Surgical lung biopsy for suspected interstitial lung disease with video-assisted thoracoscopic surgery is safe, providing exact histological and disease specific diagnosis for tailoring treatment.

Background: Surgical lung biopsy (SLB) is required for diagnosis in patients with suspected interstitial lung disease (ILD) if other less invasive diagnostic methods are non-conclusive. We evaluated the outcome of SLB by using centralized databases in a whole-nation patient-cohort. Methods: A population-based retrospective study on 68 consecutive patients (mean age 58 years, 58.8% males) that underwent SLB in Iceland between the years 2008 and 2020. Patient information was obtained from patient charts and peri- and postoperative complications were registered together with 30- and 90-day mortality. Computed tomography (CT) scans, histological biopsies and spirometry results were reviewed, and overall survival (Kaplan-Meier) estimated. Mean follow-up was 61.3 months (range, 3-155 months). Results: Out of 68 SLB-patients 41 (60.3%) had preoperatively undergone non-conclusive transbronchial biopsies (TBB) obtained with bronchoscopy. Spirometry showed forced vital capacity (FVC) 3.0 L and forced expiratory volume in 1 second (FEV1) 2.3 L, or 73.0% and 71.6% of predicted value, respectively. Video-assisted thoracoscopic surgery (VATS) technique was used in all cases and provided a histologic and disease specific diagnosis in 92.6% of cases; most often being nonspecific interstitial pneumonia (NSIP) (29.4%) and usual interstitial pneumonia (UIP) (23.5%). One patient (1.5%) sustained a major postoperative complication (excessive bleeding) and seven patients (10.3%) minor complications. Median chest tube time and length of stay was 1 and 2 days, respectively. No patients died <90 days postoperatively. Overall survival at 1 and 5 years was 95.6% and 73.5%, respectively, and 5-year survival for NSIP and UIP was 85% and 43.7%, respectively. Long-term mortality for UIP was four times higher when compared with NSIP and other diagnosis. Conclusions: Lung biopsy with VATS-technique provided a definitive histological and disease specific diagnosis in majority of cases. The procedure is safe, reflected in low complication-rates and short hospital stay, and can therefore be used to diagnose and tailor treatment of ILD patients.

Global mortality and readmission rates following COPD exacerbation-related hospitalisation: a meta-analysis of 65 945 individual patients.

Background: Exacerbations of COPD (ECOPD) have a major impact on patients and healthcare systems across the world. Precise estimates of the global burden of ECOPD on mortality and hospital readmission are needed to inform policy makers and aid preventive strategies to mitigate this burden. The aims of the present study were to explore global in-hospital mortality, post-discharge mortality and hospital readmission rates after ECOPD-related hospitalisation using an individual patient data meta-analysis (IPDMA) design. Methods: A systematic review was performed identifying studies that reported in-hospital mortality, post-discharge mortality and hospital readmission rates following ECOPD-related hospitalisation. Data analyses were conducted using a one-stage random-effects meta-analysis model. This study was conducted and reported in accordance with the PRISMA-IPD statement. Results: Data of 65 945 individual patients with COPD were analysed. The pooled in-hospital mortality rate was 6.2%, pooled 30-, 90- and 365-day post-discharge mortality rates were 1.8%, 5.5% and 10.9%, respectively, and pooled 30-, 90- and 365-day hospital readmission rates were 7.1%, 12.6% and 32.1%, respectively, with noticeable variability between studies and countries. Strongest predictors of mortality and hospital readmission included noninvasive mechanical ventilation and a history of two or more ECOPD-related hospitalisations <12 months prior to the index event. Conclusions: This IPDMA stresses the poor outcomes and high heterogeneity of ECOPD-related hospitalisation across the world. Whilst global standardisation of the management and follow-up of ECOPD-related hospitalisation should be at the heart of future implementation research, policy makers should focus on reimbursing evidence-based therapies that decrease (recurrent) ECOPD.

Proteomic associations with forced expiratory volume: a Mendelian randomisation study.

BACKGROUND: A decline in forced expiratory volume (FEV1) is a hallmark of respiratory diseases that are an important cause of morbidity among the elderly. While some data exist on biomarkers that are related to FEV1, we sought to do a systematic analysis of causal relations of biomarkers with FEV1. METHODS: Data from the population-based AGES-Reykjavik study were used. Serum proteomic measurements were done using 4782 DNA aptamers (SOMAmers). Data from 1479 participants with spirometric data were used to assess the association of SOMAmer measurements with FEV1 using linear regression. Bi-directional two-sample Mendelian randomisation (MR) analyses were done to assess causal relations of observationally associated SOMAmers with FEV1, using genotype and SOMAmer data from 5368 AGES-Reykjavik participants and genetic associations with FEV1 from a publicly available GWAS (n = 400,102). RESULTS: In observational analyses, 530 SOMAmers were associated with FEV1 after multiple testing adjustment (FDR < 0.05). The most significant were Retinoic Acid Receptor Responder 2 (RARRES2), R-Spondin 4 (RSPO4) and Alkaline Phosphatase, Placental Like 2 (ALPPL2). Of the 257 SOMAmers with genetic instruments available, eight were associated with FEV1 in MR analyses. Three were directionally consistent with the observational estimate, Thrombospondin 2 (THBS2), Endoplasmic Reticulum Oxidoreductase 1 Beta (ERO1B) and Apolipoprotein M (APOM). THBS2 was further supported by a colocalization analysis. Analyses in the reverse direction, testing whether changes in SOMAmer levels were caused by changes in FEV1, were performed but no significant associations were found after multiple testing adjustments. CONCLUSIONS: In summary, this large scale proteogenomic analyses of FEV1 reveals circulating protein markers of FEV1, as well as several proteins with potential causality to lung function.

Ambient air pollution and emergency department visits and hospitalisation for cardiac arrest: a population-based case-crossover study in Reykjavik, Iceland.

OBJECTIVES: To assess the association between traffic-related ambient air pollution and emergency hospital visits for cardiac arrest. DESIGN: Case-crossover design was used with a lag time to 4 days. SETTING: The Reykjavik capital area and the study population was the inhabitants 18 years and older identified by encrypted personal identification numbers and zip codes. PARTICIPANTS AND EXPOSURE: Cases were those with emergency visits to Landspitali University Hospital during the period 2006-2017 and who were given the primary discharge diagnosis of cardiac arrest according to the International Classification of Diseases 10th edition (ICD-10) code I46. The pollutants were nitrogen dioxide (NO2), particulate matter with aerodynamic diameter less than 10 µm (PM10), particulate matter with aerodynamic diameter less than 2.5 µm (PM2.5) and sulfur dioxide (SO2) with adjustment for hydrogen sulfide (H2S), temperature and relative humidity. MAIN OUTCOME MEASURE: OR and 95% CIs per 10 µg/m3 increase in concentration of pollutants. RESULTS: The 24-hour mean NO2 was 20.7 µg/m3, mean PM10 was 20.5 µg/m3, mean PM2.5 was 12.5 µg/m3 and mean SO2 was 2.5 µg/m3. PM10 level was positively associated with the number of emergency hospital visits (n=453) for cardiac arrest. Each 10 µg/m3 increase in PM10 was associated with increased risk of cardiac arrest (ICD-10: I46), OR 1.096 (95% CI 1.033 to 1.162) on lag 2, OR 1.118 (95% CI 1.031 to 1.212) on lag 0-2, OR 1.150 (95% CI 1.050 to 1.261) on lag 0-3 and OR 1.168 (95% CI 1.054 to 1.295) on lag 0-4. Significant associations were shown between exposure to PM10 on lag 2 and lag 0-2 and increased risk of cardiac arrest in the age, gender and season strata. CONCLUSIONS: A new endpoint was used for the first time in this study: cardiac arrest (ICD-10 code: I46) according to hospital discharge registry. Short-term increase in PM10 concentrations was associated with cardiac arrest. Future ecological studies of this type and their related discussions should perhaps concentrate more on precisely defined endpoints.

Idiopathic Pulmonary Fibrosis Is Associated with Common Genetic Variants and Limited Rare Variants.

Rationale: Idiopathic pulmonary fibrosis (IPF) is a rare, irreversible, and progressive disease of the lungs. Common genetic variants, in addition to nongenetic factors, have been consistently associated with IPF. Rare variants identified by candidate gene, family-based, and exome studies have also been reported to associate with IPF. However, the extent to which rare variants, genome-wide, may contribute to the risk of IPF remains unknown. Objectives: We used whole-genome sequencing to investigate the role of rare variants, genome-wide, on IPF risk. Methods: As part of the Trans-Omics for Precision Medicine Program, we sequenced 2,180 cases of IPF. Association testing focused on the aggregated effect of rare variants (minor allele frequency ⩽0.01) within genes or regions. We also identified individual rare variants that are influential within genes and estimated the heritability of IPF on the basis of rare and common variants. Measurements and Main Results: Rare variants in both TERT and RTEL1 were significantly associated with IPF. A single rare variant in each of the TERT and RTEL1 genes was found to consistently influence the aggregated test statistics. There was no significant evidence of association with other previously reported rare variants. The SNP heritability of IPF was estimated to be 32% (SE = 3%). Conclusions: Rare variants within the TERT and RTEL1 genes and well-established common variants have the largest contribution to IPF risk overall. Efforts in risk profiling or the development of therapies for IPF that focus on TERT, RTEL1, common variants, and environmental risk factors are likely to have the largest impact on this complex disease.

The relationship between interstitial lung abnormalities, mortality, and multimorbidity: a cohort study.

BACKGROUND: Interstitial lung abnormalities (ILAs) are associated with increased mortality. It is unclear whether multimorbidity accounts for the mortality association or how strongly ILA is associated with mortality relative to other common age-associated diseases. We determined the association of ILA with all-cause mortality adjusted for multimorbidity, compared mortality associated with ILA and prevalent cardiovascular disease (CVD), diabetes mellitus, chronic kidney disease, chronic obstructive pulmonary disease and cancer and also determined the association between ILA and these diseases. METHODS: We measured ILA (none, indeterminant, definite) using blinded reads of CT images, prevalent chronic diseases and potential confounders in two observational cohorts, the Framingham Heart Study (FHS) (n=2449) and Age, Gene/Environment Susceptibility - Reykjavik Study (AGES-Reykjavik) (n=5180). We determined associations with mortality using Cox proportional hazards models and between ILA and diseases with multinomial logistic regression. RESULTS: Over a median (IQR) follow-up of 8.8 (1.4) years in FHS and 12.0 (7.7) years in AGES-Reykjavik, in adjusted models, ILAs were significantly associated with increased mortality (HR, 95% CI 1.95, 1.23 to 3.08, p=0.0042, in FHS; HR 1.60, 1.41 to 1.82, p<0.0001, in AGES-Reykjavik) adjusted for multimorbidity. In both cohorts, the association of ILA with mortality was of similar magnitude to the association of most other diseases. In adjusted models, ILAs were associated only with prevalent kidney disease (OR, 95% CI 1.90, 1.01 to 3.57, p=0.0452) in FHS and with prevalent CVD (OR 1.42, 1.12 to 1.81, p=0.0040) in AGES-Reykjavik. CONCLUSIONS: ILAs were associated with mortality adjusted for multimorbidity and were similarly associated with increased mortality compared with several common chronic diseases. ILAs were not consistently associated with the prevalence of these diseases themselves.

Respiratory function and CT abnormalities among survivors of COVID-19 pneumonia: a nationwide follow-up study.

INTRODUCTION: Considering the pulmonary burden caused by acute COVID-19, questions remain of respiratory consequences after recovery. The aim of the study was to describe respiratory function of COVID-19 pneumonia survivors at mid-term follow-up (median 68 days) and assess whether impairments were predicted by acute illness severity or residual CT abnormalities. METHODS: Residents of Iceland that had COVID-19 and oxygen saturation ≤94% from 28 February 2020 to 30 April 2021 were offered a clinical follow-up visit with an interview, a 6 min walk test (6MWT), spirometry with gas exchange measurement and chest CT. The results of these examinations were described, grouped by the level of care during acute illness. The associations of disease severity and CT abnormalities at follow-up with subjective dyspnoea, 6MWT results and lung function test results were estimated with regression analyses. RESULTS: Of 190 eligible patients, 164 (86%) participated in the study. Of those, 32 had never been admitted to hospital, 103 were admitted to hospital without intensive care and 29 had required intensive care. At a follow-up, need for intensive care during acute illness was associated with shorter walking distance on 6MWT, lower oxygen saturation and lower DLCO. Imaging abnormalities at follow-up were observed for most participants (74%) and the magnitude of these changes was associated with decrements in 6MWT distance, oxygen saturation, forced vital capacity and DLCO. CONCLUSIONS: The findings show that impaired exercise capacity and lung physiology at follow-up were primarily observed for patients with COVID-19 pneumonia that required intensive care treatment and/or had persistent imaging abnormalities.

Ethical Dilemmas in Physicians' Consultations with COPD Patients.

Aim: This phenomenological study was aimed at exploring principal physicians' (participants') experience of attending to COPD patients and motivating their self-management, in light of the GOLD clinical guidelines of COPD therapy. Methods: Interviews were conducted with nine physicians, who had referred patients to PR, five general practitioners (GPs) and four lung specialists (LSs). The interviews were recorded, transcribed, and analyzed through a process of deconstruction and reconstruction. Results: The participants experienced several ethical dilemmas in being principal physicians of COPD patients and motivating their self-management; primarily in the balancing act of adhering to the Hippocratic Oath of promoting health and saving lives, while respecting their patients' choice regarding non-adherence eg, by still smoking. It was also a challenge to deal with COPD as a nicotine addiction disease, deal with patients' denial regarding the harm of smoking and in motivating patient mastery of the disease. The participants used various strategies to motivate their patients' self-management such as active patient education, enhancing the patients' inner motivation, by means of an interdisciplinary approach, involving the patients' significant other when appropriate, and by proposing PR. Conclusion: The findings indicate that being a principal physician of COPD patients and motivating their self-management is a balancing act, involving several dilemmas. Patients' nicotine addiction and physicians' ethical obligations are likely to create ethical dilemmas as the physician is obligated to respect the patients' will, even though it contradicts what is best for the patient. The participants suggest strategies to motivate COPD patients' self-management.

The Proteomic Profile of Interstitial Lung Abnormalities.

Rationale: Knowledge on biomarkers of interstitial lung disease is incomplete. Interstitial lung abnormalities (ILAs) are radiologic changes that may present in its early stages. Objectives: To uncover blood proteins associated with ILAs using large-scale proteomics methods. Methods: Data from two prospective cohort studies, the AGES-Reykjavik (Age, Gene/Environment Susceptibility-Reykjavik) study (N = 5,259) for biomarker discovery and the COPDGene (Genetic Epidemiology of COPD) study (N = 4,899) for replication, were used. Blood proteins were measured using DNA aptamers, targeting more than 4,700 protein analytes. The association of proteins with ILAs and ILA progression was assessed with regression modeling, as were associations with genetic risk factors. Adaptive Least Absolute Shrinkage and Selection Operator models were applied to bootstrap data samples to discover sets of proteins predictive of ILAs and their progression. Measurements and Main Results: Of 287 associations, SFTPB (surfactant protein B) (odds ratio [OR], 3.71 [95% confidence interval (CI), 3.20-4.30]; P = 4.28 × 10-67), SCGB3A1 (Secretoglobin family 3A member 1) (OR, 2.43 [95% CI, 2.13-2.77]; P = 8.01 × 10-40), and WFDC2 (WAP four-disulfide core domain protein 2) (OR, 2.42 [95% CI, 2.11-2.78]; P = 4.01 × 10-36) were most significantly associated with ILA in AGES-Reykjavik and were replicated in COPDGene. In AGES-Reykjavik, concentrations of SFTPB were associated with the rs35705950 MUC5B (mucin 5B) promoter polymorphism, and SFTPB and WFDC2 had the strongest associations with ILA progression. Multivariate models of ILAs in AGES-Reykjavik, ILAs in COPDGene, and ILA progression in AGES-Reykjavik had validated areas under the receiver operating characteristic curve of 0.880, 0.826, and 0.824, respectively. Conclusions: Novel, replicated associations of ILA, its progression, and genetic risk factors with numerous blood proteins are demonstrated as well as machine-learning-based models with favorable predictive potential. Several proteins are revealed as potential markers of early fibrotic lung disease.

Interstitial lung abnormalities are associated with decreased mean telomere length.

BACKGROUND: Interstitial lung abnormalities (ILA) share many features with idiopathic pulmonary fibrosis; however, it is not known if ILA are associated with decreased mean telomere length (MTL). METHODS: Telomere length was measured with quantitative PCR in the Genetic Epidemiology of Chronic Obstructive Pulmonary Disease (COPDGene) and Age Gene/Environment Susceptibility Reykjavik (AGES-Reykjavik) cohorts and Southern blot analysis was used in the Framingham Heart Study (FHS). Logistic and linear regression were used to assess the association between ILA and MTL; Cox proportional hazards models were used to assess the association between MTL and mortality. RESULTS: In all three cohorts, ILA were associated with decreased MTL. In the COPDGene and AGES-Reykjavik cohorts, after adjustment there was greater than twofold increase in the odds of ILA when comparing the shortest quartile of telomere length to the longest quartile (OR 2.2, 95% CI 1.5-3.4, p=0.0001, and OR 2.6, 95% CI 1.4-4.9, p=0.003, respectively). In the FHS, those with ILA had shorter telomeres than those without ILA (-767 bp, 95% CI 76-1584 bp, p=0.03). Although decreased MTL was associated with chronic obstructive pulmonary disease (OR 1.3, 95% CI 1.1-1.6, p=0.01) in COPDGene, the effect estimate was less than that noted with ILA. There was no consistent association between MTL and risk of death when comparing the shortest quartile of telomere length in COPDGene and AGES-Reykjavik (HR 0.82, 95% CI 0.4-1.7, p=0.6, and HR 1.2, 95% CI 0.6-2.2, p=0.5, respectively). CONCLUSION: ILA are associated with decreased MTL.

Ambient nitrogen dioxide is associated with emergency hospital visits for atrial fibrillation: a population-based case-crossover study in Reykjavik, Iceland.

BACKGROUND: In Iceland air quality is generally good; however, previous studies indicate that there is an association between air pollution in Reykjavik and adverse health effects as measured by dispensing of medications, mortality, and increase in health care utilisation. The aim was to study the association between traffic-related ambient air pollution in the Reykjavik capital area and emergency hospital visits for heart diseases and particularly atrial fibrillation and flutter (AF). METHODS: A multivariate time-stratified case-crossover design was used to study the association. Cases were those patients aged 18 years or older living in the Reykjavik capital area during the study period, 2006-2017, who made emergency visits to Landspitali University Hospital for heart diseases. In this population-based study, the primary discharge diagnoses were registered according to International Classification of Diseases, 10th edition (ICD-10). The pollutants studied were NO2, PM10, PM2.5, and SO2, with adjustment for H2S, temperature, and relative humidity. The 24-h mean of pollutants was used with lag 0 to lag 4. RESULTS: During the study period 9536 cases of AF were identified. The 24-h mean NO2 was 20.7 µg/m3. Each 10 µg/m3 increase in NO2 was associated with increased risk of heart diseases (ICD-10: I20-I25, I44-I50), odds ratio (OR) 1.023 (95% CI 1.012-1.034) at lag 0. Each 10 µg/m3 increase in NO2 was associated with an increased risk of AF (ICD-10: I48) on the same day, OR 1.030 (95% CI: 1.011-1.049). Females were at higher risk for AF, OR 1.051 (95% CI 1.019-1.083) at lag 0, and OR 1.050 (95% CI 1.019-1.083) at lag 1. Females aged younger than 71 years had even higher risk for AF, OR 1.077 (95% CI: 1.025-1.131) at lag 0. Significant associations were found for other pollutants and emergency hospital visits, but they were weaker and did not show a discernable pattern. CONCLUSIONS: Short-term increase in NO2 concentrations was associated with heart diseases, more precisely with AF. The associations were stronger among females, and among females at younger age. This is the first study in Iceland that finds an association between air pollution and cardiac arrhythmias, so the results should be interpreted with caution.

Obstructive sleep apnea is an independent risk factor for severe COVID-19: a population-based study.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) has been proposed as a risk factor for severe COVID-19. Confounding is an important consideration as OSA is associated with several known risk factors for severe COVID-19. Our aim was to assess the association of OSA with hospitalization due to COVID-19 using a population-based cohort with detailed information on OSA and comorbidities. METHODS: Included were all community-dwelling Icelandic citizens 18 years of age and older diagnosed with SARS-CoV-2 infection in 2020. Data on demographics, comorbidities, and outcomes of COVID-19 was obtained from centralized national registries. Diagnosis of OSA was retrieved from the centralized Sleep Department Registry at Landspitali - The National University Hospital. Severe COVID-19 was defined as the composite outcome of hospitalization and death. The associations between OSA and the outcome were expressed as odds ratios (OR) with 95% confidence intervals (95% CI), calculated using logistic regression models and inverse probability weighting. RESULTS: A total of 4,756 individuals diagnosed with SARS-CoV-2 infection in Iceland were included in the study (1.3% of the Icelandic population), of whom 185 had a diagnosis of OSA. In total, 238 were hospitalized or died, 38 of whom had OSA. Adjusted for age, sex, and BMI, OSA was associated with poor outcome (OR 2.2, 95% CI 1.4-3.5). This association was slightly attenuated (OR 2.0, 95% CI 2.0, 1.2-3.2) when adjusted for demographic characteristics and various comorbidities. CONCLUSIONS: OSA was associated with twofold increase in risk of severe COVID-19, and the association was not explained by obesity or other comorbidities.

Associations of Monocyte Count and Other Immune Cell Types with Interstitial Lung Abnormalities.

Rationale: Higher blood monocyte counts are associated with worse survival in adults with clinically diagnosed pulmonary fibrosis. Their association with the development and progression of interstitial lung abnormalities (ILA) in humans is unknown. Objectives: We evaluated the associations of blood monocyte count, and other immune cell types, with ILA, high-attenuation areas, and FVC in four independent cohorts. Methods: We included participants with measured monocyte counts and computed tomographic (CT) imaging enrolled in MESA (Multi-Ethnic Study of Atherosclerosis, n = 484), AGES-Reykjavik (Age/Gene Environment Susceptibility Study, n = 3,547), COPDGene (Genetic Epidemiology of COPD, n = 2,719), and the ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points, n = 646). Measurements and Main Results: After adjustment for covariates, a 1-SD increment in blood monocyte count was associated with ILA in MESA (odds ratio [OR], 1.3; 95% confidence interval [CI], 1.0-1.8), AGES-Reykjavik (OR, 1.2; 95% CI, 1.1-1.3), COPDGene (OR, 1.3; 95% CI, 1.2-1.4), and ECLIPSE (OR, 1.2; 95% CI, 1.0-1.4). A higher monocyte count was associated with ILA progression over 5 years in AGES-Reykjavik (OR, 1.2; 95% CI, 1.0-1.3). Compared with participants without ILA, there was a higher percentage of activated monocytes among those with ILA in MESA. Higher monocyte count was associated with greater high-attenuation areas in MESA and lower FVC in MESA and COPDGene. Associations of other immune cell types were less consistent. Conclusions: Higher blood monocyte counts were associated with the presence and progression of interstitial lung abnormalities and lower FVC.

Interstitial lung abnormalities - current knowledge and future directions.

Efforts to grasp the significance of radiologic changes similar to interstitial lung disease (ILD) in undiagnosed individuals have intensified in the recent decade. The term interstitial lung abnormalities (ILA) is an emerging definition of such changes, defined by visual examination of computed tomography scans. Substantial insights have been made in the origins and clinical consequences of these changes, as well as automated measures of early lung fibrosis, which will likely lead to increased recognition of early fibrotic lung changes among clinicians and researchers alike. Interstitial lung abnormalities have an estimated prevalence of 7-10% in elderly populations. They correlate with many ILD risk factors, both epidemiologic and genetic. Additionally, histopathological similarities with IPF exist in those with ILA. While no established blood biomarker of ILA exists, several have been suggested. Distinct imaging patterns indicating advanced fibrosis correlate with worse clinical outcomes. ILA are also linked with adverse clinical outcomes such as increased mortality and risk of lung cancer. Progression of ILA has been noted in a significant portion of those with ILA and is associated with many of the same features as ILD, including advanced fibrosis. Those with ILA progression are at risk of accelerated FVC decline and increased mortality. Radiologic changes resembling ILD have also been attained by automated measures. Such measures associate with some, but not all the same factors as ILA. ILA and similar radiologic changes are in many ways analogous to ILD and likely represent a precursor of ILD in some cases. While warranting an evaluation for ILD, they are associated with poor clinical outcomes beyond possible ILD development and thus are by themselves a significant finding. Among the present objectives of this field are the stratification of patients with regards to progression and the discovery of biomarkers with predictive value for clinical outcomes.

[Parenchymal lung changes on CT in patients with coronavirus disease 2019 (COVID-19)].

Introduction Infections due to COVID-19 can lead to life threatening pneumonia. Accompanying severe disease are more prominent pulmonary changes on Computed Tomography (CT) scan of the chest. The goal of this study was to describe pulmonary CT changes during acute COVID-19 and at follow up and whether the extent of changes correlate with severity of illness, demographics or other risk factors. Materials and methods Included in this study are all individuals that had confirmed COVID-19 and came for a follow up CT of the chest at Landspitali from May to September 2020. Information regarding medical history was obtained retrospectively from medical charts. All CT scans were reviewed using an international staging system to evaluate the extent of lung changes. Results Eighty-five patients with a mean age of 59 years were included in the study. Sixty patients (71%) were hospitalized during the acute phase and 18 (21%) were admitted to the ICU. During the acute phase more pronounced lung involvement was seen in males and patients admitted to the ICU. At follow-up females had less lung involvement but there was a significant relationship between a higher CT score and age, ICU admissions and days in the ICU. Full recovery was seen at follow-up CT in 31% of patients (median 68,5 days between acute and follow-up imaging). Conclusion Patients with severe COVID-19 have more pronounced lung involvement on CT than patients with milder disease during the acute phase and follow-up. Older patients and males are at greater risk of acute and persistent COVID-19 related lung changes.

Illness severity and risk of mental morbidities among patients recovering from COVID-19: a cross-sectional study in the Icelandic population.

OBJECTIVE: To test if patients recovering from COVID-19 are at increased risk of mental morbidities and to what extent such risk is exacerbated by illness severity. DESIGN: Population-based cross-sectional study. SETTING: Iceland. PARTICIPANTS: A total of 22 861 individuals were recruited through invitations to existing nationwide cohorts and a social media campaign from 24 April to 22 July 2020, of which 373 were patients recovering from COVID-19. MAIN OUTCOME MEASURES: Symptoms of depression (Patient Health Questionnaire), anxiety (General Anxiety Disorder Scale) and posttraumatic stress disorder (PTSD; modified Primary Care PTSD Screen for DSM-5) above screening thresholds. Adjusting for multiple covariates and comorbidities, multivariable Poisson regression was used to assess the association between COVID-19 severity and mental morbidities. RESULTS: Compared with individuals without a diagnosis of COVID-19, patients recovering from COVID-19 had increased risk of depression (22.1% vs 16.2%; adjusted relative risk (aRR) 1.48, 95% CI 1.20 to 1.82) and PTSD (19.5% vs 15.6%; aRR 1.38, 95% CI 1.09 to 1.75) but not anxiety (13.1% vs 11.3%; aRR 1.24, 95% CI 0.93 to 1.64). Elevated relative risks were limited to patients recovering from COVID-19 that were 40 years or older and were particularly high among individuals with university education. Among patients recovering from COVID-19, symptoms of depression were particularly common among those in the highest, compared with the lowest tertile of influenza-like symptom burden (47.1% vs 5.8%; aRR 6.42, 95% CI 2.77 to 14.87), among patients confined to bed for 7 days or longer compared with those never confined to bed (33.3% vs 10.9%; aRR 3.67, 95% CI 1.97 to 6.86) and among patients hospitalised for COVID-19 compared with those never admitted to hospital (48.1% vs 19.9%; aRR 2.72, 95% CI 1.67 to 4.44). CONCLUSIONS: Severe disease course is associated with increased risk of depression and PTSD among patients recovering from COVID-19.

Delirium and fever - a rare but dangerous cause - Case report

Fever complicated by delirium is a common problem in emergency departments and inpatient wards. There are various possible causes that must all be contemplated. Infections are prominent causes due to acuteness and severity, but when generating a differential diagnosis, other causes may be life-threatening and require swift diagnosis and management. We present here a case of a 58 year old man presenting at the emergency department with fever and delirium. After comprehensive history-taking and examination, alongside targeted testing, the correct diagnosis was ascertained, leading to appropriate treatment.