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Hall, Andrew J.; Clement, Nicholas D.; Ojeda-Thies, Cristina, MacLullich, Alasdair M. J.; Toro, Giuseppe, Johansen, Antony, White, Tim O.; Duckworth, Andrew D.; Abdul-Jabar, Hani, Abu-Rajab, Rashid, Abugarja, Ahmed, Adam, Karen, Aguado Hernández, Héctor J.; Améstica Lazcano, Gedeón, Anderson, Sarah, Ansar, Mahmood, Antrobus, Jonathan, Aragón Achig, Esteban Javier, Archunan, Maheswaran, Arrieta Salinas, Mirentxu, Ashford-Wilson, Sarah, Assens Gibert, Cristina, Athanasopoulou, Katerina, Awadelkarim, Mohamed, Baird, Stuart, Bajada, Stefan, Balakrishnan, Shobana, Balasubramanian, Sathishkumar, Ballantyne, James A.; Bárcena Goitiandia, Leopoldo, Barkham, Benjamin, Barmpagianni, Christina, Barres-Carsi, Mariano, Barrett, Sarah, Baskaran, Dinnish, Bell, Jean, Bell, Katrina, Bell, Stuart, Bellelli, Giuseppe, Benchimol, Javier Alberto, Boietti, Bruno Rafael, Boswell, Sally, Braile, Adriano, Brennan, Caitlin, Brent, Louise, Brooke, Ben, Bruno, Gaetano, Burahee, Abdus, Burns, Shirley, Calabrò, Giampiero, Campbell, Lucy, Carabelli, Guido Sebastian, Carnegie, Carol, Carretero Cristobal, Guillermo, Caruana, Ethan, Cassinello Ogea, M. Concepción, Castellanos Robles, Juan, Castillon, Pablo, Chakrabarti, Anil, Cecere, Antonio Benedetto, Chen, Ping, Clarke, Jon V.; Collins, Grace, Corrales Cardenal, Jorge E.; Corsi, Maurizio, Cózar Adelantado, Gara María, Craxford, Simon, Crooks, Melissa, Cuarental-García, Javier, Cuthbert, Rory, Dall, Graham, Daskalakis, Ioannis, De Cicco, Annalisa, Diana, de la Fuente de Dios, Demaria, Pablo, Dereix, John, Díaz Jiménez, Julian, Dinamarca Montecinos, José Luis, Do Le, Ha Phuong, Donoso Coppa, Juan Pablo, Drosos, Georgios, Duffy, Andrew, East, Jamie, Eastwood, Deborah, Elbahari, Hassan, Elias de Molins Peña, Carmen, Elmamoun, Mamoun, Emmerson, Ben, Escobar Sánchez, Daniel, Faimali, Martina, Farré-Mercadé, Maria Victòria, Farrow, Luke, Fayez, Almari, Fell, Adam, Fenner, Christopher, Ferguson, David, Finlayson, Louise, Flores Gómez, Aldo, Freeman, Nicholas, French, Jonathan, Gabardo Calvo, Santiago, Gagliardo, Nicola, Garcia Albiñana, Joan, García Cruz, Guillermo, García de Cortázar Antolín, Unai, García Virto, Virginia, Gealy, Sophie, Gil Caballero, Sandra Marcela, Gill, Moneet, González González, María Soledad, Gopireddy, Rajesh, Guntley, Diane, Gurung, Binay, Guzmán Rosales, Guadalupe, Haddad, Nedaa, Hafeez, Mahum, Haller, Petra, Halligan, Emer, Hardie, John, Hawker, Imogen, Helal, Amr, Herrera Cruz, Mariana, Herreros Ruiz-Valdepeñas, Ruben, Horton, James, Howells, Sean, Howieson, Alan, Hughes, Luke, Hünicken Torrez, Flavia Lorena, Hurtado Ortega, Ana, Huxley, Peter, Hamid, Hytham K. S.; Ilahi, Nida, Iliadis, Alexis, Inman, Dominic, Jadhao, Piyush, Jandoo, Rajan, Jawad, Lucy, Jayatilaka, Malwattage Lara Tania, Jenkins, Paul J.; Jeyapalan, Rathan, Johnson, David, Johnston, Andrew, Joseph, Sarah, Kapoor, Siddhant, Karagiannidis, Georgios, Karanam, Krishna Saga, Kattakayam, Freddy, Konarski, Alastair, Kontakis, Georgios, Labrador Hernández, Gregorio, Lancaster, Victoria, Landi, Giovanni, Le, Brian, Liew, Ignatius, Logishetty, Kartik, Lopez Marquez, Andrew Carlomaria Daniel, Lopez, Judit, Lum, Joann, Macpherson, Gavin J.; Madan, Suvira, Mahroof, Sabreena, Malik-Tabassum, Khalid, Mallina, Ravi, Maqsood, Afnan, Marson, Ben, Martin Legorburo, M. José, Martin-Perez, Encarna, Martínez Jiménez, Tania, Martinez Martin, Javier, Mayne, Alistair, Mayor, Amy, McAlinden, Gavan, McLean, Lucille, McDonald, Lorna, McIntyre, Joshua, McKay, Pamela, McKean, Greg, McShane, Heather, Medici, Antonio, Meeke, Chelsea, Meldrum, Evonne, Mendez, Mijail, Mercer, Scott, Merino Perez, Josu, Mesa-Lampré, María-Pilar, Mighton, Shuna, Milne, Kirsty, Mohamed Yaseen, Muhammed, Moppett, Iain, Mora, Jesus, Morales-Zumel, Sira, Moreno Fenoll, Irene Blanca, Mousa, Adham, Murray, Alastair W.; Murray, Elspeth V.; Nair, Radhika, Neary, Fiona, Negri, Giacomo, Negus, Oliver, Newham-Harvey, Fiona, Ng, Nigel, Nightingale, Jess, Noor Mohamed Anver, Sumiya, Nunag, Perrico, O'Hare, Matthew, Ollivere, Ben, Ortés Gómez, Raquel, Owens, AnneMarie, Page, Siobhan, Palloni, Valentina, Panagiotopoulos, Andreas, Panagiotopoulos, Elias, Panesar, Paul, Papadopoulos, Antonios, Spyridon, Papagiannis, Pareja Sierra, Teresa, Park, Chang, Parwaiz, Hammad, Paterson-Byrne, Paul, Patton, Sam, Pearce, Jack, Porter, Marina, Pellegrino, Achille, Pèrez Cuellar, Arturo, Pezzella, Raffaele, Phadnis, Ashish, Pinder, Charlotte, Piper, Danielle, Powell-Bowns, Matilda, Prieto Martín, Rocío, Probert, Annabel, Ramesh, Ashwanth, Ramírez de Arellano, Manuel Vicente Mejía, Renton, Duncan, Rickman, Stephen, Robertson, Alastair, Roche Albero, Adrian, Rodrigo Verguizas, José Alberto, Rodríguez Couso, Myriam, Rooney, Joanna, Sáez-López, Pilar, Saldaña-Díaz, Andres, Santulli, Adriano, Sanz Pérez, Marta Isabel, Sarraf, Khaled M.; Scarsbrook, Christine, Scott, Chloe E. H.; Scott, Jennifer, Shah, Sachi, Sharaf, Sharief, Sharma, Sidharth, Shirley, Denise, Siano, Antonio, Simpson, James, Singh, Abhinav, Singh, Amit, Sinnett, Tim, Sisodia, Gurudatt, Smith, Philomena, Sophena Bert, Eugenia, Steel, Michael, Stewart, Avril, Stewart, Claire, Sugand, Kapil, Sullivan, Niall, Sweeting, Lauren, Symes, Michael, Tan, Dylan Jun Hao, Tancredi, Francesco, Tatani, Irini, Thomas, Philip, Thomson, Fraser, Toner, Niamh S.; Tong, Anna, Toro, Antonio, Tosounidis, Theodoros, Tottas, Stylianos, Trinidad Leo, Andrea, Tucker, Damien, Vemulapalli, Krishna, Ventura Garces, Diego, Vernon, Olivia Katherine, Viveros Garcia, Juan Carlos, Ward, Alex, Ward, Kirsty, Watson, Kate, Weerasuriya, Thisara, Wickramanayake, Udara, Wilkinson, Hannah, Windley, Joseph, Wood, Janet, Wynell-Mayow, William, Zatti, Giovanni, Zeiton, Moez, Zurrón Lobato, Miriam.
The Surgeon ; 2022.
Article in English | ScienceDirect | ID: covidwho-1763986

ABSTRACT

Aims This international study aimed to assess: 1) the prevalence of preoperative and postoperative COVID-19 among patients with hip fracture, 2) the effect on 30-day mortality, and 3) clinical factors associated with the infection and with mortality in COVID-19-positive patients. Methods A multicentre collaboration among 112 centres in 14 countries collected data on all patients presenting with a hip fracture between 1st March-31st May 2020. Demographics, residence, place of injury, presentation blood tests, Nottingham Hip Fracture Score, time to surgery, management, ASA grade, length of stay, COVID-19 and 30-day mortality status were recorded. Results A total of 7090 patients were included, with a mean age of 82.2 (range 50-104) years and 4959 (70%) being female. Of 651 (9.2%) patients diagnosed with COVID-19, 225 (34.6%) were positive at presentation and 426 (65.4%) became positive postoperatively. Positive COVID-19 status was independently associated with male sex (odds ratio (OR) 1.38, p=0.001), residential care (OR 2.15, p<0.001), inpatient fall (OR 2.23, p=0.003), cancer (OR 0.63, p=0.009), ASA grade 4-5 (OR 1.59, p=0.008;OR 8.28, p<0.001), and longer admission (OR 1.06 for each increasing day, p<0.001). Patients with COVID-19 at any time had a significantly lower chance of 30-day survival versus those without COVID-19 (72.7% versus 92.6%, p<0.001). COVID-19 was independently associated with an increased 30-day mortality risk (hazard ratio (HR) 2.83, p<0.001). Increasing age (HR 1.03, p=0.028), male sex (HR 2.35, p<0.001), renal disease (HR 1.53, p=0.017), and pulmonary disease (HR 1.45, p=0.039) were independently associated with a higher 30-day mortality risk in patients with COVID-19 when adjusting for confounders. Conclusion The prevalence of COVID-19 in hip fracture patients during the first wave of the pandemic was 9%, and was independently associated with a three-fold increased 30-day mortality risk. Among COVID-19-positive patients, those who were older, male, with renal or pulmonary disease had a significantly higher mortality risk.

2.
Immunology ; 2022 Feb 14.
Article in English | MEDLINE | ID: covidwho-1685320

ABSTRACT

SARS-CoV-2 infection results in different outcomes ranging from asymptomatic infection to mild or severe disease and death. Reasons for this diversity of outcome include differences in challenge dose, age, gender, comorbidity and host genomic variation. Human leukocyte antigen (HLA) polymorphisms may influence immune response and disease outcome. We investigated the association of HLAII alleles with case definition symptomatic COVID-19, virus-specific antibody and T-cell immunity. A total of 1364 UK healthcare workers (HCWs) were recruited during the first UK SARS-CoV-2 wave and analysed longitudinally, encompassing regular PCR screening for infection, symptom reporting, imputation of HLAII genotype and analysis for antibody and T-cell responses to nucleoprotein (N) and spike (S). Of 272 (20%) HCW who seroconverted, the presence of HLA-DRB1*13:02 was associated with a 6·7-fold increased risk of case definition symptomatic COVID-19. In terms of immune responsiveness, HLA-DRB1*15:02 was associated with lower nucleocapsid T-cell responses. There was no association between DRB1 alleles and anti-spike antibody titres after two COVID vaccine doses. However, HLA DRB1*15:01 was associated with increased spike T-cell responses following both first and second dose vaccination. Trial registration: NCT04318314 and ISRCTN15677965.

3.
Sci Transl Med ; 13(609): eabj0847, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1406600

ABSTRACT

Understanding the impact of prior infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the response to vaccination is a priority for responding to the coronavirus disease 2019 (COVID-19) pandemic. In particular, it is necessary to understand how prior infection plus vaccination can modulate immune responses against variants of concern. To address this, we sampled 20 individuals with and 25 individuals without confirmed previous SARS-CoV-2 infection from a large cohort of health care workers followed serologically since April 2020. All 45 individuals had received two doses of the Pfizer-BioNTech BNT162b2 vaccine with a delayed booster at 10 weeks. Absolute and neutralizing antibody titers against wild-type SARS-CoV-2 and variants were measured using enzyme immunoassays and pseudotype neutralization assays. We observed antibody reactivity against lineage A, B.1.351, and P.1 variants with increasing antigenic exposure, through either vaccination or natural infection. This improvement was further confirmed in neutralization assays using fixed dilutions of serum samples. The impact of antigenic exposure was more evident in enzyme immunoassays measuring SARS-CoV-2 spike protein­specific IgG antibody concentrations. Our data show that multiple exposures to SARS-CoV-2 spike protein in the context of a delayed booster expand the neutralizing breadth of the antibody response to neutralization-resistant SARS-CoV-2 variants. This suggests that additional vaccine boosts may be beneficial in improving immune responses against future SARS-CoV-2 variants of concern.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibody Formation , COVID-19 Vaccines , Humans
4.
Sci Transl Med ; 13(609): eabj0847, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1352520

ABSTRACT

Understanding the impact of prior infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the response to vaccination is a priority for responding to the coronavirus disease 2019 (COVID-19) pandemic. In particular, it is necessary to understand how prior infection plus vaccination can modulate immune responses against variants of concern. To address this, we sampled 20 individuals with and 25 individuals without confirmed previous SARS-CoV-2 infection from a large cohort of health care workers followed serologically since April 2020. All 45 individuals had received two doses of the Pfizer-BioNTech BNT162b2 vaccine with a delayed booster at 10 weeks. Absolute and neutralizing antibody titers against wild-type SARS-CoV-2 and variants were measured using enzyme immunoassays and pseudotype neutralization assays. We observed antibody reactivity against lineage A, B.1.351, and P.1 variants with increasing antigenic exposure, through either vaccination or natural infection. This improvement was further confirmed in neutralization assays using fixed dilutions of serum samples. The impact of antigenic exposure was more evident in enzyme immunoassays measuring SARS-CoV-2 spike protein­specific IgG antibody concentrations. Our data show that multiple exposures to SARS-CoV-2 spike protein in the context of a delayed booster expand the neutralizing breadth of the antibody response to neutralization-resistant SARS-CoV-2 variants. This suggests that additional vaccine boosts may be beneficial in improving immune responses against future SARS-CoV-2 variants of concern.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibody Formation , COVID-19 Vaccines , Humans
5.
EClinicalMedicine ; 34: 100835, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1184950

ABSTRACT

BACKGROUND: : Healthcare workers (HCWs) have increased rates of SARS-CoV-2 infection compared with the general population. We aimed to understand ethnic differences in SARS-CoV-2 seropositivity among hospital healthcare workers depending on their hospital role, socioeconomic status, Covid-19 symptoms and basic demographics. METHODS: A prospective longitudinal observational cohort study. 1364 HCWs at five UK hospitals were studied with up to 16 weeks of symptom questionnaires and antibody testing (to both nucleocapsid and spike protein) during the first UK wave in five NHS hospitals between March 20 and July 10 2020. The main outcome measures were SARS-CoV-2 infection (seropositivity at any time-point) and symptoms. Registration number: NCT04318314. FINDINGS: 272 of 1364 HCWs (mean age 40.7 years, 72% female, 74% White, ≥6 samples per participant) seroconverted, reporting predominantly mild or no symptoms. Seropositivity was lower in Intensive Therapy Unit (ITU) workers (OR=0.44 95%CI 0.24, 0.77; p=0.0035). Seropositivity was higher in Black (compared to White) participants, independent of age, sex, role and index of multiple deprivation (OR=2.61 95%CI 1.47-4.62 p=0.0009). No association was seen between White HCWs and other minority ethnic groups. INTERPRETATION: In the UK first wave, Black ethnicity (but not other ethnicities) more than doubled HCWs likelihood of seropositivity, independent of age, sex, measured socio-economic factors and hospital role.

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