RATIONALE:Asthma and chronic obstructive pulmonary disease (COPD) significantly overlap by conventional diagnostic criteria, yet important treatment differences remain, and people with both asthma and COPD (asthma + COPD) have worse clinical outcomes than people with a single diagnosis. Hyperpolarized xenon-129 magnetic resonance imaging (129Xe MRI) and pulmonary function tests (PFTs) are sensitive to lung function and structure. OBJECTIVE:To determine whether 129Xe MRI alongside PFTs can aid phenotyping of real-world patients with asthma and/or COPD. METHODS:Patients ≥16 years with physician-assigned asthma and/or COPD were recruited from primary care. 129Xe and proton MRI, multiple-breath nitrogen washout, airwave oscillometry, transfer factor of the lung for carbon monoxide (TLco), body plethysmography, and spirometry were assessed post-bronchodilator. Differences between diagnostic groups were assessed. RESULTS:The study assessed 165 patients. 129Xe MRI and PFT metrics differed significantly between diagnostic groups. On 129Xe MRI, patients with COPD had significantly reduced and more heterogeneous ventilation, greater acinar dimensions, and lower gas transfer, in addition to lower spirometry, greater airways resistance and reactance, and more air trapping than patients with asthma. Similarly, 129Xe MRI metrics demonstrated greater abnormalities in COPD than asthma when comparing only those with normal forced expiratory volume in 1 s or TLco. Lung function and structure were worse in asthma + COPD than asthma and better than COPD. CONCLUSIONS:129Xe MRI alongside PFTs provide phenotypically distinct airway disease signatures to aid diagnosis of asthma and/or COPD. 129Xe MRI is highly sensitive to minimal lung disease and identifies functional/structural phenotypes that may help to guide treatment decisions.

Background Breathlessness is a common symptom in Long COVID (LC). Using hyperpolarised xenon MRI ( 129 Xe-MRI), we assessed whether this symptom could be attributed to abnormalities in the alveolar-capillary membrane not detected by standard investigations. We focused on never-hospitalised individuals without an identified cause for breathlessness. Methods In this prospective, multicentre study, we compared 129 Xe-MRI, lung function, exercise capacity, and symptom questionnaires in LC patients with breathlessness (BLC) to those without breathlessness (NBLC) and healthy controls. Primary outcome was whether BLC demonstrated measurable impairments in gas exchange focusing on dissolved-phase 129 Xe-MRI metrics: red-blood cell to membrane ratio (RBC:M) and red-blood cell to gas ratio (RBC:Gas). We also explored associations between symptoms and physiological measures. Results Of 269 participants recruited, 196 were included in the analysis (109 BLC, 43 NBLC, 44 controls), with age and sex well matched across groups. BLC had a significantly longer interval from infection to imaging (median 632 days; p<0·001). No significant differences in global or regional RBC:M or RBC:Gas were observed across groups. BLC showed lower FEV 1 , FVC, TLCO, and KCO z-scores compared to controls, though >90% of values remained within normal range. A subset of BLC participants with low TLCO (14/109) showed reduced 129 Xe-MRI metrics and higher breathlessness scores. Interpretation Most non-hospitalised LC participants exhibited no detectable pulmonary abnormalities, including those with breathlessness. However, approximately 13% of breathless individuals demonstrated minor reductions in TLCO and 129 Xe-MRI gas exchange suggesting a potential pulmonary contribution for symptoms in this subgroup.

Purpose To evaluate pulmonary arterial pulse wave velocity (PWV) derived from phase-resolved functional lung (PREFUL) MRI in participants with suspected pulmonary hypertension (PH), assess its association with established markers, and investigate its prognostic value for 12-month mortality. Materials and Methods This post hoc analysis of a prospective multicenter Chronic Thromboembolic Pulmonary Hypertension Diagnosis Europe MRI (CHANGE MRI) study included participants with suspected chronic thromboembolic PH and complete PREFUL MRI between July 2016 and November 2023. PREFUL MRI-based two-dimensional images acquired at 1.5 T using spoiled gradient-echo sequences were used to calculate quantified perfusion, perfusion defect percentages, and PWV. Group comparisons were performed between PH and no PH and among PH groups using age- and sex-adjusted models (analysis of covariance framework). Spearman correlations with right heart catheterization and cardiac MRI parameters and associations with 12-month mortality were assessed using multivariable regression and Cox proportional hazard models. A P value less than .05 was considered statistically significant. Results A total of 632 participants (median age, 66 years; IQR, 22 years; 368 [58%] female) were included. Of these, 415 had confirmed PH, and 13 died within 12 months. PWV was higher in pulmonary arterial hypertension than in chronic thromboembolic PH (2.76 m/sec ± 1.32 vs 1.84 m/sec ± 1.29; P < .001). In participants with PH, PWV was associated with mortality (hazard ratio, 2.28 per SD increase [1.47 m/sec]; P < .001). PWV showed independent associations with right ventricular ejection fraction (β = -0.024 m/sec per percentage point; P < .001) and perfusion defect percentage (β = 0.014 m/sec per percentage point; P = .02). Conclusion Pulmonary arterial PWV derived from PREFUL MRI was higher in PH and independently associated with right ventricular function and 12-month mortality. Keywords: Functional Lung MRI, Pulmonary Arteries, Lung ClinicalTrials.gov identifier: NCT02791282 Supplemental material is available for this article. © RSNA, 2026.

Positron emission tomography combined with magnetic resonance imaging (PET/MR) has not yet achieved the level of adoption of PET/CT. This study aimed to harmonise PET imaging protocols across a national PET/MR network and to quantitatively assess whether PET/MR can achieve reliability comparable to PET/CT. While previous PET test-retest studies have demonstrated good repeatability, they have typically been limited to small cohorts or restricted site configurations. We conducted a multi-site harmonisation and rigorous test-retest study across the network of eight PET/MR scanners. Thirty-seven healthy older participants (65-90 years) underwent harmonised one-hour amyloid PET/MR scans using either [ ^18 F]flutemetamol or [ ^18 F]florbetaben on two occasions. Retest scans were performed under conditions of same-site repeatability or multi-site reproducibility. Harmonised acquisition and reconstruction protocols were applied, and amyloid burden was quantified on the Centiloid (CL) scale. CL values across 74 scans showed excellent test-retest agreement (ICC = 0.968), improving to 0.987 after exclusion of one attenuation correction related outlier. Mean test-retest variability was 2.58

Background:Multi-system impacts of long COVID remain unknown. We aimed to compare multi-system deficits between people with long COVID and controls. Methods:We conducted a case-control study and recruited participants from two UK population-based cohorts: the Avon Longitudinal Study of Parents and Children (ALSPAC) and TwinsUK. Participants provided samples for SARS-CoV-2 serology between 2020 and 2021 and were asked about duration of COVID-19 symptoms between July and December 2021. Cases had long COVID (evidence of COVID-19 infection and persistent symptoms ≥4 weeks post infection); controls comprised 3 groups: acute COVID-19 only (symptoms reported for <4 weeks) and serological evidence of infection; self-reported long COVID-like symptoms but without wild-type SARS-CoV-2 virus antibodies; no symptoms or history of COVID-19 infection. People who were severely unwell or pregnant were excluded. Participants attended a clinic follow-up visit between 2021 and 2023 and underwent multi-system MRI, (cardiac, brain, lung, kidney), measurement of blood pressure and autonomic function, spirometry, renal function, exercise tests, strength and physical capability. Severity of deficit was then scored for each system as 0 (none) to 3 (severe). Primary outcome was a single composite multi-domain score summing each of nine domains: autonomic, brain, exercise capacity, heart, lungs, physical, renal, strength and vascular, with a maximum score of 27. Findings:In total, 349 participants, 141 with long COVID (40%) and 208 (60%) controls were recruited. Overall deficit score in cases was 0.22 (95% CI -0.44, 0.88) units greater than controls, adjusted for age, sex, ethnicity, cohort membership and relatedness. This estimate was little changed (0.32 (-0.34, 0.98)) when additionally adjusted for educational status, index of multiple deprivation, physical activity, smoking and co-morbidity. Restricting cases to those reporting symptoms including fatigue (n = 46) increased the excess deficit score to 0.81 (-0.19, 1.81) units in the minimally adjusted model. A difference was only observed in the vascular domain, largely attributable to elevated blood pressure, showing a 1.76 (1.04, 2.97) multivariable adjusted odds ratio excess in cases, and 3.04 (1.36, 6.80) when restricted to cases with fatigue. Interpretation:There was no evidence of marked residual subclinical deficits in most systems in people with long-COVID, although there was evidence of persistent deficits in the vascular system, largely related to elevated blood pressure. Mechanisms unrelated to organ dysfunction may contribute to symptoms. Blood pressure measurement and control should be included in clinical follow-up. Funding:Jointly funded by the National Institute for Health and Care Research and UK Research and Innovation (CONVALESCENCE, COV-LT-0009, MC_PC_20051).

Background:Breathlessness is a common symptom in long COVID (LC). Using hyperpolarised xenon magnetic resonance imaging (129Xe-MRI), we assessed whether this symptom could be attributed to abnormalities in the alveolar-capillary membrane not detected by standard investigations. We focused on never-hospitalised individuals without an identified cause for breathlessness. Methods:In this prospective, multicentre study, we compared 129Xe-MRI, lung function, exercise capacity and symptom questionnaires in LC patients with breathlessness (BLC) to those without breathlessness (NBLC) and healthy controls. Primary outcome was whether BLC demonstrated measurable impairments in gas exchange focusing on dissolved-phase 129Xe-MRI metrics: red blood cell to membrane ratio (RBC:M) and red blood cell to gas ratio (RBC:Gas). We also explored associations between symptoms and physiological measures. Results:Of 269 participants recruited, 196 were included in the analysis (109 BLC, 43 NBLC, 44 controls), with age and sex well matched across groups. BLC had a significantly longer interval from infection to MRI (median 632 days; p<0.001). No significant differences in global or regional RBC:M or RBC:Gas were observed across groups. BLC showed lower forced expiratory volume in 1 s, forced vital capacity, transfer factor of the lung for carbon monoxide (T L CO), and carbon monoxide transfer coefficient (K CO) z-scores compared to controls, though >90% of values remained within normal range. A subset of BLC participants with low T L CO (14 out of 109) showed reduced 129Xe-MRI metrics and higher breathlessness scores. Interpretation:Most nonhospitalised LC participants exhibited no detectable pulmonary abnormalities, including those with breathlessness. However, ∼13% of breathless individuals demonstrated minor reductions in T L CO and 129Xe-MRI gas exchange suggesting a potential pulmonary contribution for symptoms in this subgroup.

RATIONALE:Airways dysanapsis is defined by CT or spirometry as a mismatch between the size of the airways and lung volume and is associated with increased risk of developing chronic obstructive pulmonary disease (COPD). Lung disease in participants with dysanapsis and a label of asthma and/or COPD remains poorly understood. METHODS:In participants with asthma and/or COPD, we used 129Xe-MRI to assess ventilation, acinar dimensions and gas exchange, and pulmonary function tests, and compared people with spirometric dysanapsis (forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC)<-1.64 z and FEV1>-1.64 z) to those with normal spirometry (FEV1, FVC and FEV1/FVC>-1.64 z). RESULTS:From 165 participants assessed in the NOVELTY (NOVEL observational longiTudinal studY) ADPro (advanced diagnostic profiling) study with a physician-assigned diagnosis of asthma and/or COPD, 43 had spirometric dysanapsis and were age-matched to 43 participants with normal spirometry. Participants with dysanapsis had significantly increased ventilation defects (median difference (md) (95% CI) = 4.0% (1.42% to 5.38%), p<0.001), ventilation heterogeneity (md (95% CI) = 2.56% (1.31% to 3.56%), p<0.001) and measures of acinar dimensions (md (95% CI) = 0.004 cm2.s-1 (0.0009 to 0.007), p=0.009) from 129Xe-MRI, than those with normal spirometry. At the 1-year follow-up, only participants with dysanapsis had a significant increase in ventilation defects (md (95% CI)=0.45% (0.09% to 2.1%),p=0.016). Lower FEV1/FVC in the dysanapsis cohort was associated with increased ventilation defects (r=-0.64, R2=0.41, p<0.001) and increased acinar dimensions (r=-0.52, R2=0.38, p<0.001), with the highest values seen in those with an FVC above the upper limit of normal. CONCLUSIONS:Participants with asthma and/or COPD, presenting to primary care with spirometric dysanapsis, exhibited increased lung abnormalities on 129Xe-MRI, when compared with those with normal spirometry. Spirometric dysanapsis in asthma and/or COPD is therefore associated with significant lung disease, and the FEV1/FVC is related to the degree of airways abnormality on 129Xe-MRI.

INTRODUCTION:The pulmonary vasculature has been implicated in chronic obstructive pulmonary disease (COPD). Whether platelet activation is associated with COPD-related characteristics is unknown. METHODS:The Multi-Ethnic Study of Atherosclerosis (MESA) COPD Study enrolled participants with 10+ pack-years with and without COPD from 2 cohort studies. Platelet activation was measured in platelet-free plasma as von Willebrand factor (vWF), beta-thromboglobulin (BTG) and platelet factor 4 (PF4). Phenotyping included spirometry, percent emphysema-950HU, air trapping on computed tomography (CT), low-ventilated lung volume on 3He-magnetic resonance imaging (MRI) and contrast-enhanced MRI pulmonary perfusion on and off oxygen. Linear and logistic regression adjusted for demographics, anthropometry, platelet count, aspirin use, COPD status and cohort; the final model adjusted for smoking, pack-years, oxygen saturation and hypertension. RESULTS:The 116 with vWF were a mean age of 73.5 ± 7.3 years old, 60 % male, 58 % Non-Hispanic White, 28 % Black, 14 % Hispanic/Latino, 23 % smoked currently and 55 % had COPD. vWF was associated with lower FEV1/FVC (-2.0 %/SD vWF, 95 %CI: -3.5, -0.6), and greater percent low-ventilated lung volume on 3He-MRI (6.5 %/SD vWF, 95 %CI: 1.5, 11.5), CT air trapping (3.2 %/SD vWF, 95 %CI: 1.4, 5.1) and heterogeneity (CV) of pulmonary microvascular blood flow (PMBF) and pulmonary microvascular blood volume (PMBV) on oxygen. Higher BTG and PF4 were associated with greater PMBF and PMBV. There was increased odds of COPD with higher PF4 (final model only: OR 1.8/SD PF4, 95 %CI: 1.01, 3.20). CONCLUSIONS:Platelet activation was associated with measures of small airways disease and pulmonary microvascular perfusion in this sample of smokers with and without COPD.

Rubidium (Rb) vapor density ([Rb]) is a key parameter in xenon-129 polarization (PXe) build up in spin-exchange optical pumping. In practice, [Rb] within the cell often falls below saturation levels and is spatially heterogeneous leading to system underperformance. In this study, finite element modeling was performed to investigate the role of Rb source distribution in heterogeneous in-cell [Rb], and to optimize a Rb presaturator to achieve homogeneous [Rb] and reduce the flow rate dependence of [Rb]. Lower than expected PXe in previous iterations of our polarizer can be attributed to sub-saturation [Rb] due to the small surface area of the Rb source in the main cell body and the absence of upstream Rb vapor presaturation, leading to lower than desired PXe. We found that increasing the surface area of the Rb source in the main cell body does not effectively reduce [Rb] heterogeneity. Instead, achieving a more uniform distribution of [Rb] necessitates the use of a sufficiently long presaturator at a given gas flow rate, increasing PXe. We also report discrepancy between modeled and experimentally measured laser absorption, highlighting limitations of the existing optical pumping model and suggesting directions for future model revisions and the investigation of currently unexplored areas.

Background Pulmonary gas exchange is assessed by the transfer factor of the lungs (TL) for carbon monoxide (TLCO), and can also be measured with inhaled xenon-129 (129Xe) magnetic resonance imaging (MRI). A model has been proposed to estimate TL from 129Xe MRI metrics, but this approach has not been fully validated and does not utilise the spatial information provided by three-dimensional 129Xe MRI. Methods Three models for predicting TL from 129Xe MRI metrics were compared: 1) a previously-published physiology-based model, 2) multivariable linear regression and 3) random forest regression. Models were trained on data from 150 patients with asthma and/or COPD. The random forest model was applied voxel-wise to 129Xe images to yield regional TL maps. Results Coefficients of the physiological model were found to differ from previously reported values. All models had good prediction accuracy with small mean absolute error (MAE): 1) 1.24±0.15 mmol·min−1·kPa−1, 2) 1.01±0.06 mmol·min−1·kPa−1, 3) 0.995±0.129 mmol·min−1·kPa−1. The random forest model performed well when applied to a validation group of post-COVID-19 patients and healthy volunteers (MAE=0.840 mmol·min−1·kPa−1), suggesting good generalisability. The feasibility of producing regional maps of predicted TL was demonstrated and the whole-lung sum of the TL maps agreed with measured TLCO (MAE=1.18 mmol·min−1·kPa−1). Conclusion The best prediction of TLCO from 129Xe MRI metrics was with a random forest regression framework. Applying this model on a voxel-wise level to create parametric TL maps provides a useful tool for regional visualisation and clinical interpretation of 129Xe gas exchange MRI.

Rationale: Hyperpolarized 129Xe magnetic resonance imaging (129XeMRI) is an innovative, clinically approved imaging technique that provides novel insights into lung structure and function such as the ventilation defect percent (VDP). An upper limit of normal (ULN) for VDP has previously been proposed (McIntosh et al, 2023), but ULN accounting for variations in age as well as imaging sites, scanner platforms, and acquisition protocols remain undefined. We aimed to determine the ULN for VDP in healthy individuals across sites, scanners, acquisition methods, and VDP-quantification techniques, offering a reference for assessing age-related lung function and setting benchmarks for clinical interpretation and multisite comparisons. Methods: Hyperpolarized 129Xe and anatomical MRI were collected from 281 healthy participants (age 33±17yrs [5-84yrs]; 142F/139M) at 10 sites (Figure-A), all of which are part of the 129XeMRI Clinical Trials Consortium (https://www.129xectc.org/). Participants inhaled 129Xe dosed based on a percentage of TLC, FVC, or up to 1L, followed by a <20-second breath-hold. Images were acquired using Siemens, Philips, or GE MRI systems (1.5T/3T) with different acquisitions protocols (2D/3D, cartesian/spiral, axial/coronal). Anatomical images were registered to 129Xe ventilation images, and lung masks were generated using pretrained segmentation models with manual corrections. N4-bias correction was applied to correct 129Xe signal variations. VDP was calculated using six methods: 60% thresholding of the mean lung signal (TH60%), K-means, Adaptive-K-means (AKmeans), linear-binning normalized by mean-signal (LBmean), and generalized-linear-binning normalized by median (GLBmed) and 99-percentile (GLB99p). The ULN for VDP was calculated for the total group and for age subgroups as Mean(VDP)+1.96·(SD(VDP)/√N), where N is the number of participants in the respective group. Results: Representative 129Xe ventilation images with VDP for four healthy participants across age and VDP methods (Figure-B) demonstrated a clear trend of increased VDP with increasing age. Across all participants, VDP correlated significantly with age (P<0.001) for all methods (Figure-C). However, mean VDP and variability were numerically greater for TH60% (2.47±2.12%), GLBmed (1.73±1.62%), and GLB99p (1.64±2.19%) compared to Kmeans (0.34±0.53%), AKmeans (0.33±0.67%), and LBmean (0.33±0.83%). ULN values stratified by age group are shown for each method in Figure-D. Conclusions: The observed age-dependent increase in the ULN for 129XeMRI VDP across sites, platforms, acquisition protocols, and VDP quantification methods reflects “real-world” conditions and serves as a critical reference for clinical interpretation. Notably, significant differences in mean and variability of VDP were observed across methods, highlighting the need for method-specific benchmarks to ensure consistent interpretation and facilitate comparisons across studies and clinical settings.

BACKGROUND:COPD is traditionally associated with pulmonary hypertension, but treatments targeting elevated pulmonary artery pressure in COPD have largely failed, possibly due to an incomplete understanding of subphenotypes of the disease. RESEARCH QUESTION:Are novel machine-learned CT emphysema subtypes associated with specific cardiac hemodynamic profiles? STUDY DESIGN AND METHODS:The Multi-Ethnic Study of Atherosclerosis (MESA) COPD Study recruited participants with and without COPD aged 50 to 79 years with ≥ 10 pack-years of smoking and without clinical cardiovascular disease, predominantly from MESA and a lung cancer screening cohort. COPD and COPD severity were defined by standard spirometric criteria. CT emphysema subtypes were defined by unsupervised machine learning in an independent study and labeled on chest CT scans. Hemodynamics were estimated on cardiac MRI using validated equations. Linear regression models were weighted by the inverse probability of sampling and adjusted for potential confounders. RESULTS:The mean age of the 300 participants was 68 ± 7 years, 60% were male, 28% currently smoked, and 47% had COPD (45% of mild and 41% of moderate severity). More severe COPD was associated with lower estimated pulmonary arterial wedge pressure (ePAWP; P trend = .02) and greater estimated pulmonary vascular resistance (ePVR; P trend = .03) but not estimated pulmonary artery pressure (ePAP; P trend = 0.83). Only the combined bronchitic-apical emphysema subtype was associated with greater ePAP (1.08 mm Hg/10%; 95% CI, 0.40-1.75). The diffuse emphysema subtype was associated with lower ePAWP (-0.49 mm Hg/10%; 95% CI, -0.75 to -0.24) and greater ePVR (0.36 Wood units/10%; 95% CI, 0.10-0.61). INTERPRETATION:In this case-control study of predominantly mild-moderate COPD, greater ePAP was specific to the combined bronchitic-apical emphysema subtype whereas the diffuse emphysema subtype and COPD severity were associated with lower ePAWP and greater ePVR. The CT emphysema subtype findings suggest more precise avenues to therapeutic interventions in cardiopulmonary dysfunction.

MR imaging holds the potential to enhance drug development efficiency by de-risking early phase studies and increasing confidence in results. It can improve patient selection, increase repeatability, and provide greater sensitivity to change, thereby enabling smaller, faster clinical trials. For trials in the pulmonary space, hyperpolarized 129Xe MRI is appealing because it provides 3-dimensional imaging of pulmonary ventilation and gas exchange in a brief, non-invasive exam. Metrics derived from 129Xe MRI may be more sensitive to disease progression than conventional lung function assessments and may thus provide a valuable means to evaluate numerous novel pharmacologic and biologic therapies now in development. However, despite the acute need for better patient selection and for prognostic and monitoring biomarkers, 129Xe MR imaging is not yet widely utilized in pulmonary drug development, partly because such trials must be conducted at multiple centers to enroll enough participants. Thus, incorporating 129Xe MRI requires broader dissemination, harmonized image acquisition protocols, standardized dose delivery, visualization, and quantification. Multi-site trials must also be able to operate across all major MRI vendor platforms and diverse software/hardware revisions. To this end, the 129Xe MRI Clinical trials consortium has published a harmonized protocol describing four recommended acquisitions. Here we report on the first industry-sponsored study to deploy this 129Xe MRI/MRS protocol in a multi-center, multi-platform, multi-national study to evaluate longitudinal progression of chronic obstructive pulmonary disease (COPD). We demonstrate the steps necessary to implement standardized 129Xe-MRI acquisition techniques across multiple sites and discuss the practices implemented, quality control approaches, and lessons learned for facilitating and accelerating the implementation of future trials that incorporate this technology. Level of Evidence: 5.

Background: Despite widespread vaccination and reduced SARS-CoV-2 pathogenicity, post-COVID syndrome (PCS) remains a significant public health issue. It is widely thought to represent a single, multi-systemic disorder, yet its pathophysiology remains poorly defined. Endothelial dysfunction and thrombosis have been proposed as central mechanisms. Aims: To assess the long-term impact of SARS-CoV-2 infection on plasma biomarkers of endothelial, thrombotic and renal function. Methods: Plasma samples were obtained from prospective observational cohort studies of patients previously infected with SARS-CoV-2, stratified by recovery status. Patients not previously hospitalised provided a single sample at 3–36 months post-infection (recovered: n=22; PCS: n=34-35). Post-hospitalisation patients provided samples at 6, 12, and 24 months (recovered: n=4-6; PCS: n=8-16). Commercial ELISAs and colorimetric assays quantified markers of endothelial-mediated vasomotor control (ET-1, nitrate/nitrite, prostacyclin, ADMA, arginine), thrombosis (sCD40L, P-selectin, PSGL-1, tPA, PAI-1, D-dimer) and renal injury (uromodulin, NGAL, cystatin C, TFF3, OPN). Statistical analysis used a mixed-effects model with Dunnett’s test to correct for multiple comparisons. Results: In non-hospitalised cohorts, no significant differences were found between groups across any biomarker. In the post-hospitalisation cohort, arginine levels increased in the recovered group at 24 months (p=0.035; trend vs PCS group p=0.051), with no changes in other markers of endothelial function (Fig. 1). In the PCS group, higher plasma levels of P-selectin (p=0.021), PSGL-1 (p=0.0006), PAI-1 (p=0.018), tPA (p=0.006&0.002) and D-dimer (trend; p=0.087) were seen in comparison with the recovered group (Fig. 1). Longitudinally, P-selectin (p=0.003), sCD40L (p=0.013), and PAI-1 (p=0.017) increased between 6 and 24 months in the PCS group. Renal markers were also altered in PCS: cystatin C (p=0.014) and TFF3 (p=0.002&0.014) were elevated, while OPN decreased between 6 and 12 months (p=0.034). Conclusions: Post-hospitalisation PCS is associated within increased markers of thrombosis, indicating persistent platelet and endothelial activation, impaired fibrinolysis and evidence of renal stress up to two years post-infection. We found no change in markers of vasomotor control except for arginine, the ‘recovery’ of which over time may reflect partial vascular restoration and warrants further investigation.