Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly infectious respiratory virus which is responsible for the coronavirus disease 2019 (COVID-19) pandemic. It is increasingly ...clear that recovered individuals, even those who had mild COVID-19, can suffer from persistent symptoms for many months after infection, a condition referred to as "long COVID", post-acute sequelae of COVID-19 (PASC), post-acute COVID-19 syndrome, or post COVID-19 condition. However, despite the plethora of research on COVID-19, relatively little is known about the molecular underpinnings of these long-term effects.
We have undertaken an integrated analysis of immune responses in blood at a transcriptional, cellular, and serological level at 12, 16, and 24 weeks post-infection (wpi) in 69 patients recovering from mild, moderate, severe, or critical COVID-19 in comparison to healthy uninfected controls. Twenty-one of these patients were referred to a long COVID clinic and > 50% reported ongoing symptoms more than 6 months post-infection.
Anti-Spike and anti-RBD IgG responses were largely stable up to 24 wpi and correlated with disease severity. Deep immunophenotyping revealed significant differences in multiple innate (NK cells, LD neutrophils, CXCR3+ monocytes) and adaptive immune populations (T helper, T follicular helper, and regulatory T cells) in convalescent individuals compared to healthy controls, which were most strongly evident at 12 and 16 wpi. RNA sequencing revealed significant perturbations to gene expression in COVID-19 convalescents until at least 6 months post-infection. We also uncovered significant differences in the transcriptome at 24 wpi of convalescents who were referred to a long COVID clinic compared to those who were not.
Variation in the rate of recovery from infection at a cellular and transcriptional level may explain the persistence of symptoms associated with long COVID in some individuals.
Purpose
Hyperglycaemia is common in the critically ill. The objectives of this study were to determine the prevalence of critical illness-associated hyperglycaemia (CIAH) and recognised and ...unrecognised diabetes in the critically ill as well as to evaluate the impact of premorbid glycaemia on the association between acute hyperglycaemia and mortality.
Methods
In 1,000 consecutively admitted patients we prospectively measured glycated haemoglobin (HbA
1c
) on admission, and blood glucose concentrations during the 48 h after admission, to the intensive care unit. Patients with blood glucose ≥7.0 mmol/l when fasting or ≥11.1 mmol/l during feeding were deemed hyperglycaemic. Patients with acute hyperglycaemia and HbA
1c
<6.5 % (48 mmol/mol) were categorised as ‘CIAH’, those with known diabetes as ‘recognised diabetes’, and those with HbA
1c
≥6.5 % but no previous diagnosis of diabetes as ‘unrecognised diabetes’. The remainder were classified as ‘normoglycaemic’. Hospital mortality, HbA
1c
and acute peak glycaemia were assessed using a logistic regression model.
Results
Of 1,000 patients, 498 (49.8 %) had CIAH, 220 (22 %) had recognised diabetes, 55 (5.5 %) had unrecognised diabetes and 227 (22.7 %) were normoglycaemic. The risk of death increased by approximately 20 % for each increase in acute glycaemia of 1 mmol/l in patients with CIAH and those with diabetes and HbA
1c
levels <7 % (53 mmol/mol), but not in patients with diabetes and HbA
1c
≥7 %. This association was lost when adjusted for severity of illness.
Conclusions
Critical illness-associated hyperglycaemia is the most frequent cause of hyperglycaemia in the critically ill. Peak glucose concentrations during critical illness are associated with increased mortality in patients with adequate premorbid glycaemic control, but not in patients with premorbid hyperglycaemia. Optimal glucose thresholds in the critically ill may, therefore, be affected by premorbid glycaemia.
Objectives
To describe the characteristics and outcomes of patients with COVID‐19 admitted to intensive care units (ICUs) during the initial months of the pandemic in Australia.
Design, setting
...Prospective, observational cohort study in 77 ICUs across Australia.
Participants
Patients admitted to participating ICUs with laboratory‐confirmed COVID‐19 during 27 February – 30 June 2020.
Main outcome measures
ICU mortality and resource use (ICU length of stay, peak bed occupancy).
Results
The median age of the 204 patients with COVID‐19 admitted to intensive care was 63.5 years (IQR, 53–72 years); 140 were men (69%). The most frequent comorbid conditions were obesity (40% of patients), diabetes (28%), hypertension treated with angiotensin‐converting enzyme inhibitors or angiotensin II receptor blockers (24%), and chronic cardiac disease (20%); 73 patients (36%) reported no comorbidity. The most frequent source of infection was overseas travel (114 patients, 56%). Median peak ICU bed occupancy was 14% (IQR, 9–16%). Invasive ventilation was provided for 119 patients (58%). Median length of ICU stay was greater for invasively ventilated patients than for non‐ventilated patients (16 days; IQR, 9–28 days v 3 days; IQR, 2–5 days), as was ICU mortality (26 deaths, 22%; 95% CI, 15–31% v four deaths, 5%; 95% CI, 1–12%). Higher Acute Physiology and Chronic Health Evaluation II (APACHE‐II) scores on ICU day 1 (adjusted hazard ratio aHR, 1.15; 95% CI, 1.09–1.21) and chronic cardiac disease (aHR, 3.38; 95% CI, 1.46–7.83) were each associated with higher ICU mortality.
Conclusion
Until the end of June 2020, mortality among patients with COVID‐19 who required invasive ventilation in Australian ICUs was lower and their ICU stay longer than reported overseas. Our findings highlight the importance of ensuring adequate local ICU capacity, particularly as the pandemic has not yet ended.
Introduction
Acute ischemic stroke (AIS) can be a catastrophic complication of cardiac surgery previously without effective treatment. Endovascular thrombectomy (EVT) is a potentially life‐saving ...intervention. We examined patients at our institution who had EVT to treat AIS post cardiac surgery.
Methods
We retrospectively reviewed a stroke database from January 1, 2016 to October 31, 2021 to identify patients who had undergone EVT to treat AIS following cardiac surgery. Demographic data, operation type, stroke severity, imaging features, management and outcomes (mortality and modified Rankin Score (mRS)) were assessed.
Results
Of 5022 consecutive patients with AIS, 870 underwent EVT. Seven patients (0.8%) had EVT following cardiac surgery. Operations varied: two coronary artery bypass grafting (CABG), two transcatheter AVR, one redo surgical aortic valve replacement (AVR), one mitral valve repair and one patient with combined aortic and mitral valve replacements and CABG. Meantime postsurgery to stroke symptoms onset was 3 days (range 0–9 days). Median NIHSS was 26 (range 10–32). Five patients had middle cerebral artery occlusion and two internal carotid artery (n = 2). Median time between onset of symptoms and recanalization was 157 min (range 97–263). Two patients received Intra‐arterial Thrombolysis. All patients survived and were discharged to another hospital (n = 3), home (n = 2), or rehabilitation facility (n = 2). Median 3‐month mRS was 3 (range 0–6).
Conclusion
We report the largest case series of EVT after cardiac surgery. EVT can be associated with excellent outcomes in these patients. Close neurological monitoring postoperatively to identify patients who may benefit from intervention is key.
Coronavirus disease 2019 (COVID-19) convalescents living in regions with low vaccination rates rely on post-infection immunity for protection against re-infection with severe acute respiratory ...syndrome coronavirus 2 (SARS-CoV-2). We evaluate humoral and T cell immunity against five variants of concern (VOCs) in mild-COVID-19 convalescents at 12 months after infection with ancestral virus. In this cohort, ancestral, receptor-binding domain (RBD)-specific antibody and circulating memory B cell levels are conserved in most individuals, and yet serum neutralization against live B.1.1.529 (Omicron) is completely abrogated and significantly reduced for other VOCs. Likewise, ancestral SARS-CoV-2-specific memory T cell frequencies are maintained in >50% of convalescents, but the cytokine response in these cells to mutated spike epitopes corresponding to B.1.1.529 and B.1.351 (Beta) VOCs were impaired. These results indicate that increased antigen variability in VOCs impairs humoral and spike-specific T cell immunity post-infection, strongly suggesting that COVID-19 convalescents are vulnerable and at risk of re-infection with VOCs, thus stressing the importance of vaccination programs.
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•Most mild COVID-19 convalescents maintain immunity at 12 months after disease onset•B.1.1.529 escapes antibodies in convalescents infected with ancestral SARS-CoV-2•SARS-CoV-2 VOCs can partially avoid recognition by antigen-specific T cells•Antigenic drift in SARS-CoV-2 VOCs significantly challenges convalescent immunity
Garcia-Valtanen et al. investigate immunity in mild COVID-19 convalescents at 12 months after infection in the absence of re-exposure to the virus and vaccination. Both neutralizing antibody and spike-specific T cell responses were significantly affected by the spike amino-acid differences incorporated in B.1.1.529 and other VOCs.
Elective cardiac surgery accounts for a significant proportion of perioperative resource allocation in Australasia. Preoperative pulmonary function testing (PFT) is routinely undertaken in some ...centres to identify patients who may require prolonged ventilation and intensive care unit (ICU) stay, although there are currently no data supporting this practice. Routine PFT places a burden on respiratory diagnostic laboratories, is inconvenient to patients and may delay surgery.We aimed to identify whether PFT parameters identify patients requiring prolonged mechanical ventilation after elective cardiac surgery. Adult patients admitted to the Royal Adelaide Hospital ICU following elective cardiac surgery between July 2013 and December 2017 were identified retrospectively from the local ICU database. Preoperative PFT and operative and postoperative outcome data were retrieved from local databases, and multivariable logistic regression was undertaken to identify which PFT variables were associated with prolonged mechanical ventilation. PFT data were available for 835/1139 (73%) elective cardiac surgical cases. The best independent predictors of prolonged mechanical ventilation were post-bronchodilator forced vital capacity (FVC) and single-breath diffusing capacity for carbon monoxide (DLCO). Patients with FVC <80% predicted and DLCO <60% predicted had an odds ratio for prolonged postoperative ventilation of 7.5 (95% confidence intervals 3.6-15.6; P<0.001). The area under the receiver operating characteristic curve derived from this model was 0.68. Abnormal PFT results were associated with prolonged postoperative mechanical ventilation. A PFT-based prediction tool does not accurately predict individual patient outcome but identifies a cohort of patients at higher risk of requiring prolonged ventilation, potentially informing ICU resource allocation and surgical planning.
Introduction:
Comprehensive clinical examination can be compromised in patients on veno-venous extracorporeal membrane oxygenation (VV-ECMO). Adjunctive diagnostic imaging strategies range from ...bedside imaging only to routine computed tomography (CT). The risk-benefit of either approach remains to be evaluated. Patients retrieved to the Royal Brompton Hospital (RBH) on VV-ECMO routinely undergo admission CT imaging of head, chest, abdomen and pelvis.
This study aimed to identify how frequently changes in therapy or adverse events could be attributed to routine CT scanning.
Methods:
Demographic and clinical data were gathered retrospectively from patients retrieved to RBH on VV-ECMO (January 2014-2016). Scans were categorized as ‘routine’ or requested to clarify a specific clinical uncertainty. Clinical records were reviewed to identify attributable management changes and CT- related adverse events.
Seventy-two patients were retrieved on VV-ECMO (median age 44 years) and 65 scanned on admission (mean radiation dose 2344mGy-cm). Routine head CT head yielded novel clinical information in 11 patients, 10 of whom had unexpected intracranial haemorrhage and, subsequently, had their anticoagulation withheld. Routine thoracic CT identified unexpected positive findings in three patients (early fibrosis, pulmonary vasculitis, pneumomediastinum), eliciting management variation in one (steroid administration). Routine abdomen/pelvis CT identified new information in three patients (adrenal haemorrhage, hepatosteatosis, splenic infarction), changing the management in one (withholding anticoagulation).
Results:
CT scanning was not associated with consequential adverse events (e.g. accidental decannulation, gas entrainment into the circuit, hypoxia, hypotension). Median transfer/scan time was 78 minutes, requiring five ITU staff-members. In our cohort, a policy of routine head CT changed the management in 17% of patients; the yield from routine chest, abdomen and pelvis CT was modest. CT transfer was safe, but resource intensive.
Conclusion:
Prospective studies should evaluate whether routine CT impacts outcome.
Critically ill patients experience acute muscle wasting and long-term functional impairments, yet this has been inadequately categorised early in recovery.
This observational study aimed to evaluate ...anthropometry, strength, and muscle function after intensive care unit discharge.
Adult patients able to complete study measures after prolonged intensive care unit stay (≥5 d) were eligible. Demographic and clinical data were collected, and bodyweight, height, triceps skinfold, trunk length, handgrip strength, 6-minute walk test, whole-body dual-energy x-ray absorptiometry, and mid-thigh, knee, and above-ankle circumferences were measured. Body cell mass was calculated from these data. Data are presented as mean (standard deviation) or median interquartile range.
Fourteen patients (50% male; 57 10.5 years) were assessed 11.1 (6.9) d after intensive care unit discharge. Patients lost 4.76 (6.66) kg in the intensive care unit. Triceps skinfold thickness (17.00 8.65 mm) and handgrip strength (12.60 8.57 kg) were lower than normative data. No patient could commence the 6-minute walk test. Dual-energy x-ray absorptiometry–derived muscle mass correlated with handgrip strength (R = 0.57; 95% confidence interval = 0.06–0.85; p = 0.03), but body cell mass did not.
Anthropometry and strength in intensive care unit survivors are below normal. Muscle mass derived from dual-energy x-ray absorptiometry correlates with handgrip strength but body cell mass does not.
In Australia, extracorporeal membrane oxygenation (ECMO) is one of the most expensive diagnosis-related groups, costing $305 463 per complex admission to the intensive care unit (ICU). Mortality in ...this group of patients is high, about 43% for respiratory failure and 68% for cardiac failure. ECMO is associated with significant risk to the patient and requires specialist training and expertise. Variation in clinical practice for patients supported with ECMO may compromise patient care and outcomes.
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