Blood levels of the soluble receptor for advanced glycation end-products (sRAGE) are acutely elevated during the host inflammatory response to infection and predict mortality in COVID-19. However, the prognostic performance of this biomarker in the context of treatments to reduce inflammation is unclear. In this study we investigated the association between sRAGE and mortality in dexamethasone-treated COVID-19 patients. We studied 89 SARS-CoV-2 positive subjects and 22 controls attending the emergency department of a University Teaching Hospital during the second wave of COVID-19 and measured sRAGE at admission. In positive individuals sRAGE increased with disease severity and correlated with the National Early Warning Score 2 (Pearson’s r = 0.56, p < 0.001). Fourteen out of 72 patients treated with dexamethasone died during 28 days of follow-up. Survival rates were significantly lower in patients with high sRAGE (> 3532 pg/mL) than in those with low sRAGE (p = 0.01). Higher sRAGE levels were associated with an increased risk of death after adjustment for relevant covariates. In contrast, IL-6 did not predict mortality in these patients. These results demonstrate that sRAGE remains an independent predictor of mortality among COVID-19 patients treated with dexamethasone. Determination of sRAGE could be useful for the clinical management of this patient population.

Introduction. Fungal infection is a cause of increased morbidity and mortality in intensive care patients. Critically unwell patients are at increased risk of developing invasive fungal infections. COVID‐19 patients in the intensive care unit (ICU) may be at a particularly high risk. The primary aim of this study was to establish the incidence of secondary fungal infections in patients admitted to the ICU with COVID‐19. Secondary aims were to investigate factors that may contribute to an increased risk of fungal infections and to calculate the mortality between fungal and nonfungal groups. Methods. We undertook a retrospective observational study in a tertiary ICU in Wales, United Kingdom. 174 patients admitted with COVID‐19 infection from March 2020 until May 2021 were included. Data were collected through a retrospective review of patient’s clinical notes and microbiology investigation results obtained from the online clinical portal. Results. 81/174 (47%) COVID‐19 patients developed fungal infections, 93% of which were Candida species, including Candida albicans (88%), and 6% had an Aspergillus infection. Age and smoking history did not appear to be contributing factors. The nonfungal group had a significantly higher body mass index (33 ± 8 vs. 31 ± 7, p = 0.01). The ICU length of stay (23 (1–116) vs. 8 (1–60), p < 0.001), hospital length of stay (30 (3–183) vs. 15 (1–174) ± 7, p < 0.001), steroid days (10 (1–116) vs. 4 (0–28), p = 0.02), and ventilation days (18 (0–120) vs. 2 (0–55), p < 0.001) were significantly higher in the fungal group. The mortality rate in both groups was similar (51% vs. 52%). The Kaplan–Meier survival analysis showed that the fungal group survived more than the nonfungal group (log rank (Mantel–Cox), p < 0.001). Conclusion. Secondary fungal infections are common in COVID‐19 patients admitted to the ICU. Longer treatment with corticosteroids, increased length of hospital and ICU stay, and greater length of mechanical ventilation significantly increase the risk of fungal infections. Fungal infection, however, was not associated with an increase in mortality.

Background Chronic Obstructive Pulmonary Disease (COPD) patients are prone to thrombogenic events, particularly during exacerbations. Fractal dimension (d f), a functional biomarker of clot microstructure is useful in assessing thrombogenicity in other diseases. The aim of this study was to compare the changes in d f during acute exacerbation of COPD with stable disease. Methods This prospective study recruited 30 patients with stable disease from the chest clinic and 85 patients with acute exacerbations from the Emergency Department. The stable group had blood samples taken at one time point, whilst the exacerbation group were sampled at four time points (0 hours, 4-6 hours, 24 hours and 3-7 days). Biomarkers of inflammation, haemostasis and rheology were determined. Results At presentation, the acute exacerbation group had significantly elevated d f when compared to the stable group (1.71 ± 0.06 vs 1.69 ± 0.05, p=0.03) but with no significant changes in d f over the four time points (p=0.28) sampled. The patients who died in the acute exacerbation group had significantly elevated d f when compared to those who survived (1.76 ± 0.03 vs 1.71 ± 0.06, p=0.02) with additional logistic regression analysis confirming that d f was a significant predictor of mortality (p=0.024). Conclusions Clot microstructural analysis demonstrates that COPD patients during acute exacerbation are more thrombogenic when compared to those with stable disease. This thrombogenic state is not aggravated with appropriate treatment on admission. Patients who died during exacerbations were in a significantly enhanced thrombogenic state when compared to those who survived as demonstrated by significantly elevated d f.

Introduction: Methamoglobinemia is a condition characterized by impaired oxygen delivery to the tissues due to the formation of methemoglobin (Met‐Hb). Diagnosis is established when Met‐Hb levels exceed 5%. Levels over 30% are associated with severe symptoms and can be life‐threatening. Pulse oximetry may provide misleading readings, often reporting oxygen saturation around 85%, irrespective of actual oxygenation levels. Management involves discontinuing offending agents, providing supportive care, and use of specific treatment agents. Most commonly, cases report a quick and effective recovery following treatment. Case Presentation: We describe a case of a patient requiring four separate admissions over a 9‐month period, all for methemoglobinemia, where the cause remained uncertain. A 25‐year‐old female was admitted to the intensive care unit (ICU) with sudden onset shortness of breath and cyanosis, and Met‐Hb level 55.5%, suspected due to dapsone. She was treated with 1 mg/kg of methylene blue intravenously. Met‐Hb levels remained persistently above 20% for a number of days, and reaccumulated following initial decline. Repeated doses of methylene blue were required, and activated charcoal was given. She was readmitted 3 days later, with reaccumulation of Met‐Hb. This was again thought secondary to dapsone, given the long half‐life of dapsone and potential for enterohepatic recirculation. She had a third admission with methemoglobinemia almost 2 months after the first admission, and again 8 months later. Suggestion was that azathioprine could be the causative agent; however, this has not been reported previously. Discussion: We report a case of a 25‐year‐old female with repeated admissions with methemoglobinemia. This case highlights the potential for refractory methemoglobinemia requiring repeated treatment, and the importance of longer periods of close observation. It is important to consider the diagnosis in patients without a clear trigger for methemoglobinemia, as an identifiable cause may not always be clear.

Introduction: Smoking is known to be harmful to health, contributing to increased severity in respiratory infections such as influenza. The impact in COVID‐19 remains controversial. Social deprivation and inequality are associated with worse outcomes in infectious disease and may impact on mortality in COVID‐19. Methods: A retrospective cohort study in a tertiary hospital general adult Intensive Care Unit (ICU). 174 patients with COVID‐19 confirmed by polymerase chain reaction (PCR) testing between March 21st 2020 and May 15th 2021 included. Data collection was by retrospective review of clinical notes. Patients were grouped into three categories: current smokers, former smokers (ex‐smokers) and never smokers. Statistical analysis carried out on IBM Statistical Package for Social Sciences (SPSS) for Windows, version 28.0 (Armonk, NY:IBM Corp). Values reported as means, standard deviation (SD), median and interquartile ranges (IQR). Comparisons with the Mann–Whitney U test for median and IQR and two sample t ‐test for mean and SD. Survival analysis was performed using Kaplan–Meier. Results: Of 174 patients, 11 were current smokers (6.3%), 51 were former smokers (29%) and 112 were never smokers (64%). Current smokers were younger and frailer, with longer hospital and ICU length of stay (ICULOS). Welsh Index of Multiple Deprivation (WIMD) scores were collected using UK postcodes and ranked 1909 areas, showing current smokers from the most deprived areas. Kaplan–Meier survival analysis showed current smokers are less likely to survive. Discussion: Despite 6.3% prevalence of smoking in patients with severe COVID‐19 in the ICU, smokers had increased hospital and ICU LOS with reduced survival. The relationship between COVID‐19 and deprivation is multifaceted and complex and may relate to demographic, socioeconomic and environmental factors; health‐related risk factors; and practices. From our data we can see that current smokers admitted to ICU with severe COVID‐19 were from the most deprived areas in Wales, with a higher mortality risk.

Physiological proteins such as fibrinogen and albumin are key biomarkers in diseases like chronic obstructive pulmonary disease (COPD), cardiovascular conditions, and sepsis. Studying the rheology of these proteins not only enhances clinical understanding but also provides a valuable framework to test polymer physics theories, particularly those describing flexible polymers in biologically relevant conditions. However, experimental characterization, especially of elasticity, remains limited due to measurement challenges. In this study, we employ the μ-rheometer microfluidic rheometer to systematically investigate blood plasma with varying fibrinogen concentrations and bovine serum albumin solutions. We found that the protein data can either be described by models for suspension of rigid spheres or by models for flexible polymers. We further demonstrate the clinical utility of these rheological parameters by applying them as rheological biomarkers to patients with acute exacerbation of COPD (AECOPD) in a UK tertiary hospital. Our study effectively connects fundamental polymer physics concepts with clinical diagnostics, underscoring the potential of protein rheology research to enhance healthcare monitoring and therapeutic strategies.