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Background Chronic respiratory insufficiency associated with severe resting hypoxemia necessitates long-term oxygen therapy (LTOT), yet existing devices often impede daily activities due to cumbersome flow adjustments, increasing reliance on caregivers. FlexO2 is a novel mechanical regulator that enables switching between preset oxygen flow rates for rest and activity. This proof-of-concept study evaluated its impact on patient autonomy, physical activity, and quality of life. Methods In a consecutive, non-randomized pre-post intervention proof-of-concept study at Karolinska University Hospital, 26 patients on LTOT (median age 77; 69% COPD) used FlexO2 for three months. The device, worn around the neck, allowed patients to self-adjust oxygen doses without accessing the concentrator. Outcomes included ease of use measured by visual analogue scale (VAS), physical activity levels, COPD Assessment Test (CAT), EQ-5D-5 L index, and frequency of dose adjustments. Results Ease of dose adjustment increased from a VAS score of 14 to 92 ( p  < 0.001), with 92% of patients reporting improved ease of adjustment (baseline 7.7%; p  < 0.001). Daily adjustment frequency doubled (8 to 15; p  = 0.001). Patient-reported activity capacity improved from a VAS of 11 to 80 ( p  < 0.001). Quality-of-life scores measured by VAS increased from 19 to 61 ( p  < 0.001), while CAT scores decreased from a median of 26.0 to 22.5 ( p  = 0.05). The EQ-5D-5 L index remained stable (0.68 to 0.70; p  = 0.7), although 38% of patients showed individual improvements. Device usability was high (83% satisfaction), though 15% reported tubing tangling or airflow issues. Conclusion FlexO2 significantly improved the ease of oxygen dose adjustment and physical activity capacity, potentially enhancing patient autonomy in LTOT. While overall patient-reported quality-of-life scores improved, objective quality-of-life outcomes remained stable. Further studies are warranted to explore long-term clinical outcomes and the potential impact on caregiver burden.

Post-acute COVID-19 (PACS) are associated with cardiovascular dysfunction, especially postural orthostatic tachycardia syndrome (POTS). Patients with PACS, both in the absence or presence of POTS, exhibit a wide range of persisting symptoms long after the acute infection. Some of these symptoms may stem from alterations in cardiovascular homeostasis, but the exact mechanisms are poorly understood. The aim of this study was to provide a broad molecular characterization of patients with PACS with (PACS + POTS) and without (PACS-POTS) POTS compared to healthy subjects, including a broad proteomic characterization with a focus on plasma cardiometabolic proteins, quantification of cytokines/chemokines and determination of plasma sphingolipid levels. Twenty-one healthy subjects without a prior COVID-19 infection (mean age 43 years, 95% females), 20 non-hospitalized patients with PACS + POTS (mean age 39 years, 95% females) and 22 non-hospitalized patients with PACS-POTS (mean age 44 years, 100% females) were studied. PACS patients were non-hospitalized and recruited ≈18 months after the acute infection. Cardiometabolic proteomic analyses revealed a dysregulation of ≈200 out of 700 analyzed proteins in both PACS groups vs. healthy subjects with the majority (> 90%) being upregulated. There was a large overlap (> 90%) with no major differences between the PACS groups. Gene ontology enrichment analysis revealed alterations in hemostasis/coagulation, metabolism, immune responses, and angiogenesis in PACS vs. healthy controls. Furthermore, 11 out of 33 cytokines/chemokines were significantly upregulated both in PACS + POTS and PACS-POTS vs. healthy controls and none of the cytokines were downregulated. There were no differences in between the PACS groups in the cytokine levels. Lastly, 16 and 19 out of 88 sphingolipids were significantly dysregulated in PACS + POTS and PACS-POTS, respectively, compared to controls with no differences between the groups. Collectively, these observations suggest a clear and distinct dysregulation in the proteome, cytokines/chemokines, and sphingolipid levels in PACS patients compared to healthy subjects without any clear signature associated with POTS. This enhances our understanding and might pave the way for future experimental and clinical investigations to elucidate and/or target resolution of inflammation and micro-clots and restore the hemostasis and immunity in PACS.

Persistent respiratory symptoms in COVID-19 patients have raised concerns about structural remodelling in the lung. We assessed structural changes and their correlation with reduced DLCO, eight months after discharge, in previously hospitalised COVID-19 patients. An exploratory observational study was conducted on 26 male patients (mean age: 60 years, range: 50-69) previously hospitalised for COVID-19. CT scans, performed eight months post-discharge, were analysed using functional respiratory imaging (FRI) to assess lung structure and function. Analyses were made based on diffusion capacity for carbon monoxide (DLCO). Patients with low DLCO (≤75%; n = 9) exhibited a significantly lower proportion of small blood vessels with a cross-sectional area < 5 mm² compared to patients with normal DLCO (>75%; n = 17) (median (IQR) 56 (51-59) % vs. 60 (56-64) %, p = 0.008), as well as a reduced absolute volume of small vessels with a cross-sectional area < 5 mm² (129 (121-151) ml vs. 155 (132-175) ml, p = 0.025). Bronchial dilatation was more evident in the low DLCO group, with a higher ratio of airway volume to lobar volume (siVaw) (149 (138-165) % vs. 117 (93-132) %, p = 0.002). SiVaw showed a significant inverse relationship with DLCO (r = -0.56, p = 0.004, R² = 0.31). Lobar volumes were reduced in both DLCO groups, and more pronounced in the low DLCO group (72 (65-81) % vs. 90 (79-95) %, p = 0.001), as was total lung capacity (TLC) (73 (64-85) % vs. 92 (85-98) % of predicted, p = 0.003). FEV₁/FVC ratios were elevated in both groups, with a potential difference observed between the low and normal DLCO groups (110 (103-118) % vs. 105 (95-113) %, p = 0.074). We demonstrate long-term vascular and airway remodelling detected with FRI in previously hospitalised COVID-19 patients and highlight potential mechanisms underlying persistent pulmonary dysfunction and emphasise the need to investigate the underlying pathophysiology to identify potential individualised treatment strategies for this patient group.

Covid-19 can cause chronic hypoxic respiratory failure, but the impact on the need for long-term oxygen therapy (LTOT) is unknown. The aim was to investigate change in incidence and characteristics of patients starting LTOT in Sweden 2020 after the outbreak of the pandemic. Population-based observational study using data from the National Registry for Respiratory Failure (Swedevox) and from a survey to all centres prescribing LTOT in Sweden. Swedevox data provided information on incidence of LTOT and characteristics of patients starting LTOT during 2015-2020. Between March-Dec 2020, 131 patients started LTOT due to covid-19, corresponding to 20.5% of incident LTOT in Sweden. Compared with 2015-19, the total number of patients starting LTOT did not increase. No significant differences in patient characteristics or underlying causes of hypoxemia were found between patients starting LTOT during 2020 compared 2015-2019. The majority of the LTOT centres estimated that, since the start of the pandemic, the incidence of LTOT was unchanged and the time devoted for LTOT work was the same or slightly less. Covid-19 caused one fifth of all LTOT starts during the pandemic in 2020. The LTOT incidence overall did not increase possibly due to reduction in other infections.

Background Knowledge regarding the clinical course and prognosis in non-hospitalised individuals with post-COVID-19 condition (PCC) remains limited. This study aimed to explore the impact of PCC on physical function, physical activity, and mental health in non-hospitalised adults, and to identify risk factors for low self-rated health. Extended knowledge may inform follow-up strategies and targeted interventions in non-hospitalised individuals with PCC. Methods A cohort study was conducted at a specialised post-COVID clinic, with assessments of physical function (six-minute walk test, one-minute sit-to-stand test, maximal inspiratory pressure, mMRC dyspnoea), physical activity (Frändin/Grimby activity scale), mental health (depression: PHQ-9; anxiety: GAD-7), and self-rated health (EQ VAS) at 12 and 30 months after COVID-19. A total of 130 non-hospitalised adults with PCC were included. Data were collected between August 2020 and December 2024. Results Participants were predominantly middle-aged, previously physically active women. Physical and mental impairments, and low physical activity remained prevalent at follow-up, despite some improvements over time. Impaired performance in the one-minute sit-to-stand test, a Frändin/Grimby activity level < 3, and a PHQ-9 score ≥ 10 at baseline were associated with lower EQ VAS scores at follow-up. Conclusion There were long-term negative impacts of PCC on health outcomes 2.5 years after COVID-19 in non-hospitalised individuals, including impairments in physical and mental health, low physical activity, and low self-rated health. Impaired physical function, low physical activity, and depressive symptoms were identified as risk factors for low self-rated health. These findings expand current knowledge of prognosis in PCC, underscore the need for systematic follow-up using simple clinical tools to identify individuals at high risk, and inform targeted interventions to improve long-term outcomes.

Objectives Long COVID, defined as diverse symptoms persisting > 3 months post-infection, remains a major post-pandemic healthcare burden. Here we investigate risk factor posed by pre-existing respiratory symptoms and illnesses for development of long COVID, with focus on individuals with mild-to-moderate COVID-19 at the primary infection, that did not require hospitalization during the primary SARS-CoV-2 infection. Methods This case-control study was designed to investigate the prevalence of respiratory system-related diagnoses in adult; non-hospitalized long COVID patients (cases) compared to matched controls without a history of long COVID. Data was extracted from the Stockholm Region’s database (VAL) and included diagnoses 12 months pre- and 6 months post-long COVID diagnosis as well as pre-pandemic diagnoses (year 2019). Conditional logistic regression models were applied. Results Patients with Long COVID displayed higher frequencies of pre-pandemic respiratory conditions (year 2019) as well as 12 months before long COVID diagnosis compared to controls, including acute upper respiratory tract infections (men: Odds ratio (OR) 2.47, women: OR 2.22), asthma (men: OR 1.76, women: OR 1.95), and bronchitis (men: OR 2.15, women: OR 2.71). ORs for asthma were the highest 12 months before long COVID diagnosis (men: OR 4.18, women: OR 3.76). Conclusion Patients with Long COVID with a mild-to-moderate primary SARS-CoV-2 infection had higher prevalence of pre-existing respiratory conditions than controls, suggesting that respiratory diseases including asthma were a significant risk factor for long COVID also in the non-hospitalized population. Understanding the link between common respiratory conditions managed in primary care, including asthma and bronchitis, and long COVID is vital for refining clinical strategies and improving outcomes in post-viral conditions. Key take-home message Pre-pandemic respiratory diagnoses, including asthma, were more common among individuals later diagnosed with long COVID compared with matched controls. In line with previous literature, most long COVID cases in our cohort were female.

Background With ~ 50 million individuals suffering from post-COVID condition (PCC), low health related quality of life (HRQoL) is a vast problem. Common symptoms of PCC, that persists 3 months from the onset of COVID-19 are fatigue, shortness of breath and cognitive dysfunction. No effective treatment options have been widely adopted in clinical practice. Hyperbaric oxygen (HBO 2 ) is a candidate drug. Methods The objective of this interim analysis is to describe our cohort and evaluate the safety of HBO 2 for post covid condition. In an ongoing randomised, placebo-controlled, double blind, clinical trial, 20 previously healthy subjects with PCC were assigned to HBO 2 or placebo. Primary endpoints are physical domains in RAND-36; Physical functioning (PF) and Role Physical (RP) at 13 weeks. Secondary endpoints include objective physical tests. Safety endpoints are occurrence, frequency, and seriousness of Adverse Events (AEs). An independent data safety monitoring board (DSMB) reviewed unblinded data. The trial complies with Good Clinical Practice. Safety endpoints are evaluated descriptively. Comparisons against norm data was done using t-test. Results Twenty subjects were randomised, they had very low HRQoL compared to norm data. Mean (SD) PF 31.75 (19.55) (95% Confidence interval; 22.60–40.90) vs 83.5 (23.9) p < 0.001 in Rand-36 PF and mean 0.00 (0.00) in RP. Very low physical performance compared to norm data. 6MWT 442 (180) (95% CI 358–525) vs 662 (18) meters p < 0.001. 31 AEs occurred in 60% of subjects. In 20 AEs, there were at least a possible relationship with the study drug, most commonly cough and chest pain/discomfort. Conclusions An (unexpectedly) high frequency of AEs was observed but the DSMB assessed HBO 2 to have a favourable safety profile. Our data may help other researchers in designing trials. Trial Registration ClinicalTrials.gov: NCT04842448. Registered 13 April 2021, https://clinicaltrials.gov/ct2/show/NCT04842448 . EudraCT: 2021-000764-30. Registered 21 May 2021, https://www.clinicaltrialsregister.eu/ctr-search/trial/2021-000764-30/SE

Background The aim of our study was to determine whether the application of machine learning could predict PASC by using diagnoses from primary care and prescribed medication 1 year prior to PASC diagnosis. Methods This population-based case–control study included subjects aged 18–65 years from Sweden. Stochastic gradient boosting was used to develop a predictive model using diagnoses received in primary care, hospitalization due to acute COVID- 19, and prescribed medication. The variables with normalized relative influence (NRI) ≥ 1% showed were considered predictive. Odds ratios of marginal effects (OR ME ) were calculated. Results The study included 47,568 PASC cases and controls. More females ( n  = 5113) than males ( n  = 2815) were diagnosed with PASC. Key predictive factors identified in both sexes included prior hospitalization due to acute COVID- 19 (NRI 16.1%, OR ME 18.8 for females; NRI 41.7%, OR ME 31.6 for males), malaise and fatigue (NRI 14.5%, OR ME 4.6 for females; NRI 11.5%, OR ME 7.9 for males), and post-viral and related fatigue syndromes (NRI 10.1%, OR ME 21.1 for females; NRI 6.4%, OR ME 28.4 for males). Conclusions Machine learning can predict PASC based on previous diagnoses and medications. Use of this AI method could support diagnostics of PASC in primary care and provide insight into PASC etiology.

Severe Covid-19 may cause a cascade of cardiovascular complications beyond viral pneumonia. The severe inflammation may affect the microcirculation which can be assessed by cardiovascular magnetic resonance (CMR) imaging using quantitative perfusion mapping and calculation of myocardial perfusion reserve (MPR). Furthermore, native T1 and T2 mapping have previously been shown to identify changes in myocardial perfusion by the change in native T1 and T2 during adenosine stress. However, the relationship between native T1, native T2, ΔT1 and ΔT2 with myocardial perfusion and MPR during long-term follow-up in severe Covid-19 is currently unknown. Therefore, patients with severe Covid-19 (n = 37, median age 57 years, 24% females) underwent 1.5 T CMR median 292 days following discharge. Quantitative myocardial perfusion (ml/min/g), and native T1 and T2 maps were acquired during adenosine stress, and rest, respectively. Both native T1 (R 2  = 0.35, p < 0.001) and native T2 (R 2  = 0.28, p < 0.001) correlated with myocardial perfusion. However, there was no correlation with ΔT1 or ΔT2 with MPR, respectively (p > 0.05 for both). Native T1 and native T2 correlate with myocardial perfusion during adenosine stress, reflecting the coronary circulation in patients during long-term follow-up of severe Covid-19. Neither ΔT1 nor ΔT2 can be used to assess MPR in patients with severe Covid-19.

ObjectivesTo evaluate if 10 sessions of hyperbaric oxygen treatments (HBOTs) improve short- and long-term health related quality of life, symptoms and physical performance in long covid patients compared with placebo.DesignParallel, randomised, placebo-controlled, double-blind trial.SettingSingle-centre, university hospital, Sweden.ParticipantsPreviously healthy subjects aged 18–60 years, diagnosed with long covid were included. We excluded pregnant women, patients with RAND-36 (role limitations due to physical health (RP) and physical functioning (PF)) above 70, diabetes, hypertension and contraindications for HBOT.InterventionsSubjects were randomly assigned to 10 sessions of HBOT or sham (placebo) treatments over 6 weeks. HBOT involved 100% oxygen, 2.4 bar, 90 min, placebo medical air, 1.34–1.2 bar. Randomisation (1:1) was done electronically, in blocks stratified by sex and disease severity. Subjects and investigators were blinded to allocation.Primary and secondary outcome measuresPrimary endpoints were changes from baseline in RAND-36 PF and RP at 13 weeks. Efficacy was analysed on an intention-to-treat basis. Harms were evaluated according to the actual treatment given.ResultsBetween 15 September 2021 and 20 June 2023, 80 subjects (65 women, 15 men) were enrolled and randomised (40 in each group). The trial is completed. The primary endpoint analysis included 79 subjects (40 in HBOT and 39 in control). At 13 weeks, both groups showed improvement, with no significant difference between HBOT and placebo in PF (least square mean difference between groups (LSD), 0.63 (95% CI −7.04 to 8.29), p=0.87) and RP (LSD, 2.35 (95% CI −5.95 to 10.66), p=0.57). Harms: 43 adverse events (AEs), most commonly cough and chest pain/discomfort, occurred in 19 subjects (49%) of the HBOT group and 38 AEs in 18 subjects (44%) of the placebo group, one serious AE in HBOT and one death in the placebo group.Conclusions10 HBOT sessions did not show more short-term benefits than placebo for long covid patients. Both groups improved, with a notable sex difference. HBOT has a favourable harm profile.Trial registration numberClinicalTrials.gov (NCT04842448), EudraCT (2021-000764-30). The trial was funded by Vetenskapsrådet (2022-00834), Region Stockholm (2020-0731, 2022-0674), Hjärt-Lungfonden and OuraHealth Oy.