Lipoprotein (a) is not associated with thrombus burden derived from CT pulmonary angiography in patients with acute pulmonary embolism.

Lipoprotein (a) [Lp(a)] is suspected to have antifibrinolytic effects, however, its relevance for the severity of venous thromboembolic events remains unclear. We studied the association of Lp(a) levels with thrombus load in pulmonary embolism (PE). 90 patients (40% female, median age 70 [56-79] years) at our tertiary care hospital with a diagnosis of acute PE, available Lp(a) levels and CT pulmonary angiography (CT-PA) performed between April 2017 and December 2019 were included. All CT-PA scans were reanalyzed and thrombus load was determined via Qanadli CT obstruction index (CTOI) and most proximal thrombus location. Median Lp(a) levels were 11.4 [9.3-29.1] mg/dL, median D-dimer levels were 4.6 [2.1-9.8] mg/L, median CTOI was 23 [8-50], central PE was present in 27 (30%) patients. Lp(a) did not correlate with CTOI (r = 0.02, p = 0.922) and was not associated with thrombus location (p = 0.369). CTOI significantly correlated with D-dimer (r = 0.43, p < 0.001) and right to left ventricular diameter ratio (r=-0.49, p = < 0.001). Our findings showed that Lp(a) is not associated with thrombus burden in PE, which suggests that a relevant effect of Lp(a) on the extent of venous thromboembolism is unlikely.

Candidate Signature miRNAs from Secreted miRNAome of Human Lung Microvascular Endothelial Cells in Response to Different Oxygen Conditions: A Pilot Study.

Oxygen conditions in the lung determine downstream organ functionality by setting the partial pressure of oxygen, regulating the redox homeostasis and by activating mediators in the lung that can be propagated in the blood stream. Examples for such mediators are secreted soluble or vesicle-bound molecules (proteins and nucleic acids) that can be taken up by remote target cells impacting their metabolism and signaling pathways. MicroRNAs (miRNAs) have gained significant interest as intercellular communicators, biomarkers and therapeutic targets in this context. Due to their high stability in the blood stream, they have also been attributed a role as "memory molecules" that are able to modulate gene expression upon repeated (stress) exposures. In this study, we aimed to identify and quantify released miRNAs from lung microvascular endothelial cells in response to different oxygen conditions. We combined next-generation sequencing (NGS) of secreted miRNAs and cellular mRNA sequencing with bioinformatic analyses in order to delineate molecular events on the cellular and extracellular level and their putative interdependence. We show that the identified miRNA networks have the potential to co-mediate some of the molecular events, that have been observed in the context of hypoxia, hyperoxia, intermittent hypoxia and intermittent hypoxia/hyperoxia.

Estimating synthetic hematocrit and extracellular volume from native blood pool T1 times at 3 Tesla CMR: Derivation of a conversion equation, accuracy and comparison with published formulas.

PURPOSE: Calculation of extracellular volume fraction (ECV), a marker of myocardial fibrosis in cardiac magnetic resonance imaging (CMR), requires hematocrit (Hct). We aimed to correlate Hct levels with native blood T1 times, to derive a formula for estimating synthetic Hct (Hctsyn) and synthetic ECV (ECVsyn), to assess accuracy of ECVsyn and to compare our model with published formulas. METHOD: In this retrospective study, a cohort of 250 CMR scans with T1 mapping (3T, MOLLI 5(3)3, endsystolic aquisition), was divided into a derivation and validation cohort. Native T1 times of the left ventricular blood pool (T1native,midLV) were correlated with Hct levels from blood sampling within 24 h (Hct24h) and a formula for calculation of Hctsyn was derived by linear regression. RESULTS: In the derivation cohort (n = 167), Hct24h showed a good association with T1native,midLV (r = -0.711, p < 0.001). The resulting regression equation was Hctsyn = 1/T1native,midLV * 1355.52-0.310. In the validation cohort (n = 83), Hctsyn and Hct24h showed good correlation (r = 0.726, p < 0.001), while ECVsyn, and ECV24h demonstrated excellent correlation (r = 0.940, p < 0.001). ECVsyn had a minimal bias of 0.28 % and the misclassification rate (8.8 %) was comparable to the variability introduced by repeated Hct measurements (misclassification in 7.5 %). Applying published formulas in our cohort resulted in incorrect classification in up to 60 %. CONCLUSION: We provide a formula for estimating Hctsyn from native blood T1 on a 3T scanner. The measurement error of ECVsyn is low and comparable to the error due to retest variability of conventional Hct. Scanner- and sequence-specific formulas should be used.

Pulmonary manifestations of VEXAS syndrome with acute interstitial pneumonia and diffuse alveolar hemorrhage: a case report and literature review.

Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is an emerging adult-onset systemic autoinflammatory disorder affecting multiple organ systems. While lung involvement is common in this syndrome, literature regarding specific patterns is sparse. In this report, we present a case description of a patient with VEXAS syndrome who presented at the emergency department on two separate occasions with acute interstitial pneumonia (AIP) and diffuse alveolar hemorrhage (DAH). A literature review with a comparison of our observed findings to the general findings of VEXAS syndrome, AIP, and DAH is provided. This report underscores the rarity of specific pulmonary manifestations associated with VEXAS syndrome, contributing valuable insight to the limited literature available on this topic.

C-Geranylated flavanone diplacone enhances in vitro antiproliferative and anti-inflammatory effects in its copper(II) complexes.

Two copper(II) complexes containing diplacone (H4dipl), a naturally occurring C-geranylated flavanone derivative, in combination with bathophenanthroline (bphen) or 1,10-phenanthroline (phen) with the composition [Cu3(bphen)3(Hdipl)2]⋅2H2O (1) and {[Cu(phen)(H2dipl)2]⋅1.25H2O}n (2) were prepared and characterized. As compared to diplacone, the complexes enhanced in vitro cytotoxicity against A2780 and A2780R human ovarian cancer cells (IC50 ≈ 0.4-1.2 µM), human lung carcinoma (A549, with IC50 ≈ 2 µM) and osteosarcoma (HOS, with IC50 ≈ 3 µM). Cellular effects of the complexes in A2780 cells were studied using flow cytometry, covering studies concerning cell-cycle arrest, induction of cell death and autophagy and induction of intracellular ROS/superoxide production. These results uncovered a possible mechanism of action characterized by the G2/M cell cycle arrest. The studies on human endothelial cells revealed that complexes 1 and 2, as well as their parental compound diplacone, do possess anti-inflammatory activity in terms of NF-κB inhibition. As for the effects on PPARα and/or PPARγ, complex 2 reduced the expression of leukocyte adhesion molecules VCAM-1 and E-selectin suggesting its dual anti-inflammatory capacity. A wide variety of Cu-containing coordination species and free diplacone ligand were proved by mass spectrometry studies in water-containing media, which might be responsible for multimodal effect of the complexes.

Type B Aortic Dissection CTA Collection with True and False Lumen Expert Annotations for the Development of AI-based Algorithms.

Aortic dissections (ADs) are serious conditions of the main artery of the human body, where a tear in the inner layer of the aortic wall leads to the formation of a new blood flow channel, named false lumen. ADs affecting the aorta distally to the left subclavian artery are classified as a Stanford type B aortic dissection (type B AD). This is linked to substantial morbidity and mortality, however, the course of the disease for the individual case is often unpredictable. Computed tomography angiography (CTA) is the gold standard for the diagnosis of type B AD. To advance the tools available for the analysis of CTA scans, we provide a CTA collection of 40 type B AD cases from clinical routine with corresponding expert segmentations of the true and false lumina. Segmented CTA scans might aid clinicians in decision making, especially if it is possible to fully automate the process. Therefore, the data collection is meant to be used to develop, train and test algorithms.

Effects of Chronic Inflammatory Activation of Murine and Human Arterial Endothelial Cells at Normal Lipoprotein and Cholesterol Levels In Vivo and In Vitro.

The activation of endothelial cells is crucial for immune defense mechanisms but also plays a role in the development of atherosclerosis. We have previously shown that inflammatory stimulation of endothelial cells on top of elevated lipoprotein/cholesterol levels accelerates atherogenesis. The aim of the current study was to investigate how chronic endothelial inflammation changes the aortic transcriptome of mice at normal lipoprotein levels and to compare this to the inflammatory response of isolated endothelial cells in vitro. We applied a mouse model expressing constitutive active IκB kinase 2 (caIKK2)-the key activator of the inflammatory NF-κB pathway-specifically in arterial endothelial cells and analyzed transcriptomic changes in whole aortas, followed by pathway and network analyses. We found an upregulation of cell death and mitochondrial beta-oxidation pathways with a predicted increase in endothelial apoptosis and necrosis and a simultaneous reduction in protein synthesis genes. The highest upregulated gene was ACE2, the SARS-CoV-2 receptor, which is also an important regulator of blood pressure. Analysis of isolated human arterial and venous endothelial cells supported these findings and also revealed a reduction in DNA replication, as well as repair mechanisms, in line with the notion that chronic inflammation contributes to endothelial dysfunction.

How to hit the allergy target: A critical appraisal of intralymphatic immunotherapy with practical recommendations on ultrasound-guided injections.

BACKGROUND: Intralymphatic immunotherapy (ILIT) represents a promising novel approach treating allergic diseases. However, no standardized procedures or recommendations have been established or reported, despite the recognized fact that treatment efficacy relies on the ability to inject the allergen intranodally. OBJECTIVE: We aim to provide a critical appraisal of ILIT as a method of allergen immunotherapy and to deliver practical recommendations for accurate ILIT. METHODS: One hundred and seventy-three ILIT injections were performed in 28 (47%) women and 32 (53%) men with median age of 29 years (21-59). The injections were ultrasound-guided and recorded for retrospective analysis with respect to injection location, needle visibility, medication release, and patient characteristics. RESULTS: The results show that the correct positioning of the needle within the lymph node (LN) was most critical. If the whole length of the needle bevel was not inserted into the LN, substance backflush into the interstitium was observed. Selecting a more superficial LN and inserting the needle at a smaller angle towards the LN significantly improved needle visibility in the ultrasound. Longitudinal results showed that continuous practice significantly correlated with improved needle visibility and more accurate ILIT injections. CONCLUSION: Based on our results and practical experience, we propose several recommendations for LN selection and the correct handling of ultrasound probe and needle. We are confident that ILIT standardization and training will be important as to meet the goals of good safety and efficacy of ILIT.

Prevalence and prognostic impact of bone disease in chronic heart failure with reduced ejection fraction.

AIMS: Chronic heart failure is associated with a bone-catabolic state and increases the risk of osteoporosis and fractures. Prospective studies investigating the clinical relevance of bone disease in heart failure are lacking. We aimed to assess the prevalence and prognostic impact of osteoporosis and vertebral fractures (VFs) in chronic heart failure with reduced ejection fraction (HFrEF). METHODS AND RESULTS: Symptomatic outpatients with chronic heart failure and a previous diagnosis of overtly reduced left ventricular ejection fraction < 40% on stable, optimal HFrEF therapy and left ventricular ejection fraction < 50% at enrolment were included into a prospective single-centre study. Osteoporosis was determined with dual-energy X-ray absorptiometry and defined as a T-score ≤ 2.5 at any site. VFs were assessed using X-ray of both thoracic and lumbar spine applying the semiquantitative Genant score. We enrolled 205 patients (22% women), with a median age of 66 (IQR 58-74) years. Median left ventricular ejection fraction was 37 (IQR 30-43) % and median N-terminal pro B-type natriuretic peptide was 964 (IQR 363-2173) pg/mL. Osteoporosis, as defined by bone mineral density, and at least one VF were prevalent in 31 (15%) and 29 patients (14%). Osteoporosis or VF were present in 55 patients (27%) and 5 patients (2%) had both osteoporosis and a VF. During a median follow-up of 4.7 (IQR 4.0-5.3) years, 18 patients (9%) died due to cardiovascular (CV) cause, and 46 patients (22%) had a worsening heart failure (WHF) hospitalization. In multivariate Cox regression analyses, presence of VF independently predicted CV death (HR 2.82, 95% CI 1.04-7.65, P = 0.042), WHF hospitalizations (HR 2.39, 95% CI 1.18-4.82, P = 0.015), and a composite endpoint of CV death and WHF hospitalizations (HR 2.44, 95% CI 1.23-4.82, P = 0.011). Osteoporosis was not significantly associated with CV events. CONCLUSIONS: In a prospective study, bone disease affected every fourth patient with HFrEF, and patients with VF at baseline had a two-fold risk of subsequent CV death or WHF hospitalization. Prevalent bone disease, particularly VF, should be considered as a clinically relevant comorbidity in HFrEF.

The Proteome of Extracellular Vesicles Released from Pulmonary Microvascular Endothelium Reveals Impact of Oxygen Conditions on Biotrauma.

The lung can experience different oxygen concentrations, low as in hypoxia, high as under supplemental oxygen therapy, or oscillating during intermittent hypoxia as in obstructive sleep apnea or intermittent hypoxia/hyperoxia due to cyclic atelectasis in the ventilated patient. This study aimed to characterize the oxygen-condition-specific protein composition of extracellular vesicles (EVs) released from human pulmonary microvascular endothelial cells in vitro to decipher their potential role in biotrauma using quantitative proteomics with bioinformatic evaluation, transmission electron microscopy, flow cytometry, and non-activated thromboelastometry (NATEM). The release of vesicles enriched in markers CD9/CD63/CD81 was enhanced under intermittent hypoxia, strong hyperoxia and intermittent hypoxia/hyperoxia. Particles with exposed phosphatidylserine were increased under intermittent hypoxia. A small portion of vesicles were tissue factor-positive, which was enhanced under intermittent hypoxia and intermittent hypoxia/hyperoxia. EVs from treatment with intermittent hypoxia induced a significant reduction of Clotting Time in NATEM analysis compared to EVs isolated after normoxic exposure, while after intermittent hypoxia/hyperoxia, tissue factor in EVs seems to be inactive. Gene set enrichment analysis of differentially expressed genes revealed that EVs from individual oxygen conditions potentially induce different biological processes such as an inflammatory response under strong hyperoxia and intermittent hypoxia/hyperoxia and enhancement of tumor invasiveness under intermittent hypoxia.

Tobacco Exposure and Efficacy of Biologic Therapy in Patients With Severe Asthma: A Nationwide Study From the Danish Severe Asthma Register.

BACKGROUND: Randomized trials of biologics in severe, uncontrolled asthma have excluded patients with a cumulative tobacco exposure of more than 10 pack-years. Therefore, our knowledge of the impact of smoking exposure on the clinical effects of biologics in severe asthma remains incomplete. However, because many patients with asthma are current or former smokers, investigating the potential impacts of tobacco exposure on the effects of biologic treatment is clinically important. OBJECTIVE: To investigate the impact of smoking history and tobacco exposure on the effectiveness of biologic therapy in real-life patients with severe asthma. METHODS: We used data from a complete nationwide cohort of patients with severe asthma who were receiving biologics, the Danish Severe Asthma Register. We divided patients according to smoking history and cumulative tobacco exposure and analyzed data at baseline and after 12 months of biologic treatment. RESULTS: A total of 724 bio-naive patients were identified in the Danish Severe Asthma Register, 398 of whom had never been smokers (55%), 316 were previous smokers (44%), and 10 were current smokers (1%). Within the group of current and former smokers, 37% had 1 to 9 pack-years of tobacco exposure, 26% had 10 to 19 pack-years, and 37% had 20 or more pack-years of tobacco exposure. Patients with tobacco exposure had similar reductions in the number of exacerbations, reductions in maintenance oral corticosteroid use, and improvements in asthma symptoms compared with patients with 0 pack-years. CONCLUSION: Former smoking history and lifetime tobacco exposure do not have an impact on the efficacy of biologics in patients with severe asthma.

Clinical Response and Remission in Patients With Severe Asthma Treated With Biologic Therapies.

BACKGROUND: The development of novel targeted biologic therapies for severe asthma has provided an opportunity to consider remission as a new treatment goal. RESEARCH QUESTION: How many patients with severe asthma treated with biologic therapy achieve clinical remission, and what predicts response to treatment? STUDY DESIGN AND METHODS: The Danish Severe Asthma Register is a nationwide cohort including all adult patients receiving biologic therapy for severe asthma in Denmark. This observational cohort study defined "clinical response" to treatment following 12 months as a ≥ 50% reduction in exacerbations and/or a ≥ 50% reduction in maintenance oral corticosteroid dose, if required. "Clinical remission" was defined by cessation of exacerbations and maintenance oral corticosteroids, as well as a normalization of lung function (FEV1 > 80%) and a six-question Asthma Control Questionnaire score ≤ 1.5 following 12 months of treatment. RESULTS: Following 12 months of treatment, 104 (21%) of 501 biologic-naive patients had no response to treatment, and 397 (79%) had a clinical response. Among the latter, 97 (24%) fulfilled the study criteria of clinical remission, corresponding to 19% of the entire population. Remission was predicted by shorter duration of disease and lower BMI in the entire population of patients treated with biologic therapy. INTERPRETATION: Clinical response was achieved in most adult patients initiating biologic therapy, and clinical remission was observed in 19% of the patients following 12 months of treatment. Further studies are required to assess the long-term outcome of achieving clinical remission with biologic therapy.

Gallstone as a cause of intestinal obstruction (Bouveret syndrome).

Gallstone ileus is a rare cause of bowel obstruction. Here we report about two cases with clinical findings and therapy options. Both patients were presented with typical ileus-like symptoms, although the surgical treatment differs due to the CT scan and intraoperative findings. There are many methods for treating patients with Bouveret syndrome. Endoscopy should be the first treatment option for young patients with no significant diseases in the medical history, depending on the size of the stone. Surgical approach is the next possible option. Combination of these two methods is associated with higher mortality. In case there is no extraluminal gas or intraperitoneal fluid in CT-scan, there is no need for an acute surgery. Conservative therapy prior to the intervention enables a precise planning of whether the endoscopic approach or open surgery would be beneficial for the patient.

Realistic prediction and engineering of high-Q modes to implement stable Fano resonances in acoustic devices.

Quasi-bound states in the continuum (QBICs) coupling into the propagating spectrum manifest themselves as high-quality factor (Q) modes susceptible to perturbations. This poses a challenge in predicting stable Fano resonances for realistic applications. Besides, where and when the maximum field enhancement occurs in real acoustic devices remains elusive. In this work, we theoretically predict and experimentally demonstrate the existence of a Friedrich-Wintgen BIC in an open acoustic cavity. We provide direct evidence for a QBIC by mapping the pressure field inside the cavity using a Laser Doppler Vibrometer (LDV), which provides the missing field enhancement data. Furthermore, we design a symmetry-reduced BIC and achieve field enhancement by a factor of about three compared to the original cavity. LDV measurements are a promising technique for obtaining high-Q modes' missing field enhancement data. The presented results facilitate the future applications of BICs in acoustics as high-intensity sound sources, filters, and sensors.

Domperidone Protects Cells from Intoxication with Clostridioides difficile Toxins by Inhibiting Hsp70-Assisted Membrane Translocation.

Clostridioides difficile infections cause severe symptoms ranging from diarrhea to pseudomembranous colitis due to the secretion of AB-toxins, TcdA and TcdB. Both toxins are taken up into cells through receptor-mediated endocytosis, autoproteolytic processing and translocation of their enzyme domains from acidified endosomes into the cytosol. The enzyme domains glucosylate small GTPases such as Rac1, thereby inhibiting processes such as actin cytoskeleton regulation. Here, we demonstrate that specific pharmacological inhibition of Hsp70 activity protected cells from TcdB intoxication. In particular, the established inhibitor VER-155008 and the antiemetic drug domperidone, which was found to be an Hsp70 inhibitor, reduced the number of cells with TcdB-induced intoxication morphology in HeLa, Vero and intestinal CaCo-2 cells. These drugs also decreased the intracellular glucosylation of Rac1 by TcdB. Domperidone did not inhibit TcdB binding to cells or enzymatic activity but did prevent membrane translocation of TcdB's glucosyltransferase domain into the cytosol. Domperidone also protected cells from intoxication with TcdA as well as CDT toxin produced by hypervirulent strains of Clostridioides difficile. Our results reveal Hsp70 requirement as a new aspect of the cellular uptake mechanism of TcdB and identified Hsp70 as a novel drug target for potential therapeutic strategies required to combat severe Clostridioides difficile infections.

Screening for impaired pulmonary function using peak expiratory flow: Performance of different interpretation strategies.

BACKGROUND: Spirometry is the gold standard for diagnosis of impaired pulmonary function, but is often unavailable in resource-constrained settings. Some authors have suggested using peak expiratory flow (PEF) to screen for impaired pulmonary function when spirometry is unavailable, but with no consensus on how to define abnormally low PEF. Strategies have included cutoffs based on absolute value of PEF, PEF in percent predicted, PEF Z-score, PEF × height-2, and gender-specific cutoffs of absolute PEF. The objective of this paper is to determine the PEF interpretation strategy with the highest predictive ability for low pulmonary function, with spirometry as the gold standard. METHODS: We analyzed data on individuals aged 40-79 years in the United States National Health and Nutrition Examination Survey 2007-2012. 6,144 individuals fulfilled inclusion criteria for the main analysis. For each PEF interpretation strategy, we calculated the area under the receiver operating curve (AUC) for the detection of low pulmonary function (defined by FEV1 Z-score < -1.645, < -2, < -2.5 or < -3). RESULTS: The AUC was substantially and statistically significantly higher for PEF in percent predicted and PEF Z-score than for absolute value and PEF × height-2, including after stratification by gender. There was no difference in AUC between PEF in percent predicted and PEF Z-score. CONCLUSION: If using PEF to screen adults aged 40 years or older for impaired pulmonary function defined by low FEV1 Z-score, basing cutoffs on PEF in percent predicted or PEF Z-score may result in improved predictive ability. As percent predicted is a mathematically simpler term than Z-score, it may be preferable to use cutoffs based on PEF in percent predicted.

NF-κB in monocytes and macrophages - an inflammatory master regulator in multitalented immune cells.

Nuclear factor κB (NF-κB) is a dimeric transcription factor constituted by two of five protein family members. It plays an essential role in inflammation and immunity by regulating the expression of numerous chemokines, cytokines, transcription factors, and regulatory proteins. Since NF-κB is expressed in almost all human cells, it is important to understand its cell type-, tissue-, and stimulus-specific roles as well as its temporal dynamics and disease-specific context. Although NF-κB was discovered more than 35 years ago, many questions are still unanswered, and with the availability of novel technologies such as single-cell sequencing and cell fate-mapping, new fascinating questions arose. In this review, we will summarize current findings on the role of NF-κB in monocytes and macrophages. These innate immune cells show high plasticity and dynamically adjust their effector functions against invading pathogens and environmental cues. Their versatile functions can range from antimicrobial defense and antitumor immune responses to foam cell formation and wound healing. NF-κB is crucial for their activation and balances their phenotypes by finely coordinating transcriptional and epigenomic programs. Thereby, NF-κB is critically involved in inflammasome activation, cytokine release, and cell survival. Macrophage-specific NF-κB activation has far-reaching implications in the development and progression of numerous inflammatory diseases. Moreover, recent findings highlighted the temporal dynamics of myeloid NF-κB activation and underlined the complexity of this inflammatory master regulator. This review will provide an overview of the complex roles of NF-κB in macrophage signal transduction, polarization, inflammasome activation, and cell survival.

Estimating the Interaction Strength Between PTS1-Peptides and Their Receptor PEX5 in Living Cells Using Flow-Cytometer-Based FRET (flowFRET) Measurements.

The import of many peroxisomal matrix proteins is initiated by the interaction of type-1 peroxisomal targeting signals (PTS1) residing at the extreme C-terminus of cargo proteins and their receptor protein PEX5. This interaction has been amply investigated by biophysical methods using isolated proteins and peptides or heterologous systems such as two-hybrid assays. However, a recently developed novel application of Fluorescence resonance energy transfer (FRET) allows a quantifying measurement of this interaction in living cells. This method combines the systematic measurement of FRET-efficiency in a high number of cells with a well-suited normalization protocol and a fitting algorithm, which together allow the estimation of numerical values for the apparent interaction strength that correlates with other measures of binding strength but can be obtained under rather physiological conditions.

Twelve-month follow-up after hospitalization for SARS-COV-2: Physiology improves, symptoms remain.

OBJECTIVES: Persistent symptoms on short-term follow-up after infection with COVID-19 are common, but long-term consequences have been insufficiently studied. The aim of this study was to characterize pulmonary function and ongoing symptoms 12 months after hospitalization with COVID-19. METHODS: This prospective multicenter study included 222 patients hospitalized with PCR-confirmed COVID-19 in the Central Denmark Region. Disease severity was stratified using WHO Clinical Progression Scale. Clinical characteristics, pulmonary function test (PFT), 6-minute walk test (6MWT), and patient-reported outcome measures were collected at follow-up 3 and 12 months after discharge. Outcome measures from follow-up 3 months after discharge have previously been published. RESULTS: A total of 179 (81%) patients completed the 12-month follow-up. Median age was 60 years (IQR 51, 69) and 58% were male patients. At 12-month follow-up 49.7% had a normal diffusion capacity for carbon monoxide (DLCO), while 39.4% had DLCO < 80%. The 6MWT distance increased significantly (29 m 95% CI 19, 40; p < 0.01). An mMRC score of 0 was reported by 51% and an mMRC ≥ 2 by 20%. The frequency and severity of fatigue, depression, and anxiety did not improve over time. CONCLUSIONS: The study found that impaired DLCO percentage is common 12 months after hospitalization with SARS-CoV-2 and reduction in DLCO percentage is associated to dyspnea.