5 research outputs found
Whole-genome sequencing reveals host factors underlying critical COVID-19
- Author
- Abd Elghafar M.S.
- Abdel-Aziz M.
- Abdelrazik M.
- Abdollahi H.
- Abdullah T.
- Abecasis G.R.
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- Publication venue
- Springer Science and Business Media LLC
- Publication date
- 07/07/2022
- Field of study
Get PDFCritical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease
The introduction of a chest pain nurse and fast-track troponin service reduces the length of stay of patients presenting with chest pain.
- Publication venue
- Publication date
- 01/01/2007
- Field of study
No full textBackground Troponin I (TnI) measurement is important in decision making and management of patients who present with chest pain. Undetectable levels of TnI in these patients are associated with a low risk of death or myocardial infarction at 30 days, and may allow early discharge from hospital.
Methods An audit was performed tracking patients who presented with chest pain and had a TnI blood test requested. Routine clinical service was audited for three months. A "fast-track" troponin service and chest pain specialist nurse was then introduced to assist in the management of patients. This was continued for three months to assess the impact on length of stay.
Results 446 patients were admitted during the first three month period and 511 patients admitted during the second monitoring period when the new measures were introduced. The time from chest pain onset until the TnI blood test was taken reduced from 23.0 hours to 20.3 hours. The percentage of patients admitted to hospital wards from the Acute Medical Receiving Unit (AMRU) fell from 62% to 53% (p < 0.001). The new measures resulted in a reduction in admission time from 73.1 hours to 51.0 hours.
Conclusion A fast-track troponin and specialist nurse achieved a reduction of nearly 24 hours in length of stay in patients presenting with chest pain. This would result in a saving of approximately 2000 bed-days per annum, releasing 5-6 acute beds per day
The introduction of a chest pain nurse and fast-track troponin service reduces the length of stay of patients presenting with chest pain
- Publication venue
- Publication date
- 01/01/2007
- Field of study
No full textBackground Troponin I (TnI) measurement is important in decision making and management of patients who present with chest pain. Undetectable levels of TnI in these patients are associated with a low risk of death or myocardial infarction at 30 days, and may allow early discharge from hospital.
Methods An audit was performed tracking patients who presented with chest pain and had a TnI blood test requested. Routine clinical service was audited for three months. A "fast-track" troponin service and chest pain specialist nurse was then introduced to assist in the management of patients. This was continued for three months to assess the impact on length of stay.
Results 446 patients were admitted during the first three month period and 511 patients admitted during the second monitoring period when the new measures were introduced. The time from chest pain onset until the TnI blood test was taken reduced from 23.0 hours to 20.3 hours. The percentage of patients admitted to hospital wards from the Acute Medical Receiving Unit (AMRU) fell from 62% to 53% (p < 0.001). The new measures resulted in a reduction in admission time from 73.1 hours to 51.0 hours.
Conclusion A fast-track troponin and specialist nurse achieved a reduction of nearly 24 hours in length of stay in patients presenting with chest pain. This would result in a saving of approximately 2000 bed-days per annum, releasing 5-6 acute beds per day
Crystal and molecular structure of (3aR,8bS,5′R)3-[(2,5-dihydro-3-methyl-2-oxo-5-furanyl)oxymethylene]-3,3a,4,8b-tetrahydroindeno[1,2-b]furan-2-one
- Author
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- Field of study
No full textWhole-genome sequencing reveals host factors underlying critical COVID-19
- Author
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- Åsvold Bjørn Olav
- Publication venue
- Publication date
- 01/01/2022
- Field of study
No full textAltres ajuts: Department of Health and Social Care (DHSC); Illumina; LifeArc; Medical Research Council (MRC); UKRI; Sepsis Research (the Fiona Elizabeth Agnew Trust); the Intensive Care Society, Wellcome Trust Senior Research Fellowship (223164/Z/21/Z); BBSRC Institute Program Support Grant to the Roslin Institute (BBS/E/D/20002172, BBS/E/D/10002070, BBS/E/D/30002275); UKRI grants (MC_PC_20004, MC_PC_19025, MC_PC_1905, MRNO2995X/1); UK Research and Innovation (MC_PC_20029); the Wellcome PhD training fellowship for clinicians (204979/Z/16/Z); the Edinburgh Clinical Academic Track (ECAT) programme; the National Institute for Health Research, the Wellcome Trust; the MRC; Cancer Research UK; the DHSC; NHS England; the Smilow family; the National Center for Advancing Translational Sciences of the National Institutes of Health (CTSA award number UL1TR001878); the Perelman School of Medicine at the University of Pennsylvania; National Institute on Aging (NIA U01AG009740); the National Institute on Aging (RC2 AG036495, RC4 AG039029); the Common Fund of the Office of the Director of the National Institutes of Health; NCI; NHGRI; NHLBI; NIDA; NIMH; NINDS.Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care or hospitalization after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes-including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)-in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease
