Characterising biological mechanisms underlying ethnicity-associated outcomes in COVID-19 through biomarker trajectories: a multicentre registry analysis

Background Differences in routinely collected biomarkers between ethnic groups could reflect dysregulated host responses to disease and to treatments, and be associated with excess morbidity and mortality in COVID-19. Methods A multicentre registry analysis from patients aged ≥16 yr with SARS-CoV-2 infection and emergency admission to Barts Health NHS Trust hospitals during 01/01/2020-13/05/2020 (wave 1) and 01/09/2020-17/02/2021 (wave 2) was subjected to unsupervised longitudinal clustering techniques to identify distinct phenotypic patient clusters based on trajectories of routine blood results over the first 15 days of hospital admission. Distribution of trajectory clusters across ethnic categories was determined, and associations between ethnicity, trajectory clusters, and 30-day survival were assessed using multivariable Cox proportional hazards modelling. Secondary outcomes were intensive care unit admission, survival to hospital discharge, and long-term survival to 640 days. Results We included 3237 patients with hospital length of stay ≥7 days. In patients who died, there was greater representation of Black and Asian ethnicity in trajectory clusters for C-reactive protein (CRP) and urea-to-creatinine ratio (UCR) associated with increased risk of death. Inclusion of trajectory clusters in survival analyses attenuated or abrogated the higher risk of death in Asian and Black patients. Inclusion of CRP went from hazard ratio (HR) 1.36 [0.95-1.94] to HR 0.97 [0.59-1.59] (wave 1), and from HR 1.42 [1.15-1.75]) to HR 1.04 [0.78-1.39] (wave 2) in Asian patients. Trajectory clusters associated with reduced 30-day survival were similarly associated with worse secondary outcomes. Conclusions Clinical biochemical monitoring of COVID-19 and progression and treatment response in SARS-CoV-2 infection should be interpreted in the context of ethnic background.

COVID-19-associated AKI.

PURPOSE OF REVIEW: While it is now widely established acute kidney injury (AKI) is a common and important complication of coronavirus disease (COVID-19) disease, there is marked variability in its reported incidence and outcomes. This narrative review provides a mid-2022 summary of the latest epidemiological evidence on AKI in COVID-19. RECENT FINDINGS: Large observational studies and meta-analyses report an AKI incidence of 28-34% in all inpatients and 46-77% in intensive care unit (ICU). The incidence of more severe AKI requiring renal replacement therapy (RRT) in ICU appears to have declined over time, in data from England and Wales RRT use declined from 26% at the start of the pandemic to 14% in 2022. The majority of survivors apparently recover their kidney function by hospital discharge; however, these individuals appear to remain at increased risk of future AKI, estimated glomerular filtration rate (eGFR) decline and chronic kidney disease. Importantly even in the absence of overt AKI a significant proportion of survivors of COVID-19 hospitalisation had reduced eGFR on follow-up. SUMMARY: This review summarises the epidemiology, risk factors, outcomes and treatment of COVID-19-associated AKI across the global pandemic. In particular the long-term impact of COVID-19 disease on kidney health is uncertain and requires further characterisation.

Characteristics and Outcomes of Patients With Frailty Admitted to ICU With Coronavirus Disease 2019: An Individual Patient Data Meta-Analysis.

Frailty is often used in clinical decision-making for patients with coronavirus disease 2019, yet studies have found a variable influence of frailty on outcomes in those admitted to the ICU. In this individual patient data meta-analysis, we evaluated the characteristics and outcomes across the range of frailty in patients admitted to ICU with coronavirus disease 2019. DATA SOURCES: We contacted the corresponding authors of 16 eligible studies published between December 1, 2019, and February 28, 2021, reporting on patients with confirmed coronavirus disease 2019 admitted to ICU with a documented Clinical Frailty Scale. STUDY SELECTION: Individual patient data were obtained from seven studies with documented Clinical Frailty Scale were included. We classified patients as nonfrail (Clinical Frailty Scale = 1-4) or frail (Clinical Frailty Scale = 5-8). DATA EXTRACTION: We collected patient demographics, Clinical Frailty Scale score, ICU organ supports, and clinically relevant outcomes (ICU and hospital mortality, ICU and hospital length of stays, and discharge destination). The primary outcome was hospital mortality. DATA SYNTHESIS: Of the 2,001 patients admitted to ICU, 388 (19.4%) were frail. Increasing age and Sequential Organ Failure Assessment score, Clinical Frailty Scale score greater than or equal to 4, use of mechanical ventilation, vasopressors, renal replacement therapy, and hyperlactatemia were risk factors for death in a multivariable analysis. Hospital mortality was higher in patients with frailty (65.2% vs 41.8%; p < 0.001), with adjusted mortality increasing with a rising Clinical Frailty Scale score beyond 3. Younger and nonfrail patients were more likely to receive mechanical ventilation. Patients with frailty spent less time on mechanical ventilation (median days [interquartile range], 9 [5-16] vs 11 d [6-18 d]; p = 0.012) and accounted for only 12.3% of total ICU bed days. CONCLUSIONS: Patients with frailty with coronavirus disease 2019 were commonly admitted to ICU and had greater hospital mortality but spent relatively fewer days in ICU when compared with nonfrail patients. Patients with frailty receiving mechanical ventilation were at greater risk of death than patients without frailty.

Acute kidney injury in COVID-19: multicentre prospective analysis of registry data.

BACKGROUND: Acute kidney injury (AKI) is a common and important complication of coronavirus disease 2019 (COVID-19). Further characterization is required to reduce both short- and long-term adverse outcomes. METHODS: We examined registry data including adults with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection admitted to five London Hospitals from 1 January to 14 May 2020. Prior end-stage kidney disease was excluded. Early AKI was defined by Kidney Disease: Improving Global Outcomes creatinine criteria within 7 days of admission. Independent associations of AKI and survival were examined in multivariable analysis. Results are given as odds ratios (ORs) or hazard ratios (HRs) with 95% confidence intervals. RESULTS: Among 1855 admissions, 455 patients (24.5%) developed early AKI: 200 (44.0%) Stage 1, 90 (19.8%) Stage 2 and 165 (36.3%) Stage 3 (74 receiving renal replacement therapy). The strongest risk factor for AKI was high C-reactive protein [OR 3.35 (2.53-4.47), P < 0.001]. Death within 30 days occurred in 242 (53.2%) with AKI compared with 255 (18.2%) without. In multivariable analysis, increasing severity of AKI was incrementally associated with higher mortality: Stage 3 [HR 3.93 (3.04-5.08), P < 0.001]. In 333 patients with AKI surviving to Day 7, 134 (40.2%) recovered, 47 (14.1%) recovered then relapsed and 152 (45.6%) had persistent AKI at Day 7; an additional 105 (8.2%) patients developed AKI after Day 7. Persistent AKI was strongly associated with adjusted mortality at 90 days [OR 7.57 (4.50-12.89), P < 0.001]. CONCLUSIONS: AKI affected one in four hospital in-patients with COVID-19 and significantly increased mortality. Timing and recovery of COVID-19 AKI is a key determinant of outcome.

Natural history, trajectory, and management of mechanically ventilated COVID-19 patients in the United Kingdom.

PURPOSE: The trajectory of mechanically ventilated patients with coronavirus disease 2019 (COVID-19) is essential for clinical decisions, yet the focus so far has been on admission characteristics without consideration of the dynamic course of the disease in the context of applied therapeutic interventions. METHODS: We included adult patients undergoing invasive mechanical ventilation (IMV) within 48 h of intensive care unit (ICU) admission with complete clinical data until ICU death or discharge. We examined the importance of factors associated with disease progression over the first week, implementation and responsiveness to interventions used in acute respiratory distress syndrome (ARDS), and ICU outcome. We used machine learning (ML) and Explainable Artificial Intelligence (XAI) methods to characterise the evolution of clinical parameters and our ICU data visualisation tool is available as a web-based widget ( https://www.CovidUK.ICU ). RESULTS: Data for 633 adults with COVID-19 who underwent IMV between 01 March 2020 and 31 August 2020 were analysed. Overall mortality was 43.3% and highest with non-resolution of hypoxaemia [60.4% vs17.6%; P < 0.001; median PaO2/FiO2 on the day of death was 12.3(8.9-18.4) kPa] and non-response to proning (69.5% vs.31.1%; P < 0.001). Two ML models using weeklong data demonstrated an increased predictive accuracy for mortality compared to admission data (74.5% and 76.3% vs 60%, respectively). XAI models highlighted the increasing importance, over the first week, of PaO2/FiO2 in predicting mortality. Prone positioning improved oxygenation only in 45% of patients. A higher peak pressure (OR 1.42[1.06-1.91]; P < 0.05), raised respiratory component (OR 1.71[ 1.17-2.5]; P < 0.01) and cardiovascular component (OR 1.36 [1.04-1.75]; P < 0.05) of the sequential organ failure assessment (SOFA) score and raised lactate (OR 1.33 [0.99-1.79]; P = 0.057) immediately prior to application of prone positioning were associated with lack of oxygenation response. Prone positioning was not applied to 76% of patients with moderate hypoxemia and 45% of those with severe hypoxemia and patients who died without receiving proning interventions had more missed opportunities for prone intervention [7 (3-15.5) versus 2 (0-6); P < 0.001]. Despite the severity of gas exchange deficit, most patients received lung-protective ventilation with tidal volumes less than 8 mL/kg and plateau pressures less than 30cmH2O. This was despite systematic errors in measurement of height and derived ideal body weight. CONCLUSIONS: Refractory hypoxaemia remains a major association with mortality, yet evidence based ARDS interventions, in particular prone positioning, were not implemented and had delayed application with an associated reduced responsiveness. Real-time service evaluation techniques offer opportunities to assess the delivery of care and improve protocolised implementation of evidence-based ARDS interventions, which might be associated with improvements in survival.

Ethnicity and outcomes in patients hospitalised with COVID-19 infection in East London: an observational cohort study.

OBJECTIVE: To describe outcomes within different ethnic groups of a cohort of hospitalised patients with confirmed COVID-19 infection. To quantify and describe the impact of a number of prognostic factors, including frailty and inflammatory markers. SETTING: Five acute National Health Service Hospitals in east London. DESIGN: Prospectively defined observational study using registry data. PARTICIPANTS: 1737 patients aged 16 years or over admitted to hospital with confirmed COVID-19 infection between 1 January and 13 May 2020. MAIN OUTCOME MEASURES: The primary outcome was 30-day mortality from time of first hospital admission with COVID-19 diagnosis during or prior to admission. Secondary outcomes were 90-day mortality, intensive care unit (ICU) admission, ICU and hospital length of stay and type and duration of organ support. Multivariable survival analyses were adjusted for potential confounders. RESULTS: 1737 were included in our analysis of whom 511 had died by day 30 (29%). 538 (31%) were from Asian, 340 (20%) black and 707 (40%) white backgrounds. Compared with white patients, those from minority ethnic backgrounds were younger, with differing comorbidity profiles and less frailty. Asian and black patients were more likely to be admitted to ICU and to receive invasive ventilation (OR 1.54, (95% CI 1.06 to 2.23); p=0.023 and OR 1.80 (95% CI 1.20 to 2.71); p=0.005, respectively). After adjustment for age and sex, patients from Asian (HR 1.49 (95% CI 1.19 to 1.86); p<0.001) and black (HR 1.30 (95% CI 1.02 to 1.65); p=0.036) backgrounds were more likely to die. These findings persisted across a range of risk factor-adjusted analyses accounting for major comorbidities, obesity, smoking, frailty and ABO blood group. CONCLUSIONS: Patients from Asian and black backgrounds had higher mortality from COVID-19 infection despite controlling for all previously identified confounders and frailty. Higher rates of invasive ventilation indicate greater acute disease severity. Our analyses suggest that patients of Asian and black backgrounds suffered disproportionate rates of premature death from COVID-19.