Tuberculosis (TB) and acquired immunodeficiency syndrome (AIDS) are the leading causes of death from single infectious agents in low- and middle-income countries. Moreover, in the individual host, the two pathogens, Mycobacterium tuberculosis and human immunodeficiency virus (HIV), potentiate one another, accelerating the deterioration of immunological functions. In high-burden settings, HIV coinfection is the most important risk factor for TB disease, due to reactivation. Susceptibility to primary TB infection, or reinfection, is also elevated in people living with HIV (PLWH). TB disease also has a negative impact in PLWH not receiving antiretroviral therapy (ART), accelerating the progression to AIDS. The clinical management of HIV-associated TB includes the integration of effective TB treatment, use of concurrent ART, prevention of HIV-related comorbidities, management of drug cytotoxicity, and prevention/treatment of immune reconstitution inflammatory syndrome.

Abstract Background This study aimed to identify, analyse and compare adults with and without respiratory symptoms over time after COVID-19 and identify predictors of persistent respiratory symptoms, in hospitalised and non-hospitalised patients. Methods Participants were recruited at the Post COVID-19 clinic at Karolinska University hospital, Sweden, between May 2020 until December 2022, with longitudinal data collected until February 2025. Data from medical records and two clinical follow-up visits were analysed. Participants were categorised based on presence or absence of self-reported respiratory symptoms. Clinical outcomes included physical function, patient-reported outcomes, lung function and other clinically relevant parameters. Results A total of 963 out of 1976 participants were included, of whom 760 (79%) were identified with respiratory symptoms and 203 (21%) were not at first follow-up visit. The respiratory symptom group showed poorer physical function and worse patient-reported outcomes at the first follow-up (adjusted p < 0.05). Lung function was generally preserved, although diffusing lung capacity for carbon monoxide (DLCO) was lower in the respiratory symptom group (79% vs 84%, adjusted p < 0.05). Both groups improved over time, and the magnitude of change did not differ significantly between groups. However, participants in the respiratory symptom group remained more impaired across several outcomes at follow-up. Presence of respiratory symptoms at the first follow-up visit was the strongest independent predictor of belonging to the respiratory symptom group at second follow-up visit (OR 5.31, 95% CI 2.74–10.89). Conclusions Respiratory symptoms after acute COVID-19 were highly prevalent and were associated with poorer clinical outcomes, despite similar recovery over time. Further research is needed to better clarify underlying mechanisms and to guide targeted rehabilitation strategies.

Developing shorter treatment regimens for tuberculosis requires careful characterization of the clinical phenotype, which is defined by patient characteristics, radiological extent of disease, mycobacterial burden, drug susceptibility, and host response. Advances in ’omics and model-informed precision dosing, as well as integrated algorithms using artificial intelligence, need to be adapted and validated in clinical trials to improve classification of patients for stratified treatment. When treatment is initiated based on the clinical phenotype, monitoring of treatment response can be improved by quantification of bacterial load, transcriptomic and epigenetic biosignatures for sputum-free monitoring, and assessing disease burden by radiological and symptom scoring tools. Many of these tools are suitable for high-endemic settings. Such integrated monitoring allows prompt drug adjustments for rapid reduction in bacterial load, which prevents development of drug resistance and achieves relapse-free cure even with shorter treatment.

Background:Cardiovascular autonomic dysfunction is a major complication in a large proportion of patients with long coronavirus disease (LC). As one of the most typical phenotypes of cardiovascular autonomic dysfunction, postural orthostatic tachycardia syndrome (POTS) is commonly observed as a sequelae of coronavirus disease infection. Objective:This study aimed to develop and test a 24-hour electrocardiogram (ECG) recording to direct the clinical suspicion toward the diagnosis of POTS. Methods:Consecutive patients referred to the Karolinska University Hospital in Stockholm from April 2021 to April 2022 were included. Patients with POTS were compared with patients with LC without POTS (verified by active standing tests) and control healthy subjects according to 3 specific analyses based on 24-hour ECG recording: (1) heart rate (HR) spikes of > 30 beats per minute, (2) awakening HR increase, and (3) HR variability (root mean square of successive difference). The control group consisted of healthy subjects from the database of the University Hospital of Saint-Etienne. Results:A total of 100 patients with LC (mean age, 42.54 ± 10.45 years; 92% women) and 100 healthy subjects (41.40 ± 7.21 years; 96% women) were included. LC POTS (n = 45) was associated with (1) a higher number of HR spikes/h (1.47 ± 0.84 vs 0.68 ± 0.50 and 0.40 ± 0.28/h; P < .01), (2) an abrupt and sustained increase in HR after awakening (P < .05), and (3) a reduction of HR variability: mean root mean square of successive difference of 34.90 ± 12.48 vs 30.47 ± 19.15 and 43.35 ± 21.10 ms (P < .01) compared with patients with LC without POTS (n = 55) and healthy subjects. Conclusion:A triple analysis of 24-hour ECG recordings could reveal a characteristic POTS signature in LC. More research in other populations is needed to draw any firm conclusions about its generalizability.

BACKGROUND:The Xpert MTB Host Response (MTB-HR) assay has reached World Health Organization (WHO) test targets for pulmonary tuberculosis (PTB) with high bacillary loads. We investigated the contribution of MTB-HR as a nonsputum, near point-of-care diagnostic method in other prioritized groups, such as extrapulmonary tuberculosis (EPTB) and paucibacillary PTB. METHODS:Individuals with presumed tuberculosis disease were prospectively included in Stockholm, Sweden (n = 307), and underwent MTB-HR venous and capillary testing in parallel. Clinical characterization was based on symptoms, microbiological results (microscopy, polymerase chain reaction [PCR], and culture), radiological assessment, and a panel of biochemical tests. Receiver operating characteristic analysis was performed to calculate cut-offs for maximized sensitivity and specificity, including WHO targets for screening and diagnostic tests. RESULTS:MTB-HR performed equally well in microbiologically confirmed PTB (area under the curve [AUC], 0.84 [95% confidence interval {CI}, .78-.90]; n = 69) and EPTB (AUC, 0.82 [95% CI, .75-.90]; n = 34). Based on Youden index cut-offs, the negative predictive value (NPV) was high both in PCR-negative PTB (-1.27, NPV 94%) and in EPTB (-1.58, NPV 95%) and fulfilled the minimum target product profile sensitivity requirement for confirmed EPTB. In individuals without tuberculosis (n = 204), the majority had pulmonary infections. There was a close to perfect correlation between venous and capillary samples (r = 0.97, P < .001). CONCLUSIONS:Capillary Xpert MTB-HR improves detection of sputum PCR-negative, culture-verified PTB and is promising as a rule-out test in EPTB. MTB-HR score and bacterial burden were highly correlated. We suggest a graded MTB-HR score as more clinically relevant than a binary result.

Importance:COVID-19 can lead to long-term cardiopulmonary symptoms and is associated with coronary microvascular dysfunction (CMD). However, long-term data on CMD after severe COVID-19 are lacking. Objective:To investigate long-term left ventricular function and the presence of CMD after severe COVID-19. Design, Setting, and Participants:This case-control study was conducted among patients at a single center from the prospective Follow-Up of Patients With Severe COVID-19 (UppCov) study, with follow-up multiparametric perfusion cardiovascular magnetic resonance (CMR) at 10 months after discharge from November 2020 to February 2021. Patients previously hospitalized due to severe COVID-19 (ventilatory support, oxygen flow ≥5 L/min, or both) with or without cardiac involvement (troponin t > 14 ng/L, pulmonary artery pressure >34 mm Hg, or both) were compared with historical sex- and age-matched volunteers without symptomatic ischemic heart disease. Standard contraindications to adenosine CMR were applied. Data were analyzed between March 2023 and March 2025. Exposure:Hospitalization due to severe COVID-19. Main Measures and Outcomes:Comprehensive CMR included native T1, native T2, extracellular volume, adenosine stress and rest perfusion mapping, gadolinium enhancement, and cine imaging. Comorbidities, medications, symptoms at follow-up, and details regarding hospitalization were obtained from patient records. Results:The study included 37 patients with COVID-19 (mean age, 56 years [95% CI, 53 to 61 years]; 28 male [75.7%]) and 22 healthy volunteers (mean age, 51 years [95% CI, 45 to 57 years]; 12 male [54.4%]). Patients with COVID-19 compared with healthy patients demonstrated reduced mean stress perfusion (2.80 mL/min/g [95% CI, 2.53 to 3.07 mL/min/g] vs 3.43 mL/min/g [95% CI, 3.13 to 3.74 mL/min/g]; P = .003), impaired mean global longitudinal strain (-17% [95% CI, -18% to -16%] vs -19% [-20% to -18%]; P = .003), and impaired mean global circumferential strain (-16% [95% CI, -17% to -15%] vs -19% [-20% to -18%]; P = .001). There were no differences in stress perfusion or myocardial perfusion reserve in the COVID-19 group between patients with vs without cardiovascular risk factors or cardiac symptoms. Conclusions and Relevance:In this study, patients with COVID-19 exhibited long-term reduced stress perfusion indicating CMD, along with declined left ventricular function by global longitudinal strain and global circumferential strain. Lack of variation in stress perfusion between patients with and without cardiovascular risk factors may suggest CMD due to severe COVID-19, warranting further investigation to elucidate mechanisms and guide potential therapies.

Non-sputum-based biomarkers for early diagnosis of TB disease are urgently needed to control transmission and achieve the World Health Organizations goals of ending TB. We previously identified a 12-marker plasma protein signature associated with TB disease severity. In this study we assessed the signatures performance in identifying TB disease in independent Swedish and Italian cohorts, including individuals with TB infection and other respiratory diseases (total n=317 samples from 273 donors). We condensed the 12 proteins to smaller 6 (CDCP1, VEGFA, IFN-γ, CXCL9, IL6 and MCP-3) and 4 (CDCP1, VEGFA, IFN-γ, CXCL9)-protein signatures which remained highly enriched and even improved accuracy when compared with ten other published protein signatures for TB disease. Sensitivity in TB disease was 89% in the entire cohort and 97% in the Italian cohort, with specificity fixed at 70%. These signatures merit further evaluation as clinically relevant markers for a non-sputum-based test for TB disease. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was supported by grants from the Swedish Research Council (2021-03706 and 2023-01943), the Swedish Medical Association (SLS-934363 and SLS-960484), the Swedish Society for Medical Research (CG-24-0012-B), and the Heart-Lung Foundation (20220566 and 20230244) to CS. Grants from Swedish Research Council (2019-04663 and 2020-03602) and the Heart- and Lung Foundation (20180386 and 20200194) to GK. ZM was supported by grants from the VALIDATE Network and the Erik and Edith Fernströ m Foundation for Medical Research. The Italian team was funded by the Italian Ministry of Health (Ricerca Corrente, Linea 4, Progetto 2), and TBVACHORIZON, funded by the European Union HORIZON program under Grant No. 101080309. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: All study participants received written and verbal information and signed a written informed consent form prior to study inclusion. In relevant cases professional interpreter services were used. The Swedish study cohort received ethical permission from the Swedish Ethical Review Authority, EPN-number 2019-05438 with addendums 2022-00231-02, 2022-07053-02 with ÖN 29-2023, and 2024-03955-02. The Italian study cohort was approved by the Ethical Committee of the National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS (approval number 72/2015 and approval number 27/ 2019). After obtaining the clinical and demographic information, the samples from Italy were anonymized. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data is available upon reasonable request to the corresponding author and pending confirmation of relevant permits.

BACKGROUND:Post-acute COVID-19 syndrome (PACS) has been linked to microvascular endothelial dysfunction as a potential underlying pathomechanism and can manifest even following a mild course of the initial infection. Prevalence of microvascular endothelial dysfunction and circulating natriuretic peptides in such PACS patients remains unknown. METHODS:This prospective, cross-sectional cohort study enrolled 92 patients (82% females, median age 48 years) with PACS. Reactive hyperemia index (RHI) was evaluated with peripheral arterial tonometry, where <1.67 was defined as microvascular endothelial dysfunction, 1.67-2.0 as impaired function, and >2 normal endothelial function, on average 31 months after the acute infection. N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were collected at 2 different time points within over a 1-year span. RESULTS:In total, 41% of PACS subjects had microvascular endothelial dysfunction and 20% had impaired RHI. No major differences in clinical characteristics, routine chemistry laboratory testing, or symptom burden were observed across the groups. Only subjects with microvascular endothelial dysfunction and impaired endothelial function had a significant increase in NT-proBNP levels over time, and those with larger increase in NT-proBNP had significantly lower RHI. There was a significant correlation between relative or absolute increase in NT-proBNP and RHI, which remained significant in a multivariable adjusted linear regression. CONCLUSIONS:Peripheral microvascular endothelial dysfunction was prevalent in a symptomatic PACS population long after recovery from a mild acute infection. Increases in NT-proBNP levels were associated with microvascular endothelial dysfunction, suggesting a link between, and providing a foundation for, future studies on post viral microvascular endothelial dysfunction in PACS.

Objective: This study aimed to explore physical activity and sedentary time in adults with post-COVID-19 condition, and to identify associated factors. Design: Cross-sectional, observational study. Subjects/Patients: Adults with post-COVID-19 condition. Methods: Physical activity and sedentary time were measured using activity monitors alongside assessment of potential associated factors. Results: Among 159 participants (mean age: 50 years, women: 64%), 36% took < 5,000 steps, 60% spent < 22 min in brisk walking, and 57% spent ≥ 8 h sedentarily daily. Additionally, 29% exhibited low activity combined with prolonged sedentary time. Postural orthostatic tachycardia syndrome and palpitations were associated with taking fewer steps, while paraesthesia, greater distance in the 6-min walk test, previous activity levels, and self-rated health were associated with taking more steps. Palpitations were associated with less brisk walking, whereas greater distance in the 6-min walk test and lung function were associated with more brisk walking. Postural orthostatic tachycardia syndrome was associated with increased sedentary time and with exhibiting low activity combined with prolonged sedentary time. Conclusion: A substantial proportion of individuals with post-COVID-19 condition exhibit low physical activity and prolonged sedentary behaviour, posing potential health risks. The associated factors underscore the importance of comprehensive assessments to inform safe, individualized interventions.

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. 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

Tuberculosis (TB) remains a major global health challenge, with approximately 25% of the global population estimated to have been infected with the causative pathogen Mycobacterium tuberculosis (Mtb). Current diagnostic methods based on Interferon-gamma (IFN) release assays (IGRA) have limitations in detecting infection and cannot distinguish those with TB infection from those with disease. In this study, we evaluated a multiplex FluoroSpot assay measuring IFNγ, TNF, and IL2-secreting cells in response to the Mtb antigens ESAT-6, CFP-10, and EspC. The assay was tested on peripheral blood mononuclear cells from individuals with TB disease (n=24), TB infection (n=63), and IGRA-negative controls (n=27). Results indicate that triple cytokine-secreting cells (IFNγ/IL2/TNF) could detect Mtb-specific immune responses with higher sensitivity and specificity compared to commercially available IGRA methods. Furthermore, we identified distinct cytokine profiles associated with different stages of TB infection and disease. The study suggests that this multiplex assay could improve current TB diagnostics while also improving our understanding of Mtb-specific T cell responses associated with recent or remote TB infection and disease. Further studies are now needed to validate these findings in larger cohorts, including individuals with immunosuppressive conditions. ### Competing Interest Statement Bartek Makower is an employee with the biotech company Mabtech AB. All other authors declare no competing financial interests. ### Clinical Protocols ### Funding Statement We thank the study participants for their contribution to the study. We also thank the study nurses Monica Modin, Jan Bellbrant, Anna Dahlberg, Lena Jansson, and Anna Löwhagen Welander for patient inclusion and Mabtech for providing FluoroSpot kits. This study was supported by grants from the Swedish Research Council (2021-03706 and 2023-01943), the Swedish Medical Association (SLS-934363 and SLS-960484), the Swedish Society for Medical Research (CG-24-0012-B), and the Heart-Lung Foundation (20220566 and 20230244) to CS. Grants from Swedish Research Council (2019-04663 and 2020-03602) and the Heart and Lung Foundation (20180386 and 20200194) to GK. Grants from The Swedish Physicians Against AIDS Research Fund (Fob2022-0012) to EF. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was registered and granted ethical permission from the Swedish Ethical Review Board, EPN-numbers 2013/1347-31/2 and 2019-05438. All study participants received written and verbal information and signed a written informed consent form prior to study inclusion. In relevant cases professional interpreter services were used. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data is available upon reasonable request to the corresponding author and pending confirmation of relevant permits.

BACKGROUND: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. MATERIALS AND METHODS: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). RESULTS: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). CONCLUSIONS: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.

Tuberculosis (TB) remains a major global health challenge, with current diagnostic tools unable to reliably distinguish between individuals at different stages of the TB spectrum of infection (TBI) and disease (TBD). Interferon-gamma release assays (IGRAs), while commonly used, are limited by their reliance on a single cytokine and inability to differentiate disease states. In this study, we evaluated a multiplex FluoroSpot assay that simultaneously detects interferon gamma (IFNγ), interleukin (IL)2, and tumor necrosis factor (TNF)-secretion in response to Mycobacterium tuberculosis (Mtb) antigens ESAT-6, CFP-10, and EspC. PBMCs from individuals with TBD (n = 24), TBI (n = 64), and IGRA-negative controls (n = 26) were analyzed. The assay demonstrated high sensitivity and specificity, particularly through the detection of triple cytokine-secreting T cells (IFNγ/IL-2/TNF), minimizing false-positive rates. Moreover, distinct cytokine secretion patterns were associated with different stages of infection. Individuals with TBD had more IFNγ/TNF-producing cells, while those with TBI had more cells producing IFNγ/IL-2 or IL-2/TNF. Separating individuals with TBI based on time since likely Mtb exposure revealed that more recent infection was associated with reduced IFNγ responses and a higher proportion of IL-2/TNF-secreting cells. The use of spot volume analysis provided semi-quantitative insights into cytokine production. These findings suggest that multiplex cytokine profiling can improve TB diagnostics and offer a deeper understanding of host immune responses across the TB spectrum. Including non-IFNγ responses may be particularly valuable in identifying individuals at higher risk of disease progression, such as recently infected individuals, and in populations where current diagnostics underperform.IMPORTANCEAccurate diagnosis of Mycobacterium tuberculosis (Mtb) infection remains a cornerstone in tuberculosis (TB) control. Current interferon-gamma release assays (IGRAs) lack the ability to distinguish between individuals at different stages of the TB infection spectrum, limiting their utility. This study evaluates a multiplex FluoroSpot assay that simultaneously detects interferon gamma (IFNγ), interleukin 2, and tumor necrosis factor secretion in response to Mtb-specific antigens ESAT-6, CFP-10, and EspC. The assay demonstrated improved performance compared to standard IGRA methods, particularly through the identification of triple cytokine-secreting T cells. Importantly, it revealed distinct cytokine profiles associated with different stages of TB infection, offering potential for improved risk stratification and infection monitoring. These findings support the FluoroSpot assay as a promising tool for enhancing TB diagnostics and understanding host immune responses. Its application could be especially valuable in contact tracing, where Mtb-specific T-cell responses may not yet produce detectable amounts of IFNγ.

Anecdotal information suggests that clinical practice regarding the use of putative hepatoprotective agents in TB treatment varies across countries in the WHO European Region.Between November 2023 and May 2024, we conducted a standardised questionnaire survey on the use of putative hepatoprotective agents in patients receiving TB treatment among Tuberculosis Network European Trials Group (TBnet) representatives in countries in the WHO European Region.We received valid responses from 37 of 53 countries (69.8%), with 16 (43.2%) reporting regular use of putative hepatoprotective agents during anti-TB treatment. Half of these countries ( n = 8) are part of the former Soviet Union. In five countries, these agents are recommended by national guidelines. The most commonly used hepatoprotective agents were silibin/silymarin ( n = 9, 56.3%), ursodeoxycholic acid ( n = 5, 31.3%), and soy phospholipids ( n = 4, 25.0%). Treatment duration varied, with 56.3% ( n = 9) using them for less than 1 month, 18.8% ( n = 3) for 1–3 months, and 18.8% ( n = 3) for 4–6 months.Putative hepatoprotective agents are widely used as an adjunct to TB treatment in the WHO European Region, particularly in the countries of the former Soviet Union, some of which have included them in their national guidelines.

Cardiovascular autonomic dysfunction is a major complication in a large proportion of patients with long coronavirus disease (LC). As one of the most typical phenotypes of cardiovascular autonomic dysfunction, postural orthostatic tachycardia syndrome (POTS) is commonly observed as a sequelae of coronavirus disease infection. This study aimed to develop and test a 24-hour electrocardiogram (ECG) recording to direct the clinical suspicion toward the diagnosis of POTS. Consecutive patients referred to the Karolinska University Hospital in Stockholm from April 2021 to April 2022 were included. Patients with POTS were compared with patients with LC without POTS (verified by active standing tests) and control healthy subjects according to 3 specific analyses based on 24-hour ECG recording: (1) heart rate (HR) spikes of > 30 beats per minute, (2) awakening HR increase, and (3) HR variability (root mean square of successive difference). The control group consisted of healthy subjects from the database of the University Hospital of Saint-Etienne. A total of 100 patients with LC (mean age, 42.54 ± 10.45 years; 92% women) and 100 healthy subjects (41.40 ± 7.21 years; 96% women) were included. LC POTS (n = 45) was associated with (1) a higher number of HR spikes/h (1.47 ± 0.84 vs 0.68 ± 0.50 and 0.40 ± 0.28/h; P < .01), (2) an abrupt and sustained increase in HR after awakening (P < .05), and (3) a reduction of HR variability: mean root mean square of successive difference of 34.90 ± 12.48 vs 30.47 ± 19.15 and 43.35 ± 21.10 ms (P < .01) compared with patients with LC without POTS (n = 55) and healthy subjects. A triple analysis of 24-hour ECG recordings could reveal a characteristic POTS signature in LC. More research in other populations is needed to draw any firm conclusions about its generalizability.

BACKGROUND:The incidence of postural orthostatic tachycardia syndrome (POTS) in long COVID has been a growing concern since the first cases were reported in 2021. The aim of this study was to assess the prevalence and clinical impact of POTS in a series of well-characterized patients with long COVID. METHODS:We prospectively analyzed 467 nonhospitalized, highly symptomatic (sick leave ≥50%) patients with long COVID, and studied differences in demographics and clinical assessment outcomes between those diagnosed with POTS and the remaining long COVID patients. Examinations were performed at a median of 12 months after acute COVID-19, followed by a cardiologist evaluation with 48-hour ECG, head-up tilt test, and Active Stand Test for those with clinically suspected POTS. RESULTS:Of all long COVID patients, 143 (31%) were diagnosed with POTS, 128 (27%) did not fulfill POTS criteria, while 196 (42%) had no clinical signs of POTS. Patients with POTS were younger (mean age, 40.0 versus 44.0 versus 47.0 years, respectively; P≤0.001) and predominantly female (91%). They had significantly lower physical activity compared with the other 2 groups, as measured with the Frändin-Grimby scale (P=0.001). Heart rates during the 6-minute walk test were significantly higher in the POTS group, both during walking and at rest afterward, with a significantly shorter walking distance (448 m versus 472 m versus 509 m, respectively; P≤0.001). However, the distribution of symptoms showed no significant differences between the groups. CONCLUSIONS:In this cohort of predominantly younger women with highly symptomatic long COVID, POTS is common and presents with overlapping symptoms between POTS and non-POTS patients. Long COVID POTS confers lower physical activity and capacity compared with non-POTS long COVID and should be systematically assessed in this condition.

Background:In this study, we combine proteomics with functional parameters and imaging to examine potential biomarkers that may identify patients at risk of developing persistent lung sequelae following coronavirus disease 2019 (COVID-19). Methods:We performed multiplex profiling of serum and collected clinical data from intensive care unit (ICU)-treated patients with COVID-19 (n=43) at 4 and 10 months post hospitalisation. Results:Four months post discharge, patients with COVID-19 demonstrated lower % predicted forced vital capacity (72.2% versus 113% (p<0.0001)) and % predicted forced expiratory volume in 1 s (74.5% versus 103% (p<0.0001)) compared with healthy controls. A persistent upregulation (versus healthy controls) of inflammatory and remodelling factors, including among others, Galectin-1 (Gal-1), C-X-C motif chemokine 13 (CXCL13), monocyte chemoattractant protein 3 (MCP-3) and matrix metalloproteinase 7 (MMP7), were observed. Patients with moderate to severe parenchymal involvement (>5% of lung tissue) on high-resolution computed tomography (HRCT) had higher levels of the proteins lysosomal associated membrane protein-3 (LAMP3) and MMP7 compared with patients with minor (<5%) or no findings on HRCT. Both proteins demonstrated consecutive associations to lung function and parenchymal involvement. Histological evaluation of LAMP3 in lung tissue confirmed LAMP3 localisation to alveolar type 2 cells in more preserved areas of the parenchyma. However, areas of remodelling were devoid of LAMP3 concurrent with the appearance of KRT5+ and KRT17+ basal cells. Conclusion:Despite functional and radiological improvements following COVID-19, persistent upregulation of inflammation and remodelling factors were observed. Similarities in the expression of LAMP3 in COVID-19 and idiopathic pulmonary fibrosis may suggest it as a potential biomarker for chronic lung damage.

Understanding the clinical implications of minimum inhibitory concentration (MIC) may facilitate optimal drug selection in Mycobacterium avium complex pulmonary disease (MAC-PD) treatment. This study aimed to investigate the association of individual MICs with treatment response of MAC-PD. A retrospective cohort study was conducted in China, including eligible patients diagnosed with MAC-PD between 2018 and 2021. Treatment success rates were calculated across different MIC levels in a subgroup of patients receiving relatively uniform regimens. Associations between MICs and treatment outcomes were investigated by logistic regression analysis. In total, 209 patients with confirmed MAC-PD and initiated treatment were included. The median age was 60.0 years. Among 155 patients who completed treatment, 67.1% achieved treatment success. The treatment success rate was low in patients with clarithromycin MIC ≥ 64 mg/L (25.0%, 1/4) or ethambutol MIC > 16 mg/L (42.9%, 3/7), while remaining relatively stable (75–100%) at other MIC levels. Univariate analyses showed that clarithromycin and ethambutol MICs above these thresholds were associated with increased risk of treatment failure. Our findings suggest an association between clarithromycin MICs and treatment outcomes in patients with MAC-PD receiving standard guideline-recommended regimens. Meanwhile, elevated ethambutol MICs exhibited potential clinical relevance, warranting further investigation.