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1.
Expert Rev Mol Diagn ; 2022.
Article in English | PubMed | ID: covidwho-2017392

ABSTRACT

INTRODUCTION: Detection of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has been critical to support and management of the COVID-19 pandemic. Point of care testing (POCT) for SARS-CoV-2 has been a widely used tool for detection of SARS-CoV-2. AREAS COVERED: POCT nucleic acid amplification tests (NAATs) and rapid antigen tests (RATs) have been the most readily used POCT for SARS-CoV-2. Here, current knowledge on the utility of POCT NAATs and RATs for SARS-CoV-2 are reviewed and discussed alongside aspects of quality assurance factors that must be considered for successful and safe implementation of POCT. EXPERT OPINION: Use cases for implementation of POCT must be evidence based, regardless of the test used. A quality assurance framework must be in place to ensure accuracy and safety of POCT.

3.
PLoS One ; 17(9), 2022.
Article in English | PMC | ID: covidwho-2009711

ABSTRACT

Purpose: To demonstrate the diagnostic performance of rapid SARS-CoV-2 RT-LAMP assays, comparing the performance of genomic versus sub-genomic sequence target with subsequent application in an asymptomatic screening population. Methods: RT-LAMP diagnostic specificity (DSe) and sensitivity (DSe) was determined using 114 RT-PCR clinically positive and 88 RT-PCR clinically negative swab samples processed through the diagnostic RT-PCR service within the University Hospitals of Leicester NHS Trust. A swab-based RT-LAMP SARS-CoV-2 screening programme was subsequently made available to all staff and students at the University of Leicester (Autumn 2020), implemented to ISO 15189:2012 standards using NHS IT infrastructure and supported by University Hospital Leicester via confirmatory NHS diagnostic laboratory testing of RT-LAMP ‘positive’ samples. Results: Validation samples reporting a Ct < 20 were detected at 100% DSe and DSp, reducing to 95% DSe (100% DSp) for all samples reporting a Ct < 30 (both genomic dual sub-genomic assays). Advisory screening identified nine positive cases in 1680 symptom free individuals (equivalent to 540 cases per 100,000) with results reported back to participants and feed into national statistics within 48 hours. Conclusion: This work demonstrates the utility of a rapid RT-LAMP assay for collapsing transmission of SARS-CoV-2 in an asymptomatic screening population.

4.
Annals of the Rheumatic Diseases ; 81:971-972, 2022.
Article in English | EMBASE | ID: covidwho-2009130

ABSTRACT

Background: Enpatoran is a selective and potent dual toll-like receptor (TLR) 7/8 inhibitor in development for the treatment of cutaneous and systemic lupus erythematosus (CLE/SLE). Enpatoran inhibits TLR7/8 activation in vitro and suppresses disease activity in lupus mouse models.1 Enpatoran was well tolerated and had linear pharmacokinetic (PK) parameters in healthy volunteers.2 As TLR7/8 mediate immune responses to single-stranded RNA viruses, including SARS-CoV-2, it was postulated that enpatoran may prevent hyperinfammation and cytokine storm in COVID-19. Objectives: In response to the COVID-19 pandemic, we conducted an exploratory Phase II trial to assess safety and determine whether enpatoran prevents clinical deterioration in patients (pts) hospitalized with COVID-19 pneumonia. PK and pharmacodynamics (PD) of enpatoran were also evaluated. Methods: ANEMONE was a randomized, double-blind, placebo (PBO)-con-trolled study conducted in Brazil, the Philippines, and the USA (NCT04448756). Pts aged 18-75 years, hospitalized with COVID-19 pneumonia (WHO 9-point scale score =4) but not mechanically ventilated, with SpO2 <94% and PaO2/FiO2 ≥150 (FiO2 maximum 0.4) were eligible. Those with a history of uncontrolled illness, active/unstable cardiovascular disease and SARS-CoV-2 vaccination were excluded. Pts received PBO or enpatoran (50 or 100 mg twice daily [BID]) for 14 days, with monitoring to Day 28 and safety follow-up to Day 60. Primary outcomes were safety and time to recovery (WHO 9-point scale ≤3). Clinical deterioration (time to clinical status >4, WHO 9-point scale) was a secondary outcome. Exploratory endpoints were enpatoran and biomarker concentrations (cytokines, C-reactive protein [CRP], D-dimer and interferon gene signature [IFN-GS] scores) assessed over time. Results: 149 pts received either PBO (n=49), or enpatoran 50 mg (n=54) or 100 mg (n=46) BID;88% completed treatment and 86% received concomitant steroids. Median age was 50 years (77% <60 years old), 66% were male, and 50% had ≥1 comorbidity (40% hypertension, 24% diabetes). Overall, 59% pts reported a treatment-emergent adverse event (TEAE) with three non-treatment-related deaths;11% reported a treatment-related TEAE. The proportion of pts in the enpatoran group reporting serious TEAEs was low (50 mg BID 9%;100 mg BID 2%) vs PBO (18%). Gastrointestinal disorders were most common (PBO 8%;50 mg BID 28%;100 mg BID 9%). The primary outcome of time to recovery with enpatoran vs PBO was not met;medians were 3.4-3.9 days. A positive signal in time to clinical deterioration from Day 1 through Day 28 was observed;hazard ratios [95% CI] for enpatoran vs PBO were 0.39 [0.13, 1.15] (50 mg BID) and 0.30 [0.08, 1.08] (100 mg BID). Mean enpatoran exposure was dose-proportional, and PK properties were within expectations. The median (quartile [Q]1-Q3) interleukin 6 (IL-6), CRP and D-dimer baseline concentration across the groups were 5.7 (4.0-13.5) pg/mL, 30.04 (11.40-98.02) and 0.62 (0.39-1.01) mg/L, respectively. Baseline IFN-GS scores were similar across groups. Conclusion: The ANEMONE trial was the frst to evaluate the safety and efficacy of a TLR7/8 inhibitor in an infectious disease for preventing cytokine storm. Enpa-toran up to 100 mg BID for 14 days was well tolerated by patients acutely ill with COVID-19 pneumonia. Time to recovery was not improved with enpatoran, perhaps due to the younger age of patients who had fewer comorbidities compared to those in similar COVID-19 trials. However, there was less likelihood for clinical deterioration with enpatoran than placebo. This trial provides important safety, tolerability, PK and PD data supporting continued development of enpatoran in SLE and CLE (NCT04647708, NCT05162586).

6.
Journal of Hepatology ; 77:S49-S50, 2022.
Article in English | EMBASE | ID: covidwho-1967493

ABSTRACT

Background and aims: A global study with equitable participation for cirrhosis and chronic liver disease (CLD) outcomes is needed. We initiated the Chronic Liver disease Evolution And Registry for Events and Decompensation (CLEARED) study to provide this global perspective. Aim to evaluate determinants of inpatient mortality and organ dysfunction in a multi-center worldwide study. Method: We prospectively enrolled pts with CLD/Cirrhosis >18 years without organ transplant or COVID-19 who were admitted non-electively. To maintain equity in outcome analysis, a maximum of 50 pts/site were allowed. Data for admission variables, hospital course, and inpatient outcomes (ICU, death, organ dysfunction [ODF]) were recorded. This was analyzed for death and ODs using significant variables on admission and including World Bank classification of low/middle-income countries (LMIC). A model for in-hospital mortality for all variables during the hospital course, including ODs) was analyzed. Results: 1383 pts (55 ± 13 yrs, 64% men, 39% White, 30% Asian, 10% Hispanic, 9% Black, 12% other) were enrolled from 49 centers (Fig A). 39% were from high-income while the rest were from LMICs. Admission MELDNa 23 (6–40) with history in past 6 months of hospitalizations 51%, infections 25%, HE 32%, AKI 23%, prior LVP 15%, hydrothorax 8% and HCC 4%. Leading etiologies were Alcohol 46% then NASH 23%, HCV 11% and HBV 13%. Most were on lactulose 52%, diuretics 53%, PPI 49% and statins 11%, SBP prophylaxis 16%, beta-blockers 35% and rifaximin 31%. 90% were admitted for liver-related reasons;GI bleed 30%, HE 34%, AKI 33%, electrolyte issues 30%, anasarca 24% and 25% admission infections. In-hospital course: Median LOS was 7 (1–140) days with 25% needing ICU. 15% died in hospital, 3% were transplanted, 46% developed AKI,15% grade 3–4 HE, 14% shock, 13% nosocomial infections and 13% needed ventilation. Logistic Regression: Fig B shows that liver-related/unrelated factors on admission which predicted in-hospital mortality and development of organ dysfunction with MELDNa and Infections being common among all models. Nosocomial infections and organ dysfunctions predicted mortality when all variables were considered. High-income countries had better mortality outcomes likely due to transplant and ICU availability. AUCs were >0.75 (Figure Presented) Conclusion: In this worldwide equitable experience, admission cirrhosis severity and infections are associated with inpatient outcomes, which are greater in low-income settings. Liver-related and unrelated factors and regional variations are important in defining critical care goals and outcome models in inpatients with cirrhosis.

7.
American Journal of Biological Anthropology ; 2022.
Article in English | Web of Science | ID: covidwho-1905782

ABSTRACT

COVID-19 has highlighted a brutal reality known for decades, that Black, Indigenous, and People of Color bear a disproportionate burden of US annual sepsis cases. While plentiful research funds have been spent investigating genetic reasons for racial disparities in sepsis, an abundance of research shows that sepsis incidence and mortality maps to indicators of colonial practices including residential segregation, economic and marginalization sepsis, and denial of care. Here we argue that sepsis risk is an immunological embodiment of racism in colonial states, that the factors contributing to sepsis disparities are insidious and systemic. We show that regardless of causative pathogen, or host ancestry, racialized people get and die of sepsis most frequently in a pattern repeatedly reiterated worldwide. Lastly, we argue that while alleviation of sepsis disparities requires radical, multiscale intervention, biological anthropologists have a responsibility in this crisis. While some of us can harness our expertise to take on the ground action in sepsis prevention, all of us can leverage our positions as the first point of contact for in depth human biology instruction on most college campuses. As a leading cause of death worldwide, and a syndrome that exhibits the interplay between human physiology, race and environment, sepsis is at the nexus of major themes in biological anthropology and is a natural fit for the field's curriculum. In adopting a discussion of race and sepsis in our courses, we not only develop new research areas but increase public awareness of both sepsis and the factors contributing to uneven sepsis burden.

8.
Fertility and Sterility ; 116(3 SUPPL):e90, 2021.
Article in English | EMBASE | ID: covidwho-1880434

ABSTRACT

OBJECTIVE: COVID-19 has influenced family building, delayed fertility care, and affected people's decisions about where to live.We sought to understand differences in movement of cryopreserved reproductive tissue before and during the pandemic. MATERIALS AND METHODS: This was a retrospective cohort study of patients who transported tissue into or out of a single academic fertility center in New York City (NYC). Tissue transport was compared the year before (PRE, 4/1/2019-3/31/2020) and after (DUR, 4/1/2020-3/31/2021) the height of the COVID-19 pandemic in NYC, an epicenter. The primary outcome was the number of patients transporting tissue DUR compared to PRE. Secondary outcomes were the number of geographic changes, type of tissue, geographic origin/destination, and type of movement (in or out). Statistical analyses were performed using Kolmogorov-Smirnov, Wilcoxon Signed Rank Sum, Chi-Square, and Fisher's Exact tests with p<0.05 considered significant. RESULTS: A total of 367 tissue transports were included, with similar rates between cohorts (PRE 46.3% (170/367) vs DUR 53.7% (197/367), p=0.16). The median age at transport was the same (PRE 41 (range 29-54) vs DUR 41 (range 28-54) years, p=0.54). A similar amount of tissue was transported in (PRE 30.0% (51/170) vs DUR 35.0% (69/197)) and out (PRE 70.0% (119/170) vs DUR 65.0% (128/197), p=0.32). Patients were more likely to transport embryos pre-pandemic (37.6% (64/170) oocytes vs 61.8% (105/170) embryos, PRE) and oocytes during COVID-19 (51.8% (102/197) oocytes vs 44.2% (87/197) embryos, DUR) (p<0.01). A subgroup analysis excluding tissue moved for a gestational carrier or donor gametes found a similar number of transports were due to patient geographic relocation (PRE 50.0% (61/122) vs DUR 40.5% (60/148), p=0.12). Examination of geographic origin and destination of tissue PRE vs DUR produced no identifiable trends (p=0.38). Timing of tissue transport varied. The monthly transport rates were relatively even PRE (average 8% per month). However, during the pandemic, there were few transports in the beginning (April-May 2020, 0-1% per month) followed by a peak of transports in June-August 2020 (10-11% per month) and February-March 2021 (11-16% per month) (p<0.01). Transport activities were impacted by closure of clinics and courier service availability. CONCLUSIONS: The rate of cryopreserved tissue movement did not differ in the year before versus during the pandemic at our center, despite being in a COVID-19 epicenter, although transport activities were concentrated into fewer days. There was peak movement of tissue three months after the pandemic onset and roughly one year from the start of the pandemic. The type of tissue transported shifted to favor oocytes during the pandemic, warranting more investigation in how COVID-19 impacted family building activities. IMPACT STATEMENT: Despite the impact of COVID-19 on reproductive and place of living choices, the pandemic did not affect the amount of cryopreserved tissue that was relocated. However, insight into the increased movement of oocytes and potential impacts on warming outcomes or timelines is necessary.

9.
PubMed; 2021.
Preprint in English | PubMed | ID: ppcovidwho-333872

ABSTRACT

BACKGROUND: The COVID-19 pandemic led to dramatic threats to health and social life. Study objectives - develop a prediction model leveraging subsample of known Patient/Controls and evaluate the relationship of predicted mental health status to clinical outcome measures and pandemic-related psychological and behavioral responses during lockdown (spring/summer 2020). METHODS: Online cohort study conducted by National Institute of Mental Health Intramural Research Program. Convenience sample of English-speaking adults (enrolled 4/4-5/16/20;n=1,992). Enrollment measures: demographics, clinical history, functional status, psychiatric and family history, alcohol/drug use. Outcome measures (enrollment and q2 weeks/6 months): distress, loneliness, mental health symptoms, and COVID-19 survey. NIMH IRP Patient/Controls survey responses informed assignment of Patient Probability Scores (PPS) for all participants. Regression models analyzed the relationship between PPS and outcome measures. OUTCOMES: Mean age 46.0 (+/-14.7), female (82.4%), white (88.9 %). PPS correlated with distress, loneliness, depression, and mental health factors. PPS associated with negative psychological responses to COVID-19. Worry about mental health (OR 1.46) exceeded worry about physical health (OR 1.13). PPS not associated with adherence to social distancing guidelines but was with stress related to social distancing and worries about infection of self/others. INTERPRETATION: Mental health status (PPS) was associated with concurrent clinical ratings and COVID-specific negative responses. A focus on mental health during the pandemic is warranted, especially among those with mental health vulnerabilities. We will include PPS when conducting longitudinal analyses of mental health trajectories and risk and resilience factors that may account for differing clinical outcomes. Funding: Nimh (ziamh002922);nccih (ziaat000030).

10.
Open Forum Infectious Diseases ; 8(SUPPL 1):S360-S361, 2021.
Article in English | EMBASE | ID: covidwho-1746479

ABSTRACT

Background. Enpatoran, formerly known as M5049, is a potential first-in-class small molecule antagonist of toll-like receptors (TLR) 7 and 8, which may prevent viral-associated hyperinflammatory response and progression to 'cytokine storm' in coronavirus disease 2019 (COVID-19) patients. The objective of this study was to leverage existing population pharmacokinetic/pharmacodynamic (popPK/PD) models for enpatoran to inform dose selection for an accelerated Phase II study in COVID-19 patients with pneumonia. Methods. The popPK/PD models were based on plasma PK and PD biomarker (ex vivo-stimulated interleukin [IL]6 and interferon α [IFNα] secretion) data from the enpatoran first-in-human Phase I study in healthy participants (Port A, et al. Lupus Sci Med 2020;7(Suppl. 1): P135). A two-compartment model describing PK used a sigmoidal Emax model with proportional decrease from baseline characterizing the PD response across the investigated single and multiple daily dose range of 1-200 mg (N=72). Concentrations that inhibited 50% and 90% (IC50/IC90) of cytokine secretion were estimated and stochastic simulations were performed to assess target coverage under different dosing regimens. Results. Simulations suggested that, to achieve maximal inhibition of IL-6 over time, enpatoran PK concentrations would be maintained above the IC90 throughout the dosing interval with doses of 100 mg and 50 mg twice daily in 90% and 30% of participants, respectively. In comparison, IFNα inhibition was predicted to be lower, with IC90 coverage in 60% and 8% of participants with twice daily doses of 100 mg and 50 mg enpatoran, respectively. Conclusion. Utilization of existing popPK/PD models allowed for the accelerated development of enpatoran in COVID-19 to address an unprecedented global pandemic. Rational model-informed dose selection was supported by data from a Phase I study in which there were no safety concerns.

11.
Journal of Vascular Surgery ; 74(4):e354, 2021.
Article in English | EMBASE | ID: covidwho-1734792

ABSTRACT

Objective: Paravisceral aortic thrombus in an otherwise normal aorta is rare. A hemodynamically significant thrombus burden in such patients can result in visceral malperfusion and bilateral lower extremity ischemia, both of which, historically, have a high mortality rate. Open thrombectomy via a thoracoabdominal approach is associated with high mortality. Other endovascular alternatives, including Fogerty embolectomy and mechanical thrombectomy, are associated with visceral embolization. The Penumbra CAT-12 lightning device (Penumbra Inc, Alameda, Calif) most commonly used to treat ileofemoral deep vein thrombosis is a 12F suction catheter with the ability to remove large amounts of clot burden with minimal blood loss owing to its sensor mechanism. The ability to suction thrombectomy-focused areas in the aorta reduces the likelihood of embolization. We have presented the cases of two patients with acute symptomatic paravisceral aortic thrombus who were treated with this device and their outcomes. Methods: Two patients had presented to the emergency room with acute onset abdominal pain and bilateral lower extremity rest pain and numbness. Patient 1 was a 46-year-old woman with antithrombin III and protein C deficiency (Fig 1). Patient 2 was a 78-year-old woman with recent coronavirus disease 2019 infection, chronic obstructive pulmonary disease, and congestive heart failure (Fig 2). Computed tomography angiography of patients demonstrated aortic thrombus in the paravisceral aorta extending from the supraceliac to the infrarenal aorta. Both patients underwent percutaneous suction thrombectomy of the aorta using the Penumbra CAT-12 lightning device. Patient 2 also underwent bilateral femoral cutdown, thrombectomy, and kissing iliac stents, followed by diagnostic laparoscopy without any further intervention. Results: The intraoperative angiographic images demonstrated the initial aortic thrombus in the paravisceral aorta with resolution of thrombus after suction thrombectomy (Figs 1 and 2). The abdominal pain and bilateral lower extremity rest pain had resolved in both patients postoperatively and did not require any further surgical intervention. Patient 1 was discharged home on postoperative day 3. Patient 2 was discharged to a rehabilitation facility on postoperative day 10. Conclusions: Percutaneous suction thrombectomy devices such as the Penumbra CAT-12 lightning device is effective in removing a large paravisceral aortic clot burden without any embolization to the visceral vessels. This is a newly available alternative to consider for such patients with symptomatic paravisceral aortic thrombus considered to have a high mortality risk with open intervention. [Formula presented] [Formula presented]

14.
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.

15.
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.

16.
MEDLINE;
Preprint in English | MEDLINE | ID: ppcovidwho-326578

ABSTRACT

Drug repurposing is the only method capable of delivering treatments on the shortened time-scale required for patients afflicted with lung disease arising from SARS-CoV-2 infection. Mucin-1 (MUC1), a membrane-bound molecule expressed on the apical surfaces of most mucosal epithelial cells, is a biochemical marker whose elevated levels predict the development of acute lung injury (ALI) and respiratory distress syndrome (ARDS), and correlate with poor clinical outcomes. In response to the pandemic spread of SARS-CoV-2, we took advantage of a high content screen of 3,713 compounds at different stages of clinical development to identify FDA-approved compounds that reduce MUC1 protein abundance. Our screen identified Fostamatinib (R788), an inhibitor of spleen tyrosine kinase (SYK) approved for the treatment of chronic immune thrombocytopenia, as a repurposing candidate for the treatment of ALI. In vivo , Fostamatinib reduced MUC1 abundance in lung epithelial cells in a mouse model of ALI. In vitro , SYK inhibition by Fostamatinib promoted MUC1 removal from the cell surface. Our work reveals Fostamatinib as a repurposing drug candidate for ALI and provides the rationale for rapidly standing up clinical trials to test Fostamatinib efficacy in patients with COVID-19 lung injury.

17.
Patient education and counseling ; 2022.
Article in English | EuropePMC | ID: covidwho-1660990

ABSTRACT

Objective Cancer patients, carers and oncology health professionals have been impacted by the COVID-19 pandemic in many ways, but their experiences and psychosocial responses to the pandemic are still being explored. This study aimed to document the experience of Australians living with cancer, family carers, and Oncology health professionals (HPs) when COVID-19 first emerged. Methods In this qualitative study, participants (cancer patients currently receiving treatment, family carers and HPs) completed a semi-structured interview exploring their experiences of COVID-19 and the impact it had on cancer care. Participants also completed the Hospital Anxiety and Depression Scale (patients) and the Depression, Anxiety and Stress Scale (carers and HPs) to assess emotional morbidity. Thematic analysis was undertaken on qualitative data. Results 32 patients, 16 carers and 29 HPs participated. Qualitative analysis yielded three shared themes: fear and death anxiety, isolation, and uncertainty. For HPs, uncertainty incorporated the potential for moral distress and work-stress. Patients and carers scoring high on anxiety/depression measures were more likely to have advanced disease, expressed greater death anxiety, talked about taking more extreme precautionary measures, and felt more impacted by isolation. Conclusion Cancer and COVID-19 can have compounding psychological impacts on all those receiving or giving care. Practice Implications Screening for distress in patients, and burnout in HPs, is recommended. Increased compassionate access and provision of creative alternatives to face-to-face support are warrented.

18.
Asia-Pacific Journal of Clinical Oncology ; 17(SUPPL 9):86-87, 2021.
Article in English | EMBASE | ID: covidwho-1592492

ABSTRACT

Aims: The COVID-19 pandemic triggered rapid implementation of telephone and videoconference telehealth across Australia. The Psycho-Oncology Cooperative Research Group (PoCoG) investigated the barriers and enablers to wider implementation post pandemic. Psychologists working in oncology face unique challenges such as working with patients experiencing existential issues and report inadequate training in conducting telehealth psychology. This research aimed to address the paucity of evidence available to guide adaption of therapy to telehealth through the development of evidence-based consensus recommendations for Psycho-oncology . Methods : Content for the recommendations was developed based on a review of the psychology and Psycho-Oncology literature and stakeholder feedback through an expert advisory group (n = 14) comprising clinical psychology, Psycho-Oncology and health communication/education experts, guiding the focus of the content. The compilation of recommendations involved an iterative co-design process. Clinical scenarios, self-reflection exercises and clinical guidance were incorporated to facilitate clinical relevance. The relative importance of content topics was assessed based on a Delphi consensus process that is ongoing. Results : The co-design approach identified key recommendations;(1) adaptations to therapeutic techniques, (2) clinical/practical strategies (including worksheets and case studies), (3) communication challenges, (4) maintaining the therapeutic alliance, and (5) managing patient presentations. A national Delphi consensus process involving clinical psychologists working in oncology is ongoing and will guide further refinement of the educational resource. Conclusions : These recommendations fill an identified gap in the literature and provide a robust expert-endorsed document to guide clinicians through telehealth in the Psycho-Oncology field. This will support an increase in sustainability of, and confidence in, Psycho-Oncology telehealth moving forward.

20.
PUBMED; 2021.
Preprint in English | PUBMED | ID: ppcovidwho-292933

ABSTRACT

The DSM-5 Level 1 Cross-Cutting Symptom Measure (DSM-XC) is a transdiagnostic mental health symptom measure that has shown promise in informing clinical diagnostic evaluations and as a screening tool for research. However, few studies have assessed the latent dimensionality of the DSM-XC or provided guidance on how to score the survey. In this report, we examined the factor structure of the DSM-XC in a sample of over 3500 participants enrolled in a protocol on the mental health impact of COVID-19 conducted through the National Institute of Mental Health Intramural Research Program (NIMH IRP) ( ClinicalTrials.gov identifier: NCT04339790 ). We began by conducting an exploratory factor analysis (EFA) to identify the best solution for our data, and then employed a confirmatory factor analyses (CFAs) to evaluate the fit of the two-factor solution proposed by Lace and Merz (Lace & Merz, 2020), the fit of our proposed solution, and the measurement invariance of our proposed solution across age, sex, and calendar time. We found a six-factor solution stemming from our EFAs to best fit our data. Each factor captures symptoms related to a specific construct of psychopathology: mood, worry, activation, somatic, confusion, and substance use. Future research should evaluate this six-factor structure using additional datasets to confirm its consistency across research populations and settings.

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