-baseline can reduce these variations in spGRE and improve, ImPhys/Weingärtner group, ImPhys/Tao group
Published: 2023
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5. Identification of subclinical cardiac amyloidosis in aortic stenosis patients undergoing transaortic valve replacement using radiomic analysis of computed tomography myocardial texture

Author: Cardiologie, Team Medisch, Lo Iacono, Francesca, Maragna, Riccardo, Guglielmo, Marco, Chiesa, Mattia, Fusini, Laura, Annoni, Andrea, Babbaro, Mario, Baggiano, Andrea, Carerj, Maria Ludovica, Cilia, Francesco, Del Torto, Alberico, Formenti, Alberto, Mancini, Maria Elisabetta, Marchetti, Francesca, Muratori, Manuela, Mushtaq, Saima, Penso, Marco, Pirola, Sergio, Tassetti, Luigi, Volpe, Alessandra, Guaricci, Andrea Igoren, Fontana, Marianna, Tamborini, Gloria, Treibel, Thomas, Moon, James, D. A. Corino, Valentina, Pontone, Gianluca, Cardiologie, Team Medisch, Lo Iacono, Francesca, Maragna, Riccardo, Guglielmo, Marco, Chiesa, Mattia, Fusini, Laura, Annoni, Andrea, Babbaro, Mario, Baggiano, Andrea, Carerj, Maria Ludovica, Cilia, Francesco, Del Torto, Alberico, Formenti, Alberto, Mancini, Maria Elisabetta, Marchetti, Francesca, Muratori, Manuela, Mushtaq, Saima, Penso, Marco, Pirola, Sergio, Tassetti, Luigi, Volpe, Alessandra, Guaricci, Andrea Igoren, Fontana, Marianna, Tamborini, Gloria, Treibel, Thomas, Moon, James, D. A. Corino, Valentina, and Pontone, Gianluca
Published: 2023

6. Immune boosting by B.1.1.529 (Omicron) depends on previous SARS-CoV-2 exposure

Author: Reynolds, Catherine J., Pade, Corinna, Gibbons, Joseph M., Otter, Ashley D., Lin, Kai-Min, Muñoz Sandoval, Diana, Pieper, Franziska P., Butler, David K., Liu, Siyi, Joy, George, Forooghi, Nasim, Treibel, Thomas A., Manisty, Charlotte, Moon, James C., Semper, Amanda, Brooks, Tim, McKnight, Áine, Altmann, Daniel M., Boyton, Rosemary J., Abbass, Hakam, Abiodun, Aderonke, Alfarih, Mashael, Alldis, Zoe, Amin, Oliver E., 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, Bullock, Natalie, Captur, Gabriella, Carr, Olivia, Champion, Nicola, Chan, Carmen, Chandran, Aneesh, Coleman, Tom, Couto de Sousa, Jorge, Couto-Parada, Xose, Cross, Eleanor, Cutino-Moguel, Teresa, D’Arcangelo, Silvia, Davies, Rhodri H., Douglas, Brooke, Di Genova, Cecilia, Dieobi-Anene, Keenan, Diniz, Mariana O., Ellis, Anaya, Feehan, Karen, Finlay, Malcolm, Fontana, Marianna, Francis, Sasha, Gillespie, David, Gilroy, Derek, Hamblin, Matt, Harker, Gabrielle, Hemingway, Georgia, Hewson, Jacqueline, Heywood, Wendy, Hickling, Lauren M., Hicks, Bethany, Hingorani, Aroon D., Howes, Lee, Itua, Ivie, Jardim, Victor, Lee, Wing-Yiu Jason, Jensen, Melaniepetra, Jones, Jessica, Jones, Meleri, Kapil, Vikas, Kelly, Caoimhe, Kurdi, Hibba, Lambourne, Jonathan, Lloyd, Aaron, Louth, Sarah, Maini, Mala K., Mandadapu, Vineela, Menacho, Katia, Mfuko, Celina, Mills, Kevin, Millward, Sebastian, Mitchelmore, Oliver, Moon, Christopher, Moon, James, Murray, Sam M., Noursadeghi, Mahdad, Otter, Ashley, Palma, Susana, Parker, Ruth, Patel, Kush, Pawarova, Mihaela, Petersen, Steffen E., Piniera, Brian, Rannigan, Lisa, Rapala, Alicja, Richards, Amy, Robathan, Matthew, Rosenheim, Joshua, Rowe, Cathy, Royds, Matthew, Sackville West, Jane, Sambile, Genine, Schmidt, Nathalie M., Selman, Hannah, Seraphim, Andreas, Simion, Mihaela, Smit, Angelique, Sugimoto, Michelle, Swadling, Leo, Taylor, Stephen, Temperton, Nigel J., Thomas, Stephen, Thornton, George D., Tucker, Art, Varghese, Ann, Veerapen, Jessry, Vijayakumar, Mohit, Warner, Tim, Welch, Sophie, White, Hannah, Wodehouse, Theresa, Wynne, Lucinda, Zahedi, Dan, Chain, Benjamin, Reynolds, Catherine J., Pade, Corinna, Gibbons, Joseph M., Otter, Ashley D., Lin, Kai-Min, Muñoz Sandoval, Diana, Pieper, Franziska P., Butler, David K., Liu, Siyi, Joy, George, Forooghi, Nasim, Treibel, Thomas A., Manisty, Charlotte, Moon, James C., Semper, Amanda, Brooks, Tim, McKnight, Áine, Altmann, Daniel M., Boyton, Rosemary J., Abbass, Hakam, Abiodun, Aderonke, Alfarih, Mashael, Alldis, Zoe, Amin, Oliver E., 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, Bullock, Natalie, Captur, Gabriella, Carr, Olivia, Champion, Nicola, Chan, Carmen, Chandran, Aneesh, Coleman, Tom, Couto de Sousa, Jorge, Couto-Parada, Xose, Cross, Eleanor, Cutino-Moguel, Teresa, D’Arcangelo, Silvia, Davies, Rhodri H., Douglas, Brooke, Di Genova, Cecilia, Dieobi-Anene, Keenan, Diniz, Mariana O., Ellis, Anaya, Feehan, Karen, Finlay, Malcolm, Fontana, Marianna, Francis, Sasha, Gillespie, David, Gilroy, Derek, Hamblin, Matt, Harker, Gabrielle, Hemingway, Georgia, Hewson, Jacqueline, Heywood, Wendy, Hickling, Lauren M., Hicks, Bethany, Hingorani, Aroon D., Howes, Lee, Itua, Ivie, Jardim, Victor, Lee, Wing-Yiu Jason, Jensen, Melaniepetra, Jones, Jessica, Jones, Meleri, Kapil, Vikas, Kelly, Caoimhe, Kurdi, Hibba, Lambourne, Jonathan, Lloyd, Aaron, Louth, Sarah, Maini, Mala K., Mandadapu, Vineela, Menacho, Katia, Mfuko, Celina, Mills, Kevin, Millward, Sebastian, Mitchelmore, Oliver, Moon, Christopher, Moon, James, Murray, Sam M., Noursadeghi, Mahdad, Otter, Ashley, Palma, Susana, Parker, Ruth, Patel, Kush, Pawarova, Mihaela, Petersen, Steffen E., Piniera, Brian, Rannigan, Lisa, Rapala, Alicja, Richards, Amy, Robathan, Matthew, Rosenheim, Joshua, Rowe, Cathy, Royds, Matthew, Sackville West, Jane, Sambile, Genine, Schmidt, Nathalie M., Selman, Hannah, Seraphim, Andreas, Simion, Mihaela, Smit, Angelique, Sugimoto, Michelle, Swadling, Leo, Taylor, Stephen, Temperton, Nigel J., Thomas, Stephen, Thornton, George D., Tucker, Art, Varghese, Ann, Veerapen, Jessry, Vijayakumar, Mohit, Warner, Tim, Welch, Sophie, White, Hannah, Wodehouse, Theresa, Wynne, Lucinda, Zahedi, Dan, and Chain, Benjamin
Abstract: The Omicron, or Pango lineage B.1.1.529, variant of SARS-CoV-2 carries multiple spike mutations with high transmissibility and partial neutralizing antibody (nAb) escape. Vaccinated individuals show protection from severe disease, often attributed to primed cellular immunity. We investigated T and B cell immunity against B.1.1.529 in triple mRNA vaccinated healthcare workers (HCW) with different SARS-CoV-2 infection histories. B and T cell immunity against previous variants of concern was enhanced in triple vaccinated individuals, but magnitude of T and B cell responses against B.1.1.529 spike protein was reduced. Immune imprinting by infection with the earlier B.1.1.7 (Alpha) variant resulted in less durable binding antibody against B.1.1.529. Previously infection-naïve HCW who became infected during the B.1.1.529 wave showed enhanced immunity against earlier variants, but reduced nAb potency and T cell responses against B.1.1.529 itself. Previous Wuhan Hu-1 infection abrogated T cell recognition and any enhanced cross-reactive neutralizing immunity on infection with B.1.1.529.
Published: 2022

7. Immune boosting by B.1.1.529 (Omicron) depends on previous SARS-CoV-2 exposure

Author: Reynolds, Catherine J., Pade, Corinna, Gibbons, Joseph M., Otter, Ashley D., Lin, Kai-Min, Muñoz Sandoval, Diana, Pieper, Franziska P., Butler, David K., Liu, Siyi, Joy, George, Forooghi, Nasim, Treibel, Thomas A., Manisty, Charlotte, Moon, James C., Semper, Amanda, Brooks, Tim, McKnight, Áine, Altmann, Daniel M., Boyton, Rosemary J., Abbass, Hakam, Abiodun, Aderonke, Alfarih, Mashael, Alldis, Zoe, Amin, Oliver E., 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, Bullock, Natalie, Captur, Gabriella, Carr, Olivia, Champion, Nicola, Chan, Carmen, Chandran, Aneesh, Coleman, Tom, Couto de Sousa, Jorge, Couto-Parada, Xose, Cross, Eleanor, Cutino-Moguel, Teresa, D’Arcangelo, Silvia, Davies, Rhodri H., Douglas, Brooke, Di Genova, Cecilia, Dieobi-Anene, Keenan, Diniz, Mariana O., Ellis, Anaya, Feehan, Karen, Finlay, Malcolm, Fontana, Marianna, Francis, Sasha, Gillespie, David, Gilroy, Derek, Hamblin, Matt, Harker, Gabrielle, Hemingway, Georgia, Hewson, Jacqueline, Heywood, Wendy, Hickling, Lauren M., Hicks, Bethany, Hingorani, Aroon D., Howes, Lee, Itua, Ivie, Jardim, Victor, Lee, Wing-Yiu Jason, Jensen, Melaniepetra, Jones, Jessica, Jones, Meleri, Kapil, Vikas, Kelly, Caoimhe, Kurdi, Hibba, Lambourne, Jonathan, Lloyd, Aaron, Louth, Sarah, Maini, Mala K., Mandadapu, Vineela, Menacho, Katia, Mfuko, Celina, Mills, Kevin, Millward, Sebastian, Mitchelmore, Oliver, Moon, Christopher, Moon, James, Murray, Sam M., Noursadeghi, Mahdad, Otter, Ashley, Palma, Susana, Parker, Ruth, Patel, Kush, Pawarova, Mihaela, Petersen, Steffen E., Piniera, Brian, Rannigan, Lisa, Rapala, Alicja, Richards, Amy, Robathan, Matthew, Rosenheim, Joshua, Rowe, Cathy, Royds, Matthew, Sackville West, Jane, Sambile, Genine, Schmidt, Nathalie M., Selman, Hannah, Seraphim, Andreas, Simion, Mihaela, Smit, Angelique, Sugimoto, Michelle, Swadling, Leo, Taylor, Stephen, Temperton, Nigel J., Thomas, Stephen, Thornton, George D., Tucker, Art, Varghese, Ann, Veerapen, Jessry, Vijayakumar, Mohit, Warner, Tim, Welch, Sophie, White, Hannah, Wodehouse, Theresa, Wynne, Lucinda, Zahedi, Dan, Chain, Benjamin, Reynolds, Catherine J., Pade, Corinna, Gibbons, Joseph M., Otter, Ashley D., Lin, Kai-Min, Muñoz Sandoval, Diana, Pieper, Franziska P., Butler, David K., Liu, Siyi, Joy, George, Forooghi, Nasim, Treibel, Thomas A., Manisty, Charlotte, Moon, James C., Semper, Amanda, Brooks, Tim, McKnight, Áine, Altmann, Daniel M., Boyton, Rosemary J., Abbass, Hakam, Abiodun, Aderonke, Alfarih, Mashael, Alldis, Zoe, Amin, Oliver E., 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, Bullock, Natalie, Captur, Gabriella, Carr, Olivia, Champion, Nicola, Chan, Carmen, Chandran, Aneesh, Coleman, Tom, Couto de Sousa, Jorge, Couto-Parada, Xose, Cross, Eleanor, Cutino-Moguel, Teresa, D’Arcangelo, Silvia, Davies, Rhodri H., Douglas, Brooke, Di Genova, Cecilia, Dieobi-Anene, Keenan, Diniz, Mariana O., Ellis, Anaya, Feehan, Karen, Finlay, Malcolm, Fontana, Marianna, Francis, Sasha, Gillespie, David, Gilroy, Derek, Hamblin, Matt, Harker, Gabrielle, Hemingway, Georgia, Hewson, Jacqueline, Heywood, Wendy, Hickling, Lauren M., Hicks, Bethany, Hingorani, Aroon D., Howes, Lee, Itua, Ivie, Jardim, Victor, Lee, Wing-Yiu Jason, Jensen, Melaniepetra, Jones, Jessica, Jones, Meleri, Kapil, Vikas, Kelly, Caoimhe, Kurdi, Hibba, Lambourne, Jonathan, Lloyd, Aaron, Louth, Sarah, Maini, Mala K., Mandadapu, Vineela, Menacho, Katia, Mfuko, Celina, Mills, Kevin, Millward, Sebastian, Mitchelmore, Oliver, Moon, Christopher, Moon, James, Murray, Sam M., Noursadeghi, Mahdad, Otter, Ashley, Palma, Susana, Parker, Ruth, Patel, Kush, Pawarova, Mihaela, Petersen, Steffen E., Piniera, Brian, Rannigan, Lisa, Rapala, Alicja, Richards, Amy, Robathan, Matthew, Rosenheim, Joshua, Rowe, Cathy, Royds, Matthew, Sackville West, Jane, Sambile, Genine, Schmidt, Nathalie M., Selman, Hannah, Seraphim, Andreas, Simion, Mihaela, Smit, Angelique, Sugimoto, Michelle, Swadling, Leo, Taylor, Stephen, Temperton, Nigel J., Thomas, Stephen, Thornton, George D., Tucker, Art, Varghese, Ann, Veerapen, Jessry, Vijayakumar, Mohit, Warner, Tim, Welch, Sophie, White, Hannah, Wodehouse, Theresa, Wynne, Lucinda, Zahedi, Dan, and Chain, Benjamin
Abstract: The Omicron, or Pango lineage B.1.1.529, variant of SARS-CoV-2 carries multiple spike mutations with high transmissibility and partial neutralizing antibody (nAb) escape. Vaccinated individuals show protection from severe disease, often attributed to primed cellular immunity. We investigated T and B cell immunity against B.1.1.529 in triple mRNA vaccinated healthcare workers (HCW) with different SARS-CoV-2 infection histories. B and T cell immunity against previous variants of concern was enhanced in triple vaccinated individuals, but magnitude of T and B cell responses against B.1.1.529 spike protein was reduced. Immune imprinting by infection with the earlier B.1.1.7 (Alpha) variant resulted in less durable binding antibody against B.1.1.529. Previously infection-naïve HCW who became infected during the B.1.1.529 wave showed enhanced immunity against earlier variants, but reduced nAb potency and T cell responses against B.1.1.529 itself. Previous Wuhan Hu-1 infection abrogated T cell recognition and any enhanced cross-reactive neutralizing immunity on infection with B.1.1.529.
Published: 2022

8. HLA‐DR polymorphism in SARS‐CoV‐2 infection and susceptibility to symptomatic COVID‐19

Author: Astbury, Stuart, Reynolds, Catherine J, Butler, David K, Munoz‐Sandoval, Diana C, Lin, Kai‐Min, Pieper, Franziska P, Otter, Ashley, Kouraki, Afroditi, Cusin, Lola, Nightingale, Jessica, Vijay, Amrita, Craxford, Simon, Aithal, Guruprasad P, Tighe, Patrick J, Gibbons, Joseph M, Pade, Corinna, Joy, George, Maini, Mala, Chain, Benny, Semper, Amanda, Brooks, Timothy, Ollivere, Benjamin J, McKnight, Áine, Noursadeghi, Mahdad, Treibel, Thomas A, Manisty, Charlotte, Moon, James C, Valdes, Ana M, Boyton, Rosemary J, Altmann, Daniel M, Astbury, Stuart, Reynolds, Catherine J, Butler, David K, Munoz‐Sandoval, Diana C, Lin, Kai‐Min, Pieper, Franziska P, Otter, Ashley, Kouraki, Afroditi, Cusin, Lola, Nightingale, Jessica, Vijay, Amrita, Craxford, Simon, Aithal, Guruprasad P, Tighe, Patrick J, Gibbons, Joseph M, Pade, Corinna, Joy, George, Maini, Mala, Chain, Benny, Semper, Amanda, Brooks, Timothy, Ollivere, Benjamin J, McKnight, Áine, Noursadeghi, Mahdad, Treibel, Thomas A, Manisty, Charlotte, Moon, James C, Valdes, Ana M, Boyton, Rosemary J, and Altmann, Daniel M
Abstract: SARS-CoV-2 infection results in different outcomes ranging from asymptomatic infection, to mild or severe disease and death. Reasons for this diversity of outcome include differences in challenge dose, age, gender, comorbidity and host genomic variation. Human leukocyte antigen (HLA) polymorphisms may influence immune response and disease outcome. We investigated the association of HLAII alleles with case definition symptomatic COVID-19, virus-specific antibody and T cell immunity. 1,364 UK healthcare workers (HCW) were recruited during the first U.K. SARS-CoV-2 wave and analyzed longitudinally, encompassing regular PCR screening for infection, symptom reporting, imputation of HLAII genotype and analysis for antibody and T cell responses to nucleoprotein (N) and spike (S). Of 272 (20%) HCW who seroconverted, the presence of HLA-DRB1*13:02 was associated with a 6.7-fold increased risk of case definition symptomatic COVID-19. In terms of immune responsiveness, HLA-DRB1*15:02 was associated with lower nucleocapsid T cell responses. There was no association between DRB1 alleles and anti-spike antibody titres after two COVID vaccine doses. However, HLA DRB1*15:01 was associated with increased spike T cell responses following both first and second dose vaccination.
Published: 2022

9. HLA‐DR polymorphism in SARS‐CoV‐2 infection and susceptibility to symptomatic COVID‐19

Author: Astbury, Stuart, Reynolds, Catherine J, Butler, David K, Munoz‐Sandoval, Diana C, Lin, Kai‐Min, Pieper, Franziska P, Otter, Ashley, Kouraki, Afroditi, Cusin, Lola, Nightingale, Jessica, Vijay, Amrita, Craxford, Simon, Aithal, Guruprasad P, Tighe, Patrick J, Gibbons, Joseph M, Pade, Corinna, Joy, George, Maini, Mala, Chain, Benny, Semper, Amanda, Brooks, Timothy, Ollivere, Benjamin J, McKnight, Áine, Noursadeghi, Mahdad, Treibel, Thomas A, Manisty, Charlotte, Moon, James C, Valdes, Ana M, Boyton, Rosemary J, Altmann, Daniel M, Astbury, Stuart, Reynolds, Catherine J, Butler, David K, Munoz‐Sandoval, Diana C, Lin, Kai‐Min, Pieper, Franziska P, Otter, Ashley, Kouraki, Afroditi, Cusin, Lola, Nightingale, Jessica, Vijay, Amrita, Craxford, Simon, Aithal, Guruprasad P, Tighe, Patrick J, Gibbons, Joseph M, Pade, Corinna, Joy, George, Maini, Mala, Chain, Benny, Semper, Amanda, Brooks, Timothy, Ollivere, Benjamin J, McKnight, Áine, Noursadeghi, Mahdad, Treibel, Thomas A, Manisty, Charlotte, Moon, James C, Valdes, Ana M, Boyton, Rosemary J, and Altmann, Daniel M
Abstract: SARS-CoV-2 infection results in different outcomes ranging from asymptomatic infection, to mild or severe disease and death. Reasons for this diversity of outcome include differences in challenge dose, age, gender, comorbidity and host genomic variation. Human leukocyte antigen (HLA) polymorphisms may influence immune response and disease outcome. We investigated the association of HLAII alleles with case definition symptomatic COVID-19, virus-specific antibody and T cell immunity. 1,364 UK healthcare workers (HCW) were recruited during the first U.K. SARS-CoV-2 wave and analyzed longitudinally, encompassing regular PCR screening for infection, symptom reporting, imputation of HLAII genotype and analysis for antibody and T cell responses to nucleoprotein (N) and spike (S). Of 272 (20%) HCW who seroconverted, the presence of HLA-DRB1*13:02 was associated with a 6.7-fold increased risk of case definition symptomatic COVID-19. In terms of immune responsiveness, HLA-DRB1*15:02 was associated with lower nucleocapsid T cell responses. There was no association between DRB1 alleles and anti-spike antibody titres after two COVID vaccine doses. However, HLA DRB1*15:01 was associated with increased spike T cell responses following both first and second dose vaccination.
Published: 2022

10. Model-free phasor image analysis of quantitative myocardial T1 mapping

Author: Franssen, Wouter M.J. (author), Treibel, Thomas A. (author), Seraphim, Andreas (author), Weingärtner, S.D. (author), Terenzi, Camilla (author), Franssen, Wouter M.J. (author), Treibel, Thomas A. (author), Seraphim, Andreas (author), Weingärtner, S.D. (author), and Terenzi, Camilla (author)
Abstract: Model-free phasor image analysis, well established in fluorescence lifetime imaging and only recently applied to qMRI T2 data processing, is here adapted and validated for myocardial qMRI T1 mapping. Contrarily to routine mono-exponential fitting procedures, phasor enables mapping the lifetime information from all image voxels to a single plot, without resorting to any regression fitting analysis, and describing multi-exponential qMRI decays without biases due to violated modelling assumptions. In this feasibility study, we test the performance of our recently developed full-harmonics phasor method for unravelling partial-volume effects, motion or pathological tissue alteration, respectively on a numerically-simulated dataset, a healthy subject scan, and two pilot patient datasets. Our results show that phasor analysis can be used, as alternative method to fitting analysis or other model-free approaches, to identify motion artifacts or partial-volume effects at the myocardium-blood interface as characteristic deviations, or delineations of scar and remote myocardial tissue in patient data., ImPhys/Computational Imaging, ImPhys/Medical Imaging
Published: 2022
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11. Cardiac phase-resolved late gadolinium enhancement imaging

Author: Weingärtner, S.D. (author), Demirel, Omer Burak (author), Gama, Francisco. (author), Pierce, Iain (author), Treibel, Thomas A. (author), Schulz-Menger, Jeanette (author), Akcakaya, Mehmet (author), Weingärtner, S.D. (author), Demirel, Omer Burak (author), Gama, Francisco. (author), Pierce, Iain (author), Treibel, Thomas A. (author), Schulz-Menger, Jeanette (author), and Akcakaya, Mehmet (author)
Abstract: Late gadolinium enhancement (LGE) with cardiac magnetic resonance (CMR) imaging is the clinical reference for assessment of myocardial scar and focal fibrosis. However, current LGE techniques are confined to imaging of a single cardiac phase, which hampers assessment of scar motility and does not allow cross-comparison between multiple phases. In this work, we investigate a three step approach to obtain cardiac phase-resolved LGE images: (1) Acquisition of cardiac phase-resolved imaging data with varying T1 weighting. (2) Generation of semi-quantitative T*1 maps for each cardiac phase. (3) Synthetization of LGE contrast to obtain functional LGE images. The proposed method is evaluated in phantom imaging, six healthy subjects at 3T and 20 patients at 1.5T. Phantom imaging at 3T demonstrates consistent contrast throughout the cardiac cycle with a coefficient of variation of 2.55 ± 0.42%. In-vivo results show reliable LGE contrast with thorough suppression of the myocardial tissue is healthy subjects. The contrast between blood and myocardium showed moderate variation throughout the cardiac cycle in healthy subjects (coefficient of variation 18.2 ± 3.51%). Images were acquired at 40–60 ms and 80 ms temporal resolution, at 3T and 1.5, respectively. Functional LGE images acquired in patients with myocardial scar visualized scar tissue throughout the cardiac cycle, albeit at noticeably lower imaging resolution and noise resilience than the reference technique. The proposed technique bears the promise of integrating the advantages of phase-resolved CMR with LGE imaging, but further improvements in the acquisition quality are warranted for clinical use., ImPhys/Computational Imaging, ImPhys/Medical Imaging
Published: 2022
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12. Myocardial Approximate Spin-lock Dispersion Mapping using a Simultaneous T2 and TRAFF2 Mapping at 3T MRI

Author: Tourais, Joao (author), Demirel, Omer Burak (author), Tao, Q. (author), Pierce, Iain (author), Thornton, George D. (author), Treibel, Thomas A. (author), Akcakaya, Mehmet (author), Weingärtner, S.D. (author), Tourais, Joao (author), Demirel, Omer Burak (author), Tao, Q. (author), Pierce, Iain (author), Thornton, George D. (author), Treibel, Thomas A. (author), Akcakaya, Mehmet (author), and Weingärtner, S.D. (author)
Abstract: Ischemic heart disease (IHD) is one of the leading causes of death worldwide. Myocardial infarction (MI) represents a third of all IHD cases, and cardiac magnetic resonance imaging (MRI) is often used to assess its damage to myocardial viability. Late gadolinium enhancement (LGE) is the current gold standard, but the use of gadolinium-based agents limits the clinical applicability in some patients. Spin-lock (SL) dispersion has recently been proposed as a promising non-contrast biomarker for the assessment of MI. However, at 3T, the required range of SL preparations acquired at different amplitudes suffers from specific absorption rate (SAR) limitations and off-resonance artifacts. Relaxation Along a Fictitious Field (RAFF) is an alternative to SL preparations with lower SAR requirements, while still sampling relaxation in the rotating frame. In this study, a single breath-hold simultaneous TRAFF2 and T2 mapping sequence is proposed for SL dispersion mapping at 3T. Excellent reproducibility (coefficient of variations lower than 10%) was achieved in phantom experiments, indicating good intrascan repeatability. The average myocardial TRAFF2, T2, and SL dispersion obtained with the proposed sequence (68.0±10.7 ms, 44.0±4.0 ms, and 0.4±0.2 ×10-4 s2, respectively) were comparable to the reference methods (62.7±11.7 ms, 41.2±2.4 ms, and 0.3±0.2x 10-4s2, respectively). High visual map quality, free of B0 and B1+ related artifacts, for T2, TRAFF2, and SL dispersion maps were obtained in phantoms and in vivo, suggesting promise in clinical use at 3T. Clinical relevance - and imaging promises non-contrast assessment of scar and focal fibrosis in a single breath-hold using approximate spin-lock dispersion mapping., ImPhys/Medical Imaging, ImPhys/Computational Imaging
Published: 2022
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13. Model-free phasor image analysis of quantitative myocardial T1 mapping

Author: Franssen, Wouter M.J., Treibel, Thomas A., Seraphim, Andreas, Weingärtner, Sebastian, Terenzi, Camilla, Franssen, Wouter M.J., Treibel, Thomas A., Seraphim, Andreas, Weingärtner, Sebastian, and Terenzi, Camilla
Abstract: Model-free phasor image analysis, well established in fluorescence lifetime imaging and only recently applied to qMRI T2 data processing, is here adapted and validated for myocardial qMRI T1 mapping. Contrarily to routine mono-exponential fitting procedures, phasor enables mapping the lifetime information from all image voxels to a single plot, without resorting to any regression fitting analysis, and describing multi-exponential qMRI decays without biases due to violated modelling assumptions. In this feasibility study, we test the performance of our recently developed full-harmonics phasor method for unravelling partial-volume effects, motion or pathological tissue alteration, respectively on a numerically-simulated dataset, a healthy subject scan, and two pilot patient datasets. Our results show that phasor analysis can be used, as alternative method to fitting analysis or other model-free approaches, to identify motion artifacts or partial-volume effects at the myocardium-blood interface as characteristic deviations, or delineations of scar and remote myocardial tissue in patient data.
Published: 2022

14. Markers of myocardial damage predict mortality in patients with aortic stenosis

Author: Kwak, Soongu, Everett, Russell J., Treibel, Thomas Alexander, Yang, Seokhun, Hwang, Doyeon, Ko, Taehoon, Williams, Michelle C., Bing, Rong, Singh, Trisha, Joshi, Shruti, Lee, Heesun, Lee, Whal, Kim, Yong-Jin, Chin, Calvin W.L., Fukui, Miho, Musa, Tarique Al, Rigolli, Marzia, Singh, Anvesha, Tastet, Lionel, Dobson, Laura, Wiesemann, Stephanie, Ferreira, Vanessa M., Captur, Gabriella, Lee, Sahmin, Schulz-Menger, Jeanette, Schelbert, Erik B., Clavel, Marie-Annick, Park, Sung-Ji, Rheude, Tobias, Hadamitzky, Martin, Gerber, Bernhard L., Newby, David E., Myerson, Saul G., Pibarot, Philippe, Cavalcante, João L., McCann, Gerry P., Greenwood, John P., Moon, James C., Dweck, Marc R., Lee, Seung-Pyo, Kwak, Soongu, Everett, Russell J., Treibel, Thomas Alexander, Yang, Seokhun, Hwang, Doyeon, Ko, Taehoon, Williams, Michelle C., Bing, Rong, Singh, Trisha, Joshi, Shruti, Lee, Heesun, Lee, Whal, Kim, Yong-Jin, Chin, Calvin W.L., Fukui, Miho, Musa, Tarique Al, Rigolli, Marzia, Singh, Anvesha, Tastet, Lionel, Dobson, Laura, Wiesemann, Stephanie, Ferreira, Vanessa M., Captur, Gabriella, Lee, Sahmin, Schulz-Menger, Jeanette, Schelbert, Erik B., Clavel, Marie-Annick, Park, Sung-Ji, Rheude, Tobias, Hadamitzky, Martin, Gerber, Bernhard L., Newby, David E., Myerson, Saul G., Pibarot, Philippe, Cavalcante, João L., McCann, Gerry P., Greenwood, John P., Moon, James C., Dweck, Marc R., and Lee, Seung-Pyo
Abstract: Background: Cardiovascular magnetic resonance (CMR) is increasingly used for risk stratification in aortic stenosis (AS). However, the relative prognostic power of CMR markers and their respective thresholds remains undefined. Objectives: Using machine learning, the study aimed to identify prognostically important CMR markers in AS and their thresholds of mortality. Methods: Patients with severe AS undergoing AVR (n = 440, derivation; n = 359, validation cohort) were prospectively enrolled across 13 international sites (median 3.8 years' follow-up). CMR was performed shortly before surgical or transcatheter AVR. A random survival forest model was built using 29 variables (13 CMR) with post-AVR death as the outcome. Results: There were 52 deaths in the derivation cohort and 51 deaths in the validation cohort. The 4 most predictive CMR markers were extracellular volume fraction, late gadolinium enhancement, indexed left ventricular end-diastolic volume (LVEDVi), and right ventricular ejection fraction. Across the whole cohort and in asymptomatic patients, risk-adjusted predicted mortality increased strongly once extracellular volume fraction exceeded 27%, while late gadolinium enhancement >2% showed persistent high risk. Increased mortality was also observed with both large (LVEDVi >80 mL/m2) and small (LVEDVi ≤55 mL/m2) ventricles, and with high (>80%) and low (≤50%) right ventricular ejection fraction. The predictability was improved when these 4 markers were added to clinical factors (3-year C-index: 0.778 vs 0.739). The prognostic thresholds and risk stratification by CMR variables were reproduced in the validation cohort. Conclusions: Machine learning identified myocardial fibrosis and biventricular remodeling markers as the top predictors of survival in AS and highlighted their nonlinear association with mortality. These markers may have potential in optimizing the decision of AVR.
Published: 2021

15. Diagnosis and risk stratification in hypertrophic cardiomyopathy using machine learning wall thickness measurement: a comparison with human test-retest performance.

Author: UCL - SSS/IREC/CARD - Pôle de recherche cardiovasculaire, UCL - (SLuc) Service de pathologie cardiovasculaire, Augusto, João B, Davies, Rhodri H, Bhuva, Anish N, Knott, Kristopher D, Seraphim, Andreas, Alfarih, Mashael, Lau, Clement, Hughes, Rebecca K, Lopes, Luís R, Shiwani, Hunain, Treibel, Thomas A, Gerber, Bernhard, Hamilton-Craig, Christian, Ntusi, Ntobeko A B, Pontone, Gianluca, Desai, Milind Y, Greenwood, John P, Swoboda, Peter P, Captur, Gabriella, Cavalcante, João, Bucciarelli-Ducci, Chiara, Petersen, Steffen E, Schelbert, Erik, Manisty, Charlotte, Moon, James C, UCL - SSS/IREC/CARD - Pôle de recherche cardiovasculaire, UCL - (SLuc) Service de pathologie cardiovasculaire, Augusto, João B, Davies, Rhodri H, Bhuva, Anish N, Knott, Kristopher D, Seraphim, Andreas, Alfarih, Mashael, Lau, Clement, Hughes, Rebecca K, Lopes, Luís R, Shiwani, Hunain, Treibel, Thomas A, Gerber, Bernhard, Hamilton-Craig, Christian, Ntusi, Ntobeko A B, Pontone, Gianluca, Desai, Milind Y, Greenwood, John P, Swoboda, Peter P, Captur, Gabriella, Cavalcante, João, Bucciarelli-Ducci, Chiara, Petersen, Steffen E, Schelbert, Erik, Manisty, Charlotte, and Moon, James C
Abstract: Left ventricular maximum wall thickness (MWT) is central to diagnosis and risk stratification of hypertrophic cardiomyopathy, but human measurement is prone to variability. We developed an automated machine learning algorithm for MWT measurement and compared precision (reproducibility) with that of 11 international experts, using a dataset of patients with hypertrophic cardiomyopathy. 60 adult patients with hypertrophic cardiomyopathy, including those carrying hypertrophic cardiomyopathy gene mutations, were recruited at three institutes in the UK from August, 2018, to September, 2019: Barts Heart Centre, University College London Hospital (The Heart Hospital), and Leeds Teaching Hospitals NHS Trust. Participants had two cardiovascular magnetic resonance scans (test and retest) on the same day, ensuring no biological variability, using four cardiac MRI scanner models represented across two manufacturers and two field strengths. End-diastolic short-axis MWT was measured in test and retest by 11 international experts (from nine centres in six countries) and an automated machine learning method, which was trained to segment endocardial and epicardial contours on an independent, multicentre, multidisease dataset of 1923 patients. Machine learning MWT measurement was done with a method based on solving Laplace's equation. To assess test-retest reproducibility, we estimated the absolute test-retest MWT difference (precision), the coefficient of variation (CoV) for duplicate measurements, and the number of patients reclassified between test and retest according to different thresholds (MWT >15 mm and >30 mm). We calculated the sample size required to detect a prespecified MWT change between pairs of scans for machine learning and each expert. 1440 MWT measurements were analysed, corresponding to two scans from 60 participants by 12 observers (11 experts and machine learning). Experts differed in the MWT they measured, ranging from 14·9 mm (SD 4·2) to 19·0 mm (4·7; p<0·0001
Published: 2021

16. Markers of Myocardial Damage Predict Mortality in Patients With Aortic Stenosis.

Author: UCL - SSS/IREC/CARD - Pôle de recherche cardiovasculaire, UCL - (SLuc) Service de pathologie cardiovasculaire, Kwak, Soongu, Everett, Russell J, Treibel, Thomas A, Yang, Seokhun, Hwang, Doyeon, Ko, Taehoon, Williams, Michelle C, Bing, Rong, Singh, Trisha, Joshi, Shruti, Lee, Heesun, Lee, Whal, Kim, Yong-Jin, Chin, Calvin W L, Fukui, Miho, Al Musa, Tarique, Rigolli, Marzia, Singh, Anvesha, Tastet, Lionel, Dobson, Laura E, Wiesemann, Stephanie, Ferreira, Vanessa M, Captur, Gabriella, Lee, Sahmin, Schulz-Menger, Jeanette, Schelbert, Erik B, Clavel, Marie-Annick, Park, Sung-Ji, Rheude, Tobias, Hadamitzky, Martin, Gerber, Bernhard, Newby, David E, Myerson, Saul G, Pibarot, Phillipe, Cavalcante, João L, McCann, Gerry P, Greenwood, John P, Moon, James C, Dweck, Marc R, Lee, Seung-Pyo, UCL - SSS/IREC/CARD - Pôle de recherche cardiovasculaire, UCL - (SLuc) Service de pathologie cardiovasculaire, Kwak, Soongu, Everett, Russell J, Treibel, Thomas A, Yang, Seokhun, Hwang, Doyeon, Ko, Taehoon, Williams, Michelle C, Bing, Rong, Singh, Trisha, Joshi, Shruti, Lee, Heesun, Lee, Whal, Kim, Yong-Jin, Chin, Calvin W L, Fukui, Miho, Al Musa, Tarique, Rigolli, Marzia, Singh, Anvesha, Tastet, Lionel, Dobson, Laura E, Wiesemann, Stephanie, Ferreira, Vanessa M, Captur, Gabriella, Lee, Sahmin, Schulz-Menger, Jeanette, Schelbert, Erik B, Clavel, Marie-Annick, Park, Sung-Ji, Rheude, Tobias, Hadamitzky, Martin, Gerber, Bernhard, Newby, David E, Myerson, Saul G, Pibarot, Phillipe, Cavalcante, João L, McCann, Gerry P, Greenwood, John P, Moon, James C, Dweck, Marc R, and Lee, Seung-Pyo
Abstract: Cardiovascular magnetic resonance (CMR) is increasingly used for risk stratification in aortic stenosis (AS). However, the relative prognostic power of CMR markers and their respective thresholds remains undefined. Using machine learning, the study aimed to identify prognostically important CMR markers in AS and their thresholds of mortality. Patients with severe AS undergoing AVR (n = 440, derivation; n = 359, validation cohort) were prospectively enrolled across 13 international sites (median 3.8 years' follow-up). CMR was performed shortly before surgical or transcatheter AVR. A random survival forest model was built using 29 variables (13 CMR) with post-AVR death as the outcome. There were 52 deaths in the derivation cohort and 51 deaths in the validation cohort. The 4 most predictive CMR markers were extracellular volume fraction, late gadolinium enhancement, indexed left ventricular end-diastolic volume (LVEDVi), and right ventricular ejection fraction. Across the whole cohort and in asymptomatic patients, risk-adjusted predicted mortality increased strongly once extracellular volume fraction exceeded 27%, while late gadolinium enhancement >2% showed persistent high risk. Increased mortality was also observed with both large (LVEDVi >80 mL/m) and small (LVEDVi ≤55 mL/m) ventricles, and with high (>80%) and low (≤50%) right ventricular ejection fraction. The predictability was improved when these 4 markers were added to clinical factors (3-year C-index: 0.778 vs 0.739). The prognostic thresholds and risk stratification by CMR variables were reproduced in the validation cohort. Machine learning identified myocardial fibrosis and biventricular remodeling markers as the top predictors of survival in AS and highlighted their nonlinear association with mortality. These markers may have potential in optimizing the decision of AVR.
Published: 2021

17. Markers of myocardial damage predict mortality in patients with aortic stenosis

Author: Kwak, Soongu, Pibarot, Philippe, Everett, Russell J., Clavel, Marie-Annick, Treibel, Thomas Alexander, Tastet, Lionel, Yang, Seokhun, Hwang, Doyeon, Ko, Taehoon, Williams, Michelle C., Bing, Rong, Singh, Trisha, Joshi, Shruti, Lee, Heesun, Lee, Whal, Kim, Yong-Jin, Chin, Calvin W.L., Fukui, Miho, Musa, Tarique Al, Rigolli, Marzia, Singh, Anvesha, Dobson, Laura, Wiesemann, Stephanie, Ferreira, Vanessa M., Captur, Gabriella, Lee, Sahmin, Schulz-Menger, Jeanette, Schelbert, Erik B., Park, Sung-Ji, Rheude, Tobias, Hadamitzky, Martin, Gerber, Bernhard L., Newby, David E., Myerson, Saul G., Cavalcante, João L., McCann, Gerry P., Greenwood, John P., Moon, James C., Dweck, Marc R., Lee, Seung-Pyo, Kwak, Soongu, Pibarot, Philippe, Everett, Russell J., Clavel, Marie-Annick, Treibel, Thomas Alexander, Tastet, Lionel, Yang, Seokhun, Hwang, Doyeon, Ko, Taehoon, Williams, Michelle C., Bing, Rong, Singh, Trisha, Joshi, Shruti, Lee, Heesun, Lee, Whal, Kim, Yong-Jin, Chin, Calvin W.L., Fukui, Miho, Musa, Tarique Al, Rigolli, Marzia, Singh, Anvesha, Dobson, Laura, Wiesemann, Stephanie, Ferreira, Vanessa M., Captur, Gabriella, Lee, Sahmin, Schulz-Menger, Jeanette, Schelbert, Erik B., Park, Sung-Ji, Rheude, Tobias, Hadamitzky, Martin, Gerber, Bernhard L., Newby, David E., Myerson, Saul G., Cavalcante, João L., McCann, Gerry P., Greenwood, John P., Moon, James C., Dweck, Marc R., and Lee, Seung-Pyo
Abstract: Background: Cardiovascular magnetic resonance (CMR) is increasingly used for risk stratification in aortic stenosis (AS). However, the relative prognostic power of CMR markers and their respective thresholds remains undefined. Objectives: Using machine learning, the study aimed to identify prognostically important CMR markers in AS and their thresholds of mortality. Methods: Patients with severe AS undergoing AVR (n = 440, derivation; n = 359, validation cohort) were prospectively enrolled across 13 international sites (median 3.8 years' follow-up). CMR was performed shortly before surgical or transcatheter AVR. A random survival forest model was built using 29 variables (13 CMR) with post-AVR death as the outcome. Results: There were 52 deaths in the derivation cohort and 51 deaths in the validation cohort. The 4 most predictive CMR markers were extracellular volume fraction, late gadolinium enhancement, indexed left ventricular end-diastolic volume (LVEDVi), and right ventricular ejection fraction. Across the whole cohort and in asymptomatic patients, risk-adjusted predicted mortality increased strongly once extracellular volume fraction exceeded 27%, while late gadolinium enhancement >2% showed persistent high risk. Increased mortality was also observed with both large (LVEDVi >80 mL/m2) and small (LVEDVi ≤55 mL/m2) ventricles, and with high (>80%) and low (≤50%) right ventricular ejection fraction. The predictability was improved when these 4 markers were added to clinical factors (3-year C-index: 0.778 vs 0.739). The prognostic thresholds and risk stratification by CMR variables were reproduced in the validation cohort. Conclusions: Machine learning identified myocardial fibrosis and biventricular remodeling markers as the top predictors of survival in AS and highlighted their nonlinear association with mortality. These markers may have potential in optimizing the decision of AVR.
Published: 2021

18. Heterologous infection and vaccination shapes immunity against SARS-CoV-2 variants

Author: Reynolds, Catherine J., Gibbons, Joseph M., Pade, Corinna, Lin, Kai-Min, Sandoval, Diana Munoz, Pieper, Franziska, Butler, David K., Liu, Siyi, Otter, Ashley, Joy, George, Menacho, Katia, Fontana, Marianna, Smit, Angelique, Kele, Beatrix, Cutino-Moguel, Teresa, Maini, Mala K., Brooks, Tim, Noursadeghi, Mahdad, Semper, Amanda, Manisty, Charlotte, Treibel, Thomas A., Moon, James C., Altmann, Daniel M., McKnight, Áine, Boyton, Rosemary J., Reynolds, Catherine J., Gibbons, Joseph M., Pade, Corinna, Lin, Kai-Min, Sandoval, Diana Munoz, Pieper, Franziska, Butler, David K., Liu, Siyi, Otter, Ashley, Joy, George, Menacho, Katia, Fontana, Marianna, Smit, Angelique, Kele, Beatrix, Cutino-Moguel, Teresa, Maini, Mala K., Brooks, Tim, Noursadeghi, Mahdad, Semper, Amanda, Manisty, Charlotte, Treibel, Thomas A., Moon, James C., Altmann, Daniel M., McKnight, Áine, and Boyton, Rosemary J.
Abstract: The impact of initial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infecting strain on downstream immunity to heterologous variants of concern (VOC) is unknown. Studying a longitudinal healthcare worker cohort, we found that after three antigen exposures (infection+two vaccine doses), S1 antibody, memory B cells and heterologous neutralization of B.1.351, P.1 and B.1.617.2 plateaued, while B.1.1.7 neutralization and spike T cell responses increased. Serology using Wuhan Hu-1 spike receptor binding domain poorly predicted neutralizing immunity against VOCs. Neutralization potency against VOCs changed with heterologous virus encounter and number of antigen exposures. Neutralization potency fell differentially depending on targeted VOCs over 5-months from the second vaccine dose. Heterologous combinations of spike encountered during infection and vaccination shape subsequent cross-protection against VOC, with implications for future-proof next-generation vaccines.
Published: 2021

19. Heterologous infection and vaccination shapes immunity against SARS-CoV-2 variants

Author: Reynolds, Catherine J., Gibbons, Joseph M., Pade, Corinna, Lin, Kai-Min, Sandoval, Diana Munoz, Pieper, Franziska, Butler, David K., Liu, Siyi, Otter, Ashley, Joy, George, Menacho, Katia, Fontana, Marianna, Smit, Angelique, Kele, Beatrix, Cutino-Moguel, Teresa, Maini, Mala K., Brooks, Tim, Noursadeghi, Mahdad, Semper, Amanda, Manisty, Charlotte, Treibel, Thomas A., Moon, James C., Altmann, Daniel M., McKnight, Áine, Boyton, Rosemary J., Reynolds, Catherine J., Gibbons, Joseph M., Pade, Corinna, Lin, Kai-Min, Sandoval, Diana Munoz, Pieper, Franziska, Butler, David K., Liu, Siyi, Otter, Ashley, Joy, George, Menacho, Katia, Fontana, Marianna, Smit, Angelique, Kele, Beatrix, Cutino-Moguel, Teresa, Maini, Mala K., Brooks, Tim, Noursadeghi, Mahdad, Semper, Amanda, Manisty, Charlotte, Treibel, Thomas A., Moon, James C., Altmann, Daniel M., McKnight, Áine, and Boyton, Rosemary J.
Abstract: The impact of initial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infecting strain on downstream immunity to heterologous variants of concern (VOC) is unknown. Studying a longitudinal healthcare worker cohort, we found that after three antigen exposures (infection+two vaccine doses), S1 antibody, memory B cells and heterologous neutralization of B.1.351, P.1 and B.1.617.2 plateaued, while B.1.1.7 neutralization and spike T cell responses increased. Serology using Wuhan Hu-1 spike receptor binding domain poorly predicted neutralizing immunity against VOCs. Neutralization potency against VOCs changed with heterologous virus encounter and number of antigen exposures. Neutralization potency fell differentially depending on targeted VOCs over 5-months from the second vaccine dose. Heterologous combinations of spike encountered during infection and vaccination shape subsequent cross-protection against VOC, with implications for future-proof next-generation vaccines.
Published: 2021

20. Blood transcriptional biomarkers of acute viral infection for detection of pre-symptomatic SARS-CoV-2 infection: a nested, case-control diagnostic accuracy study

Author: Gupta, Rishi K, Rosenheim, Joshua, Bell, Lucy C, Chandran, Aneesh, Guerra-Assuncao, Jose A, Pollara, Gabriele, Whelan, Matthew, Artico, Jessica, Joy, George, Kurdi, Hibba, Altmann, Daniel M, Boyton, Rosemary J, Maini, Mala K, McKnight, Aine, Lambourne, Jonathan, Cutino-Moguel, Teresa, Manisty, Charlotte, Treibel, Thomas A, Moon, James C, Chain, Benjamin M, Noursadeghi, Mahdad, Abbass, Hakam, Abiodun, Aderonke, Alfarih, Mashael, Alldis, Zoe, Amin, Oliver E, Andiapen, Mervyn, Augusto, João B, Baca, Georgiana L, Bailey, Sasha NL, 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, Couto de Sousa, Jorge, Couto-Parada, Xose, Davies, Rhodri H, Douglas, Brooke, Di Genova, Cecilia, Dieobi-Anene, Keenan, Diniz, Mariana O, Ellis, Anaya, Feehan, Karen, Finlay, Malcolm, Fontana, Marianna, Forooghi, Nasim, Gaier, Celia, Gibbons, Joseph M, 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, Melaniepetra, Jones, Jessica, Jones, Meleri, Kapil, Vikas, Lin, Kai-Min, Louth, Sarah, Mandadapu, Vineela, Manisty,, Charlotte, McKnight, Áine, Menacho, Katia, Mfuko, Celina, Mitchelmore, Oliver, Moon, Christopher, Moon,, James C, Munoz Sandoval, Diana, Murray, Sam M, Otter, Ashley, Pade, Corinna, Palma, Susana, Parker, Ruth, Patel, Kush, Pawarova, Babita, Petersen, Steffen E, Piniera, Brian, Pieper, Franziska P, Pope, Daniel, Prossora, Maria, Rannigan, Lisa, Rapala, Alicja, Reynolds, Catherine J, Richards, Amy, Robathan, Matthew, Sambile, Genine, Schmidt, Nathalie M, Semper, Amanda, Seraphim, Andreas, Simion, Mihaela, Smit, Angelique, Sugimoto, Michelle, Swadling, Leo, Taylor, Stephen, Temperton, Nigel J., Thomas, Stephen, Thornton, George D, Tucker, Art, Veerapen, Jessry, Vijayakumar, Mohit, Welch, Sophie, Wodehouse, Theresa, Wynne, Lucinda, Zahedi, Dan, Gupta, Rishi K, Rosenheim, Joshua, Bell, Lucy C, Chandran, Aneesh, Guerra-Assuncao, Jose A, Pollara, Gabriele, Whelan, Matthew, Artico, Jessica, Joy, George, Kurdi, Hibba, Altmann, Daniel M, Boyton, Rosemary J, Maini, Mala K, McKnight, Aine, Lambourne, Jonathan, Cutino-Moguel, Teresa, Manisty, Charlotte, Treibel, Thomas A, Moon, James C, Chain, Benjamin M, Noursadeghi, Mahdad, Abbass, Hakam, Abiodun, Aderonke, Alfarih, Mashael, Alldis, Zoe, Amin, Oliver E, Andiapen, Mervyn, Augusto, João B, Baca, Georgiana L, Bailey, Sasha NL, 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, Couto de Sousa, Jorge, Couto-Parada, Xose, Davies, Rhodri H, Douglas, Brooke, Di Genova, Cecilia, Dieobi-Anene, Keenan, Diniz, Mariana O, Ellis, Anaya, Feehan, Karen, Finlay, Malcolm, Fontana, Marianna, Forooghi, Nasim, Gaier, Celia, Gibbons, Joseph M, 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, Melaniepetra, Jones, Jessica, Jones, Meleri, Kapil, Vikas, Lin, Kai-Min, Louth, Sarah, Mandadapu, Vineela, Manisty,, Charlotte, McKnight, Áine, Menacho, Katia, Mfuko, Celina, Mitchelmore, Oliver, Moon, Christopher, Moon,, James C, Munoz Sandoval, Diana, Murray, Sam M, Otter, Ashley, Pade, Corinna, Palma, Susana, Parker, Ruth, Patel, Kush, Pawarova, Babita, Petersen, Steffen E, Piniera, Brian, Pieper, Franziska P, Pope, Daniel, Prossora, Maria, Rannigan, Lisa, Rapala, Alicja, Reynolds, Catherine J, Richards, Amy, Robathan, Matthew, Sambile, Genine, Schmidt, Nathalie M, Semper, Amanda, Seraphim, Andreas, Simion, Mihaela, Smit, Angelique, Sugimoto, Michelle, Swadling, Leo, Taylor, Stephen, Temperton, Nigel J., Thomas, Stephen, Thornton, George D, Tucker, Art, Veerapen, Jessry, Vijayakumar, Mohit, Welch, Sophie, Wodehouse, Theresa, Wynne, Lucinda, and Zahedi, Dan
Abstract: Background We hypothesised that host-response biomarkers of viral infections might contribute to early identification of individuals infected with SARS-CoV-2, which is critical to breaking the chains of transmission. We aimed to evaluate the diagnostic accuracy of existing candidate whole-blood transcriptomic signatures for viral infection to predict positivity of nasopharyngeal SARS-CoV-2 PCR testing.Methods We did a nested case-control diagnostic accuracy study among a prospective cohort of health-care workers (aged ≥18 years) at St Bartholomew’s Hospital (London, UK) undergoing weekly blood and nasopharyngeal swab sampling for whole-blood RNA sequencing and SARS-CoV-2 PCR testing, when fit to attend work. We identified candidate blood transcriptomic signatures for viral infection through a systematic literature search. We searched MEDLINE for articles published between database inception and Oct 12, 2020, using comprehensive MeSH and keyword terms for “viral infection”, “transcriptome”, “biomarker”, and “blood”. We reconstructed signature scores in blood RNA sequencing data and evaluated their diagnostic accuracy for contemporaneous SARS-CoV-2 infection, compared with the gold standard of SARS-CoV-2 PCR testing, by quantifying the area under the receiver operating characteristic curve (AUROC), sensitivities, and specificities at a standardised Z score of at least 2 based on the distribution of signature scores in test-negative controls. We used pairwise DeLong tests compared with the most discriminating signature to identify the subset of best performing biomarkers. We evaluated associations between signature expression, viral load (using PCR cycle thresholds), and symptom status visually and using Spearman rank correlation. The primary outcome was the AUROC for discriminating between samples from participants who tested negative throughout the study (test-negative controls) and samples from participants with PCR-confirmed SARS-CoV-2 infection (test-positive part
Published: 2021

21. Prior SARS-CoV-2 infection rescues B and T cell responses to variants after first vaccine dose

Author: Reynolds, Catherine J., Pade, Corinna, Gibbons, Joseph M., Butler, David K., Otter, Ashley D., Menacho, Katia, Fontana, Marianna, Smit, Angelique, Sackville-West, Jane E., Cutino-Moguel, Teresa, Maini, Mala K., Chain, Benjamin, Noursadeghi, Mahdad, Brooks, Tim, Semper, Amanda, Manisty, Charlotte, Treibel, Thomas A., Moon, James C., Valdes, Ana M., McKnight, Áine, Altmann, Daniel M., Boyton, Rosemary, Reynolds, Catherine J., Pade, Corinna, Gibbons, Joseph M., Butler, David K., Otter, Ashley D., Menacho, Katia, Fontana, Marianna, Smit, Angelique, Sackville-West, Jane E., Cutino-Moguel, Teresa, Maini, Mala K., Chain, Benjamin, Noursadeghi, Mahdad, Brooks, Tim, Semper, Amanda, Manisty, Charlotte, Treibel, Thomas A., Moon, James C., Valdes, Ana M., McKnight, Áine, Altmann, Daniel M., and Boyton, Rosemary
Abstract: SARS-CoV-2 vaccine rollout has coincided with the spread of variants of concern. We investigated if single dose vaccination, with or without prior infection, confers cross protective immunity to variants. We analyzed T and B cell responses after first dose vaccination with the Pfizer/BioNTech mRNA vaccine BNT162b2 in healthcare workers (HCW) followed longitudinally, with or without prior Wuhan-Hu-1 SARS-CoV-2 infection. After one dose, individuals with prior infection showed enhanced T cell immunity, antibody secreting memory B cell response to spike and neutralizing antibodies effective against B.1.1.7 and B.1.351. By comparison, HCW receiving one vaccine dose without prior infection showed reduced immunity against variants. B.1.1.7 and B.1.351 spike mutations resulted in increased, abrogated or unchanged T cell responses depending on human leukocyte antigen (HLA) polymorphisms. Single dose vaccination with BNT162b2 in the context of prior infection with a heterologous variant substantially enhances neutralizing antibody responses against variants.
Published: 2021

22. Blood transcriptional biomarkers of acute viral infection for detection of pre-symptomatic SARS-CoV-2 infection: a nested, case-control diagnostic accuracy study

Author: Gupta, Rishi K, Rosenheim, Joshua, Bell, Lucy C, Chandran, Aneesh, Guerra-Assuncao, Jose A, Pollara, Gabriele, Whelan, Matthew, Artico, Jessica, Joy, George, Kurdi, Hibba, Altmann, Daniel M, Boyton, Rosemary J, Maini, Mala K, McKnight, Aine, Lambourne, Jonathan, Cutino-Moguel, Teresa, Manisty, Charlotte, Treibel, Thomas A, Moon, James C, Chain, Benjamin M, Noursadeghi, Mahdad, Abbass, Hakam, Abiodun, Aderonke, Alfarih, Mashael, Alldis, Zoe, Amin, Oliver E, Andiapen, Mervyn, Augusto, João B, Baca, Georgiana L, Bailey, Sasha NL, 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, Couto de Sousa, Jorge, Couto-Parada, Xose, Davies, Rhodri H, Douglas, Brooke, Di Genova, Cecilia, Dieobi-Anene, Keenan, Diniz, Mariana O, Ellis, Anaya, Feehan, Karen, Finlay, Malcolm, Fontana, Marianna, Forooghi, Nasim, Gaier, Celia, Gibbons, Joseph M, 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, Melaniepetra, Jones, Jessica, Jones, Meleri, Kapil, Vikas, Lin, Kai-Min, Louth, Sarah, Mandadapu, Vineela, Manisty,, Charlotte, McKnight, Áine, Menacho, Katia, Mfuko, Celina, Mitchelmore, Oliver, Moon, Christopher, Moon,, James C, Munoz Sandoval, Diana, Murray, Sam M, Otter, Ashley, Pade, Corinna, Palma, Susana, Parker, Ruth, Patel, Kush, Pawarova, Babita, Petersen, Steffen E, Piniera, Brian, Pieper, Franziska P, Pope, Daniel, Prossora, Maria, Rannigan, Lisa, Rapala, Alicja, Reynolds, Catherine J, Richards, Amy, Robathan, Matthew, Sambile, Genine, Schmidt, Nathalie M, Semper, Amanda, Seraphim, Andreas, Simion, Mihaela, Smit, Angelique, Sugimoto, Michelle, Swadling, Leo, Taylor, Stephen, Temperton, Nigel J., Thomas, Stephen, Thornton, George D, Tucker, Art, Veerapen, Jessry, Vijayakumar, Mohit, Welch, Sophie, Wodehouse, Theresa, Wynne, Lucinda, Zahedi, Dan, Gupta, Rishi K, Rosenheim, Joshua, Bell, Lucy C, Chandran, Aneesh, Guerra-Assuncao, Jose A, Pollara, Gabriele, Whelan, Matthew, Artico, Jessica, Joy, George, Kurdi, Hibba, Altmann, Daniel M, Boyton, Rosemary J, Maini, Mala K, McKnight, Aine, Lambourne, Jonathan, Cutino-Moguel, Teresa, Manisty, Charlotte, Treibel, Thomas A, Moon, James C, Chain, Benjamin M, Noursadeghi, Mahdad, Abbass, Hakam, Abiodun, Aderonke, Alfarih, Mashael, Alldis, Zoe, Amin, Oliver E, Andiapen, Mervyn, Augusto, João B, Baca, Georgiana L, Bailey, Sasha NL, 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, Couto de Sousa, Jorge, Couto-Parada, Xose, Davies, Rhodri H, Douglas, Brooke, Di Genova, Cecilia, Dieobi-Anene, Keenan, Diniz, Mariana O, Ellis, Anaya, Feehan, Karen, Finlay, Malcolm, Fontana, Marianna, Forooghi, Nasim, Gaier, Celia, Gibbons, Joseph M, 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, Melaniepetra, Jones, Jessica, Jones, Meleri, Kapil, Vikas, Lin, Kai-Min, Louth, Sarah, Mandadapu, Vineela, Manisty,, Charlotte, McKnight, Áine, Menacho, Katia, Mfuko, Celina, Mitchelmore, Oliver, Moon, Christopher, Moon,, James C, Munoz Sandoval, Diana, Murray, Sam M, Otter, Ashley, Pade, Corinna, Palma, Susana, Parker, Ruth, Patel, Kush, Pawarova, Babita, Petersen, Steffen E, Piniera, Brian, Pieper, Franziska P, Pope, Daniel, Prossora, Maria, Rannigan, Lisa, Rapala, Alicja, Reynolds, Catherine J, Richards, Amy, Robathan, Matthew, Sambile, Genine, Schmidt, Nathalie M, Semper, Amanda, Seraphim, Andreas, Simion, Mihaela, Smit, Angelique, Sugimoto, Michelle, Swadling, Leo, Taylor, Stephen, Temperton, Nigel J., Thomas, Stephen, Thornton, George D, Tucker, Art, Veerapen, Jessry, Vijayakumar, Mohit, Welch, Sophie, Wodehouse, Theresa, Wynne, Lucinda, and Zahedi, Dan
Abstract: Background We hypothesised that host-response biomarkers of viral infections might contribute to early identification of individuals infected with SARS-CoV-2, which is critical to breaking the chains of transmission. We aimed to evaluate the diagnostic accuracy of existing candidate whole-blood transcriptomic signatures for viral infection to predict positivity of nasopharyngeal SARS-CoV-2 PCR testing.Methods We did a nested case-control diagnostic accuracy study among a prospective cohort of health-care workers (aged ≥18 years) at St Bartholomew’s Hospital (London, UK) undergoing weekly blood and nasopharyngeal swab sampling for whole-blood RNA sequencing and SARS-CoV-2 PCR testing, when fit to attend work. We identified candidate blood transcriptomic signatures for viral infection through a systematic literature search. We searched MEDLINE for articles published between database inception and Oct 12, 2020, using comprehensive MeSH and keyword terms for “viral infection”, “transcriptome”, “biomarker”, and “blood”. We reconstructed signature scores in blood RNA sequencing data and evaluated their diagnostic accuracy for contemporaneous SARS-CoV-2 infection, compared with the gold standard of SARS-CoV-2 PCR testing, by quantifying the area under the receiver operating characteristic curve (AUROC), sensitivities, and specificities at a standardised Z score of at least 2 based on the distribution of signature scores in test-negative controls. We used pairwise DeLong tests compared with the most discriminating signature to identify the subset of best performing biomarkers. We evaluated associations between signature expression, viral load (using PCR cycle thresholds), and symptom status visually and using Spearman rank correlation. The primary outcome was the AUROC for discriminating between samples from participants who tested negative throughout the study (test-negative controls) and samples from participants with PCR-confirmed SARS-CoV-2 infection (test-positive part
Published: 2021

23. Prior SARS-CoV-2 infection rescues B and T cell responses to variants after first vaccine dose

Author: Reynolds, Catherine J., Pade, Corinna, Gibbons, Joseph M., Butler, David K., Otter, Ashley D., Menacho, Katia, Fontana, Marianna, Smit, Angelique, Sackville-West, Jane E., Cutino-Moguel, Teresa, Maini, Mala K., Chain, Benjamin, Noursadeghi, Mahdad, Brooks, Tim, Semper, Amanda, Manisty, Charlotte, Treibel, Thomas A., Moon, James C., Valdes, Ana M., McKnight, Áine, Altmann, Daniel M., Boyton, Rosemary, Reynolds, Catherine J., Pade, Corinna, Gibbons, Joseph M., Butler, David K., Otter, Ashley D., Menacho, Katia, Fontana, Marianna, Smit, Angelique, Sackville-West, Jane E., Cutino-Moguel, Teresa, Maini, Mala K., Chain, Benjamin, Noursadeghi, Mahdad, Brooks, Tim, Semper, Amanda, Manisty, Charlotte, Treibel, Thomas A., Moon, James C., Valdes, Ana M., McKnight, Áine, Altmann, Daniel M., and Boyton, Rosemary
Abstract: SARS-CoV-2 vaccine rollout has coincided with the spread of variants of concern. We investigated if single dose vaccination, with or without prior infection, confers cross protective immunity to variants. We analyzed T and B cell responses after first dose vaccination with the Pfizer/BioNTech mRNA vaccine BNT162b2 in healthcare workers (HCW) followed longitudinally, with or without prior Wuhan-Hu-1 SARS-CoV-2 infection. After one dose, individuals with prior infection showed enhanced T cell immunity, antibody secreting memory B cell response to spike and neutralizing antibodies effective against B.1.1.7 and B.1.351. By comparison, HCW receiving one vaccine dose without prior infection showed reduced immunity against variants. B.1.1.7 and B.1.351 spike mutations resulted in increased, abrogated or unchanged T cell responses depending on human leukocyte antigen (HLA) polymorphisms. Single dose vaccination with BNT162b2 in the context of prior infection with a heterologous variant substantially enhances neutralizing antibody responses against variants.
Published: 2021

24. Extracellular myocardial volume in patients with aortic stenosis

Author: Everett, Russell J., Treibel, Thomas Alexander, Fukui, Miho, Lee, Heesun, Rigolli, Marzia, Singh, Anvesha, Bijsterveld, Petra, Tastet, Lionel, Musa, Tarique Al, Dobson, Laura, Chin, Calvin, Captur, Gabriella, Sang, Yong Om, Wiesemann, Stéphanie, Ferreira, Vanessa M., Piechnik, Stefan K., Schulz-Menger, Jeanette, Schelbert, Erik, Clavel, Marie-Annick, Newby, David E., Myerson, Saul G., Pibarot, Philippe, Lee, Sahmin, Cavalcante, João L., Lee, Seung-Pyo, McCann, Gerry P., Greenwood, John P., Moon, James, Dweck, Marc, Everett, Russell J., Treibel, Thomas Alexander, Fukui, Miho, Lee, Heesun, Rigolli, Marzia, Singh, Anvesha, Bijsterveld, Petra, Tastet, Lionel, Musa, Tarique Al, Dobson, Laura, Chin, Calvin, Captur, Gabriella, Sang, Yong Om, Wiesemann, Stéphanie, Ferreira, Vanessa M., Piechnik, Stefan K., Schulz-Menger, Jeanette, Schelbert, Erik, Clavel, Marie-Annick, Newby, David E., Myerson, Saul G., Pibarot, Philippe, Lee, Sahmin, Cavalcante, João L., Lee, Seung-Pyo, McCann, Gerry P., Greenwood, John P., Moon, James, and Dweck, Marc
Abstract: Background : Myocardial fibrosis is a key mechanism of left ventricular decompensation in aortic stenosis and can be quantified using cardiovascular magnetic resonance (CMR) measures such as extracellular volume fraction (ECV%). Outcomes following aortic valve intervention may be linked to the presence and extent of myocardial fibrosis. Objectives : This study sought to determine associations between ECV% and markers of left ventricular decompensation and post-intervention clinical outcomes. Methods : Patients with severe aortic stenosis underwent CMR, including ECV% quantification using modified Look-Locker inversion recovery–based T1 mapping and late gadolinium enhancement before aortic valve intervention. A central core laboratory quantified CMR parameters. Results : Four-hundred forty patients (age 70 ± 10 years, 59% male) from 10 international centers underwent CMR a median of 15 days (IQR: 4 to 58 days) before aortic valve intervention. ECV% did not vary by scanner manufacturer, magnetic field strength, or T1 mapping sequence (all p > 0.20). ECV% correlated with markers of left ventricular decompensation including left ventricular mass, left atrial volume, New York Heart Association functional class III/IV, late gadolinium enhancement, and lower left ventricular ejection fraction (p < 0.05 for all), the latter 2 associations being independent of all other clinical variables (p = 0.035 and p < 0.001). After a median of 3.8 years (IQR: 2.8 to 4.6 years) of follow-up, 52 patients had died, 14 from adjudicated cardiovascular causes. A progressive increase in all-cause mortality was seen across tertiles of ECV% (17.3, 31.6, and 52.7 deaths per 1,000 patient-years; log-rank test; p = 0.009). Not only was ECV% associated with cardiovascular mortality (p = 0.003), but it was also independently associated with all-cause mortality following adjustment for age, sex, ejection fraction, and late gadolinium enhancement (hazard ratio per percent increase in ECV%: 1.10; 95% c
Published: 2020

25. Extracellular myocardial volume in patients with aortic stenosis

Author: Everett, Russell J., Pibarot, Philippe, Treibel, Thomas Alexander, Clavel, Marie-Annick, Fukui, Miho, Tastet, Lionel, Lee, Heesun, Rigolli, Marzia, Singh, Anvesha, Bijsterveld, Petra, Musa, Tarique Al, Dobson, Laura, Chin, Calvin, Captur, Gabriella, Sang, Yong Om, Wiesemann, Stéphanie, Ferreira, Vanessa M., Piechnik, Stefan K., Schulz-Menger, Jeanette, Schelbert, Erik, Newby, David E., Myerson, Saul G., Lee, Sahmin, Cavalcante, João L., Lee, Seung-Pyo, McCann, Gerry P., Greenwood, John P., Moon, James, Dweck, Marc, Everett, Russell J., Pibarot, Philippe, Treibel, Thomas Alexander, Clavel, Marie-Annick, Fukui, Miho, Tastet, Lionel, Lee, Heesun, Rigolli, Marzia, Singh, Anvesha, Bijsterveld, Petra, Musa, Tarique Al, Dobson, Laura, Chin, Calvin, Captur, Gabriella, Sang, Yong Om, Wiesemann, Stéphanie, Ferreira, Vanessa M., Piechnik, Stefan K., Schulz-Menger, Jeanette, Schelbert, Erik, Newby, David E., Myerson, Saul G., Lee, Sahmin, Cavalcante, João L., Lee, Seung-Pyo, McCann, Gerry P., Greenwood, John P., Moon, James, and Dweck, Marc
Abstract: Background : Myocardial fibrosis is a key mechanism of left ventricular decompensation in aortic stenosis and can be quantified using cardiovascular magnetic resonance (CMR) measures such as extracellular volume fraction (ECV%). Outcomes following aortic valve intervention may be linked to the presence and extent of myocardial fibrosis. Objectives : This study sought to determine associations between ECV% and markers of left ventricular decompensation and post-intervention clinical outcomes. Methods : Patients with severe aortic stenosis underwent CMR, including ECV% quantification using modified Look-Locker inversion recovery–based T1 mapping and late gadolinium enhancement before aortic valve intervention. A central core laboratory quantified CMR parameters. Results : Four-hundred forty patients (age 70 ± 10 years, 59% male) from 10 international centers underwent CMR a median of 15 days (IQR: 4 to 58 days) before aortic valve intervention. ECV% did not vary by scanner manufacturer, magnetic field strength, or T1 mapping sequence (all p > 0.20). ECV% correlated with markers of left ventricular decompensation including left ventricular mass, left atrial volume, New York Heart Association functional class III/IV, late gadolinium enhancement, and lower left ventricular ejection fraction (p < 0.05 for all), the latter 2 associations being independent of all other clinical variables (p = 0.035 and p < 0.001). After a median of 3.8 years (IQR: 2.8 to 4.6 years) of follow-up, 52 patients had died, 14 from adjudicated cardiovascular causes. A progressive increase in all-cause mortality was seen across tertiles of ECV% (17.3, 31.6, and 52.7 deaths per 1,000 patient-years; log-rank test; p = 0.009). Not only was ECV% associated with cardiovascular mortality (p = 0.003), but it was also independently associated with all-cause mortality following adjustment for age, sex, ejection fraction, and late gadolinium enhancement (hazard ratio per percent increase in ECV%: 1.10; 95% c
Published: 2020

26. Discordant neutralizing antibody and T cell responses in asymptomatic and mild SARS-CoV-2 infection

Author: Reynolds, Catherine J., Swadling, Leo, Gibbons, Joseph M., Pade, Corinna, Jensen, Melanie P., Diniz, Mariana O., Schmidt, Nathalie M., Butler, David K., Amin, Oliver E., Bailey, Sasha N. L., Murray, Sam M., Pieper, Franziska P., Taylor, Stephen, Jones, Jessica, Jones, Meleri, Lee, Wing-Yiu Jason, Rosenheim, Joshua, Chandran, Aneesh, Joy, George, Di Genova, Cecilia, Temperton, Nigel, Lambourne, Jonathan, Cutino-Moguel, Teresa, Andiapen, Mervyn, Fontana, Marianna, Smit, Angelique, Semper, Amanda, O’Brien, Ben, Chain, Benjamin, Brooks, Tim, Manisty, Charlotte, Treibel, Thomas, Moon, James C., Noursadeghi, Mahdad, Altmann, Daniel M., Maini, Mala K., McKnight, Áine, Boyton, Rosemary J., Reynolds, Catherine J., Swadling, Leo, Gibbons, Joseph M., Pade, Corinna, Jensen, Melanie P., Diniz, Mariana O., Schmidt, Nathalie M., Butler, David K., Amin, Oliver E., Bailey, Sasha N. L., Murray, Sam M., Pieper, Franziska P., Taylor, Stephen, Jones, Jessica, Jones, Meleri, Lee, Wing-Yiu Jason, Rosenheim, Joshua, Chandran, Aneesh, Joy, George, Di Genova, Cecilia, Temperton, Nigel, Lambourne, Jonathan, Cutino-Moguel, Teresa, Andiapen, Mervyn, Fontana, Marianna, Smit, Angelique, Semper, Amanda, O’Brien, Ben, Chain, Benjamin, Brooks, Tim, Manisty, Charlotte, Treibel, Thomas, Moon, James C., Noursadeghi, Mahdad, Altmann, Daniel M., Maini, Mala K., McKnight, Áine, and Boyton, Rosemary J.
Abstract: Understanding the nature of immunity following mild/asymptomatic infection with SARS-CoV-2 is crucial to controlling the pandemic. We analyzed T cell and neutralizing antibody responses in 136 healthcare workers (HCW) 16-18 weeks after United Kingdom lockdown, 76 of whom had mild/asymptomatic SARS-CoV-2 infection captured by serial sampling. Neutralizing antibodies (nAb) were present in 89% of previously infected HCW. T cell responses tended to be lower following asymptomatic infection than in those reporting case-definition symptoms of COVID-19, while nAb titers were maintained irrespective of symptoms. T cell and antibody responses were sometimes discordant. Eleven percent lacked nAb and had undetectable T cell responses to spike protein but had T cells reactive with other SARS-CoV-2 antigens. Our findings suggest that the majority of individuals with mild or asymptomatic SARS-CoV-2 infection carry nAb complemented by multispecific T cell responses at 16-18 weeks after mild or asymptomatic SARS-CoV-2 infection.
Published: 2020

27. Discordant neutralizing antibody and T cell responses in asymptomatic and mild SARS-CoV-2 infection

Author: Reynolds, Catherine J., Swadling, Leo, Gibbons, Joseph M., Pade, Corinna, Jensen, Melanie P., Diniz, Mariana O., Schmidt, Nathalie M., Butler, David K., Amin, Oliver E., Bailey, Sasha N. L., Murray, Sam M., Pieper, Franziska P., Taylor, Stephen, Jones, Jessica, Jones, Meleri, Lee, Wing-Yiu Jason, Rosenheim, Joshua, Chandran, Aneesh, Joy, George, Di Genova, Cecilia, Temperton, Nigel, Lambourne, Jonathan, Cutino-Moguel, Teresa, Andiapen, Mervyn, Fontana, Marianna, Smit, Angelique, Semper, Amanda, O’Brien, Ben, Chain, Benjamin, Brooks, Tim, Manisty, Charlotte, Treibel, Thomas, Moon, James C., Noursadeghi, Mahdad, Altmann, Daniel M., Maini, Mala K., McKnight, Áine, Boyton, Rosemary J., Reynolds, Catherine J., Swadling, Leo, Gibbons, Joseph M., Pade, Corinna, Jensen, Melanie P., Diniz, Mariana O., Schmidt, Nathalie M., Butler, David K., Amin, Oliver E., Bailey, Sasha N. L., Murray, Sam M., Pieper, Franziska P., Taylor, Stephen, Jones, Jessica, Jones, Meleri, Lee, Wing-Yiu Jason, Rosenheim, Joshua, Chandran, Aneesh, Joy, George, Di Genova, Cecilia, Temperton, Nigel, Lambourne, Jonathan, Cutino-Moguel, Teresa, Andiapen, Mervyn, Fontana, Marianna, Smit, Angelique, Semper, Amanda, O’Brien, Ben, Chain, Benjamin, Brooks, Tim, Manisty, Charlotte, Treibel, Thomas, Moon, James C., Noursadeghi, Mahdad, Altmann, Daniel M., Maini, Mala K., McKnight, Áine, and Boyton, Rosemary J.
Abstract: Understanding the nature of immunity following mild/asymptomatic infection with SARS-CoV-2 is crucial to controlling the pandemic. We analyzed T cell and neutralizing antibody responses in 136 healthcare workers (HCW) 16-18 weeks after United Kingdom lockdown, 76 of whom had mild/asymptomatic SARS-CoV-2 infection captured by serial sampling. Neutralizing antibodies (nAb) were present in 89% of previously infected HCW. T cell responses tended to be lower following asymptomatic infection than in those reporting case-definition symptoms of COVID-19, while nAb titers were maintained irrespective of symptoms. T cell and antibody responses were sometimes discordant. Eleven percent lacked nAb and had undetectable T cell responses to spike protein but had T cells reactive with other SARS-CoV-2 antigens. Our findings suggest that the majority of individuals with mild or asymptomatic SARS-CoV-2 infection carry nAb complemented by multispecific T cell responses at 16-18 weeks after mild or asymptomatic SARS-CoV-2 infection.
Published: 2020

28. H3K27ac acetylome signatures reveal the epigenomic reorganization in remodeled non-failing human hearts

Author: Onderzoek Precision medicine, Other research (not in main researchprogram), Cardiologie Arts-onderzoekers, Nefro Vasculaire Geneeskunde, Regenerative Medicine and Stem Cells, Onderzoek Vrouw Hart & Vaatziekten, Circulatory Health, CDL Onderzoek Pasterkamp, UMC Utrecht, Onderzoek, MDL onderzoek 1, Infection & Immunity, Child Health, Pathologie Laboratorium diagnostiek, Genetica Sectie Genoomdiagnostiek, Pathologie Pathologen staf, Team Medisch, Pei, Jiayi, Harakalova, Magdalena, Treibel, Thomas A, Lumbers, R Thomas, Boukens, Bastiaan J, Efimov, Igor R, van Dinter, Jip T, González, Arantxa, López, Begoña, El Azzouzi, Hamid, van den Dungen, Noortje, van Dijk, Christian G M, Krebber, Merle M, den Ruijter, Hester M, Pasterkamp, Gerard, Duncker, Dirk J, Nieuwenhuis, Edward E S, de Weger, Roel, Huibers, Manon M, Vink, Aryan, Moore, Jason H, Moon, James C, Verhaar, Marianne C, Kararigas, Georgios, Mokry, Michal, Asselbergs, Folkert W, Cheng, Caroline, Onderzoek Precision medicine, Other research (not in main researchprogram), Cardiologie Arts-onderzoekers, Nefro Vasculaire Geneeskunde, Regenerative Medicine and Stem Cells, Onderzoek Vrouw Hart & Vaatziekten, Circulatory Health, CDL Onderzoek Pasterkamp, UMC Utrecht, Onderzoek, MDL onderzoek 1, Infection & Immunity, Child Health, Pathologie Laboratorium diagnostiek, Genetica Sectie Genoomdiagnostiek, Pathologie Pathologen staf, Team Medisch, Pei, Jiayi, Harakalova, Magdalena, Treibel, Thomas A, Lumbers, R Thomas, Boukens, Bastiaan J, Efimov, Igor R, van Dinter, Jip T, González, Arantxa, López, Begoña, El Azzouzi, Hamid, van den Dungen, Noortje, van Dijk, Christian G M, Krebber, Merle M, den Ruijter, Hester M, Pasterkamp, Gerard, Duncker, Dirk J, Nieuwenhuis, Edward E S, de Weger, Roel, Huibers, Manon M, Vink, Aryan, Moore, Jason H, Moon, James C, Verhaar, Marianne C, Kararigas, Georgios, Mokry, Michal, Asselbergs, Folkert W, and Cheng, Caroline
Published: 2020

29. Myocardial T1 mapping: where are we now and where are we going?

Author: Abdel-Gadir,Amna, Treibel,Thomas A, Moon,James C, Abdel-Gadir,Amna, Treibel,Thomas A, and Moon,James C
Abstract: Amna Abdel-Gadir,1,2 Thomas A Treibel,1,2 James C Moon1,2 1The Heart Hospital Imaging Centre, University College London Hospitals, London, UK; 2Institute of Cardiovascular Science, University College London, London, UK Abstract: Cardiovascular magnetic resonance offers noninvasive myocardial tissue characterization as a key unique strength over other imaging techniques. In particular T1, a tissue property that alters with disease, has gained prominence as a diagnostic tool. Prior to the administration of contrast, the native T1 changes with a number of processes such as fibrosis, edema, and infiltration. If a post-contrast scan is also acquired, the post-contrast T1 and extracellular volume fraction can be measured. Detecting and quantifying early and established myocardial pathological processes permits better diagnosis, prognostication, and tracking of therapy. Keywords: extracellular volume fraction, diffuse fibrosis, interstitium, cardiac remodeling, myocardial intracellular volume
Published: 2014

30. Sex differences in left ventricular remodeling, myocardial fibrosis and mortality after aortic valve replacement

Author: Singh, Anvesha, Al Musa, Tarique, Treibel, Thomas A, Vassiliou, Vassiliou S, Captur, Gabriella, Chin, Calvin, Dobson, Laura E, Pica, Silvia, Loudon, Margaret, Malley, Tamir, Rigolli, Marzia, Foley, James Robert John, Bijsterveld, Petra, Law, Graham, Dweck, Marc Richard, Myerson, Saul G, Prasad, Sanjay K, Moon, James C, Greenwood, John, McCann, Gerry P, Singh, Anvesha, Al Musa, Tarique, Treibel, Thomas A, Vassiliou, Vassiliou S, Captur, Gabriella, Chin, Calvin, Dobson, Laura E, Pica, Silvia, Loudon, Margaret, Malley, Tamir, Rigolli, Marzia, Foley, James Robert John, Bijsterveld, Petra, Law, Graham, Dweck, Marc Richard, Myerson, Saul G, Prasad, Sanjay K, Moon, James C, Greenwood, John, and McCann, Gerry P
Abstract: Objectives: To investigate sex-differences in left ventricular remodelingand outcome in patients undergoing surgical or transcatheter aortic valve replacement (SAVR/TAVR). Methods: In this multicentre, observational, outcome study with imaging core lab analysis, patients with severe aortic stenosis (AS) listed for intervention at one of six UK centres were prospectively recruited and underwent cardiovascular magnetic resonance imaging (CMR). The primary endpoint was all-cause mortality and secondary endpoint was cardiovascular mortality. Results: 674 patients (425 male, 249 female, age 7514 years) were included: 399 SAVR, 275 TAVR. Females were older, had higher surgical risk scores and underwent TAVR more frequently (53% vs. 33.6%, p<0.001). More men had bicuspid aortic valves (BAV) (26.7% vs. 14.9%, p<0.001) and demonstrated more advanced remodelling than females. During a median follow-up of 3.6 years, 145 (21.5%) patients died, with no significant difference in all-cause mortality (23.3% vs. 20.5%, p=0.114), but higher cardiovascular mortality in females (13.7% vs. 8.5%, p=0.012). There were no significant sex related differences in outcome in the SAVR or TAVR sub-groups, or after excluding those with BAV. Factors independently associated with all-cause mortality were age, left ventricular ejection fraction (LVEF), BAV (better) and myocardial fibrosis detected with late-gadolinium enhancement (LGE) in men; and age, LVEF and LGE in women. Age and LGE were independently associated with cardiovascular mortality in both sexes. Conclusions: Men demonstrate more advanced remodeling in response to a similar severity of AS. The higher cardiovascular mortality observed in women following AVR is accounted for by females having less BAV and higher risk scores resulting in more TAVR. LGE is associated with a worse prognosis in both sexes.

31. Myocardial Scar and Mortality in Severe Aortic Stenosis

Author: Musa, Tarique A., Treibel, Thomas A., Vassiliou, Vassiliou S., Captur, Gabriella, Singh, Anvesha, Chin, Calvin, Dobson, Laura E., Pica, Silvia, Loudon, Margaret, Malley, Tamir, Rigolli, Marzia, Foley, James R.J., Bijsterveld, Petra, Law, Graham R., Dweck, Marc R., Myerson, Saul G., McCann, Gerry P., Prasad, Sanjay K., Moon, James C., Greenwood, John P., Musa, Tarique A., Treibel, Thomas A., Vassiliou, Vassiliou S., Captur, Gabriella, Singh, Anvesha, Chin, Calvin, Dobson, Laura E., Pica, Silvia, Loudon, Margaret, Malley, Tamir, Rigolli, Marzia, Foley, James R.J., Bijsterveld, Petra, Law, Graham R., Dweck, Marc R., Myerson, Saul G., McCann, Gerry P., Prasad, Sanjay K., Moon, James C., and Greenwood, John P.
Abstract: BACKGROUND: Aortic valve replacement (AVR) for aortic stenosis is timed primarily on the development of symptoms, but late surgery can result in irreversible myocardial dysfunction and additional risk. The aim of this study was to determine whether the presence of focal myocardial scar preoperatively was associated with long-term mortality. METHODS: In a longitudinal observational outcome study, survival analysis was performed in patients with severe aortic stenosis listed for valve intervention at 6 UK cardiothoracic centers. Patients underwent preprocedural echocardiography (for valve severity assessment) and cardiovascular magnetic resonance for ventricular volumes, function and scar quantification between January 2003 and May 2015. Myocardial scar was categorized into 3 patterns (none, infarct, or noninfarct patterns) and quantified with the full width at half-maximum method as percentage of the left ventricle. All-cause mortality and cardiovascular mortality were tracked for a minimum of 2 years. RESULTS: Six hundred seventy-four patients with severe aortic stenosis (age, 75±14 years; 63% male; aortic valve area, 0.38±0.14 cm2/m2; mean gradient, 46±18 mm Hg; left ventricular ejection fraction, 61.0±16.7%) were included. Scar was present in 51% (18% infarct pattern, 33% noninfarct). Management was surgical AVR (n=399) or transcatheter AVR (n=275). During follow-up (median, 3.6 years), 145 patients (21.5%) died (52 after surgical AVR, 93 after transcatheter AVR). In multivariable analysis, the factors independently associated with all-cause mortality were age (hazard ratio [HR], 1.50; 95% CI, 1.11-2.04; P=0.009, scaled by epochs of 10 years), Society of Thoracic Surgeons score (HR, 1.12; 95% CI, 1.03-1.22; P=0.007), and scar presence (HR, 2.39; 95% CI, 1.40-4.05; P=0.001). Scar independently predicted all-cause (26.4% versus 12.9%; P<0.001) and cardiovascular (15.0% versus 4.8%; P<0.001) mortality, regardless of intervention (transcatheter AVR, P=0.002; surgical

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31 results on '"Treibel, Thomas A"'

1. Bayesian Uncertainty Estimation by Hamiltonian Monte Carlo: Applications to Cardiac MRI Segmentation

2. Quantitative, multiplexed, targeted proteomics for ascertaining variant specific SARS-CoV-2 antibody response

3. Quantitative, multiplexed, targeted proteomics for ascertaining variant specific SARS-CoV-2 antibody response

4. Improved reproducibility for myocardial ASL: Impact of physiological and acquisition parameters

5. Identification of subclinical cardiac amyloidosis in aortic stenosis patients undergoing transaortic valve replacement using radiomic analysis of computed tomography myocardial texture

6. Immune boosting by B.1.1.529 (Omicron) depends on previous SARS-CoV-2 exposure

7. Immune boosting by B.1.1.529 (Omicron) depends on previous SARS-CoV-2 exposure

8. HLA‐DR polymorphism in SARS‐CoV‐2 infection and susceptibility to symptomatic COVID‐19

9. HLA‐DR polymorphism in SARS‐CoV‐2 infection and susceptibility to symptomatic COVID‐19

10. Model-free phasor image analysis of quantitative myocardial T1 mapping

11. Cardiac phase-resolved late gadolinium enhancement imaging

12. Myocardial Approximate Spin-lock Dispersion Mapping using a Simultaneous T2 and TRAFF2 Mapping at 3T MRI

13. Model-free phasor image analysis of quantitative myocardial T1 mapping

14. Markers of myocardial damage predict mortality in patients with aortic stenosis

15. Diagnosis and risk stratification in hypertrophic cardiomyopathy using machine learning wall thickness measurement: a comparison with human test-retest performance.

16. Markers of Myocardial Damage Predict Mortality in Patients With Aortic Stenosis.

17. Markers of myocardial damage predict mortality in patients with aortic stenosis

18. Heterologous infection and vaccination shapes immunity against SARS-CoV-2 variants

19. Heterologous infection and vaccination shapes immunity against SARS-CoV-2 variants

20. Blood transcriptional biomarkers of acute viral infection for detection of pre-symptomatic SARS-CoV-2 infection: a nested, case-control diagnostic accuracy study

21. Prior SARS-CoV-2 infection rescues B and T cell responses to variants after first vaccine dose

22. Blood transcriptional biomarkers of acute viral infection for detection of pre-symptomatic SARS-CoV-2 infection: a nested, case-control diagnostic accuracy study

23. Prior SARS-CoV-2 infection rescues B and T cell responses to variants after first vaccine dose

24. Extracellular myocardial volume in patients with aortic stenosis

25. Extracellular myocardial volume in patients with aortic stenosis

26. Discordant neutralizing antibody and T cell responses in asymptomatic and mild SARS-CoV-2 infection

27. Discordant neutralizing antibody and T cell responses in asymptomatic and mild SARS-CoV-2 infection

28. H3K27ac acetylome signatures reveal the epigenomic reorganization in remodeled non-failing human hearts

29. Myocardial T1 mapping: where are we now and where are we going?

30. Sex differences in left ventricular remodeling, myocardial fibrosis and mortality after aortic valve replacement

31. Myocardial Scar and Mortality in Severe Aortic Stenosis

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