Critical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown1 to be highly efficient for discovery of genetic associations2. Despite the advanced stage of illness at presentation, we have shown that host genetics in patients who are critically ill with COVID-19 can identify immunomodulatory therapies with strong beneficial effects in this group3. Here we analyse 24,202 cases of COVID-19 with critical illness comprising a combination of microarray genotype and whole-genome sequencing data from cases of critical illness in the international GenOMICC (11,440 cases) study, combined with other studies recruiting hospitalized patients with a strong focus on severe and critical disease: ISARIC4C (676 cases) and the SCOURGE consortium (5,934 cases). To put these results in the context of existing work, we conduct a meta-analysis of the new GenOMICC genome-wide association study (GWAS) results with previously published data. We find 49 genome-wide significant associations, of which 16 have not been reported previously. To investigate the therapeutic implications of these findings, we infer the structural consequences of protein-coding variants, and combine our GWAS results with gene expression data using a monocyte transcriptome-wide association study (TWAS) model, as well as gene and protein expression using Mendelian randomization. We identify potentially druggable targets in multiple systems, including inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).
Improvements in monitoring have occurred over the last 5 yr, but observations of neurological function are not routine in all units, and are not continued after removal of the epidural catheter in the majority. The authors suggest that acute pain services should be responsible for protocols for the investigation and treatment of epidural haematomas.
Ten diabetics, nine requiring insulin, were kept alive on peritoneal dialysis and haemodialysis for varying periods of time, with a mean suvival rate of 7 months only per patient. The management of the cardiovascular problems affecting the brain, eye, heart, and peripheral vessels far exceeded the difficulties in managing their diabetic state. Two patients were maintained on home dialysis, one with full sight, the other with partial sight. One patient received a combined renal and pancreatic transplant and required no insulin for 8 days, succumbing from a pulmonary embolus. Patients with diabetes will be accepted in the future for regular dialysis, particularly before severe protein restriction has taken place, and before hypertension has complicated their retinal problems.
Background
Sepsis is one of the most frequent reasons for acute intensive care unit (ICU) admission of very old patients and mortality rates are high. However, the impact of pre-existing physical and cognitive function on long-term outcome of ICU patients ≥ 80 years old (very old intensive care patients (VIPs)) with sepsis is unclear.
Objective
To investigate both the short- and long-term mortality of VIPs admitted with sepsis and assess the relation of mortality with pre-existing physical and cognitive function.
Design
Prospective cohort study.
Setting
241 ICUs from 22 European countries in a six-month period between May 2018 and May 2019.
Subjects
Acutely admitted ICU patients aged ≥80 years with sequential organ failure assessment (SOFA) score ≥ 2.
Methods
Sepsis was defined according to the sepsis 3.0 criteria. Patients with sepsis as an admission diagnosis were compared with other acutely admitted patients. In addition to patients’ characteristics, disease severity, information about comorbidity and polypharmacy and pre-existing physical and cognitive function were collected.
Results
Out of 3,596 acutely admitted VIPs with SOFA score ≥ 2, a group of 532 patients with sepsis were compared to other admissions. Predictors for 6-month mortality were age (per 5 years): Hazard ratio (HR, 1.16 (95% confidence interval (CI), 1.09–1.25, P < 0.0001), SOFA (per one-point): HR, 1.16 (95% CI, 1.14–1.17, P < 0.0001) and frailty (CFS > 4): HR, 1.34 (95% CI, 1.18–1.51, P < 0.0001).
Conclusions
There is substantial long-term mortality in VIPs admitted with sepsis. Frailty, age and disease severity were identified as predictors of long-term mortality in VIPs admitted with sepsis.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.