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1. The influence of nutritional state on the fatty acid composition of circulating lipid fractions: implications for their use as biomarkers of dietary fat intake

Author

Sion A. Parry, Fredrik Rosqvist, Sarah Peters, Rebecca K. Young, Thomas Cornfield, Pamela Dyson, and Leanne Hodson

Subjects
postprandial, fatty acids, biomarker, lipid fractions, fatty acid composition, Medicine
Abstract

Background: The fatty acid (FA) composition of blood can be used as an objective biomarker of dietary FA intake. It remains unclear how the nutritional state influences the FA composition of plasma lipid fractions, and thus their usefulness as biomarkers in a non-fasted state. Objectives: To investigate the associations between palmitate, oleate and linoleate in plasma lipid fractions and self-reported dietary FA intake, and assess the influence of meal consumption on the relative abundance of these FA in plasma lipid fractions (i.e. triglyceride [TG], phospholipids [PLs] and cholesterol esters [CEs]). Design: Analysis was performed in plasma samples collected from 49 (34 males and 15 females) participants aged 26–57 years with a body mass index (BMI) between 21.6 and 34.2 kg/m2, all of whom had participated in multiple study visits, thus a pooled cohort of 98 data sets was available for analysis. A subset (n = 25) had undergone nutritional interventions and was therefore used to investigate the relationship between the FA composition of plasma lipid fractions and dietary fat intake. Results: Significant (P < 0.05) positive associations were observed between dietary polyunsaturated fat and linoleate abundance in plasma CE. When investigating the influence of meal consumption on postprandial FA composition, we found plasma TG palmitate significantly (P < 0.05) decreased across the postprandial period, whereas oleate and linoleate increased. A similar pattern was observed in plasma PL, whereas linoleate abundance decreased in the plasma CE. Conclusion: Our data demonstrate that the FA composition of plasma CE may be the lipid fraction to utilise as an objective biomarker when investigating recent (i.e. previous weeks-months) dietary FA intakes. In addition, we show that the consumption of a high-fat meal influences the FA composition of plasma TG, PL and CE over the course of the postprandial period, and therefore, suggest that fasting blood samples should be utilised when using FA composition as a biomarker of dietary FA intake.

Published
2021
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2. A blood atlas of COVID-19 defines hallmarks of disease severity and specificity

Author

David J. Ahern, Zhichao Ai, Mark Ainsworth, Chris Allan, Alice Allcock, Brian Angus, M. Azim Ansari, Carolina V. Arancibia-Cárcamo, Dominik Aschenbrenner, Moustafa Attar, J. Kenneth Baillie, Eleanor Barnes, Rachael Bashford-Rogers, Archana Bashyal, Sally Beer, Georgina Berridge, Amy Beveridge, Sagida Bibi, Tihana Bicanic, Luke Blackwell, Paul Bowness, Andrew Brent, Andrew Brown, John Broxholme, David Buck, Katie L. Burnham, Helen Byrne, Susana Camara, Ivan Candido Ferreira, Philip Charles, Wentao Chen, Yi-Ling Chen, Amanda Chong, Elizabeth A. Clutterbuck, Mark Coles, Christopher P. Conlon, Richard Cornall, Adam P. Cribbs, Fabiola Curion, Emma E. Davenport, Neil Davidson, Simon Davis, Calliope A. Dendrou, Julie Dequaire, Lea Dib, James Docker, Christina Dold, Tao Dong, Damien Downes, Hal Drakesmith, Susanna J. Dunachie, David A. Duncan, Chris Eijsbouts, Robert Esnouf, Alexis Espinosa, Rachel Etherington, Benjamin Fairfax, Rory Fairhead, Hai Fang, Shayan Fassih, Sally Felle, Maria Fernandez Mendoza, Ricardo Ferreira, Roman Fischer, Thomas Foord, Aden Forrow, John Frater, Anastasia Fries, Veronica Gallardo Sanchez, Lucy C. Garner, Clementine Geeves, Dominique Georgiou, Leila Godfrey, Tanya Golubchik, Maria Gomez Vazquez, Angie Green, Hong Harper, Heather A. Harrington, Raphael Heilig, Svenja Hester, Jennifer Hill, Charles Hinds, Clare Hird, Ling-Pei Ho, Renee Hoekzema, Benjamin Hollis, Jim Hughes, Paula Hutton, Matthew A. Jackson-Wood, Ashwin Jainarayanan, Anna James-Bott, Kathrin Jansen, Katie Jeffery, Elizabeth Jones, Luke Jostins, Georgina Kerr, David Kim, Paul Klenerman, Julian C. Knight, Vinod Kumar, Piyush Kumar Sharma, Prathiba Kurupati, Andrew Kwok, Angela Lee, Aline Linder, Teresa Lockett, Lorne Lonie, Maria Lopopolo, Martyna Lukoseviciute, Jian Luo, Spyridoula Marinou, Brian Marsden, Jose Martinez, Philippa C. Matthews, Michalina Mazurczyk, Simon McGowan, Stuart McKechnie, Adam Mead, Alexander J. Mentzer, Yuxin Mi, Claudia Monaco, Ruddy Montadon, Giorgio Napolitani, Isar Nassiri, Alex Novak, Darragh P. O'Brien, Daniel O'Connor, Denise O'Donnell, Graham Ogg, Lauren Overend, Inhye Park, Ian Pavord, Yanchun Peng, Frank Penkava, Mariana Pereira Pinho, Elena Perez, Andrew J. Pollard, Fiona Powrie, Bethan Psaila, T. Phuong Quan, Emmanouela Repapi, Santiago Revale, Laura Silva-Reyes, Jean-Baptiste Richard, Charlotte Rich-Griffin, Thomas Ritter, Christine S. Rollier, Matthew Rowland, Fabian Ruehle, Mariolina Salio, Stephen Nicholas Sansom, Raphael Sanches Peres, Alberto Santos Delgado, Tatjana Sauka-Spengler, Ron Schwessinger, Giuseppe Scozzafava, Gavin Screaton, Anna Seigal, Malcolm G. Semple, Martin Sergeant, Christina Simoglou Karali, David Sims, Donal Skelly, Hubert Slawinski, Alberto Sobrinodiaz, Nikolaos Sousos, Lizzie Stafford, Lisa Stockdale, Marie Strickland, Otto Sumray, Bo Sun, Chelsea Taylor, Stephen Taylor, Adan Taylor, Supat Thongjuea, Hannah Thraves, John A. Todd, Adriana Tomic, Orion Tong, Amy Trebes, Dominik Trzupek, Felicia Anna Tucci, Lance Turtle, Irina Udalova, Holm Uhlig, Erinke van Grinsven, Iolanda Vendrell, Marije Verheul, Alexandru Voda, Guanlin Wang, Lihui Wang, Dapeng Wang, Peter Watkinson, Robert Watson, Michael Weinberger, Justin Whalley, Lorna Witty, Katherine Wray, Luzheng Xue, Hing Yuen Yeung, Zixi Yin, Rebecca K. Young, Jonathan Youngs, Ping Zhang, Yasemin-Xiomara Zurke, Cribbs, AP, and Consortium, COvid-19 Multi-omics Blood ATlas (COMBAT)

Subjects
Resource, Adult, Male, Myeloid, Proteome, coronavirus, Cell Cycle Proteins, Disease, Severity of Illness Index, General Biochemistry, Genetics and Molecular Biology, Monocytes, Sepsis, Machine Learning, Mitogen-Activated Protein Kinase 14, transcriptomics, Immune system, proteomics, blood, Influenza, Human, medicine, Humans, Lymphocytes, Progenitor cell, Principal Component Analysis, epigenetics, business.industry, SARS-CoV-2, Clinical study design, Acute-phase protein, COVID-19, personalized medicine, Blood Proteins, multi-omics, Middle Aged, medicine.disease, Coronavirus, Transcription Factor AP-1, medicine.anatomical_structure, Drug development, Immunology, Female, immune, business, Biomarkers
Abstract

Treatment of severe COVID-19 is currently limited by clinical heterogeneity and incomplete description of specific immune biomarkers. We present here a comprehensive multi-omic blood atlas for patients with varying COVID-19 severity in an integrated comparison with influenza and sepsis patients versus healthy volunteers. We identify immune signatures and correlates of host response. Hallmarks of disease severity involved cells, their inflammatory mediators and networks, including progenitor cells and specific myeloid and lymphocyte subsets, features of the immune repertoire, acute phase response, metabolism and coagulation. Persisting immune activation involving AP-1/p38MAPK was a specific feature of COVID-19. The plasma proteome enabled sub-phenotyping into patient clusters, predictive of severity and outcome. Systems-based integrative analyses including tensor and matrix decomposition of all modalities revealed feature groupings linked with severity and specificity compared to influenza and sepsis. Our approach and blood atlas will support future drug development, clinical trial design and personalized medicine approaches for COVID-19., Graphical Abstract, A multi-omic analysis of patient blood samples reveals both similarities and specific features of COVID-19 when compared with samples obtained from sepsis or influenza patients which could yield better targetted therapies for severe COVID-19.

Published
2021
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3. Author response: Differential occupational risks to healthcare workers from SARS-CoV-2 observed during a prospective observational study

Author

Nellia Sande, Hannah Chase, Alan Chetwynd, Connor Thompson, Fiona Warren, Sonam Rughani, Jonathan Drake, Callum E. Harries, Rebecca te Water Naudé, Fredrik Karpe, Claire Sutton, Gabriella Kelly, Stoyan Dimitrov, Denis Volk, Olivia Ambler, Lucianne Smith, Michelle Gates, Adam J. R. Watson, Sheila F Lumley, Daniel Ebner, Gareth Watson, Tariq Ahmed-Firani, Kirsty Harper, Philip Cowie, Kaisha Patel, Bruno Holthof, Alison Howarth, Hannah Laurenson-Schafer, Christian Holland, Jane Philips, Rachel Turford, Rebecca K Young, Charlotte Lee, Philip W. Fowler, Julie Dequaire, Caitlin Rigler, James Kavanagh, Joshua Morton, Mark Campbell, Brian D. Marsden, George Doherty, Tracey Mitchell, Saxon Pattenden, Denise O'Donnell, Susan Wareing, Maria Robles, Euan Joseph McGivern, Samuel Scott, Timothy M. Walker, Laura Warren, Justyna Szczurkowska, Richard Kirton, Angus Livingstone, Emma-Jane Simons, Thomas Foord, Kenzo Motohashi, Jocelyn Lf Ward, Jeremy Swann, Francesca Back, David S Kim, Gabriella DAmato, Monique Andersson, David Axten, Seren Hannah Rose Waite, Matt J. Neville, Fan Yang-Turner, Cameron East, Holly Hendron, Elizabeth Sims, Hannah Danbury, Louise O Downs, Stefan Kourdov, Oscar Deal, Elaine Lawson, Kyla Smit, Robert Shaw, Leon Peto, Gavin R. Screaton, Trisha Bellinger, Joseph D. Wilson, Lucas Martins Ferreira, Adan Taylor, Krupa Ravi, David I. Stuart, Marcus English, Richard J. Cornall, Chris Jb Mason, Annabel Killen, Michael Luciw, Constantinos Savva, Lisa Butcher, Stuart Cox, Donal T. Skelly, Owen Sweeney, Derrick W. Crook, Maria Dudareva, Alexander J. Mentzer, Ruth Moroney, Sarah Wright, Zoe de Toledo, Roshni Ray, Thomas Christie, Lisa Morgan, Philippa C Matthews, Nicola Jones, Katherine O'Byrne, Mary Kumarendran, Nicole Stoesser, Nurul Huda Mohamad Fadzillah, Anne-Marie O'Donnell, Isabel Tol, Philip G. Drennan, Tim James, Katie Jeffery, Gemma Pill, Lydia Rylance-Knight, Stephanie B Hatch, Kevin K Chau, Evie Rothwell, Tim Davies, Lancelot J. Millar, Tim E. A. Peto, Evelyn Qian, Merline Tabirao, Thomas Christott, Heather Nevard, Liam J Peck, Madeleine E Oliver, Mary McKnight, Christopher P. Conlon, Conor Hennesey, Andrew Brent, Sarah Peters, Anita Justice, Kathryn Cann, James Gunnell, Thomas G Ritter, Claudia Salvagno, Stephanie Santos-Paulo, Vicki Wharton, S A Johnson, Samuel Sussmes, Harry Ward, Sven A. Kerneis, Edward Wa Harris, Matthew Wedlich, Alexandra S Mighiu, Ali Amini, Alexander Grassam-Rowe, Gregory D Howgego, Bernadett Gergely, Rosie Freer, Bernadette C. Young, Thomas B King, Sarah Hoosdally, Alexander Vogt, Imogen C Vorley, David W Eyre, and Gerald Jesuthasan

Subjects
medicine.medical_specialty, business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Health care, Emergency medicine, Medicine, Observational study, business
Published
2020
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