Cardiopulmonary recovery after COVID-19: an observational prospective multicentre trial.

BACKGROUND: After the 2002/2003 severe acute respiratory syndrome outbreak, 30% of survivors exhibited persisting structural pulmonary abnormalities. The long-term pulmonary sequelae of coronavirus disease 2019 (COVID-19) are yet unknown, and comprehensive clinical follow-up data are lacking. METHODS: In this prospective, multicentre, observational study, we systematically evaluated the cardiopulmonary damage in subjects recovering from COVID-19 at 60 and 100 days after confirmed diagnosis. We conducted a detailed questionnaire, clinical examination, laboratory testing, lung function analysis, echocardiography and thoracic low-dose computed tomography (CT). RESULTS: Data from 145 COVID-19 patients were evaluated, and 41% of all subjects exhibited persistent symptoms 100 days after COVID-19 onset, with dyspnoea being most frequent (36%). Accordingly, patients still displayed an impaired lung function, with a reduced diffusing capacity in 21% of the cohort being the most prominent finding. Cardiac impairment, including a reduced left ventricular function or signs of pulmonary hypertension, was only present in a minority of subjects. CT scans unveiled persisting lung pathologies in 63% of patients, mainly consisting of bilateral ground-glass opacities and/or reticulation in the lower lung lobes, without radiological signs of pulmonary fibrosis. Sequential follow-up evaluations at 60 and 100 days after COVID-19 onset demonstrated a vast improvement of symptoms and CT abnormalities over time. CONCLUSION: A relevant percentage of post-COVID-19 patients presented with persisting symptoms and lung function impairment along with radiological pulmonary abnormalities >100 days after the diagnosis of COVID-19. However, our results indicate a significant improvement in symptoms and cardiopulmonary status over time.

The impact of bacteremia on lipoprotein concentrations and patient's outcome: a retrospective analysis.

Bacteremia is a major clinical challenge requiring early treatment. Metabolic alterations occur during bacteremia, and accordingly plasma concentrations of lipoproteins LDL-C and HDL-C are substantially changed. We questioned whether bacteremia with Gram-negative versus Gram-positive bacteria causes contrasting changes of lipoprotein levels in order to differentiate between the 2-g stain types and if there is a relation with outcome parameters namely ICU-admission, 30-day mortality, duration of hospitalization. This is a retrospective dual-center cross-sectional study, including 258 patients with bacteremia. Plasma lipid levels were analyzed within 48 h to positive blood culture. Upon admission, HDL-C, LDL-C, and total cholesterol (p = 0.99) in plasma did not significantly differ between patients with Gram-negative and Gram-positive bacteremia, while significantly higher triglyceride concentrations were found in Gram-negative bacteremia (p < 0.05). 30-day mortality and ICU admission were associated with lower LDL-C and HDL-C concentrations as compared to survivors and non-ICU patients, and patients with HDL-C < 20 mg dl-1 and LDL-C < 55 mg dl-1 had a relative risk (RR) of 2.85 for ICU therapy requirement and RR = 2 of death within 30 days. Reduced HDL-C and LDL-C concentrations were associated with adverse patient's outcome in bacteremia. Discrimination between Gram-negative and Gram-positive pathogens upon lipoprotein patterns is unlikely.

Assessment of neopterin and indoleamine 2,3-dioxygenase activity in patients with seasonal influenza: A pilot study.

BACKGROUND: Seasonal influenza is an important cause of morbidity and mortality worldwide. Immune activation after stimulation with interferon-gamma leads to increased production of neopterin but also results in increased tryptophan catabolism through indoleamine 2,3-dioxygenase (IDO). Our pilot study determined neopterin serum levels and IDO activity in patients with influenza infection and investigated whether neopterin is linked to clinical outcome parameters (mortality ≤30 days, acute cardiac events (ACE) length of hospitalization, ICU admission). METHODS: Neopterin concentrations were analyzed in serum samples of 40 patients with a confirmed diagnosis of influenza infection and in-hospital treatment for >24 hours. Data were compared to values of 100 healthy blood donors and 48 age-matched pneumonia patients. In a subgroup of 14 patients, tryptophan and kynurenine concentrations, as well as kynurenine-to-tryptophan ratio, were analyzed. RESULTS: In all influenza patients, neopterin concentrations were increased and significantly higher compared to those determined in patients with pneumonia and healthy controls. Positive correlations between the duration of hospitalization and neopterin were found. Significantly higher levels of kynurenine, kynurenine-to-tryptophan ratio, and lower levels of tryptophan were seen in influenza patients compared to healthy controls. CONCLUSIONS: Neopterin seems to be related to the course of the disease and could be a valuable biomarker to identify patients at an elevated risk of a worsened outcome; however, further prospective validation studies are needed to support the here presented preliminary results.

Classical and intermediate monocytes scavenge non-transferrin-bound iron and damaged erythrocytes.

Myelomonocytic cells are critically involved in iron turnover as aged RBC recyclers. Human monocytes are divided in 3 subpopulations of classical, intermediate, and nonclassical cells, differing in inflammatory and migratory phenotype. Their functions in iron homeostasis are, however, unclear. Here, we asked whether the functional diversity of monocyte subsets translates into differences in handling physiological and pathological iron species. By microarray data analysis and flow cytometry we identified a set of iron-related genes and proteins upregulated in classical and, in part, intermediate monocytes. These included the iron exporter ferroportin (FPN1), ferritin, transferrin receptor, putative transporters of non-transferrin-bound iron (NTBI), and receptors for damaged erythrocytes. Consequently, classical monocytes displayed superior scavenging capabilities of potentially toxic NTBI, which were augmented by blocking iron export via hepcidin. The same subset and, to a lesser extent, the intermediate population, efficiently cleared damaged erythrocytes in vitro and mediated erythrophagocytosis in vivo in healthy volunteers and patients having received blood transfusions. To summarize, our data underline the physiologically important function of the classical and intermediate subset in clearing NTBI and damaged RBCs. As such, these cells may play a nonnegligible role in iron homeostasis and limit iron toxicity in iron overload conditions.

Analysis of volatile organic compounds in the breath of patients with stable or acute exacerbation of chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a major cause of death worldwide. Acute exacerbations COPD (AECOPD), caused by infectious and non-infectious agents, contribute to an increase in mortality. The diagnostic procedure of AECOPD is mainly based on clinical features. The aim of this pilot study was to identify whether volatile organic compounds (VOCs) in breath could be used to discriminate for acute exacerbated COPD. Three patient groups were included in this controlled study: AECOPD patients (n = 14, age mean ± SD: 71.4 ± 7.46), stable COPD patients (n = 16, age mean ± SD: 66.9 ± 9.05) and healthy volunteers (n = 24, age mean ± SD: 28 ± 6.08). Breath samples were collected by optimizing a sampling strategy developed by us. These samples were then analyzed using a thermal desorption-gas chromatography-time of flight-mass spectrometer (TD-GC-ToF-MS). A total of 105 VOCs were identified in the breath samples. Relevant substances were subsequently selected by overall occurrence rate, the frequency of positive alveolar gradient (AG) (i.e. the difference in exhaled and inhaled VOCs concentration), exclusion of 'smoking related' VOCs and significant differences in AGs between the three groups. These steps dramatically reduced the number of relevant analytes and resulted in 12 key VOCs having discriminative values. The performance of patients' classification described by the Receiver Operating Characteristic (ROC) curve using all 12 substances delineates an area under the curve (AUC) of 0.97. A further reduction to four VOCs (AGs only different between AECOPD and COPD) delineates an AUC of 0.92. These results indicate that breath analysis with TD-GC-ToF-MS holds promise for an accurate and easy to perform differential diagnosis between AECOPD and COPD. In this regard, ketones were observed at the highest levels in exhaled breath of AECOPD, some of which are also related to potential bacterial pathogens. Using a set of VOCs that can discriminate for AECOPD, the calculated AUCs in ROC curve analysis show far superior results in comparison to serum AECOPD biomarkers, such as C-reactive protein. The identified VOCs should be further investigated in translational studies addressing their potential for developing highly specific nanosensors for breath gas analysis which would give clinicians a tool for non-invasive diagnosis of AECOPD at the point of care.