Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 26
Filter
1.
Anal Chem ; 2022.
Article in English | PubMed | ID: covidwho-2016500

ABSTRACT

Current design of serological tests utilizes conservative immunoassay approaches and is focused on fast and convenient assay development, throughput, straightforward measurements, and affordability. Limitations of common serological assays include semiquantitative measurements, cross-reactivity, lack of reference standards, and no differentiation between human immunoglobulin subclasses. In this study, we suggested that a combination of immunoaffinity enrichments with targeted proteomics would enable rational design and development of serological assays of infectious diseases, such as COVID-19. Immunoprecipitation-targeted proteomic assays allowed for sensitive and specific measurements of NCAP_SARS2 protein with a limit of detection of 313 pg/mL in serum and enabled differential quantification of anti-SARS-CoV-2 antibody isotypes (IgG, IgA, IgM, IgD, and IgE) and individual subclasses (IgG1-4 and IgA1-2) in plasma and saliva. Simultaneous evaluation of the numerous antigen-antibody subclass combinations revealed a receptor-binding domain (RBD)-IgG1 as a combination with the highest diagnostic performance. Further validation revealed that anti-RBD IgG1, IgG3, IgM, and IgA1 levels were significantly elevated in convalescent plasma, while IgG2, IgG4, and IgA2 were not informative. Anti-RBD IgG1 levels in convalescent (2138 ng/mL) vs negative (95 ng/mL) plasma revealed 385 ng/mL as a cutoff to detect COVID-19 convalescent plasma. Immunoprecipitation-targeted proteomic assays will facilitate improvement and standardization of the existing serological tests, enable rational design of novel tests, and offer tools for the comprehensive investigation of immunoglobulin subclass cooperation in immune response.

2.
Education and Training ; : 19, 2022.
Article in English | Web of Science | ID: covidwho-1985262

ABSTRACT

Purpose This study aims to investigate graduate employer perceptions of determining factors in recruitment decisions and their preferred use of recruitment channels. This study drew on the employability capitals model to interpret findings and identify ways to better prepare higher education students for recruitment and selection. This is particularly important in declining graduate labour markets, further weakened by COVID-19. Design/methodology/approach This study gathered data from surveying 183 Australian employers from different organisational settings. Responses were analysed using descriptive and multivariate techniques, the latter exploring variations by role type, sector and organisation size. Findings Findings reaffirmed the criticality of students having the right disposition and demonstrating professional capabilities during recruitment, highlighting the value of building cultural and human capital during university years. Recruitment channels that require students to mobilise their identity and social capital were prioritised, particularly among private sector organisations. Work-based internships/placements were considered important for identifying graduate talent and developing strong industry-educator partnerships, needed for building networks between students and employers. Originality/value This study provides valuable insights into determinants of graduate recruitment decision-making from the employer perspective. These highlight to students the important role of capitals, and how they can be developed to optimise recruitment success. This study presents practical strategies for universities to build their students' human, social, cultural and identity capital. Findings on the prioritisation of recruitment channels among graduate employers from different sectors will enable students and universities to better prepare for future recruitment. It emphasises that student engagement with employability-related activities is a critical resource for an effective transition to the workplace.

3.
American Journal of Respiratory and Critical Care Medicine ; 205(1), 2022.
Article in English | EMBASE | ID: covidwho-1927846

ABSTRACT

Introduction:Dupilumab is an anti-IL4R monoclonal antibody (mAb) with proven efficacy in severe eosinophilic asthma (SEA). We have previously identified that a suboptimal response to the eosinophil targeting anti-IL5/5R mAbs mepolizumab and benralizumab is seen in 27% and 14% of patients with SEA respectively1,2. The mechanism of this is not well-understood. It is unknown whether such patients respond in a clinically meaningful way following a switch to dupilumab. Methods:We performed a retrospective analysis of the clinical effectiveness of dupilumab (minimum 6 months treatment) in patients with SEA at our tertiary severe asthma centre who had failed to adequately respond to at least one of the anti-IL-5/5R mAbs. Change in the annualised exacerbation rate (AER), maintenance oral corticosteroids (mOCS) requirements, ACQ-6 and mAQLQ was recorded. Results:Thirty-two patients (mean age 41.2, 68.8% female, 71.9% atopic) were included in the analysis. 13/32(40.6%) had co-morbid nasal polyposis and 5/32(15.6%) had eczema. The baseline FeNO was 60ppb(IQR 39.6-87.5) and peak eosinophil count prior to any mAb was 0.6(IQR 0.5-0.9). 23/32(71.8%) were switched from benralizumab, of whom, 12/23(52.2%) had also failed to respond to at least one other anti-IL5 mAb previously. At six months, the daily median mOCS dose in those requiring mOCS at baseline (n=18) fell from 10mg(IQR 5-25mg) to 3mg(IQR 0-5mg), p≤0.001. 4/18(22%) were able to stop mOCS completely. Mean(SD) AER improved from 2.34(1.89) to 0.44(0.95), p≤0.001. There were also significant improvements in ACQ6 and mAQLQ that exceeded twice the MCID for both measures: mean (SD) ACQ6 improved from 3.04(1.26) to 1.82(1.28), p≤0.001;mAQLQ improved from 3.90(SD 1.40) to 5.36(SD 1.05), p≤0.001. Due to the COVID-19 pandemic, FEV1 data was only available for 8 patients. However, there was nonetheless a significant rise in FEV1 (%predicted) from 55.6% (9.78) to 68.5%(16.9), p=0.011. One patient discontinued dupilumab during the follow-up period. Conclusion: A minority of individuals with SEA have a suboptimal response to eosinophil targeted therapy with an anti-IL5/5R mAb. In these patients, we report significant clinical improvements following initiation with dupilumab suggesting an important role for the IL-4/-13 pathway in these patients. Further research is required to understand whether these patients represent a distinct subphenotype of T2-high asthma.

4.
American Journal of Respiratory and Critical Care Medicine ; 205(1), 2022.
Article in English | EMBASE | ID: covidwho-1927815

ABSTRACT

Introduction: Interstitial lung disease (ILD) comprises a heterogeneous group of diseases affecting the lung interstitium often associated with significant morbidity and mortality. The Australasian Interstitial Lung Disease Registry (AILDR) launched in 2016 with the concurrent aims to: a) provide a valuable resource for high quality ILD research to further understanding of ILD and b) improve care for ILD patients across Australia and NZ. Consisting initially of four pilot sites, over time the registry has expanded to 21 sites across Australasia. Methods: Consecutive ILD patients attending any of the registered ILD centres across Australia and NZ are eligible to enrol in the AILDR following provision of informed consent. Comprehensive data including demographics, ILD diagnosis, objective functional markers (baseline and subsequent tests) and treatment parameters are collected and stored on a secure online platform. We report data from the AILDR since initiation in May 2016 to 30th September 2021 inclusive. Results: In total 2140 participants were enrolled from 16 sites at a mean rate of 43/month (mean age 65.8±13.3years;1185 (55.4%) male;982 (45.9%) ever-smokers;mean BMI 29.4±5.9kg/m2). Baseline functional parameters demonstrated mean FVC 85.6±21.7% predicted, mean DLCO 60.5±19.4%predicted, and mean six-minute walk test (6MWT) distance 434.3±126.5metres. ILD diagnoses included: idiopathic pulmonary fibrosis (IPF) n=545 (30.3%), connective tissue disease associated ILD (CTD-ILD) n=326 (18.1%), chronic hypersensitivity pneumonitis (CHP) n=155 (8.6%), sarcoidosis n=120 (6.7%) and unclassifiable ILD n=190 (10.6%). Patients with IPF were more likely to be male (n=403, 73.9%, p<0.001) and older (72.6±8.3years, p<0.001) compared to all other ILD subtypes. A female predominance was observed for CHP (n=92, 59%, p=0.001) and CTD-ILD (n=206, 63%, p<0.001). Baseline functional parameters were lowest for those with CHP (FVC 76.8±22.4% predicted, DLCO 54.1±16.9% predicted), significantly lower comparable to the IPF group (FVC 84.8±19.6%predicted, DLCO 58.7±17.8%predicted, p<0.001). The highest baseline functional parameters were observed in those with sarcoidosis. Conclusion: We demonstrate the feasibility of a bi-national ILD registry evidenced by steady recruitment despite the COVID-19 pandemic. In this study, lower functional baseline parameters were detected in the CHP group suggesting priority research should be afforded to this group. Through a routine approach across Australasia, the AILDR aims to improve standardisation of diagnosis and management of ILD patients.

5.
American Journal of Respiratory and Critical Care Medicine ; 205:2, 2022.
Article in English | English Web of Science | ID: covidwho-1880776
7.
PubMed; 2022.
Preprint in English | PubMed | ID: ppcovidwho-338350

ABSTRACT

Better understanding of the mechanisms of COVID-19 severity is desperately needed in current times. Although hyper-inflammation drives severe COVID-19, precise mechanisms triggering this cascade and what role glycosylation might play therein is unknown. Here we report the first high-throughput glycomic analysis of COVID-19 plasma samples and autopsy tissues. We find alpha2,6-sialylation is upregulated in plasma of patients with severe COVID-19 and in the lung. This glycan motif is enriched on members of the complement cascade, which show higher levels of sialylation in severe COVID-19. In the lung tissue, we observe increased complement deposition, associated with elevated alpha2,6-sialylation levels, corresponding to elevated markers of poor prognosis (IL-6) and fibrotic response. We also observe upregulation of the alpha2,6-sialylation enzyme ST6GAL1 in patients who succumbed to COVID-19. Our work identifies a heretofore undescribed relationship between sialylation and complement in severe COVID-19, potentially informing future therapeutic development.

11.
European Respiratory Journal ; 58:3, 2021.
Article in English | Web of Science | ID: covidwho-1700916
12.
McCrone, J. T.; Hill, V.; Bajaj, S.; Pena, R. E.; Lambert, B. C.; Inward, R.; Bhatt, S.; Volz, E.; Ruis, C.; Dellicour, S.; Baele, G.; Zarebski, A. E.; Sadilek, A.; Wu, N.; Schneider, A.; Ji, X.; Raghwani, J.; Jackson, B.; Colquhoun, R.; O'Toole, Á, Peacock, T. P.; Twohig, K.; Thelwall, S.; Dabrera, G.; Myers, R.; Faria, N. R.; Huber, C.; Bogoch, I. I.; Khan, K.; du Plessis, L.; Barrett, J. C.; Aanensen, D. M.; Barclay, W. S.; Chand, M.; Connor, T.; Loman, N. J.; Suchard, M. A.; Pybus, O. G.; Rambaut, A.; Kraemer, M. U. G.; Robson, S. C.; Connor, T. R.; Loman, N. J.; Golubchik, T.; Martinez Nunez, R. T.; Bonsall, D.; Rambaut, A.; Snell, L. B.; Livett, R.; Ludden, C.; Corden, S.; Nastouli, E.; Nebbia, G.; Johnston, I.; Lythgoe, K.; Estee Torok, M.; Goodfellow, I. G.; Prieto, J. A.; Saeed, K.; Jackson, D. K.; Houlihan, C.; Frampton, D.; Hamilton, W. L.; Witney, A. A.; Bucca, G.; Pope, C. F.; Moore, C.; Thomson, E. C.; Harrison, E. M.; Smith, C. P.; Rogan, F.; Beckwith, S. M.; Murray, A.; Singleton, D.; Eastick, K.; Sheridan, L. A.; Randell, P.; Jackson, L. M.; Ariani, C. V.; Gonçalves, S.; Fairley, D. J.; Loose, M. W.; Watkins, J.; Moses, S.; Nicholls, S.; Bull, M.; Amato, R.; Smith, D. L.; Aanensen, D. M.; Barrett, J. C.; Aggarwal, D.; Shepherd, J. G.; Curran, M. D.; Parmar, S.; Parker, M. D.; Williams, C.; Glaysher, S.; Underwood, A. P.; Bashton, M.; Pacchiarini, N.; Loveson, K. F.; Byott, M.; Carabelli, A. M.; Templeton, K. E.; de Silva, T. I.; Wang, D.; Langford, C. F.; Sillitoe, J.; Gunson, R. N.; Cottrell, S.; O'Grady, J.; Kwiatkowski, D.; Lillie, P. J.; Cortes, N.; Moore, N.; Thomas, C.; Burns, P. J.; Mahungu, T. W.; Liggett, S.; Beckett, A. H.; Holden, M. T. G.; Levett, L. J.; Osman, H.; Hassan-Ibrahim, M. O.; Simpson, D. A.; Chand, M.; Gupta, R. K.; Darby, A. C.; Paterson, S.; Pybus, O. G.; Volz, E. M.; de Angelis, D.; Robertson, D. L.; Page, A. J.; Martincorena, I.; Aigrain, L.; Bassett, A. R.; Wong, N.; Taha, Y.; Erkiert, M. J.; Spencer Chapman, M. H.; Dewar, R.; McHugh, M. P.; Mookerjee, S.; Aplin, S.; Harvey, M.; Sass, T.; Umpleby, H.; Wheeler, H.; McKenna, J. P.; Warne, B.; Taylor, J. F.; Chaudhry, Y.; Izuagbe, R.; Jahun, A. S.; Young, G. R.; McMurray, C.; McCann, C. M.; Nelson, A.; Elliott, S.; Lowe, H.; Price, A.; Crown, M. R.; Rey, S.; Roy, S.; Temperton, B.; Shaaban, S.; Hesketh, A. R.; Laing, K. G.; Monahan, I. M.; Heaney, J.; Pelosi, E.; Silviera, S.; Wilson-Davies, E.; Fryer, H.; Adams, H.; du Plessis, L.; Johnson, R.; Harvey, W. T.; Hughes, J.; Orton, R. J.; Spurgin, L. G.; Bourgeois, Y.; Ruis, C.; O'Toole, Á, Gourtovaia, M.; Sanderson, T.; Fraser, C.; Edgeworth, J.; Breuer, J.; Michell, S. L.; Todd, J. A.; John, M.; Buck, D.; Gajee, K.; Kay, G. L.; Peacock, S. J.; Heyburn, D.; Kitchman, K.; McNally, A.; Pritchard, D. T.; Dervisevic, S.; Muir, P.; Robinson, E.; Vipond, B. B.; Ramadan, N. A.; Jeanes, C.; Weldon, D.; Catalan, J.; Jones, N.; da Silva Filipe, A.; Williams, C.; Fuchs, M.; Miskelly, J.; Jeffries, A. R.; Oliver, K.; Park, N. R.; Ash, A.; Koshy, C.; Barrow, M.; Buchan, S. L.; Mantzouratou, A.; Clark, G.; Holmes, C. W.; Campbell, S.; Davis, T.; Tan, N. K.; Brown, J. R.; Harris, K. A.; Kidd, S. P.; Grant, P. R.; Xu-McCrae, L.; Cox, A.; Madona, P.; Pond, M.; Randell, P. A.; Withell, K. T.; Williams, C.; Graham, C.; Denton-Smith, R.; Swindells, E.; Turnbull, R.; Sloan, T. J.; Bosworth, A.; Hutchings, S.; Pymont, H. M.; Casey, A.; Ratcliffe, L.; Jones, C. R.; Knight, B. A.; Haque, T.; Hart, J.; Irish-Tavares, D.; Witele, E.; Mower, C.; Watson, L. K.; Collins, J.; Eltringham, G.; Crudgington, D.; Macklin, B.; Iturriza-Gomara, M.; Lucaci, A. O.; McClure, P. C.; Carlile, M.; Holmes, N.; Moore, C.; Storey, N.; Rooke, S.; Yebra, G.; Craine, N.; Perry, M.; Alikhan, N. F.; Bridgett, S.; Cook, K. F.; Fearn, C.; Goudarzi, S.; Lyons, R. A.; Williams, T.; Haldenby, S. T.; Durham, J.; Leonard, S.; Davies, R. M.; Batra, R.; Blane, B.; Spyer, M. J.; Smith, P.; Yavus, M.; Williams, R. J.; Mahanama, A. I. K.; Samaraweera, B.; Girgis, S. T.; Hansford, S. E.; Green, A.; Beaver, C.; Bellis, K. L.; Dorman, M. J.; Kay, S.; Prestwood, L.; Rajatileka, S.; Quick, J.; Poplawski, R.; Reynolds, N.; Mack, A.; Morriss, A.; Whalley, T.; Patel, B.; Georgana, I.; Hosmillo, M.; Pinckert, M. L.; Stockton, J.; Henderson, J. H.; Hollis, A.; Stanley, W.; Yew, W. C.; Myers, R.; Thornton, A.; Adams, A.; Annett, T.; Asad, H.; Birchley, A.; Coombes, J.; Evans, J. M.; Fina, L.; Gatica-Wilcox, B.; Gilbert, L.; Graham, L.; Hey, J.; Hilvers, E.; Jones, S.; Jones, H.; Kumziene-Summerhayes, S.; McKerr, C.; Powell, J.; Pugh, G.; Taylor, S.; Trotter, A. J.; Williams, C. A.; Kermack, L. M.; Foulkes, B. H.; Gallis, M.; Hornsby, H. R.; Louka, S. F.; Pohare, M.; Wolverson, P.; Zhang, P.; MacIntyre-Cockett, G.; Trebes, A.; Moll, R. J.; Ferguson, L.; Goldstein, E. J.; Maclean, A.; Tomb, R.; Starinskij, I.; Thomson, L.; Southgate, J.; Kraemer, M. U. G.; Raghwani, J.; Zarebski, A. E.; Boyd, O.; Geidelberg, L.; Illingworth, C. J.; Jackson, C.; Pascall, D.; Vattipally, S.; Freeman, T. M.; Hsu, S. N.; Lindsey, B. B.; James, K.; Lewis, K.; Tonkin-Hill, G.; Tovar-Corona, J. M.; Cox, M.; Abudahab, K.; Menegazzo, M.; Taylor, B. E. W.; Yeats, C. A.; Mukaddas, A.; Wright, D. W.; de Oliveira Martins, L.; Colquhoun, R.; Hill, V.; Jackson, B.; McCrone, J. T.; Medd, N.; Scher, E.; Keatley, J. P.; Curran, T.; Morgan, S.; Maxwell, P.; Smith, K.; Eldirdiri, S.; Kenyon, A.; Holmes, A. H.; Price, J. R.; Wyatt, T.; Mather, A. E.; Skvortsov, T.; Hartley, J. A.; Guest, M.; Kitchen, C.; Merrick, I.; Munn, R.; Bertolusso, B.; Lynch, J.; Vernet, G.; Kirk, S.; Wastnedge, E.; Stanley, R.; Idle, G.; Bradley, D. T.; Poyner, J.; Mori, M.; Jones, O.; Wright, V.; Brooks, E.; Churcher, C. M.; Fragakis, M.; Galai, K.; Jermy, A.; Judges, S.; McManus, G. M.; Smith, K. S.; Westwick, E.; Attwood, S. W.; Bolt, F.; Davies, A.; De Lacy, E.; Downing, F.; Edwards, S.; Meadows, L.; Jeremiah, S.; Smith, N.; Foulser, L.; Charalampous, T.; Patel, A.; Berry, L.; Boswell, T.; Fleming, V. M.; Howson-Wells, H. C.; Joseph, A.; Khakh, M.; Lister, M. M.; Bird, P. W.; Fallon, K.; Helmer, T.; McMurray, C. L.; Odedra, M.; Shaw, J.; Tang, J. W.; Willford, N. J.; Blakey, V.; Raviprakash, V.; Sheriff, N.; Williams, L. A.; Feltwell, T.; Bedford, L.; Cargill, J. S.; Hughes, W.; Moore, J.; Stonehouse, S.; Atkinson, L.; Lee, J. C. D.; Shah, D.; Alcolea-Medina, A.; Ohemeng-Kumi, N.; Ramble, J.; Sehmi, J.; Williams, R.; Chatterton, W.; Pusok, M.; Everson, W.; Castigador, A.; Macnaughton, E.; El Bouzidi, K.; Lampejo, T.; Sudhanva, M.; Breen, C.; Sluga, G.; Ahmad, S. S. Y.; George, R. P.; Machin, N. W.; Binns, D.; James, V.; Blacow, R.; Coupland, L.; Smith, L.; Barton, E.; Padgett, D.; Scott, G.; Cross, A.; Mirfenderesky, M.; Greenaway, J.; Cole, K.; Clarke, P.; Duckworth, N.; Walsh, S.; Bicknell, K.; Impey, R.; Wyllie, S.; Hopes, R.; Bishop, C.; Chalker, V.; et al..
Embase;
Preprint in English | EMBASE | ID: ppcovidwho-326827

ABSTRACT

The Delta variant of concern of SARS-CoV-2 has spread globally causing large outbreaks and resurgences of COVID-19 cases1-3. The emergence of Delta in the UK occurred on the background of a heterogeneous landscape of immunity and relaxation of non-pharmaceutical interventions4,5. Here we analyse 52,992 Delta genomes from England in combination with 93,649 global genomes to reconstruct the emergence of Delta, and quantify its introduction to and regional dissemination across England, in the context of changing travel and social restrictions. Through analysis of human movement, contact tracing, and virus genomic data, we find that the focus of geographic expansion of Delta shifted from India to a more global pattern in early May 2021. In England, Delta lineages were introduced >1,000 times and spread nationally as non-pharmaceutical interventions were relaxed. We find that hotel quarantine for travellers from India reduced onward transmission from importations;however the transmission chains that later dominated the Delta wave in England had been already seeded before restrictions were introduced. In England, increasing inter-regional travel drove Delta's nationwide dissemination, with some cities receiving >2,000 observable lineage introductions from other regions. Subsequently, increased levels of local population mixing, not the number of importations, was associated with faster relative growth of Delta. Among US states, we find that regions that previously experienced large waves also had faster Delta growth rates, and a model including interactions between immunity and human behaviour could accurately predict the rise of Delta there. Delta's invasion dynamics depended on fine scale spatial heterogeneity in immunity and contact patterns and our findings will inform optimal spatial interventions to reduce transmission of current and future VOCs such as Omicron.

13.
Robson, S. C.; Connor, T. R.; Loman, N. J.; Golubchik, T.; Nunez, R. T. M.; Bonsall, D.; Rambaut, A.; Snell, L. B.; Livett, R.; Ludden, C.; Corden, S.; Nastouli, E.; Nebbia, G.; Johnston, I.; Lythgoe, K.; Torok, M. E.; Goodfellow, I. G.; Prieto, J. A.; Saeed, K.; Jackson, D. K.; Houlihan, C.; Frampton, D.; Hamilton, W. L.; Witney, A. A.; Bucca, G.; Pope, C. F.; Moore, C.; Thomson, E. C.; Harrison, E. M.; Smith, C. P.; Rogan, F.; Beckwith, S. M.; Murray, A.; Singleton, D.; Eastick, K.; Sheridan, L. A.; Randell, P.; Jackson, L. M.; Ariani, C. V.; Gonçalves, S.; Fairley, D. J.; Loose, M. W.; Watkins, J.; Moses, S.; Nicholls, S.; Bull, M.; Amato, R.; Smith, D. L.; Aanensen, D. M.; Barrett, J. C.; Aggarwal, D.; Shepherd, J. G.; Curran, M. D.; Parmar, S.; Parker, M. D.; Williams, C.; Glaysher, S.; Underwood, A. P.; Bashton, M.; Loveson, K. F.; Byott, M.; Pacchiarini, N.; Carabelli, A. M.; Templeton, K. E.; de Silva, T. I.; Wang, D.; Langford, C. F.; Sillitoe, J.; Gunson, R. N.; Cottrell, S.; O'Grady, J.; Kwiatkowski, D.; Lillie, P. J.; Cortes, N.; Moore, N.; Thomas, C.; Burns, P. J.; Mahungu, T. W.; Liggett, S.; Beckett, A. H.; Holden, M. T. G.; Levett, L. J.; Osman, H.; Hassan-Ibrahim, M. O.; Simpson, D. A.; Chand, M.; Gupta, R. K.; Darby, A. C.; Paterson, S.; Pybus, O. G.; Volz, E. M.; de Angelis, D.; Robertson, D. L.; Page, A. J.; Martincorena, I.; Aigrain, L.; Bassett, A. R.; Wong, N.; Taha, Y.; Erkiert, M. J.; Chapman, M. H. S.; Dewar, R.; McHugh, M. P.; Mookerjee, S.; Aplin, S.; Harvey, M.; Sass, T.; Umpleby, H.; Wheeler, H.; McKenna, J. P.; Warne, B.; Taylor, J. F.; Chaudhry, Y.; Izuagbe, R.; Jahun, A. S.; Young, G. R.; McMurray, C.; McCann, C. M.; Nelson, A.; Elliott, S.; Lowe, H.; Price, A.; Crown, M. R.; Rey, S.; Roy, S.; Temperton, B.; Shaaban, S.; Hesketh, A. R.; Laing, K. G.; Monahan, I. M.; Heaney, J.; Pelosi, E.; Silviera, S.; Wilson-Davies, E.; Adams, H.; du Plessis, L.; Johnson, R.; Harvey, W. T.; Hughes, J.; Orton, R. J.; Spurgin, L. G.; Bourgeois, Y.; Ruis, C.; O'Toole, Á, Gourtovaia, M.; Sanderson, T.; Fraser, C.; Edgeworth, J.; Breuer, J.; Michell, S. L.; Todd, J. A.; John, M.; Buck, D.; Gajee, K.; Kay, G. L.; Peacock, S. J.; Heyburn, D.; Kitchman, K.; McNally, A.; Pritchard, D. T.; Dervisevic, S.; Muir, P.; Robinson, E.; Vipond, B. B.; Ramadan, N. A.; Jeanes, C.; Weldon, D.; Catalan, J.; Jones, N.; da Silva Filipe, A.; Williams, C.; Fuchs, M.; Miskelly, J.; Jeffries, A. R.; Oliver, K.; Park, N. R.; Ash, A.; Koshy, C.; Barrow, M.; Buchan, S. L.; Mantzouratou, A.; Clark, G.; Holmes, C. W.; Campbell, S.; Davis, T.; Tan, N. K.; Brown, J. R.; Harris, K. A.; Kidd, S. P.; Grant, P. R.; Xu-McCrae, L.; Cox, A.; Madona, P.; Pond, M.; Randell, P. A.; Withell, K. T.; Williams, C.; Graham, C.; Denton-Smith, R.; Swindells, E.; Turnbull, R.; Sloan, T. J.; Bosworth, A.; Hutchings, S.; Pymont, H. M.; Casey, A.; Ratcliffe, L.; Jones, C. R.; Knight, B. A.; Haque, T.; Hart, J.; Irish-Tavares, D.; Witele, E.; Mower, C.; Watson, L. K.; Collins, J.; Eltringham, G.; Crudgington, D.; Macklin, B.; Iturriza-Gomara, M.; Lucaci, A. O.; McClure, P. C.; Carlile, M.; Holmes, N.; Moore, C.; Storey, N.; Rooke, S.; Yebra, G.; Craine, N.; Perry, M.; Fearn, N. C.; Goudarzi, S.; Lyons, R. A.; Williams, T.; Haldenby, S. T.; Durham, J.; Leonard, S.; Davies, R. M.; Batra, R.; Blane, B.; Spyer, M. J.; Smith, P.; Yavus, M.; Williams, R. J.; Mahanama, A. I. K.; Samaraweera, B.; Girgis, S. T.; Hansford, S. E.; Green, A.; Beaver, C.; Bellis, K. L.; Dorman, M. J.; Kay, S.; Prestwood, L.; Rajatileka, S.; Quick, J.; Poplawski, R.; Reynolds, N.; Mack, A.; Morriss, A.; Whalley, T.; Patel, B.; Georgana, I.; Hosmillo, M.; Pinckert, M. L.; Stockton, J.; Henderson, J. H.; Hollis, A.; Stanley, W.; Yew, W. C.; Myers, R.; Thornton, A.; Adams, A.; Annett, T.; Asad, H.; Birchley, A.; Coombes, J.; Evans, J. M.; Fina, L.; Gatica-Wilcox, B.; Gilbert, L.; Graham, L.; Hey, J.; Hilvers, E.; Jones, S.; Jones, H.; Kumziene-Summerhayes, S.; McKerr, C.; Powell, J.; Pugh, G.; Taylor, S.; Trotter, A. J.; Williams, C. A.; Kermack, L. M.; Foulkes, B. H.; Gallis, M.; Hornsby, H. R.; Louka, S. F.; Pohare, M.; Wolverson, P.; Zhang, P.; MacIntyre-Cockett, G.; Trebes, A.; Moll, R. J.; Ferguson, L.; Goldstein, E. J.; Maclean, A.; Tomb, R.; Starinskij, I.; Thomson, L.; Southgate, J.; Kraemer, M. U. G.; Raghwani, J.; Zarebski, A. E.; Boyd, O.; Geidelberg, L.; Illingworth, C. J.; Jackson, C.; Pascall, D.; Vattipally, S.; Freeman, T. M.; Hsu, S. N.; Lindsey, B. B.; James, K.; Lewis, K.; Tonkin-Hill, G.; Tovar-Corona, J. M.; Cox, M.; Abudahab, K.; Menegazzo, M.; Taylor, B. E. W.; Yeats, C. A.; Mukaddas, A.; Wright, D. W.; de Oliveira Martins, L.; Colquhoun, R.; Hill, V.; Jackson, B.; McCrone, J. T.; Medd, N.; Scher, E.; Keatley, J. P.; Curran, T.; Morgan, S.; Maxwell, P.; Smith, K.; Eldirdiri, S.; Kenyon, A.; Holmes, A. H.; Price, J. R.; Wyatt, T.; Mather, A. E.; Skvortsov, T.; Hartley, J. A.; Guest, M.; Kitchen, C.; Merrick, I.; Munn, R.; Bertolusso, B.; Lynch, J.; Vernet, G.; Kirk, S.; Wastnedge, E.; Stanley, R.; Idle, G.; Bradley, D. T.; Poyner, J.; Mori, M.; Jones, O.; Wright, V.; Brooks, E.; Churcher, C. M.; Fragakis, M.; Galai, K.; Jermy, A.; Judges, S.; McManus, G. M.; Smith, K. S.; Westwick, E.; Attwood, S. W.; Bolt, F.; Davies, A.; De Lacy, E.; Downing, F.; Edwards, S.; Meadows, L.; Jeremiah, S.; Smith, N.; Foulser, L.; Charalampous, T.; Patel, A.; Berry, L.; Boswell, T.; Fleming, V. M.; Howson-Wells, H. C.; Joseph, A.; Khakh, M.; Lister, M. M.; Bird, P. W.; Fallon, K.; Helmer, T.; McMurray, C. L.; Odedra, M.; Shaw, J.; Tang, J. W.; Willford, N. J.; Blakey, V.; Raviprakash, V.; Sheriff, N.; Williams, L. A.; Feltwell, T.; Bedford, L.; Cargill, J. S.; Hughes, W.; Moore, J.; Stonehouse, S.; Atkinson, L.; Lee, J. C. D.; Shah, D.; Alcolea-Medina, A.; Ohemeng-Kumi, N.; Ramble, J.; Sehmi, J.; Williams, R.; Chatterton, W.; Pusok, M.; Everson, W.; Castigador, A.; Macnaughton, E.; Bouzidi, K. El, Lampejo, T.; Sudhanva, M.; Breen, C.; Sluga, G.; Ahmad, S. S. Y.; George, R. P.; Machin, N. W.; Binns, D.; James, V.; Blacow, R.; Coupland, L.; Smith, L.; Barton, E.; Padgett, D.; Scott, G.; Cross, A.; Mirfenderesky, M.; Greenaway, J.; Cole, K.; Clarke, P.; Duckworth, N.; Walsh, S.; Bicknell, K.; Impey, R.; Wyllie, S.; Hopes, R.; Bishop, C.; Chalker, V.; Harrison, I.; Gifford, L.; Molnar, Z.; Auckland, C.; Evans, C.; Johnson, K.; Partridge, D. G.; Raza, M.; Baker, P.; Bonner, S.; Essex, S.; Murray, L. J.; Lawton, A. I.; Burton-Fanning, S.; Payne, B. A. I.; Waugh, S.; Gomes, A. N.; Kimuli, M.; Murray, D. R.; Ashfield, P.; Dobie, D.; Ashford, F.; Best, A.; Crawford, L.; Cumley, N.; Mayhew, M.; Megram, O.; Mirza, J.; Moles-Garcia, E.; Percival, B.; Driscoll, M.; Ensell, L.; Lowe, H. L.; Maftei, L.; Mondani, M.; Chaloner, N. J.; Cogger, B. J.; Easton, L. J.; Huckson, H.; Lewis, J.; Lowdon, S.; Malone, C. S.; Munemo, F.; Mutingwende, M.; et al..
Embase;
Preprint in English | EMBASE | ID: ppcovidwho-326811

ABSTRACT

The scale of data produced during the SARS-CoV-2 pandemic has been unprecedented, with more than 5 million sequences shared publicly at the time of writing. This wealth of sequence data provides important context for interpreting local outbreaks. However, placing sequences of interest into national and international context is difficult given the size of the global dataset. Often outbreak investigations and genomic surveillance efforts require running similar analyses again and again on the latest dataset and producing reports. We developed civet (cluster investigation and virus epidemiology tool) to aid these routine analyses and facilitate virus outbreak investigation and surveillance. Civet can place sequences of interest in the local context of background diversity, resolving the query into different 'catchments' and presenting the phylogenetic results alongside metadata in an interactive, distributable report. Civet can be used on a fine scale for clinical outbreak investigation, for local surveillance and cluster discovery, and to routinely summarise the virus diversity circulating on a national level. Civet reports have helped researchers and public health bodies feedback genomic information in the appropriate context within a timeframe that is useful for public health.

14.
Thorax ; 76(Suppl 2):A178, 2021.
Article in English | ProQuest Central | ID: covidwho-1505966

ABSTRACT

BackgroundBlood eosinopaenia was one of the earliest reported findings in hospitalised patients with COVID-19, questioning whether eosinophils could have an anti-viral or deleterious role in the immune response against SARS-CoV2. Benralizumab is an anti-IL5R monoclonal antibody licensed for the treatment of severe eosinophilic asthma (SEA) and causes the near-complete depletion of blood and tissue eosinophils. As such, it offers the opportunity to explore the impact of eosinopaenia at the time of infection on outcome with COVID-19.MethodPatients started on treatment with benralizumab (up until April 2021) for SEA at our regional asthma centre were contacted by telephone throughout May and June 2021 to establish whether they had experienced a confirmed (PCR-positive) SARS-CoV2 infection since commencing benralizumab. Clinical and demographic characteristics were recorded along with the outcome of infection, including the need for hospitalisation or intensive care admission. Patients requiring hospitalisation were compared to those experiencing mild infections.ResultsData on 268 patients treated with benralizumab was collected with 24/268 (9%) confirming SARS-CoV2 infection with a positive PCR test. Of these 18/24 (75%) experienced mild infections that did not require hospitalisation. Of the 6/24 requiring hospitalisation, the median (IQR) length of stay was 6 (1–8) days. No patients required ICU admission or mechanical ventilation. There was no significant difference in baseline characteristics between hospitalised and non-hospitalised patients. However, it is noteworthy that a higher proportion of hospitalised patients were male (50.0% vs 38.9%) and had a higher mean BMI (32.1 vs 29.5).DiscussionIn the context of drug-induced eosinopaenia with benralizumab, 75% of patients with severe asthma experienced mild COVID-19 disease. This is likely to be an underestimate given that other patients may have experienced an asymptomatic infection or not pursued PCR testing in the context of mild infection. Although caution is needed due to the small sample size, these results do not support a significant role for eosinophils in SARS-CoV2 infection.

15.
Thorax ; 76(Suppl 2):A26-A27, 2021.
Article in English | ProQuest Central | ID: covidwho-1505867

ABSTRACT

Introduction and ObjectiveThe COVID-19 pandemic has witnessed a reduction in asthma exacerbations in the UK. Several factors may underpin this, including reduced transmission of seasonal viruses and improved use of or adherence to inhaled corticosteroids (ICS). This study aims to investigate whether ICS use has changed during the pandemic for patients with asthma.MethodsUsing the OpenPrescribing database, we analysed prescribing patterns of ICS, salbutamol and peak flow meters from January 2019 to January 2021 across England. Additionally, using a sample asthma cohort from 3 primary care practices, we assessed individual prescription patterns and ICS adherence across the two-year period. ICS adherence has been defined according to the medication possession (MPR) ratio: good (≥75%), sub-optimal (50–74%), poor (25–49%) and non-adherence (<25%).ResultsA sharp increase in national ICS prescriptions was observed at the start of the pandemic in March 2020 representing a 50% increase compared to February 2020. Thereafter national ICS prescription rates appear to have returned to normal levels. The sample asthma cohort included 1132 patients (762 patients treated with ICS across 2019 and 2020). Overall, adherence to ICS improved in 2020 (P<0.001), with the proportion of patients meeting ‘good adherence’ (≥75%) increasing from 34% to 42% (P<0.001). Analysis of this cohort suggested the March 2020 spike predominantly reflected improved adherence rather than a hoarding effect of multiple inhalers or new prescriptions for ICS-naïve individuals. Increasing age was associated with higher levels of ICS adherence. A similar spike in salbutamol occurred in March 2020, however, an overall reduction in salbutamol prescriptions was seen in 2020 (P=0.039). National figures highlighted a progressive increase in prescription of peak flow meters over 2020.ConclusionA marked spike in national ICS prescriptions occurred in March 2020. This increase appears to reflect improved adherence in patients with low levels of adherence rather than a hoarding effect or large-scale initiation in ICS-naïve patients. Despite a comparable spike in salbutamol prescriptions, 2020 saw an overall reduction in salbutamol prescriptions. Prescription of peak flow meters steadily increased over 2020 in keeping with the need for more remote monitoring.

17.
British Journal of Dermatology ; 185:105-105, 2021.
Article in English | Web of Science | ID: covidwho-1396159
18.
Thorax ; 76(SUPPL 1):A234-A235, 2021.
Article in English | EMBASE | ID: covidwho-1194362

ABSTRACT

Introduction During the first wave of the COVID-19 pandemic in the UK there was a reduction in A&E attendances and hospital admissions. Monthly excess deaths peaked in April 2020;driven by COVID-19.1 We investigated whether hospital admissions due to asthma were reduced in April 2020 compared to the previous five years and if this was accompanied by an increase in asthma deaths. Methods Five-year data were obtained from Public Health Scotland from the time period January 2015 to June 2020. Hospital admission data was sourced from Public Health Scotland's Scottish Morbidity Records, death certificate data from National Records of Scotland and A&E attendance data from Public Health Scotland. Data were analysed using statistical process control charts. Results A&E presentations in April 2020 reduced to 44% of April 2019. Hospital admissions for all conditions reduced, as did asthma admissions (figure 1a) [218 in April 2020 versus previous 5 year mean of 418]. 7958 deaths occurred in April 2020;an excess of 2731 from previous 5-year mean. In 130 deaths asthma was recorded on the death certificate as either the underlying or the contributory cause, giving rise to around 100 apparent excess deaths versus the previous 5-year mean of 27.5 (figure 1b). Asthma was recorded as the underlying cause of death in 7 cases, comparable with the previous 5 year mean of 9.2 deaths (figure 1c). The age distribution of those with asthma on the death certificate was: 97-65, 27 aged 45-65, 6 aged 18-44 and 0 <18 years. Of the 123 patients with asthma recorded as a contributory cause, 81 had COVID-19 recorded as the underlying cause of death. All 7 patients with asthma recorded as underlying cause of death were elderly and the location of death was: 3 at home, 2 in residential care, 1 in hospital and 1 in a hospice. Conclusions Reduced acute healthcare utilisation by people with asthma during the first peak of COVID-19 did not appear to result in increased mortality where asthma was the primary underlying cause of death.

19.
Thorax ; 76(SUPPL 1):A18, 2021.
Article in English | EMBASE | ID: covidwho-1194238

ABSTRACT

Introduction Severe asthma patients were assumed to be at greater risk of morbidity from infection with the novel severe acute respiratory syndrome coronavirus (COVID-19), hence, in the UK, were advised to shield. Community data on COVID-19 infection in severe asthmatics is lacking. We assessed the burden of shielding, the impact of COVID-19 and the effect of asthma medication on the UK severe asthma population. Methods Adults previously consented to inclusion in the UK Severe Asthma Registry (UKSAR) across 14 centres were contacted in June 2020 to collect data on potential COVID-19 infection, asthma control and shielding. Electronic records, where available, were reviewed for confirmation. Data was combined with clinical data from the UKSAR. Univariate and multivariate logistic regression analyses were performed to identify risk factors for COVID-19 infection. Results 1365 patients were included. 1268 (93%) were advised to shield, 1131 (89%) patients who received shielding advice followed it. Men (OR 0.4, p=0.045) and those in non-shielding households (OR 0.27, p=0.001) were less likely to follow shielding advice. 544 (47%) of patients advised to shield reported worsening of mental health;females (OR 1.59, p=0.001) and those with history of anxiety or depression (OR 2.12 p=0.001) were at greater risk. 97 (7.1%) patients had suspected/confirmed COVID-19 infection, 19 (1.39%) PCR/serology confirmed infection, 13(0.95%) were hospitalised and 2 patients (0.15%) died (table 1). 918 (67%) were on biologic therapy, 515 (37%) maintenance oral corticosteroid (mOCS). Multivariate analysis showed neither biologic therapy (OR 0.73, p=0.165) nor mOCS (OR 1.18, p=0.427) increased the risk of COVID-19 infection. Patients on biologics were less likely to require an acute course of corticosteroids for asthma symptoms (OR 0.6, p=0.002) while patients on mOCS were more likely (OR 1.96 p£0.001). Inhaled corticosteroids (ICS) were not associated with COVID-19 infection, including high dose (2000 mcg BDP equivalent) (OR 0.64, p=0.234). Hospitalised patients were on lower median doses of ICS vs non-hospitalised patients (1000 vs 2000 mcg BDP equivalent, p=0.002). Conclusion Hospitalisation and death occurred in small numbers in our severe asthma population. From this observational data, biologic agents for asthma were not associated with increased risk of COVID-19 infection or hospitalisation.

20.
Kidney International Reports ; 6(4):S140-S141, 2021.
Article in English | PMC | ID: covidwho-1192312
SELECTION OF CITATIONS
SEARCH DETAIL