Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 28
Filter
1.
ACS Omega ; 7(18): 16222-16234, 2022 May 10.
Article in English | MEDLINE | ID: covidwho-1829976

ABSTRACT

The outbreak caused by SARS-CoV-2 has taken many lives worldwide. Although vaccination has started, the development of drugs to either alleviate or abolish symptoms of COVID-19 is still necessary. Here, four synthetic peptides were assayed regarding their ability to protect Vero E6 cells from SARS-CoV-2 infection and their toxicity to human cells and zebrafish embryos. All peptides had some ability to protect cells from infection by SARS-CoV-2 with the D614G mutation. Molecular docking predicted the ability of all peptides to interact with and induce conformational alterations in the spike protein containing the D614G mutation. PepKAA was the most effective peptide, by having the highest docking score regarding the spike protein and reducing the SARS-CoV-2 plaque number by 50% (EC50) at a concentration of 0.15 mg mL-1. Additionally, all peptides had no toxicity to three lines of human cells as well as to zebrafish larvae and embryos. Thus, these peptides have potential activity against SARS-CoV-2, making them promising to develop new drugs to inhibit cell infection by SARS-CoV-2.

2.
PubMed; 2021.
Preprint in English | PubMed | ID: ppcovidwho-333870

ABSTRACT

BACKGROUND: While Coronavirus disease 2019 (Covid-19) vaccines are highly effective, breakthrough infections are occurring. Booster vaccinations have recently received emergency use authorization (EUA) for certain populations but are restricted to homologous mRNA vaccines. We evaluated homologous and heterologous booster vaccination in persons who had received an EUA Covid-19 vaccine regimen. METHODS: In this phase 1/2 open-label clinical trial conducted at ten U.S. sites, adults who received one of three EUA Covid-19 vaccines at least 12 weeks prior to enrollment and had no reported history of SARS-CoV-2 infection received a booster injection with one of three vaccines (Moderna mRNA-1273 100-mug, Janssen Ad26.COV2.S 5x10 10 virus particles, or Pfizer-BioNTech BNT162b2 30-mug;nine combinations). The primary outcomes were safety, reactogenicity, and humoral immunogenicity on study days 15 and 29. RESULTS: 458 individuals were enrolled: 154 received mRNA-1273, 150 received Ad26.CoV2.S, and 153 received BNT162b2 booster vaccines. Reactogenicity was similar to that reported for the primary series. Injection site pain, malaise, headache, and myalgia occurred in more than half the participants. Booster vaccines increased the neutralizing activity against a D614G pseudovirus (4.2-76-fold) and binding antibody titers (4.6-56-fold) for all combinations;homologous boost increased neutralizing antibody titers 4.2-20-fold whereas heterologous boost increased titers 6.2-76-fold. Day 15 neutralizing and binding antibody titers varied by 28.7-fold and 20.9-fold, respectively, across the nine prime-boost combinations. CONCLUSION: Homologous and heterologous booster vaccinations were well-tolerated and immunogenic in adults who completed a primary Covid-19 vaccine regimen at least 12 weeks earlier. (Funded by National Institute of Allergy and Infectious Diseases;Clinical Trials.gov number, NCT04889209 ).

3.
PubMed; 2021.
Preprint in English | PubMed | ID: ppcovidwho-333799

ABSTRACT

SARS-CoV-2 mutations may diminish vaccine-induced protective immune responses, and the durability of such responses has not been previously reported. Here, we present a comprehensive assessment of the impact of variants B.1.1.7, B.1.351, P.1, B.1.429, and B.1.526 on binding, neutralizing, and ACE2-blocking antibodies elicited by the vaccine mRNA-1273 over seven months. Cross-reactive neutralizing responses were rare after a single dose of mRNA-1273. At the peak of response to the second dose, all subjects had robust responses to all variants. Binding and functional antibodies against variants persisted in most subjects, albeit at low levels, for 6 months after the primary series of mRNA-1273. Across all assays, B.1.351 had the greatest impact on antibody recognition, and B.1.1.7 the least. These data complement ongoing studies of clinical protection to inform the potential need for additional boost vaccinations. ONE-SENTENCE SUMMARY: Most mRNA-1273 vaccinated individuals maintained binding and functional antibodies against SARS-CoV-2 variants for 6 months.

4.
Meng, B.; Ferreira, I. A. T. M.; Abdullahi, A.; Goonawardane, N.; Saito, A.; Kimura, I.; Yamasoba, D.; Gerba, P. P.; Fatihi, S.; Rathore, S.; Zepeda, S. K.; Papa, G.; Kemp, S. A.; Ikeda, T.; Toyoda, M.; Tan, T. S.; Kuramochi, J.; Mitsunaga, S.; Ueno, T.; Shirakawa, K.; Takaori-Kondo, A.; Brevini, T.; Mallery, D. L.; Charles, O. J.; Bowen, J. E.; Joshi, A.; Walls, A. C.; Jackson, L.; Cele, S.; Martin, D.; Smith, K. G. C.; Bradley, J.; Briggs, J. A. G.; Choi, J.; Madissoon, E.; Meyer, K.; Mlcochova, P.; Ceron-Gutierrez, L.; Doffinger, R.; Teichmann, S.; Pizzuto, M.; de Marco, A.; Corti, D.; Sigal, A.; James, L.; Veesler, D.; Hosmillo, M.; Lee, J. H.; Sampaziotis, F.; Goodfellow, I. G.; Matheson, N. J.; Thukral, L.; Sato, K.; Gupta, R. K.; Kawabata, R.; Morizako, N.; Sadamasu, K.; Asakura, H.; Nagashima, M.; Yoshimura, K.; Ito, J.; Kimura, I.; Uriu, K.; Kosugi, Y.; Suganami, M.; Oide, A.; Yokoyama, M.; Chiba, M.; Saito, A.; Butlertanaka, E. P.; Tanaka, Y. L.; Ikeda, T.; Motozono, C.; Nasser, H.; Shimizu, R.; Yuan, Y.; Kitazato, K.; Hasebe, H.; Nakagawa, S.; Wu, J.; Takahashi, M.; Fukuhara, T.; Shimizu, K.; Tsushima, K.; Kubo, H.; Kazuma, Y.; Nomura, R.; Horisawa, Y.; Nagata, K.; Kawai, Y.; Yanagida, Y.; Tashiro, Y.; Tokunaga, K.; Ozono, S.; Baker, S.; Dougan, G.; Hess, C.; Kingston, N.; Lehner, P. J.; Lyons, P. A.; Matheson, N. J.; Owehand, W. H.; Saunders, C.; Summers, C.; Thaventhiran, J. E. D.; Toshner, M.; Weekes, M. P.; Maxwell, P.; Shaw, A.; Bucke, A.; Calder, J.; Canna, L.; Domingo, J.; Elmer, A.; Fuller, S.; Harris, J.; Hewitt, S.; Kennet, J.; Jose, S.; Kourampa, J.; Meadows, A.; O’Brien, C.; Price, J.; Publico, C.; Rastall, R.; Ribeiro, C.; Rowlands, J.; Ruffolo, V.; Tordesillas, H.; Bullman, B.; Dunmore, B. J.; Fawke, S.; Gräf, S.; Hodgson, J.; Huang, C.; Hunter, K.; Jones, E.; Legchenko, E.; Matara, C.; Martin, J.; Mescia, F.; O’Donnell, C.; Pointon, L.; Pond, N.; Shih, J.; Sutcliffe, R.; Tilly, T.; Treacy, C.; Tong, Z.; Wood, J.; Wylot, M.; Bergamaschi, L.; Betancourt, A.; Bower, G.; Cossetti, C.; de Sa, A.; Epping, M.; Fawke, S.; Gleadall, N.; Grenfell, R.; Hinch, A.; Huhn, O.; Jackson, S.; Jarvis, I.; Krishna, B.; Lewis, D.; Marsden, J.; Nice, F.; Okecha, G.; Omarjee, O.; Perera, M.; Potts, M.; Richoz, N.; Romashova, V.; Yarkoni, N. S.; Sharma, R.; Stefanucci, L.; Stephens, J.; Strezlecki, M.; Turner, L.; de Bie, E. M. D. D.; Bunclark, K.; Josipovic, M.; Mackay, M.; Mescia, F.; Michael, A.; Rossi, S.; Selvan, M.; Spencer, S.; Yong, C.; Allison, J.; Butcher, H.; Caputo, D.; Clapham-Riley, D.; Dewhurst, E.; Furlong, A.; Graves, B.; Gray, J.; Ivers, T.; Kasanicki, M.; Le Gresley, E.; Linger, R.; Meloy, S.; Muldoon, F.; Ovington, N.; Papadia, S.; Phelan, I.; Stark, H.; Stirrups, K. E.; Townsend, P.; Walker, N.; Webster, J.; Scholtes, I.; Hein, S.; King, R.; Márquez, S.; Prado-Vivar, B.; Becerra-Wong, M.; Caravajal, M.; Trueba, G.; Rojas-Silva, P.; Grunauer, M.; Gutierrez, B.; Guadalupe, J. J.; Fernández-Cadena, J. C.; Andrade-Molina, D.; Baldeon, M.; Pinos, A..
Web of Science; 2021.
Preprint in English | Web of Science | ID: ppcovidwho-331154

ABSTRACT

The SARS-CoV-2 Omicron BA.1 variant emerged in late 2021 and is characterised by multiple spike mutations across all spike domains. Here we show that Omicron BA.1 has higher affinity for ACE2 compared to Delta, and confers very significant evasion of therapeutic monoclonal and vaccine-elicited polyclonal neutralising antibodies after two doses. mRNA vaccination as a third vaccine dose rescues and broadens neutralisation. Importantly, antiviral drugs remdesevir and molnupiravir retain efficacy against Omicron BA.1. We found that in human nasal epithelial 3D cultures replication was similar for both Omicron and Delta. However, in lower airway organoids, Calu-3 lung cells and gut adenocarcinoma cell lines live Omicron virus demonstrated significantly lower replication in comparison to Delta. We noted that despite presence of mutations predicted to favour spike S1/S2 cleavage, the spike protein is less efficiently cleaved in live Omicron virions compared to Delta virions. We mapped the replication differences between the variants to entry efficiency using spike pseudotyped virus (PV) entry assays. The defect for Omicron PV in specific cell types correlated with higher cellular RNA expression of TMPRSS2, and accordingly knock down of TMPRSS2 impacted Delta entry to a greater extent as compared to Omicron. Furthermore, drug inhibitors targeting specific entry pathways demonstrated that the Omicron spike inefficiently utilises the cellular protease TMPRSS2 that mediates cell entry via plasma membrane fusion. Instead, we demonstrate that Omicron spike has greater dependency on cell entry via the endocytic pathway requiring the activity of endosomal cathepsins to cleave spike. Consistent with suboptimal S1/S2 cleavage and inability to utilise TMPRSS2, syncytium formation by the Omicron spike was dramatically impaired compared to the Delta spike. Overall, Omicron appears to have gained significant evasion from neutralising antibodies whilst maintaining sensitivity to antiviral drugs targeting the polymerase. Omicron has shifted cellular tropism away from TMPRSS2 expressing cells that are enriched in cells found in the lower respiratory and GI tracts, with implications for altered pathogenesis.

5.
Int J Biol Macromol ; 208: 105-125, 2022 May 31.
Article in English | MEDLINE | ID: covidwho-1751045

ABSTRACT

Late in 2019, SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) emerged, causing an unknown type of pneumonia today called coronaviruses disease 2019 (COVID-19). COVID-19 is still an ongoing global outbreak that has claimed and threatened many lives worldwide. Along with the fastest vaccine developed in history to fight SARS-CoV-2 came a critical problem, SARS-CoV-2. These new variants are a result of the accumulation of mutations in the sequence and structure of spike (S) glycoprotein, which is by far the most critical protein for SARS-CoV-2 to recognize cells and escape the immune system, in addition to playing a role in SARS-CoV-2 infection, pathogenicity, transmission, and evolution. In this review, we discuss mutation of S protein and how these mutations have led to new variants that are usually more transmissible and can thus mitigate the immunity produced by vaccination. Here, analysis of S protein sequences and structures from variants point out the mutations among them, how they emerge, and the behavior of S protein from each variant. This review brings details in an understandable way about how the variants of SARS-CoV-2 are a result of mutations in S protein, making them more transmissible and even more aggressive than their relatives.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/epidemiology , Glycoproteins/genetics , Humans , Mutation , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/metabolism
9.
Embase;
Preprint in English | EMBASE | ID: ppcovidwho-326930

ABSTRACT

Introduction Individuals with COVID-19 frequently experience symptoms and impaired quality of life beyond 4-12 weeks, commonly referred to as Long COVID. Whether Long COVID is one or several distinct syndromes is unknown. Establishing the evidence base for appropriate therapies is needed. We aim to evaluate the symptom burden and underlying pathophysiology of Long COVID syndromes in non-hospitalised individuals and evaluate potential therapies. Methods and analysis A cohort of 4000 non-hospitalised individuals with a past COVID-19 diagnosis and 1000 matched controls will be selected from anonymised primary care records from the Clinical Practice Research Datalink (CPRD) and invited by their general practitioners to participate on a digital platform (Atom5TM). Individuals will report symptoms, quality of life, work capability, and patient reported outcome measures. Data will be collected monthly for one year. Statistical clustering methods will be used to identify distinct Long COVID symptom clusters. Individuals from the four most prevalent clusters and two control groups will be invited to participate in the BioWear sub-study which will further phenotype Long COVID symptom clusters by measurement of immunological parameters and actigraphy. We will review existing evidence on interventions for post-viral syndromes and Long COVID to map and prioritise interventions for each newly characterised Long COVID syndrome. Recommendations will be made using the cumulated evidence in an expert consensus workshop. A virtual supportive intervention will be coproduced with patients and health service providers for future evaluation. Individuals with lived experience of Long COVID will be involved throughout this programme through a patient and public involvement group. Ethics and dissemination Ethical approval was obtained from the Solihull Research Ethics Committee, West Midlands (21/WM/0203). The study is registered on the ISRCTN Registry (1567490). Research findings will be presented at international conferences, in peer-reviewed journals, to Long COVID patient support groups and to policymakers.

10.
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.

11.
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.

13.
Blood ; 138:4023, 2021.
Article in English | EMBASE | ID: covidwho-1582390

ABSTRACT

BACKGROUND: Autologous stem cell transplantation (ASCT) for multiple myeloma (MM) entails sudden life changes including acute symptom burden, changes in physical function, and shifting caregiver dynamics. Several studies have shown that anxiety, insomnia, and distress rise in the initial weeks following ASCT before slowly recovering. Long-term consequences of these acute exacerbations include persistent quality of life (QOL) impairments (El-Jawahri 2016), post-traumatic stress disorder (Griffith 2020), and the usage of potentially inappropriate medications (PIMs) for symptom management (Banerjee 2021). We have recently completed a pilot study of digital life coaching (DLC), whereby life coaches work with patients via phone calls and text messages to provide longitudinal support, education, and accountability to meet wellbeing-related goals. Our pilot study of 15 patients demonstrated the feasibility of DLC during this period, with bidirectional patient-coach engagement occurring every 5-7 days even during index hospitalizations for ASCT (Banerjee 2021). Based on these positive results, we have now launched a randomized Phase 2 study of DLC versus usual care among patients with MM undergoing ASCT. STUDY DESIGN: Our study is registered at clinicaltrials.gov as NCT04589286. We plan to enroll 60 adult patients with MM undergoing first ASCT at our institution. Inclusion criteria include English language proficiency and ownership of a personal cellphone. However, neither smartphones nor specific mobile apps are required for study participation. All patients, including those in the control arm, receive brief wellness-related tips with each request for PRO data as outlined below. As shown in the Figure, patients in the DLC arm are paired with a trained life coach beginning at Day -10 before ASCT. Coaches use structured frameworks to assist patients longitudinally with identifying and accomplishing wellbeing-related goals. Specific coaching topics can vary from week to week and are set by each patient. In addition to weekly coach-led phone calls, patients are encouraged to maintain bidirectional communication via phone/text/email as often as desired. Patients in the control arm do not receive access to DLC. Our primary endpoint is the total usage of sedative-class PIMs - including lorazepam, temazepam, zolpidem, and other similar medications - prescribed for anxiety or insomnia during each of 4 four-week study subperiods identified in the Figure. Secondary endpoints include patient-reported outcome (PRO) assessments of QOL (PROMIS Global Health), distress (NCCN Distress Thermometer), and insomnia (PROMIS Sleep Disturbances 4A). PRO assessments are collected exclusively using automated REDCap emails every 1-2 weeks as shown in the Figure. PROGRESS TO DATE: As of the data cutoff (7/31/21), 19 patients have enrolled onto our study and 5 have completed all follow-up. The median age of enrolled patients is 62 (range: 31-77), with 26% of patients aged 70 or older. As shown in our pilot study (Banerjee 2021), PRO collection via automated REDCap emails is feasible. Specifically, of 93 email-based requests for PRO assessments as of the data cutoff, 92 (99%) have been completed. Analyses of PRO assessment responses and PIM usage will be conducted after study completion. DISCUSSION: Improving patient wellbeing during the acute peri-ASCT period is an unmet need in multiple myeloma. Published supportive strategies during this time include music therapy (Bates 2017), acupuncture (Deng 2018), palliative care (El-Jawahri 2017), and programmed hospital room lighting (Valdimarsdottir 2018). DLC may offer unique advantages given its easy accessibility and unified patient-facing interface across hospital/clinic/home transitions. These strengths may be particularly relevant in light of the COVID-19 pandemic, where home-based follow-up after ASCT has become more common. That being said, broadening the accessibility of DLC to include patients with limited English proficiency or patients without personal cell phones are important priorities for fu ure studies. In summary, our randomized Phase 2 study of DLC versus usual care is ongoing. If shown to reduce PIM prescription rates while improving wellbeing-related PRO trajectories longitudinally, DLC may become a standard of care for patients with hematologic malignancies undergoing ASCT. [Formula presented] Disclosures: Banerjee: Pack Health: Research Funding;SparkCures: Consultancy;Sanofi: Consultancy. Knoche: Amgen: Honoraria. Brassil: Abbvie: Research Funding;Astellas: Research Funding;BMS: Research Funding;Daiichi Sankyo: Research Funding;Genentech: Research Funding;GSK: Research Funding;Sanofi: Research Funding;Pack Health: Current Employment. Jackson: Pack Health: Current Employment. Patel: Pack Health: Current Employment. Lo: Oncopeptides: Consultancy;EUSA Pharma: Consultancy. Chung: Caelum: Research Funding. Wong: Amgen: Consultancy;Genentech: Research Funding;Fortis: Research Funding;Janssen: Research Funding;GloxoSmithKlein: Research Funding;Dren Biosciences: Consultancy;Caelum: Research Funding;BMS: Research Funding;Sanofi: Membership on an entity's Board of Directors or advisory committees. Wolf: Adaptive Biotechnologies: Consultancy;Teneobio: Consultancy;Sanofi: Consultancy;Amgen: Consultancy. Martin: Oncopeptides: Consultancy;Sanofi: Research Funding;Amgen: Research Funding;Janssen: Research Funding;GlaxoSmithKline: Consultancy. Shah: Bluebird Bio: Research Funding;GSK: Consultancy;Janssen: Research Funding;Indapta Therapeutics: Consultancy;BMS/Celgene: Research Funding;CareDx: Consultancy;CSL Behring: Consultancy;Kite: Consultancy;Nektar: Research Funding;Karyopharm: Consultancy;Amgen: Consultancy;Oncopeptides: Consultancy;Poseida: Research Funding;Precision Biosciences: Research Funding;Sanofi: Consultancy;Sutro Biopharma: Research Funding;Teneobio: Research Funding.

14.
PubMed; 2021.
Preprint in English | PubMed | ID: ppcovidwho-296584

ABSTRACT

The emergence of the SARS-CoV-2 Omicron variant, first identified in South Africa, may compromise the ability of vaccine and previous infection (1) elicited immunity to protect against new infection. Here we investigated whether Omicron escapes antibody neutralization elicited by the Pfizer BNT162b2 mRNA vaccine in people who were vaccinated only or vaccinated and previously infected. We also investigated whether the virus still requires binding to the ACE2 receptor to infect cells. We isolated and sequence confirmed live Omicron virus from an infected person in South Africa. We then compared neutralization of this virus relative to an ancestral SARS-CoV-2 strain with the D614G mutation. Neutralization was by blood plasma from South African BNT162b2 vaccinated individuals. We observed that Omicron still required the ACE2 receptor to infect but had extensive escape of Pfizer elicited neutralization. However, 5 out of 6 of the previously infected, Pfizer vaccinated individuals, all of them with high neutralization of D614G virus, showed residual neutralization at levels expected to confer protection from infection and severe disease (2). While vaccine effectiveness against Omicron is still to be determined, these data support the notion that high neutralization capacity elicited by a combination of infection and vaccination, and possibly by boosting, could maintain reasonable effectiveness against Omicron. If neutralization capacity is lower or wanes with time, protection against infection is likely to be low. However, protection against severe disease, requiring lower neutralization levels and involving T cell immunity, would likely be maintained.

16.
Archives of Disease in Childhood ; 106(SUPPL 1):A223-A224, 2021.
Article in English | EMBASE | ID: covidwho-1495070

ABSTRACT

Background The coronavirus pandemic has resulted in major changes to the way children and their families carry about their daily lives. Public health measures have instructed families to stay at home to avoid spreading the infection and as such parents have faced the added challenge of combing educating and caring for their children with working from home. Recent literature highlights a possible increase in child abuse during the coronavirus (SARS-CoV-2) pandemic. Objectives In view of the concerns raised in the literature, Gloucestershire Paediatric Unscheduled Care Presentations were reviewed to determine local trends and to provide reassurance/ concerns as to any local or developing issues. Managing minor illnesses and reducing accidents is identified as one of the six key high impact areas of the DOH 2018 report which promotes timely interventions to support parents in keeping their children healthy and safe. Injury surveillance is an important component in detecting vulnerable children and their families' and is critical in informing local government policy and public health measures for its prevention. Methods Data was collected on all unscheduled care attendances (in children <16 years) taking place at Gloucestershire NHS foundation Trust's Emergency Department (ED) and Paediatric Assessment Unit (PAU) across each financial year (April - March). These were categorised according to 11 different injury/illness presentations. Any relevant changes during the pandemic (2020 - 2021) were highlighted and investigated further. Each dog bite presentation was explored according to patient demographic and location of bite. Each burn presentation was stratified according to patient demographics and type of burn and fracture numbers were compared across the months of the pandemic according to patient age. Results We have observed a 3-fold proportional increase in dog bites with a significant spike during the first lockdown. There was a disproportional increase in younger children (<5 years) being bitten to the head/face. Our data showed an overall reduction in fractures by 30% in 2020 in comparison to 2019. There was a considerable reduction in older child (>11 years). Younger children have presented in similar numbers thought to be due to an increase in trampoline use. There was an overall increase in burns by 10% in 2020 compared to 2019. Thermal contact burns were the most common burn in all age groups apart from <1year, where scalds from hot drinks predominated. The highest incidence of burns during the summer of 2020 was in the 6-11 years olds which may reflect increased BBQ usage in the summer weather and potentially reduced supervision. Conclusions Gloucestershire ED and PAU has seen upwards trends in burns and dog bites during the pandemic indicative of the burden and stressors placed on households. However, these injuries suggest a lack of supervision and safety in the home and are a safe-guarding concern. Injuries are a preventable cause of morbidity in the paediatric population. This data collection highlights the needs not only in strengthening our public health measures but also in strengthening the services responsible for investigating judiciously safeguarding concerns, detecting vulnerable families, protect children from maltreatment and promoting their overall welfare.

17.
Journal of the Academy of Nutrition and Dietetics ; 121(9, Supplement):A93, 2021.
Article in English | ScienceDirect | ID: covidwho-1364181
18.
Perspectives in Education ; 39(1):353-371, 2021.
Article in English | ProQuest Central | ID: covidwho-1355336

ABSTRACT

In November 2019, scholars and practitioners from ten higher education institutions celebrated the launch of the iKudu project. This project, co-funded by Erasmus[superscript +], focuses on capacity development for curriculum transformation through internationalisation and development of Collaborative Online International Learning (COIL) virtual exchange. Detailed plans for 2020 were discussed including a series of site visits and face-to-face training. However, the realities of the COVID-19 pandemic disrupted the plans in ways that could not have been foreseen and new ways of thinking and doing came to the fore. Writing from an insider perspective as project partners, in this paper we draw from appreciative inquiry, using a metaphor of a mosaic as our identity, to first provide the background on the iKudu project before sharing the impact of the pandemic on the project's adapted approach. We then discuss how alongside the focus of iKudu in the delivery of an internationalised and transformed curriculum using COIL, we have, by our very approach as project partners, adopted the principles of COIL exchange. A positive impact of the pandemic was that COIL offered a consciousness raising activity, which we suggest could be used more broadly in order to help academics think about international research practice partnerships, and, as in our situation, how internationalised and decolonised curriculum practices might be approached.

19.
Blood ; 136:2-3, 2020.
Article in English | EMBASE | ID: covidwho-1348286

ABSTRACT

BACKGROUND: Patients undergoing autologous stem cell transplantation (ASCT) for multiple myeloma (MM) face sudden exacerbations of anxiety, insomnia, and other symptoms within the initial weeks following ASCT. Even as these symptoms abate in subsequent months, long-term consequences include post-traumatic stress disorder (Griffith 2020), quality of life (QOL) impairments (El-Jawahri 2016), and chronic reliance on higher-risk medications such as benzodiazepines (Banerjee 2020). These findings are particularly relevant to MM patients given their older age at diagnosis, longer expected post-ASCT survival, and poorer QOL at baseline compared with other cancer patients (Kent 2015). Compared to other integrative interventions in the peri-ASCT setting, life coaching transcends a symptomatic focus while directly addressing the root determinants of impaired QOL. Life coaches work with patients using structured frameworks (Figure 1A) to provide longitudinal support, education, and accountability to meet patient-identified wellness goals. Digital life coaching (DLC) combines the strengths of life coaching with the capabilities of digital health by channeling patient-coach communication through patients' personal phones. Compared to in-person coaching, DLC is location-agnostic and allows patients to work their coaches more conveniently and frequently. DLC is feasible among ASCT survivors (Chen 2016) but has not yet been studied in the active peri-ASCT setting. We are conducting a pilot study of a 16-week DLC subscription to assess its feasibility and effects on QOL during an intensive period spanning from pre-ASCT hospitalization through Day +100 after ASCT. If successful, we plan to then pursue a randomized Phase II study comparing DLC versus usual care in the peri-ASCT setting. METHODS: Our study is registered at clinicaltrials.gov as NCT04432818. We plan to enroll 27 adult patients with MM undergoing first ASCT at our institution. Inclusion criteria include English language proficiency and ownership of a personal cellphone. Notably, neither ownership of a smartphone nor installation of a specific mobile app is required for patient enrollment. Enrolled patients will receive unlimited access to a certified life coach beginning at Day -5 before ASCT;bidirectional communication is encouraged via phone, text, or email. The life coaches will reach out at least once per week to help patients accomplish self-identified goals such as symptom management, stress reduction, and physical activity. Our study's primary endpoint is ongoing patient engagement, defined as least one patient-initiated outreach to their coach during each of four 4-week study subperiods. Our study's secondary endpoints include patient-reported outcome (PRO) assessments of QOL, distress, and sleep disturbances (to be collected using electronic surveys every 1-2 weeks as shown in Figure 1B). Exploratory endpoints include benzodiazepine usage and rates of electronic/phone communication with patients’ treatment teams. We will analyze endpoints using descriptive methods, including stratification of secondary & exploratory endpoints by DLC usage and specific 4-week study subperiod. PROGRESS TO DATE: Of 18 approached patients as of the data cutoff (8/1/20), 15 (83%) have expressed interest. Reasons for non-enrollment include skepticism about the value of interactions with coaches who do not themselves have MM. Of the 15 patients who have expressed interest in the study, the median age is 65 (range: 50-81) and all but one patient report owning a personal smartphone. All 6 patients with finalized ASCT hospitalization dates have been enrolled and paired with life coaches. Adherence to weekly electronic PRO assessments has been 100% (n = 9 timepoints) to date, consistent with previous studies (Wood 2013). CONCLUSIONS: Our pilot study is ongoing. Our findings to date suggest that certain MM patients are phone-savvy and would be interested in digital health tools, which will continue to gain prominence in light of the ongoing COVID-19 pandemic. Strengths of DLC include it scalability across institutional lines and its ability to reach patients at home in an integrative manner. Results of this study will inform innovative approaches to support the wellbeing of patients with hematologic malignancies, both in the peri-transplantation setting and beyond. [Formula presented] Disclosures: Brassil: Pack Health: Current Employment. Patel: Pack Health: Current Employment. Jackson: Pack Health: Current Employment. Wong: Janssen: Research Funding;Roche: Research Funding;Amgen: Consultancy;Sanofi: Membership on an entity's Board of Directors or advisory committees;GSK: Research Funding;Bristol Myers Squibb: Research Funding;Fortis: Research Funding. Wolf: Adaptive: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Martin: Seattle Genetics: Research Funding;AMGEN: Research Funding;GSK: Consultancy;Sanofi: Research Funding;Janssen: Research Funding. Shah: BMS, Janssen, Bluebird Bio, Sutro Biopharma, Teneobio, Poseida, Nektar: Research Funding;GSK, Amgen, Indapta Therapeutics, Sanofi, BMS, CareDx, Kite, Karyopharm: Consultancy.

20.
Eurochoices ; 19(3):34-39, 2021.
Article in English | CAB Abstracts | ID: covidwho-1343793

ABSTRACT

Covid-19 placed unprecedented stresses on food supply chains. Farms faced bottlenecks for some inputs, notably seasonal labour. Processing was disrupted by labour shortages and shutdowns, especially in meat processing. Air freight, important for fruits and vegetables, was severely disrupted. Demand from restaurants and food service collapsed, while retail food demand surged. Yet supply chains in the developed world have been remarkably resilient to date. Store shelves were replenished as stockpiling behaviour subsided and as supply chain actors expanded operating hours, increased staff, simplified the product range and found alternative suppliers. This rapid recovery was facilitated by policy decisions to reduce border waiting times, to streamline certification procedures and to relax regulations on trade in food. Importantly, policymakers have so far mostly avoided a repeat of the mistakes of the 2007-2008 food price crisis, which was greatly exacerbated by export bans. Some bottlenecks remain, and there may be new supply risks as Covid-19 spreads in Latin America. Overall, the biggest risk to food security is not food availability, but consumers' loss of income. Safety nets and food assistance are essential to avoid an increase in hunger, especially in developing countries.

SELECTION OF CITATIONS
SEARCH DETAIL