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1. SARS-CoV-2 seroprevalence and asymptomatic viral carriage in healthcare workers: a cross-sectional study

Author

Celina Whalley, Charlotte Poxon, Gabriella L. Morley, Kasun Wanigasooriya, Lyndsey A Dunbar, Mark T. Drayson, Dee E McLoughlin, Saly Al-Taei, Mark I. Garvey, Beena Emmanuel, Golaleh McGinnell, Sian E Jossi, Megan Richter, Andrew D Beggs, Marisol Perez-Toledo, Joel D. Allen, Adam F. Cunningham, Eloise M Walker, Agnieszka E. Zielinska, Joanna Gray, Max Crispin, Joanna O'Neill, Erin L. Aldera, Adrian M Shields, David C. Wraith, Andrew Bosworth, Oliver J Pickles, Sian E Faustini, Claire Backhouse, Alex G. Richter, Daniel Ebanks, I. Michael Kidd, Danai Papakonstantinou, and Yasunori Watanabe

Subjects
Adult, Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Cross-sectional study, Health Personnel, Prevalence, Context (language use), Antibodies, Viral, Asymptomatic, 03 medical and health sciences, 0302 clinical medicine, respiratory infection, Seroepidemiologic Studies, Internal medicine, Humans, Medicine, Seroprevalence, 030212 general & internal medicine, Seroconversion, Pandemics, Asymptomatic Diseases, 0303 health sciences, SARS-CoV-2, 030306 microbiology, business.industry, COVID-19, Respiratory infection, clinical epidemiology, Middle Aged, infection control, Cross-Sectional Studies, RNA, Viral, Female, viral infection, medicine.symptom, business
Abstract

ObjectiveTo determine the rates of asymptomatic viral carriage and seroprevalence of SARS-CoV-2 antibodies in healthcare workers.DesignA cross-sectional study of asymptomatic healthcare workers undertaken on 24/25 April 2020.SettingUniversity Hospitals Birmingham NHS Foundation Trust (UHBFT), UK.Participants545 asymptomatic healthcare workers were recruited while at work. Participants were invited to participate via the UHBFT social media. Exclusion criteria included current symptoms consistent with COVID-19. No potential participants were excluded.InterventionParticipants volunteered a nasopharyngeal swab and a venous blood sample that were tested for SARS-CoV-2 RNA and anti-SARS-CoV-2 spike glycoprotein antibodies, respectively. Results were interpreted in the context of prior illnesses and the hospital departments in which participants worked.Main outcome measureProportion of participants demonstrating infection and positive SARS-CoV-2 serology.ResultsThe point prevalence of SARS-CoV-2 viral carriage was 2.4% (n=13/545). The overall seroprevalence of SARS-CoV-2 antibodies was 24.4% (n=126/516). Participants who reported prior symptomatic illness had higher seroprevalence (37.5% vs 17.1%, χ2=21.1034, pConclusions and relevanceWe identify differences in the occupational risk of exposure to SARS-CoV-2 between hospital departments and confirm asymptomatic seroconversion occurs in healthcare workers. Further investigation of these observations is required to inform future infection control and occupational health practices.

Published
2020
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2. Vitamin D insufficiency in COVID-19 and influenza A, and critical illness survivors: a cross-sectional study

Author

Natalie Pattison, Richard J Mellanby, Ian Handel, Timothy S Walsh, Marlies Ostermann, Mark Lyttle, Adriano G Rossi, David M Griffith, Manu Shankar-Hari, Carlo Palmieri, Lance Turtle, Alexander J Mentzer, Lewis W S Fisher, James Scott-Brown, Danai Papakonstantinou, Effrossyni Gkrania-Klotsas, Kerri Devine, Daniel G Wootton, Padmasayee Papineni, Benjamin W A Catterall, Lara Lavelle-Langham, Emily Cass, Alejandra Doce Carracedo, Lisa Flaherty, Nicole Maziere, Hannah Massey, Anthony Holmes, Nicola Carlucci, Matthew K O'Shea, Emma A Hurst, Natalie Z Homer, Scott G Denham, Paul A Holloway, Romit J Samanta, Thushan de Silva, A A Roger Thompson, Ruth Lyons, Murray Wham, Sara Clohisey, Sara McDonald, Seán Keating, Lorna Finch, Lee Murphy, Nicola Wrobel, Sarah McCafferty, Kirstie Morrice, Alan MacLean, Erin L Aldera, Sneha Basude, Steven Laird, Antonia Ying Wai Ho, UKRI MRC COVID-19 Rapid Response Call, National Institute for Health Research, Commission of the European Communities, and UK Research and Innovation

Subjects
Cross-sectional study, medicine.medical_treatment, Bone remodeling, immunology, Influenza A Virus, H1N1 Subtype, Pandemic, INFECTION, Survivors, Respiratory system, Vitamin D, General Medicine, Infectious Diseases, Medicine, AUTOPHAGY, Vitamin D Deficiency/complications, Life Sciences & Biomedicine, HIGH-DOSE VITAMIN-D-3, Influenza, Human/complications, intensive & critical care, medicine.medical_specialty, D SUPPLEMENTATION, Critical Illness, vitamin D deficiency, 1117 Public Health and Health Services, respiratory infections, D DEFICIENCY, Medicine, General & Internal, Internal medicine, General & Internal Medicine, Influenza, Human, medicine, Vitamin D and neurology, Humans, Pandemics, ISARIC4C Investigators, Mechanical ventilation, Science & Technology, business.industry, SARS-CoV-2, COVID-19, 1103 Clinical Sciences, medicine.disease, Vitamin D Deficiency, Steroid hormone, Cross-Sectional Studies, business, 1199 Other Medical and Health Sciences
Abstract

ObjectivesThe steroid hormone vitamin D has roles in immunomodulation and bone health. Insufficiency is associated with susceptibility to respiratory infections. We report 25-hydroxy vitamin D (25(OH)D) measurements in hospitalised people with COVID-19 and influenza A and in survivors of critical illness to test the hypotheses that vitamin D insufficiency scales with illness severity and persists in survivors.DesignCross-sectional study.Setting and participantsPlasma was obtained from 295 hospitalised people with COVID-19 (International Severe Acute Respiratory and emerging Infections Consortium (ISARIC)/WHO Clinical Characterization Protocol for Severe Emerging Infections UK study), 93 with influenza A (Mechanisms of Severe Acute Influenza Consortium (MOSAIC) study, during the 2009–2010 H1N1 pandemic) and 139 survivors of non-selected critical illness (prior to the COVID-19 pandemic). Total 25(OH)D was measured by liquid chromatography-tandem mass spectrometry. Free 25(OH)D was measured by ELISA in COVID-19 samples.Outcome measuresReceipt of invasive mechanical ventilation (IMV) and in-hospital mortality.ResultsVitamin D insufficiency (total 25(OH)D 25–50 nmol/L) and deficiency (ConclusionsVitamin D deficiency/insufficiency was present in majority of hospitalised patients with COVID-19 or influenza A and correlated with severity and persisted in critical illness survivors at concentrations expected to disrupt bone metabolism. These findings support early supplementation trials to determine if insufficiency is causal in progression to severe disease, and investigation of longer-term bone health outcomes.

Published
2021
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3. Characterisation of in-hospital complications associated with COVID-19 using the ISARIC WHO Clinical Characterisation Protocol UK: a prospective, multicentre cohort study

Author

Thomas M Drake, Aya M Riad, Cameron J Fairfield, Conor Egan, Stephen R Knight, Riinu Pius, Hayley E Hardwick, Lisa Norman, Catherine A Shaw, Kenneth A McLean, A A Roger Thompson, Antonia Ho, Olivia V Swann, Michael Sullivan, Felipe Soares, Karl A Holden, Laura Merson, Daniel Plotkin, Louise Sigfrid, Thushan I de Silva, Michelle Girvan, Clare Jackson, Clark D Russell, Jake Dunning, Tom Solomon, Gail Carson, Piero Olliaro, Jonathan S Nguyen-Van-Tam, Lance Turtle, Annemarie B Docherty, Peter JM Openshaw, J Kenneth Baillie, Ewen M Harrison, Malcolm G Semple, Beatrice Alex, Benjamin Bach, Wendy S Barclay, Debby Bogaert, Meera Chand, Graham S Cooke, Ana da Silva Filipe, Tom Fletcher, Christopher A Green, Julian A Hiscox, Antonia YW Ho, Peter W Horby, Samreen Ijaz, Say Khoo, Paul Klenerman, Andrew Law, Wei Shen Lim, Alexander J Mentzer, Alison M Meynert, Mahdad Noursadeghi, Shona C Moore, Massimo Palmarini, William A Paxton, Georgios Pollakis, Nicholas Price, Andrew Rambaut, David L Robertson, Vanessa Sancho-Shimizu, Janet T Scott, Thushan de Silva, Shiranee Sriskandan, David Stuart, Charlotte Summers, Richard S Tedder, Emma C Thomson, AA Roger Thompson, Ryan S Thwaites, Lance CW Turtle, Rishi K Gupta, Carlo Palmieri, Maria Zambon, Marc-Emmanuel Dumas, Julian Griffin, Zoltan Takats, Kanta Chechi, Petros Andrikopoulos, Anthonia Osagie, Michael Olanipekun, Sonia Liggi, Matthew Lewis, Gonçalo dos Santos Correia, Caroline Sands, Panteleimon Takis, Lynn Maslen, Hayley Hardwick, Chloe Donohue, Fiona Griffiths, Wilna Oosthuyzen, Kenneth A Mclean, Derek Murphy, Jo Dalton, Egle Saviciute, Stephanie Roberts, Janet Harrison, Laura Marsh, Marie Connor, Sophie Halpin, Carrol Gamble, James Lee, Gary Leeming, Murray Wham, Sara Clohisey, Ross Hendry, James Scott-Brown, William Greenhalf, Victoria Shaw, Sarah E McDonald, Seán Keating, Katie A. Ahmed, Jane A Armstrong, Milton Ashworth, Innocent G Asiimwe, Siddharth Bakshi, Samantha L Barlow, Laura Booth, Benjamin Brennan, Katie Bullock, Benjamin WA Catterall, Jordan J Clark, Emily A Clarke, Sarah Cole, Louise Cooper, Helen Cox, Christopher Davis, Oslem Dincarslan, Chris Dunn, Philip Dyer, Angela Elliott, Anthony Evans, Lorna Finch, Lewis WS Fisher, Terry Foster, Isabel Garcia-Dorival, Philip Gunning, Catherine Hartley, Rebecca L Jensen, Christopher B Jones, Trevor R Jones, Shadia Khandaker, Katharine King, Robyn T. Kiy, Chrysa Koukorava, Annette Lake, Suzannah Lant, Diane Latawiec, Lara Lavelle-Langham, Daniella Lefteri, Lauren Lett, Lucia A Livoti, Maria Mancini, Sarah McDonald, Laurence McEvoy, John McLauchlan, Soeren Metelmann, Nahida S Miah, Joanna Middleton, Joyce Mitchell, Ellen G Murphy, Rebekah Penrice-Randal, Jack Pilgrim, Tessa Prince, Will Reynolds, P. Matthew Ridley, Debby Sales, Victoria E Shaw, Rebecca K Shears, Benjamin Small, Krishanthi S Subramaniam, Agnieska Szemiel, Aislynn Taggart, Jolanta Tanianis-Hughes, Jordan Thomas, Erwan Trochu, Libby van Tonder, Eve Wilcock, J. Eunice Zhang, Lisa Flaherty, Nicole Maziere, Emily Cass, Alejandra Doce Carracedo, Nicola Carlucci, Anthony Holmes, Hannah Massey, Lee Murphy, Nicola Wrobel, Sarah McCafferty, Kirstie Morrice, Alan MacLean, Kayode Adeniji, Daniel Agranoff, Ken Agwuh, Dhiraj Ail, Erin L. Aldera, Ana Alegria, Brian Angus, Abdul Ashish, Dougal Atkinson, Shahedal Bari, Gavin Barlow, Stella Barnass, Nicholas Barrett, Christopher Bassford, Sneha Basude, David Baxter, Michael Beadsworth, Jolanta Bernatoniene, John Berridge, Nicola Best, Pieter Bothma, David Chadwick, Robin Brittain-Long, Naomi Bulteel, Tom Burden, Andrew Burtenshaw, Vikki Caruth, Duncan Chambler, Nigel Chee, Jenny Child, Srikanth Chukkambotla, Tom Clark, Paul Collini, Catherine Cosgrove, Jason Cupitt, Maria-Teresa Cutino-Moguel, Paul Dark, Chris Dawson, Samir Dervisevic, Phil Donnison, Sam Douthwaite, Andrew Drummond, Ingrid DuRand, Ahilanadan Dushianthan, Tristan Dyer, Cariad Evans, Chi Eziefula, Chrisopher Fegan, Adam Finn, Duncan Fullerton, Sanjeev Garg, Atul Garg, Effrossyni Gkrania-Klotsas, Jo Godden, Arthur Goldsmith, Clive Graham, Elaine Hardy, Stuart Hartshorn, Daniel Harvey, Peter Havalda, Daniel B Hawcutt, Maria Hobrok, Luke Hodgson, Anil Hormis, Michael Jacobs, Susan Jain, Paul Jennings, Agilan Kaliappan, Vidya Kasipandian, Stephen Kegg, Michael Kelsey, Jason Kendall, Caroline Kerrison, Ian Kerslake, Oliver Koch, Gouri Koduri, George Koshy, Shondipon Laha, Steven Laird, Susan Larkin, Tamas Leiner, Patrick Lillie, James Limb, Vanessa Linnett, Jeff Little, Mark Lyttle, Michael MacMahon, Emily MacNaughton, Ravish Mankregod, Huw Masson, Elijah Matovu, Katherine McCullough, Ruth McEwen, Manjula Meda, Gary Mills, Jane Minton, Mariyam Mirfenderesky, Kavya Mohandas, Quen Mok, James Moon, Elinoor Moore, Patrick Morgan, Craig Morris, Katherine Mortimore, Samuel Moses, Mbiye Mpenge, Rohinton Mulla, Michael Murphy, Megan Nagel, Thapas Nagarajan, Mark Nelson, Lillian Norris, Matthew K. O'Shea, Igor Otahal, Marlies Ostermann, Mark Pais, Selva Panchatsharam, Danai Papakonstantinou, Hassan Paraiso, Brij Patel, Natalie Pattison, Justin Pepperell, Mark Peters, Mandeep Phull, Stefania Pintus, Jagtur Singh Pooni, Frank Post, David Price, Rachel Prout, Nikolas Rae, Henrik Reschreiter, Tim Reynolds, Neil Richardson, Mark Roberts, Devender Roberts, Alistair Rose, Guy Rousseau, Brendan Ryan, Taranprit Saluja, Aarti Shah, Prad Shanmuga, Anil Sharma, Anna Shawcross, Jeremy Sizer, Manu Shankar-Hari, Richard Smith, Catherine Snelson, Nick Spittle, Nikki Staines, Tom Stambach, Richard Stewart, Pradeep Subudhi, Tamas Szakmany, Kate Tatham, Jo Thomas, Chris Thompson, Robert Thompson, Ascanio Tridente, Darell Tupper-Carey, Mary Twagira, Nick Vallotton, Rama Vancheeswaran, Lisa Vincent-Smith, Shico Visuvanathan, Alan Vuylsteke, Sam Waddy, Rachel Wake, Andrew Walden, Ingeborg Welters, Tony Whitehouse, Paul Whittaker, Ashley Whittington, Padmasayee Papineni, Meme Wijesinghe, Martin Williams, Lawrence Wilson, Sarah Sarah, Stephen Winchester, Martin Wiselka, Adam Wolverson, Daniel G Wootton, Andrew Workman, Bryan Yates, Peter Young, investigators, ISARIC4C, Division of Computational and Systems Medicine, Imperial College London, London, SW7 2AZ, UK, Imperial College London - National Heart and Lung Institute, Centre National de la Recherche Scientifique (CNRS), Department of Pathology and Laboratory Medicine, University of California, National Institute for Health Research, and UKRI MRC COVID-19 Rapid Response Call

Subjects
MESH: United Kingdom, Male, Pediatrics, Respiratory Tract Diseases, MESH: Comorbidity, MESH: Hospitalization, Comorbidity, 030204 cardiovascular system & hematology, MESH: World Health Organization, MESH: Clinical Protocols, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: COVID-19, Medicine, Hospital Mortality, Prospective Studies, 030212 general & internal medicine, ISARIC4C investigators, Prospective cohort study, 11 Medical and Health Sciences, MESH: Aged, United Kingdom/epidemiology, Incidence (epidemiology), Clinical Protocols/standards, Age Factors, Articles, General Medicine, MESH: Hospitals, Hospitals, 3. Good health, Hospitalization, Cardiovascular Diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Cohort, COVID-19/complications, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Cohort study, medicine.medical_specialty, MEDLINE, World Health Organization, MESH: Nervous System Diseases, 03 medical and health sciences, General & Internal Medicine, Humans, MESH: SARS-CoV-2, MESH: Hospital Mortality, Survival analysis, Aged, MESH: Age Factors, MESH: Humans, SARS-CoV-2, business.industry, MESH: Cardiovascular Diseases, COVID-19, medicine.disease, MESH: Male, MESH: Prospective Studies, MESH: Respiratory Tract Diseases, Nervous System Diseases, business, Complication, MESH: Female
Abstract

BackgroundCOVID-19 is a multi-system disease and patients who survive may experience in-hospital complications. These complications are likely to have important short and long-term consequences for patients, healthcare utilisation, healthcare system preparedness, and society amidst the ongoing COVID-19 pandemic. Our aim was to characterise the extent and impact of COVID-19 complications, particularly in those who survive using the International Severe Acute Respiratory and emerging Infections Consortium (ISARIC) WHO Clinical Characterisation Protocol UK (CCP-UK).MethodsA multicentre, prospective cohort study in 302 UK healthcare facilities of adults hospitalised with COVID-19 between 17th January and 4th August 2020. Complications were defined as organ specific diagnoses occurring alone or in addition to any hallmarks of COVID-19 illness. Outcomes included death, critical care use, and ability to self-care at hospital discharge. We used multilevel logistic regression and survival models to explore associations between these outcomes and in-hospital complications, age, and pre-existing comorbidities.ResultsOf patients admitted to hospital for management of COVID-19, 49.7% (36 367/73 197) experienced at least one complication. The mean age of our cohort was 71.1 years old (SD 18.7), included more males (56.0%, 41 025/73 ) with 81.0% (59 289/73 197) of patients having at least one comorbidity. Males over 60 were most likely to experience a complication (60 y and over, 54.5% [16 579/30 416] in males and 48.2% [11 707/24 288] in females; Under 60 y, 48.8% [5179/10 609] in males, 36.6% [2814/7689] in females). Renal (24.3%, 17 752/73 197), complex respiratory 18.4% (13 486/73 197), and systemic (16.3%, 11 895/73 197) complications were most frequent. Cardiovascular (12.3%, 8973/73 197), neurological (4.3%, 3115/73 197), and gastrointestinal/liver (0.8%, 7901/73 197) complications were also reported. The presence of any complication was associated with significantly worse survival (adjusted HR 1.74, 95% CI 1.64 to 1.84) and increased admission to critical care (adjusted OR 7.25, 95% CI 6.83 to 7.69). Reduced ability to self-care at discharge was significantly greater in patients who experienced a complication (adjusted OR 2.42, 95% CI 2.31 to 2.54) and was greatest in those who experienced neurological complications (adjusted OR 4.39, 95% CI 3.95 to 4.89). ConclusionsComplications and worse functional outcomes in patients admitted to hospital with COVID-19 are high, even in young, previously healthy individuals. Acute complications are associated with reduced ability to self-care at discharge, with neurological complications being associated with the worst functional outcomes. COVID-19 complications are likely to cause significant strain on health and social care in the coming years. These data will help in the design and provision of services aimed at the post-hospitalisation care of patients with COVID-19.

Published
2021
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4. Co-infections, secondary infections, and antimicrobial use in patients hospitalised with COVID-19 during the first pandemic wave from the ISARIC WHO CCP-UK study: a multicentre, prospective cohort study

Author

Clark D Russell, Cameron J Fairfield, Thomas M Drake, Lance Turtle, R Andrew Seaton, Dan G Wootton, Louise Sigfrid, Ewen M Harrison, Annemarie B Docherty, Thushan I de Silva, Conor Egan, Riinu Pius, Hayley E Hardwick, Laura Merson, Michelle Girvan, Jake Dunning, Jonathan S Nguyen-Van-Tam, Peter J M Openshaw, J Kenneth Baillie, Malcolm G Semple, Antonia Ho, Peter JM Openshaw, Gail Carson, Beatrice Alex, Benjamin Bach, Wendy S Barclay, Debby Bogaert, Meera Chand, Graham S Cooke, Ana da Silva Filipe, Tom Fletcher, Christopher A Green, Julian A Hiscox, Antonia YW Ho, Peter W Horby, Samreen Ijaz, Say Khoo, Paul Klenerman, Andrew Law, Wei Shen Lim, Alexander J Mentzer, Alison M Meynert, Mahdad Noursadeghi, Shona C Moore, Massimo Palmarini, William A Paxton, Georgios Pollakis, Nicholas Price, Andrew Rambaut, David L Robertson, Vanessa Sancho-Shimizu, Janet T Scott, Thushan de Silva, Tom Solomon, Shiranee Sriskandan, David Stuart, Charlotte Summers, Richard S Tedder, Emma C Thomson, AA Roger Thompson, Ryan S Thwaites, Lance CW Turtle, Rishi K Gupta, Carlo Palmieri, Maria Zambon, Hayley Hardwick, Chloe Donohue, Ruth Lyons, Fiona Griffiths, Wilna Oosthuyzen, Lisa Norman, Stephen R Knight, Kenneth A Mclean, Derek Murphy, Catherine A Shaw, Jo Dalton, Egle Saviciute, Stephanie Roberts, Janet Harrison, Laura Marsh, Marie Connor, Sophie Halpin, Clare Jackson, Carrol Gamble, Gary Leeming, Murray Wham, Sara Clohisey, Ross Hendry, James Scott-Brown, William Greenhalf, Victoria Shaw, Sarah E McDonald, Seán Keating, Katie A. Ahmed, Jane A Armstrong, Milton Ashworth, Innocent G Asiimwe, Siddharth Bakshi, Samantha L Barlow, Laura Booth, Benjamin Brennan, Katie Bullock, Benjamin WA Catterall, Jordan J Clark, Emily A Clarke, Sarah Cole, Louise Cooper, Helen Cox, Christopher Davis, Oslem Dincarslan, Chris Dunn, Philip Dyer, Angela Elliott, Anthony Evans, Lorna Finch, Lewis WS Fisher, Terry Foster, Isabel Garcia-Dorival, Philip Gunning, Catherine Hartley, Rebecca L Jensen, Christopher B Jones, Trevor R Jones, Shadia Khandaker, Katharine King, Robyn T. Kiy, Chrysa Koukorava, Annette Lake, Suzannah Lant, Diane Latawiec, Lara Lavelle-Langham, Daniella Lefteri, Lauren Lett, Lucia A Livoti, Maria Mancini, Sarah McDonald, Laurence McEvoy, John McLauchlan, Soeren Metelmann, Nahida S Miah, Joanna Middleton, Joyce Mitchell, Ellen G Murphy, Rebekah Penrice-Randal, Jack Pilgrim, Tessa Prince, Will Reynolds, P. Matthew Ridley, Debby Sales, Victoria E Shaw, Rebecca K Shears, Benjamin Small, Krishanthi S Subramaniam, Agnieska Szemiel, Aislynn Taggart, Jolanta Tanianis-Hughes, Jordan Thomas, Erwan Trochu, Libby van Tonder, Eve Wilcock, J. Eunice Zhang, Lisa Flaherty, Nicole Maziere, Emily Cass, Alejandra Doce Carracedo, Nicola Carlucci, Anthony Holmes, Hannah Massey, Lee Murphy, Nicola Wrobel, Sarah McCafferty, Kirstie Morrice, Alan MacLean, Kayode Adeniji, Daniel Agranoff, Ken Agwuh, Dhiraj Ail, Erin L. Aldera, Ana Alegria, Brian Angus, Abdul Ashish, Dougal Atkinson, Shahedal Bari, Gavin Barlow, Stella Barnass, Nicholas Barrett, Christopher Bassford, Sneha Basude, David Baxter, Michael Beadsworth, Jolanta Bernatoniene, John Berridge, Nicola Best, Pieter Bothma, David Chadwick, Robin Brittain-Long, Naomi Bulteel, Tom Burden, Andrew Burtenshaw, Vikki Caruth, Duncan Chambler, Nigel Chee, Jenny Child, Srikanth Chukkambotla, Tom Clark, Paul Collini, Catherine Cosgrove, Jason Cupitt, Maria-Teresa Cutino-Moguel, Paul Dark, Chris Dawson, Samir Dervisevic, Phil Donnison, Sam Douthwaite, Ingrid DuRand, Ahilanadan Dushianthan, Tristan Dyer, Cariad Evans, Chi Eziefula, Chrisopher Fegan, Adam Finn, Duncan Fullerton, Sanjeev Garg, Atul Garg, Effrossyni Gkrania-Klotsas, Jo Godden, Arthur Goldsmith, Clive Graham, Elaine Hardy, Stuart Hartshorn, Daniel Harvey, Peter Havalda, Daniel B Hawcutt, Maria Hobrok, Luke Hodgson, Anil Hormis, Michael Jacobs, Susan Jain, Paul Jennings, Agilan Kaliappan, Vidya Kasipandian, Stephen Kegg, Michael Kelsey, Jason Kendall, Caroline Kerrison, Ian Kerslake, Oliver Koch, Gouri Koduri, George Koshy, Shondipon Laha, Steven Laird, Susan Larkin, Tamas Leiner, Patrick Lillie, James Limb, Vanessa Linnett, Jeff Little, Mark Lyttle, Michael MacMahon, Emily MacNaughton, Ravish Mankregod, Huw Masson, Elijah Matovu, Katherine McCullough, Ruth McEwen, Manjula Meda, Gary Mills, Jane Minton, Mariyam Mirfenderesky, Kavya Mohandas, Quen Mok, James Moon, Elinoor Moore, Patrick Morgan, Craig Morris, Katherine Mortimore, Samuel Moses, Mbiye Mpenge, Rohinton Mulla, Michael Murphy, Megan Nagel, Thapas Nagarajan, Mark Nelson, Matthew K. O'Shea, Igor Otahal, Marlies Ostermann, Mark Pais, Selva Panchatsharam, Danai Papakonstantino, Hassan Paraiso, Brij Patel, Natalie Pattison, Justin Pepperell, Mark Peters, Mandeep Phull, Stefania Pintus, Jagtur Singh Pooni, Frank Post, David Price, Rachel Prout, Nikolas Rae, Henrik Reschreiter, Tim Reynolds, Neil Richardson, Mark Roberts, Devender Roberts, Alistair Rose, Guy Rousseau, Brendan Ryan, Taranprit Saluja, Aarti Shah, Prad Shanmuga, Anil Sharma, Anna Shawcross, Jeremy Sizer, Manu Shankar-Hari, Richard Smith, Catherine Snelson, Nick Spittle, Nikki Staines, Tom Stambach, Richard Stewart, Pradeep Subudhi, Tamas Szakmany, Kate Tatham, Jo Thomas, Chris Thompson, Robert Thompson, Ascanio Tridente, Darell Tupper-Carey, Mary Twagira, Andrew Ustianowski, Nick Vallotton, Lisa Vincent-Smith, Shico Visuvanathan, Alan Vuylsteke, Sam Waddy, Rachel Wake, Andrew Walden, Ingeborg Welters, Tony Whitehouse, Paul Whittaker, Ashley Whittington, Padmasayee Papineni, Meme Wijesinghe, Martin Williams, Lawrence Wilson, Sarah Sarah, Stephen Winchester, Martin Wiselka, Adam Wolverson, Daniel G Wootton, Andrew Workman, Bryan Yates, Peter Young, UK Research and Innovation, and UKRI MRC COVID-19 Rapid Response Call

Subjects
Microbiology (medical), BACTERIAL, medicine.medical_specialty, Secondary infection, Psychological intervention, World Health Organization, medicine.disease_cause, Microbiology, Haemophilus influenzae, Virology, Internal medicine, Pandemic, medicine, Humans, Prospective Studies, ISARIC4C investigators, Prospective cohort study, Pandemics, Case report form, Science & Technology, Coinfection, Diagnostic Tests, Routine, business.industry, STEWARDSHIP, COVID-19, Articles, Bacterial Infections, ADULTS, Antimicrobial, United Kingdom, Anti-Bacterial Agents, Infectious Diseases, Staphylococcus aureus, business, Life Sciences & Biomedicine
Abstract

Background: Microbiological characterisation of co-infections and secondary infections in patients with COVID-19 is lacking, and antimicrobial use is high. We aimed to describe microbiologically confirmed co-infections and secondary infections, and antimicrobial use, in patients admitted to hospital with COVID-19. Methods: The International Severe Acute Respiratory and Emerging Infections Consortium (ISARIC) WHO Clinical Characterisation Protocol UK (CCP-UK) study is an ongoing, prospective cohort study recruiting inpatients from 260 hospitals in England, Scotland, and Wales, conducted by the ISARIC Coronavirus Clinical Characterisation Consortium. Patients with a confirmed or clinician-defined high likelihood of SARS-CoV-2 infection were eligible for inclusion in the ISARIC WHO CCP-UK study. For this specific study, we excluded patients with a recorded negative SARS-CoV-2 test result and those without a recorded outcome at 28 days after admission. Demographic, clinical, laboratory, therapeutic, and outcome data were collected using a prespecified case report form. Organisms considered clinically insignificant were excluded. Findings: We analysed data from 48 902 patients admitted to hospital between Feb 6 and June 8, 2020. The median patient age was 74 years (IQR 59–84) and 20 786 (42·6%) of 48 765 patients were female. Microbiological investigations were recorded for 8649 (17·7%) of 48 902 patients, with clinically significant COVID-19-related respiratory or bloodstream culture results recorded for 1107 patients. 762 (70·6%) of 1080 infections were secondary, occurring more than 2 days after hospital admission. Staphylococcus aureus and Haemophilus influenzae were the most common pathogens causing respiratory co-infections (diagnosed ≤2 days after admission), with Enterobacteriaceae and S aureus most common in secondary respiratory infections. Bloodstream infections were most frequently caused by Escherichia coli and S aureus. Among patients with available data, 13 390 (37·0%) of 36 145 had received antimicrobials in the community for this illness episode before hospital admission and 39 258 (85·2%) of 46 061 patients with inpatient antimicrobial data received one or more antimicrobials at some point during their admission (highest for patients in critical care). We identified frequent use of broad-spectrum agents and use of carbapenems rather than carbapenem-sparing alternatives. Interpretation: In patients admitted to hospital with COVID-19, microbiologically confirmed bacterial infections are rare, and more likely to be secondary infections. Gram-negative organisms and S aureus are the predominant pathogens. The frequency and nature of antimicrobial use are concerning, but tractable targets for stewardship interventions exist. Funding: National Institute for Health Research (NIHR), UK Medical Research Council, Wellcome Trust, UK Department for International Development, Bill & Melinda Gates Foundation, EU Platform for European Preparedness Against (Re-)emerging Epidemics, NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at University of Liverpool, and NIHR HPRU in Respiratory Infections at Imperial College London.

Published
2021
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5. Changes in in-hospital mortality in the first wave of COVID-19: a multicentre prospective observational cohort study using the WHO Clinical Characterisation Protocol UK

Author

Annemarie B Docherty, Rachel H Mulholland, Nazir I Lone, Christopher P Cheyne, Daniela De Angelis, Karla Diaz-Ordaz, Cara Donegan, Thomas M Drake, Jake Dunning, Sebastian Funk, Marta García-Fiñana, Michelle Girvan, Hayley E Hardwick, Janet Harrison, Antonia Ho, David M Hughes, Ruth H Keogh, Peter D Kirwan, Gary Leeming, Jonathan S Nguyen Van-Tam, Riinu Pius, Clark D Russell, Rebecca G Spencer, Brian DM Tom, Lance Turtle, Peter JM Openshaw, J Kenneth Baillie, Ewen M Harrison, Malcolm G Semple, Gail Carson, Beatrice Alex, Benjamin Bach, Wendy S Barclay, Debby Bogaert, Meera Chand, Graham S Cooke, Ana da Silva Filipe, Tom Fletcher, Christopher A Green, Julian A Hiscox, Antonia YW Ho, Peter W Horby, Samreen Ijaz, Say Khoo, Paul Klenerman, Andrew Law, Wei Shen Lim, Alexander J Mentzer, Laura Merson, Alison M Meynert, Mahdad Noursadeghi, Shona C Moore, Massimo Palmarini, William A Paxton, Georgios Pollakis, Nicholas Price, Andrew Rambaut, David L Robertson, Vanessa Sancho-Shimizu, Janet T Scott, Thushan de Silva, Louise Sigfrid, Tom Solomon, Shiranee Sriskandan, David Stuart, Charlotte Summers, Richard S Tedder, Emma C Thomson, AA Roger Thompson, Ryan S Thwaites, Lance CW Turtle, Rishi K Gupta, Carlo Palmieri, Maria Zambon, Hayley Hardwick, Chloe Donohue, Ruth Lyons, Fiona Griffiths, Wilna Oosthuyzen, Lisa Norman, Cameron J Fairfield, Stephen R Knight, Kenneth A Mclean, Derek Murphy, Catherine A Shaw, Jo Dalton, Egle Saviciute, Stephanie Roberts, Laura Marsh, Marie Connor, Sophie Halpin, Clare Jackson, Carrol Gamble, Murray Wham, Sara Clohisey, Ross Hendry, James Scott-Brown, William Greenhalf, Victoria Shaw, Sarah E McDonald, Seán Keating, Katie A Ahmed, Jane A Armstrong, Milton Ashworth, Innocent G Asiimwe, Siddharth Bakshi, Samantha L Barlow, Laura Booth, Benjamin Brennan, Katie Bullock, Benjamin WA Catterall, Jordan J Clark, Emily A Clarke, Sarah Cole, Louise Cooper, Helen Cox, Christopher Davis, Oslem Dincarslan, Chris Dunn, Philip Dyer, Angela Elliott, Anthony Evans, Lorna Finch, Lewis WS Fisher, Terry Foster, Isabel Garcia-Dorival, Philip Gunning, Catherine Hartley, Rebecca L Jensen, Christopher B Jones, Trevor R Jones, Shadia Khandaker, Katharine King, Robyn T Kiy, Chrysa Koukorava, Annette Lake, Suzannah Lant, Diane Latawiec, Lara Lavelle-Langham, Daniella Lefteri, Lauren Lett, Lucia A Livoti, Maria Mancini, Sarah McDonald, Laurence McEvoy, John McLauchlan, Soeren Metelmann, Nahida S Miah, Joanna Middleton, Joyce Mitchell, Ellen G Murphy, Rebekah Penrice-Randal, Jack Pilgrim, Tessa Prince, Will Reynolds, P. Matthew Ridley, Debby Sales, Victoria E Shaw, Rebecca K Shears, Benjamin Small, Krishanthi S Subramaniam, Agnieska Szemiel, Aislynn Taggart, Jolanta Tanianis-Hughes, Jordan Thomas, Erwan Trochu, Libby van Tonder, Eve Wilcock, J. Eunice Zhang, Lisa Flaherty, Nicole Maziere, Emily Cass, Alejandra Doce Carracedo, Nicola Carlucci, Anthony Holmes, Hannah Massey, Lee Murphy, Nicola Wrobel, Sarah McCafferty, Kirstie Morrice, Alan MacLean, Kayode Adeniji, Daniel Agranoff, Ken Agwuh, Dhiraj Ail, Erin L Aldera, Ana Alegria, Brian Angus, Abdul Ashish, Dougal Atkinson, Shahedal Bari, Gavin Barlow, Stella Barnass, Nicholas Barrett, Christopher Bassford, Sneha Basude, David Baxter, Michael Beadsworth, Jolanta Bernatoniene, John Berridge, Nicola Best, Pieter Bothma, David Chadwick, Robin Brittain-Long, Naomi Bulteel, Tom Burden, Andrew Burtenshaw, Vikki Caruth, Duncan Chambler, Nigel Chee, Jenny Child, Srikanth Chukkambotla, Tom Clark, Paul Collini, Catherine Cosgrove, Jason Cupitt, Maria-Teresa Cutino-Moguel, Paul Dark, Chris Dawson, Samir Dervisevic, Phil Donnison, Sam Douthwaite, Ingrid DuRand, Ahilanadan Dushianthan, Tristan Dyer, Cariad Evans, Chi Eziefula, Chrisopher Fegan, Adam Finn, Duncan Fullerton, Sanjeev Garg, Atul Garg, Effrossyni Gkrania-Klotsas, Jo Godden, Arthur Goldsmith, Clive Graham, Elaine Hardy, Stuart Hartshorn, Daniel Harvey, Peter Havalda, Daniel B Hawcutt, Maria Hobrok, Luke Hodgson, Anil Hormis, Michael Jacobs, Susan Jain, Paul Jennings, Agilan Kaliappan, Vidya Kasipandian, Stephen Kegg, Michael Kelsey, Jason Kendall, Caroline Kerrison, Ian Kerslake, Oliver Koch, Gouri Koduri, George Koshy, Shondipon Laha, Steven Laird, Susan Larkin, Tamas Leiner, Patrick Lillie, James Limb, Vanessa Linnett, Jeff Little, Mark Lyttle, Michael MacMahon, Emily MacNaughton, Ravish Mankregod, Huw Masson, Elijah Matovu, Katherine McCullough, Ruth McEwen, Manjula Meda, Gary Mills, Jane Minton, Mariyam Mirfenderesky, Kavya Mohandas, Quen Mok, James Moon, Elinoor Moore, Patrick Morgan, Craig Morris, Katherine Mortimore, Samuel Moses, Mbiye Mpenge, Rohinton Mulla, Michael Murphy, Megan Nagel, Thapas Nagarajan, Mark Nelson, Matthew K O'Shea, Igor Otahal, Marlies Ostermann, Mark Pais, Selva Panchatsharam, Danai Papakonstantinou, Hassan Paraiso, Brij Patel, Natalie Pattison, Justin Pepperell, Mark Peters, Mandeep Phull, Stefania Pintus, Jagtur Singh Pooni, Frank Post, David Price, Rachel Prout, Nikolas Rae, Henrik Reschreiter, Tim Reynolds, Neil Richardson, Mark Roberts, Devender Roberts, Alistair Rose, Guy Rousseau, Brendan Ryan, Taranprit Saluja, Aarti Shah, Prad Shanmuga, Anil Sharma, Anna Shawcross, Jeremy Sizer, Manu Shankar-Hari, Richard Smith, Catherine Snelson, Nick Spittle, Nikki Staines, Tom Stambach, Richard Stewart, Pradeep Subudhi, Tamas Szakmany, Kate Tatham, Jo Thomas, Chris Thompson, Robert Thompson, Ascanio Tridente, Darell Tupper-Carey, Mary Twagira, Andrew Ustianowski, Nick Vallotton, Lisa Vincent-Smith, Shico Visuvanathan, Alan Vuylsteke, Sam Waddy, Rachel Wake, Andrew Walden, Ingeborg Welters, Tony Whitehouse, Paul Whittaker, Ashley Whittington, Padmasayee Papineni, Meme Wijesinghe, Martin Williams, Lawrence Wilson, Sarah Sarah, Stephen Winchester, Martin Wiselka, Adam Wolverson, Daniel G Wooton, Andrew Workman, Bryan Yates, Peter Young, Kirwan, Peter D [0000-0001-6904-0500], Apollo - University of Cambridge Repository, Imperial College Healthcare NHS Trust- BRC Funding, GlaxoSmithKline Biologicals, National Institute for Health Research, UKRI MRC COVID-19 Rapid Response Call, and UK Research and Innovation

Subjects
Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, World Health Organization, 1117 Public Health and Health Services, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Clinical Protocols, Internal medicine, Severity of illness, Pandemic, Risk of mortality, medicine, Humans, 030212 general & internal medicine, Hospital Mortality, Prospective Studies, Prospective cohort study, ISARIC4C Investigators, Aged, COVID-19/epidemiology, Aged, 80 and over, business.industry, United Kingdom/epidemiology, Mortality rate, Confounding, COVID-19, 1103 Clinical Sciences, Odds ratio, Articles, Middle Aged, United Kingdom, 030228 respiratory system, Female, business, Cohort study, 1199 Other Medical and Health Sciences
Abstract

Background\ud \ud Mortality rates in hospitalised patients with COVID-19 in the UK appeared to decline during the first wave of the pandemic. We aimed to quantify potential drivers of this change and identify groups of patients who remain at high risk of dying in hospital.\ud \ud \ud Methods\ud \ud In this multicentre prospective observational cohort study, the International Severe Acute Respiratory and Emerging Infections Consortium WHO Clinical Characterisation Protocol UK recruited a prospective cohort of patients with COVID-19 admitted to 247 acute hospitals in England, Scotland, and Wales during the first wave of the pandemic (between March 9 and Aug 2, 2020). We included all patients aged 18 years and older with clinical signs and symptoms of COVID-19 or confirmed COVID-19 (by RT-PCR test) from assumed community-acquired infection. We did a three-way decomposition mediation analysis using natural effects models to explore associations between week of admission and in-hospital mortality, adjusting for confounders (demographics, comorbidities, and severity of illness) and quantifying potential mediators (level of respiratory support and steroid treatment). The primary outcome was weekly in-hospital mortality at 28 days, defined as the proportion of patients who had died within 28 days of admission of all patients admitted in the observed week, and it was assessed in all patients with an outcome. This study is registered with the ISRCTN Registry, ISRCTN66726260.\ud \ud \ud Findings\ud \ud Between March 9, and Aug 2, 2020, we recruited 80 713 patients, of whom 63 972 were eligible and included in the study. Unadjusted weekly in-hospital mortality declined from 32·3% (95% CI 31·8–32·7) in March 9 to April 26, 2020, to 16·4% (15·0–17·8) in June 15 to Aug 2, 2020. Reductions in mortality were observed in all age groups, in all ethnic groups, for both sexes, and in patients with and without comorbidities. After adjustment, there was a 32% reduction in the risk of mortality per 7-week period (odds ratio [OR] 0·68 [95% CI 0·65–0·71]). The higher proportions of patients with severe disease and comorbidities earlier in the first wave (March and April) than in June and July accounted for 10·2% of this reduction. The use of respiratory support changed during the first wave, with gradually increased use of non-invasive ventilation over the first wave. Changes in respiratory support and use of steroids accounted for 22·2%, OR 0·95 (0·94–0·95) of the reduction in in-hospital mortality.\ud \ud \ud Interpretation\ud \ud The reduction in in-hospital mortality in patients with COVID-19 during the first wave in the UK was partly accounted for by changes in the case-mix and illness severity. A significant reduction in in-hospital mortality was associated with differences in respiratory support and critical care use, which could partly reflect accrual of clinical knowledge. The remaining improvement in in-hospital mortality is not explained by these factors, and could be associated with changes in community behaviour, inoculum dose, and hospital capacity strain.\ud \ud \ud Funding\ud \ud National Institute for Health Research and the Medical Research Council.

Published
2021
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6. Non-steroidal anti-inflammatory drug use and outcomes of COVID-19 in the ISARIC Clinical Characterisation Protocol UK cohort: a matched, prospective cohort study

Author

Thomas M Drake, Cameron J Fairfield, Riinu Pius, Stephen R Knight, Lisa Norman, Michelle Girvan, Hayley E Hardwick, Annemarie B Docherty, Ryan S Thwaites, Peter J M Openshaw, J Kenneth Baillie, Ewen M Harrison, Malcolm G Semple, Peter JM Openshaw, Gail Carson, Beatrice Alex, Benjamin Bach, Wendy S Barclay, Debby Bogaert, Meera Chand, Graham S Cooke, Ana da Silva Filipe, Thushan de Silva, Jake Dunning, Tom Fletcher, Christopher A Green, Julian A Hiscox, Antonia YW Ho, Peter W Horby, Samreen Ijaz, Say Khoo, Paul Klenerman, Andrew Law, Wei Shen Lim, Alexander J Mentzer, Laura Merson, Alison M Meynert, Shona C Moore, Mahdad Noursadeghi, Massimo Palmarini, William A Paxton, Georgios Pollakis, Nicholas Price, Andrew Rambaut, David L Robertson, Clark D Russell, Vanessa Sancho-Shimizu, Janet T Scott, Louise Sigfrid, Tom Solomon, Shiranee Sriskandan, David Stuart, Charlotte Summers, Richard S Tedder, AA Roger Thompson, Emma C Thomson, Lance CW Turtle, Maria Zambon, Chloe Donohue, Fiona Griffiths, Hayley Hardwick, Ruth Lyons, Wilna Oosthuyzen, Kenneth A Mclean, Derek Murphy, Catherine A Shaw, Marie Connor, Jo Dalton, Carrol Gamble, Sophie Halpin, Janet Harrison, Clare Jackson, Laura Marsh, Stephanie Roberts, Egle Saviciute, Sara Clohisey, Ross Hendry, Gary Leeming, James Scott-Brown, Murray Wham, William Greenhalf, Sara McDonald, Victoria Shaw, Seán Keating, Katie A. Ahmed, Jane A Armstrong, Milton Ashworth, Innocent G Asiimwe, Siddharth Bakshi, Samantha L Barlow, Laura Booth, Benjamin Brennan, Katie Bullock, Nicola Carlucci, Emily Cass, Benjamin WA Catterall, Jordan J Clark, Emily A Clarke, Sarah Cole, Louise Cooper, Helen Cox, Christopher Davis, Oslem Dincarslan, Alejandra Doce Carracedo, Chris Dunn, Philip Dyer, Angela Elliott, Anthony Evans, Lorna Finch, Lewis WS Fisher, Lisa Flaherty, Terry Foster, Isabel Garcia-Dorival, Philip Gunning, Catherine Hartley, Anthony Holmes, Rebecca L Jensen, Christopher B Jones, Trevor R Jones, Shadia Khandaker, Katharine King, Robyn T. Kiy, Chrysa Koukorava, Annette Lake, Suzannah Lant, Diane Latawiec, Lara Lavelle-Langham, Daniella Lefteri, Lauren Lett, Lucia A Livoti, Maria Mancini, Hannah Massey, Nicole Maziere, Sarah McDonald, Laurence McEvoy, John McLauchlan, Soeren Metelmann, Nahida S Miah, Joanna Middleton, Joyce Mitchell, Ellen G Murphy, Rebekah Penrice-Randal, Jack Pilgrim, Tessa Prince, Will Reynolds, P. Matthew Ridley, Debby Sales, Victoria E Shaw, Rebecca K Shears, Benjamin Small, Krishanthi S Subramaniam, Agnieska Szemiel, Aislynn Taggart, Jolanta Tanianis-Hughes, Jordan Thomas, Erwan Trochu, Libby van Tonder, Eve Wilcock, J. Eunice Zhang, Alan MacLean, Sarah McCafferty, Kirstie Morrice, Lee Murphy, Nicola Wrobel, Kayode Adeniji, Daniel Agranoff, Ken Agwuh, Dhiraj Ail, Erin L. Aldera, Ana Alegria, Brian Angus, Abdul Ashish, Dougal Atkinson, Shahedal Bari, Gavin Barlow, Stella Barnass, Nicholas Barrett, Christopher Bassford, Sneha Basude, David Baxter, Michael Beadsworth, Jolanta Bernatoniene, John Berridge, Nicola Best, Pieter Bothma, Robin Brittain-Long, Naomi Bulteel, Tom Burden, Andrew Burtenshaw, Vikki Caruth, David Chadwick, Duncan Chambler, Nigel Chee, Jenny Child, Srikanth Chukkambotla, Tom Clark, Paul Collini, Catherine Cosgrove, Jason Cupitt, Maria-Teresa Cutino-Moguel, Paul Dark, Chris Dawson, Samir Dervisevic, Phil Donnison, Sam Douthwaite, Ingrid DuRand, Ahilanadan Dushianthan, Tristan Dyer, Cariad Evans, Chi Eziefula, Chrisopher Fegan, Adam Finn, Duncan Fullerton, Sanjeev Garg, Atul Garg, Effrossyni Gkrania-Klotsas, Jo Godden, Arthur Goldsmith, Clive Graham, Elaine Hardy, Stuart Hartshorn, Daniel Harvey, Peter Havalda, Daniel B Hawcutt, Maria Hobrok, Luke Hodgson, Anil Hormis, Michael Jacobs, Susan Jain, Paul Jennings, Agilan Kaliappan, Vidya Kasipandian, Stephen Kegg, Michael Kelsey, Jason Kendall, Caroline Kerrison, Ian Kerslake, Oliver Koch, Gouri Koduri, George Koshy, Shondipon Laha, Steven Laird, Susan Larkin, Tamas Leiner, Patrick Lillie, James Limb, Vanessa Linnett, Jeff Little, Mark Lyttle, Michael MacMahon, Emily MacNaughton, Ravish Mankregod, Huw Masson, Elijah Matovu, Katherine McCullough, Ruth McEwen, Manjula Meda, Gary Mills, Jane Minton, Mariyam Mirfenderesky, Kavya Mohandas, Quen Mok, James Moon, Elinoor Moore, Patrick Morgan, Craig Morris, Katherine Mortimore, Samuel Moses, Mbiye Mpenge, Rohinton Mulla, Michael Murphy, Thapas Nagarajan, Megan Nagel, Mark Nelson, Matthew K. O'Shea, Marlies Ostermann, Igor Otahal, Mark Pais, Selva Panchatsharam, Danai Papakonstantinou, Padmasayee Papineni, Hassan Paraiso, Brij Patel, Natalie Pattison, Justin Pepperell, Mark Peters, Mandeep Phull, Stefania Pintus, Frank Post, David Price, Rachel Prout, Nikolas Rae, Henrik Reschreiter, Tim Reynolds, Neil Richardson, Mark Roberts, Devender Roberts, Alistair Rose, Guy Rousseau, Brendan Ryan, Taranprit Saluja, Sarah Sarah, Aarti Shah, Manu Shankar-Hari, Prad Shanmuga, Anil Sharma, Anna Shawcross, Jagtur Singh Pooni, Jeremy Sizer, Richard Smith, Catherine Snelson, Nick Spittle, Nikki Staines, Tom Stambach, Richard Stewart, Pradeep Subudhi, Tamas Szakmany, Kate Tatham, Jo Thomas, Chris Thompson, Robert Thompson, Ascanio Tridente, Darell Tupper-Carey, Mary Twagira, Andrew Ustianowski, Nick Vallotton, Lisa Vincent-Smith, Shico Visuvanathan, Alan Vuylsteke, Sam Waddy, Rachel Wake, Andrew Walden, Ingeborg Welters, Tony Whitehouse, Paul Whittaker, Ashley Whittington, Meme Wijesinghe, Martin Williams, Lawrence Wilson, Stephen Winchester, Martin Wiselka, Adam Wolverson, Daniel G Wooton, Andrew Workman, Bryan Yates, Peter Young, investigators, ISARIC4C, Horby, PW, UKRI MRC COVID-19 Rapid Response Call, National Institute for Health Research, Medical Research Council (MRC), and UK Research and Innovation

Subjects
medicine.medical_specialty, business.industry, Immunology, Acute kidney injury, Articles, medicine.disease, Logistic regression, Rheumatology, Internal medicine, Cohort, Propensity score matching, Epidemiology, medicine, Immunology and Allergy, Medical prescription, business, Prospective cohort study, ISARIC4C Investigators, Cohort study
Abstract

Background Early in the pandemic it was suggested that pre-existing use of non-steroidal anti-inflammatory drugs (NSAIDs) could lead to increased disease severity in patients with COVID-19. NSAIDs are an important analgesic, particularly in those with rheumatological disease, and are widely available to the general public without prescription. Evidence from community studies, administrative data, and small studies of hospitalised patients suggest NSAIDs are not associated with poorer COVID-19 outcomes. We aimed to characterise the safety of NSAIDs and identify whether pre-existing NSAID use was associated with increased severity of COVID-19 disease. Methods This prospective, multicentre cohort study included patients of any age admitted to hospital with a confirmed or highly suspected SARS-CoV-2 infection leading to COVID-19 between Jan 17 and Aug 10, 2020. The primary outcome was in-hospital mortality, and secondary outcomes were disease severity at presentation, admission to critical care, receipt of invasive ventilation, receipt of non-invasive ventilation, use of supplementary oxygen, and acute kidney injury. NSAID use was required to be within the 2 weeks before hospital admission. We used logistic regression to estimate the effects of NSAIDs and adjust for confounding variables. We used propensity score matching to further estimate effects of NSAIDS while accounting for covariate differences in populations. Results Between Jan 17 and Aug 10, 2020, we enrolled 78 674 patients across 255 health-care facilities in England, Scotland, and Wales. 72 179 patients had death outcomes available for matching; 40 406 (56·2%) of 71 915 were men, 31 509 (43·8%) were women. In this cohort, 4211 (5·8%) patients were recorded as taking systemic NSAIDs before admission to hospital. Following propensity score matching, balanced groups of NSAIDs users and NSAIDs non-users were obtained (4205 patients in each group). At hospital admission, we observed no significant differences in severity between exposure groups. After adjusting for explanatory variables, NSAID use was not associated with worse in-hospital mortality (matched OR 0·95, 95% CI 0·84–1·07; p=0·35), critical care admission (1·01, 0·87–1·17; p=0·89), requirement for invasive ventilation (0·96, 0·80–1·17; p=0·69), requirement for non-invasive ventilation (1·12, 0·96–1·32; p=0·14), requirement for oxygen (1·00, 0·89–1·12; p=0·97), or occurrence of acute kidney injury (1·08, 0·92–1·26; p=0·33). Interpretation NSAID use is not associated with higher mortality or increased severity of COVID-19. Policy makers should consider reviewing issued advice around NSAID prescribing and COVID-19 severity. Funding National Institute for Health Research and Medical Research Council.

Published
2021
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7. SARS-CoV-2 seroconversion in health care workers

Author

Adrian M Shields, Sian E Faustini, Marisol Perez-Toledo, Sian Jossi, Erin L Aldera, Joel D Allen, Saly Al-Taei, Claire Backhouse, Andrew Bosworth, Lyndsey Dunbar, Daniel Ebanks, Beena Emmanuel, Joanne Grey, I Michael Kidd, Golaeh McGinnell, Dee McLoughlin, Gabriella Morley, Joanne O'Neill, Danai Papakonstantinou, Oliver Pickles, Charlotte Poxon, Megan Richter, Eloise Walker, Kasun Wanigasooriya, Yasunori Watanabe, Celina Whalley, Agnieszka E Zielinska, Max Crispin, David C Wraith, Andrew D Beggs, Adam F Cunningham, Mark T Drayson, and Alex G Richter

Subjects
0303 health sciences, medicine.medical_specialty, business.industry, Prevalence, Asymptomatic, 3. Good health, Serology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Intensive care, Cohort, medicine, Infection control, Seroprevalence, 030212 general & internal medicine, Seroconversion, medicine.symptom, business, 030304 developmental biology
Abstract

Background The correlates of protection against SARS-CoV-2 and their longevity remain unclear. Studies in severely ill individuals have identified robust cellular and humoral immune responses against the virus. Asymptomatic infection with SARS-CoV-2 has also been described, but it is unknown whether this is sufficient to produce antibody responses. Methods We performed a cross-sectional study recruiting 554 health care workers from University Hospitals Birmingham NHS Foundation Trust who were at work and asymptomatic. Participants were tested for current infection with SARS-CoV-2 by nasopharyngeal swab for real-time polymerase chain reaction and for seroconversion by the measurement of anti-SARS-CoV-2 spike glycoprotein antibodies by enzyme linked immunosorbent assay. Results were interpreted in the context of previous, self-reported symptoms of illness consistent with COVID-19. Results The point prevalence of infection with SARS-CoV-2, determined by the detection of SARS-CoV-2 RNA on nasopharnygeal swab was 2.39% (n=13/544). Serum was available on 516 participants. The overall rate of seroconversion in the cohort was 24.4% (n=126/516). Individuals who had previously experienced a symptomatic illness consistent with COVID-19 had significantly greater seroconversion rates than those who had remained asymptomatic (37.5% vs 17.1%, χ2 =21.1034, p Conclusions In a large cross-sectional seroprevalence study of health-care workers, we demonstrate that asymptomatic seroconversion occurs, however prior symptomatic illness is associated with quantitatively higher antibody responses. The identification that the potential for seroconversion in health-care workers can associate differentially with certain hospital departments may inform future infection control and occupational health practices. Research in context Evidence before the study To date, no study has examined the cross-sectional seroprevalence of anti-SARS-CoV-2 antibodies in health care workers during the COVID-19 pandemic. Existing evidence suggests that the levels of SARS-CoV-2 antibodies developing following infection may vary with disease severity in keeping with previous coronavirus pandemics. Added value of this study We demonstrate that seroconversion can occur in health care workers who have suffered no previous symptoms of SARS-Cov-2 infection. However, prior symptomatic infection tends to drive quantitatively superior antibody responses against the virus. We observed differential seroconversion rates in individuals working within different hospital departments. Using intensive care as a reference, the relative risk for seroconversion was greatest for those working in housekeeping, acute and general internal medicine. Implications of all the available evidence Insight into the current seroprevalence of SARS-CoV-2 antibodies within a high-risk cohort of health-care workers is of direct relevance as a reference point for future community serological surveys. We provide further evidence of asymptomatic infection and seroconversion, strengthening the argument for regular, routine screening of health-care workers. Finally, we provide evidence that individuals working in particular roles within the NHS are at greater risk of seroconversion with significant implications for their occupational health.

Published
2020
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8. Rapid implementation and validation of a cold-chain free SARS-CoV-2 diagnostic testing workflow to support surge capacity

Author

Andrew Ellis, Alex G. Richter, Oliver J Pickles, Eloise M Walker, Gabriella L. Morley, Craig Webster, Kasun Wanigasooriya, Andrew D Beggs, Celina Whalley, Andrew Bosworth, Dee E McLoughlin, Danai Papakonstantinou, Charlie Poxon, Agnieszka E. Zielinska, Tim Plant, I. Michael Kidd, and Erin L. Aldera

Subjects
0301 basic medicine, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Pneumonia, Viral, 030106 microbiology, Article, VIASURE qRT-PCR, Workflow, Betacoronavirus, 03 medical and health sciences, COVID-19 Testing, 0302 clinical medicine, West Midlands, Virology, Health care, Pandemic, Humans, Medicine, 030212 general & internal medicine, Cold chain, Saliva, Pandemics, Surge Capacity, Clinical Laboratory Techniques, business.industry, SARS-CoV-2, Diagnostic test, COVID-19, Birmingham, medicine.disease, United Kingdom, Coronavirus, Infectious Diseases, RNA, Viral, Rapid Response, Medical emergency, Coronavirus Infections, business
Abstract

Background In January 2020 reports of unidentified severe respiratory illness were described in Wuhan, China. A rapid expansion in cases affecting most countries around the globe led to major changes in the way people live their daily lives. In the United Kingdom, the Department of Health and Social Care directed healthcare providers to establish additional resources to manage the anticipated surge in cases that could overwhelm the health services. A priority area was testing for SARS-CoV-2 RNA and its detection by qualitative RT-PCR. Design A laboratory workflow twinning research environment with clinical laboratory capabilities was implemented and validated in the University of Birmingham within 4 days of the project initiation. The diagnostic capability was centred on an IVD CE-marked RT-PCR kit and designed to provide surge capacity to the nearby Queen Elizabeth Hospital. The service was initially tasked with testing healthcare workers (HCW) using throat swabs, and subsequently the process investigated the utility of using saliva as an alternative sample type. Results Between the 8th April 2020 and the 30th April 2020, the laboratory tested a total of 1282 HCW for SARS-CoV-2 RNA in throat swabs. RNA was detected in 54 % of those who reported symptoms compatible with COVID-19, but in only 4% who were asymptomatic. Conclusion This capability was established rapidly and utilised a cold-chain free methodology, applicable to a wide range of settings, and which can provide surge capacity and support to clinical laboratories facing increasing pressure during periods of national crisis.

Published
2020

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