Pulmonary embolism in patients with COVID-19: Time to change the paradigm of computed tomography.

To raise awareness for possible benefits of examining known COVID-19 patients presenting sudden clinical worsening with CT pulmonary angiography instead of standard non-contrast chest CT

Physical activity and lung function association in a healthy community-dwelling European population.

The association of physical activity (PA) and lung function (LF) varies from no measurable effect to delayed LF decline. We assessed the association between accelerometery-assessed PA and LF in a sample of apparently healthy, community-dwelling subjects. We included two cross-sectional studies using data from the PneumoLaus study (2014-17 and 2018-21), conducted in Lausanne, Switzerland. PA was assessed by accelerometry and categorised as inactivity, light, moderate or vigorous. Forced expiratory volume in 1 second (FEV <sub>1</sub> ), forced volume capacity (FVC) and maximal mid-expiratory flow (MMEF) were measured by spirometry and expressed in percentage of predicted value (PV). Overall, 1'910 (54.7% women, 62.0 ± 9.7 years) and 1'174 (53.4% women, 65.8 ± 9.5 years) participants were included in the first and the second surveys, respectively. In both surveys, moderate and vigorous PA showed a weak but significant correlation with FEV <sub>1</sub> in percentage (PV) (R = 0.106 and 0.132 for the first and 0.111 and 0.125 for the second surveys, p < 0.001). Similar correlations with FVC (p < 0.001) were found. Associations held irrespective of smoking status and remained after multivariable adjustment. Fewer associations were detected between LF and light PA or between MMEF and PA. Moderate and vigorous intensity PA are associated with increased LF regardless of smoking status in apparently healthy community-dwelling European population. These associations are statistically but not clinically significant due to the small correlation coefficients (R < 0.30), corresponding to a weak association

Imaging in the aftermath of COVID-19: what to expect.

No abstract availabl

Circulating calprotectin levels four months after severe and non-severe COVID-19.

BACKGROUND Calprotectin is an inflammatory marker mainly released by activated neutrophils that is increased in acute severe COVID-19. After initial recovery, some patients have persistent respiratory impairment with reduced diffusion capacity of the lungs for carbon monoxide (DLCO) months after infection. Underlying causes of this persistent impairment are unclear. We aimed to investigate the correlation between circulating calprotectin, persistent lung functional impairment and intensive care unit (ICU) stay after COVID-19 in two university hospital centres in Switzerland. METHODS Calprotectin levels were measured in serum from 124 patients (50% male) from the Bern cohort (post-ICU and non-ICU patients) and 68 (76% male) from the Lausanne cohort (only post-ICU patients) four months after COVID-19. Calprotectin was correlated with clinical parameters. Multivariate linear regression (MLR) was performed to evaluate the independent association of calprotectin in different models. RESULTS Overall, we found that post-ICU patients, compared to non-ICU, were significantly older (age 59.4 ± 13.6 (Bern), 60.5 ± 12.0 (Lausanne) vs. 48.8 ± 13.4 years) and more obese (BMI 28.6 ± 4.5 and 29.1 ± 5.3 vs. 25.2 ± 6.0 kg/m2, respectively). 48% of patients from Lausanne and 44% of the post-ICU Bern cohort had arterial hypertension as a pre-existing comorbidity vs. only 10% in non-ICU patients. Four months after COVID-19 infection, DLCO was lower in post-ICU patients (75.96 ± 19.05% predicted Bern, 71.11 ± 18.50% Lausanne) compared to non-ICU (97.79 ± 21.70% predicted, p < 0.01). The post-ICU cohort in Lausanne had similar calprotectin levels when compared to the cohort in Bern (Bern 2.74 ± 1.15 µg/ml, Lausanne 2.49 ± 1.13 µg/ml vs. non-ICU 1.86 ± 1.02 µg/ml; p-value < 0.01). Calprotectin correlated negatively with DLCO (r= -0.290, p < 0.001) and the forced vital capacity (FVC) (r= -0.311, p < 0.001). CONCLUSIONS Serum calprotectin is elevated in post-ICU patients in two independent cohorts and higher compared to non-ICU patients four months after COVID-19. In addition, there is a negative correlation between calprotectin levels and DLCO or FVC. The relationship between inflammation and lung functional impairment needs further investigations. TRIAL REGISTRATION NCT04581135

Pulmonary delivery of cationic gold nanoparticles boost antigen-specific CD4+ T Cell Proliferation

To address how surface charge affects the fate of potential nanocarriers in the lung, gold nanoparticles (AuNPs) coated with polyvinyl alcohol containing either positively (NH2) or negatively (COOH) charged functional groups were intra-nasally instilled in mice, and their uptake by antigen presenting cell populations (APC) in broncho-alveolar lavage (BAL) fluid, trachea, and lung parenchyma, as well as trafficking to the lung draining lymph nodes (LDLNs) was assessed by flow cytometry. Furthermore, CD4+ T cell proliferation in LDLNs was investigated following instillation. All APC subpopulations preferentially captured positively-charged AuNPs compared to their negatively-charged counterparts. Uptake of AuNPs up-regulated expression of co-stimulatory molecules on all APC populations. Furthermore, positively-charged AuNPs induced enhanced OVA-specific CD4+ T cell stimulation in LDLNs compared to negatively-charged AuNPs, or polymer alone. Our findings demonstrate surface charge as a key parameter determining particle uptake by APC, and down-stream immune responses depend on the presence of particle core-bound polymer

Long-Term Consequences of COVID-19: A 1-Year Analysis.

Long-lasting symptoms after SARS-CoV-2 infection have been described many times in the literature and are referred to as Long COVID. In this prospective, longitudinal, monocentric, observational study, we collected the health complaints of 474 patients (252 ambulatory and 222 hospitalized) at Lausanne University Hospital 1 year after COVID-19 diagnosis. Using a self-reported health survey, we explored cardiopulmonary, vascular, neurological, and psychological complaints. Our results show that age, Charlson comorbidity index, and smoking habits were associated with hospital admission. Regarding the vascular system, we found that having had thromboembolism before SARS-CoV-2 infection was significantly associated with a higher risk of recurrence of thromboembolism at 1 year. In the neurologic evaluation, the most frequent symptom was fatigue, which was observed in 87.5% of patients, followed by "feeling slowed down", headache, and smell disturbance in 71.5%, 68.5%, and 60.7% of cases, respectively. Finally, our cohort subjects scored higher overall in the STAI, CESD, Maastricht, and PSQI scores (which measure anxiety, depression, fatigue, and sleep, respectively) than the healthy population. Using cluster analysis, we identified two phenotypes of patients prone to developing Long COVID. At baseline, CCS score, prior chronic disease, stroke, and atrial fibrillation were associated with Long COVID. During COVID infection, mechanical ventilation and five neurological complaints were also associated with Long COVID. In conclusion, this study confirms the wide range of symptoms developed after COVID with the involvement of all the major systems. Early identification of risk factors associated with the development of Long COVID could improve patient follow-up; nevertheless, the low specificity of these factors remains a challenge to building a systematic approach

Gut-derived short-chain fatty acids modulate skin barrier integrity by promoting keratinocyte metabolism and differentiation

Barrier integrity is central to the maintenance of healthy immunological homeostasis. Impaired skin barrier function is linked with enhanced allergen sensitization and the development of diseases such as atopic dermatitis (AD), which can precede the development of other allergic disorders, for example, food allergies and asthma. Epidemiological evidence indicates that children suffering from allergies have lower levels of dietary fibre-derived short-chain fatty acids (SCFA). Using an experimental model of AD-like skin inflammation, we report that a fermentable fibre-rich diet alleviates systemic allergen sensitization and disease severity. The gut-skin axis underpins this phenomenon through SCFA production, particularly butyrate, which strengthens skin barrier function by altering mitochondrial metabolism of epidermal keratinocytes and the production of key structural components. Our results demonstrate that dietary fibre and SCFA improve epidermal barrier integrity, ultimately limiting early allergen sensitization and disease development. The Graphical Abstract was designed using Servier Medical Art images (https://smart.servier.com). [Image: see text

Shape-Based Tracking Allows Functional Discrimination of Two Immune Cell Subsets Expressing the Same Fluorescent Tag in Mouse Lung Explant

Dendritic Cells (DC) represent a key lung immune cell population, which play a critical role in the antigen presenting process and initiation of the adaptive immune response. The study of DCs has largely benefited from the joint development of fluorescence microscopy and knock-in technology, leading to several mouse strains with constitutively labeled DC subsets. However, in the lung most transgenic mice do express fluorescent protein not only in DCs, but also in closely related cell lineages such as monocytes and macrophages. As an example, in the lungs of CX3CR1+/gfp mice the green fluorescent protein is expressed mostly by both CD11b conventional DCs and resident monocytes. Despite this non-specific staining, we show that a shape criterion can discriminate these two particular subsets. Implemented in a cell tracking code, this quantified criterion allows us to analyze the specific behavior of DCs under inflammatory conditions mediated by lipopolysaccharide on lung explants. Compared to monocytes, we show that DCs move slower and are more confined, while both populations do not have any chemotactism-associated movement. We could generalize from these results that DCs can be automatically discriminated from other round-shaped cells expressing the same fluorescent protein in various lung inflammation models

Interrelationship between Dendritic Cell Trafficking and Francisella tularensis Dissemination following Airway Infection

Francisella tularensis, the etiological agent of the inhalation tularemia, multiplies in a variety of cultured mammalian cells. Nevertheless, evidence for its in vivo intracellular residence is less conclusive. Dendritic cells (DC) that are adapted for engulfing bacteria and migration towards lymphatic organs could serve as potential targets for bacterial residence and trafficking. Here, we focus on the in vivo interactions of F. tularensis with DC following airway infection of mice. Lethal airway infection of mice with the live vaccine strain (LVS) results in trafficking of a CD11bhigh/CD11cmed/autofluorescencelow DC subset from the respiratory tract to the draining mediastinal lymph node (MdLN). Simultaneously, a rapid, massive bacterial colonization of the MdLN occurs, characterized by large bacterial foci formation. Analysis of bacteria in the MdLN revealed a major population of extracellular bacteria, which co-exists with a substantial fraction of intracellular bacteria. The intracellular bacteria are viable and reside in cells sorted for DC marker expression. Moreover, in vivo vital staining experiments indicate that most of these intracellular bacteria (∼75%) reside in cells that have migrated from the airways to the MdLN after infection. The correlation between DC and bacteria accumulation in the MdLN was further demonstrated by manipulating DC migration to the MdLN through two independent pathways. Impairment of DC migration to the MdLN, either by a sphingosine-1-phosphate receptor agonist (FTY720) or by the D prostanoid receptor 1 agonist (BW245C), resulted in reduced bacterial colonization of MdLN. Moreover, BW245C treatment delayed the onset of morbidity and the time to death of the infected mice. Taken together, these results suggest that DC can serve as an inhabitation niche for F. tularensis in the early stages of infection, and that DC trafficking plays a role in pathogen dissemination. This underscores the therapeutic potential of DC migration impairing drugs in tularemia treatment

Modelling the Dynamics of Feral Alfalfa Populations and Its Management Implications

BACKGROUND: Feral populations of cultivated crops can pose challenges to novel trait confinement within agricultural landscapes. Simulation models can be helpful in investigating the underlying dynamics of feral populations and determining suitable management options. METHODOLOGY/PRINCIPAL FINDINGS: We developed a stage-structured matrix population model for roadside feral alfalfa populations occurring in southern Manitoba, Canada. The model accounted for the existence of density-dependence and recruitment subsidy in feral populations. We used the model to investigate the long-term dynamics of feral alfalfa populations, and to evaluate the effectiveness of simulated management strategies such as herbicide application and mowing in controlling feral alfalfa. Results suggest that alfalfa populations occurring in roadside habitats can be persistent and less likely to go extinct under current roadverge management scenarios. Management attempts focused on controlling adult plants alone can be counterproductive due to the presence of density-dependent effects. Targeted herbicide application, which can achieve complete control of seedlings, rosettes and established plants, will be an effective strategy, but the seedbank population may contribute to new recruits. In regions where roadside mowing is regularly practiced, devising a timely mowing strategy (early- to mid-August for southern Manitoba), one that can totally prevent seed production, will be a feasible option for managing feral alfalfa populations. CONCLUSIONS/SIGNIFICANCE: Feral alfalfa populations can be persistent in roadside habitats. Timely mowing or regular targeted herbicide application will be effective in managing feral alfalfa populations and limit feral-population-mediated gene flow in alfalfa. However, in the context of novel trait confinement, the extent to which feral alfalfa populations need to be managed will be dictated by the tolerance levels established by specific production systems for specific traits. The modelling framework outlined in this paper could be applied to other perennial herbaceous plants with similar life-history characteristics