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Journal articleRowntree LC, Allen LF, Hagen RR, et al., 2025,
HLA-B*15:01-positive severe COVID-19 patients lack CD8+ T cell pools with highly expanded public clonotypes
, Proceedings of the National Academy of Sciences of USA, Vol: 122, ISSN: 0027-8424Understanding host factors driving asymptomatic versus severe disease outcomes is of key importance if we are to control emerging and re-emerging viral infections. HLA-B*15:01 has been associated with asymptomatic SARS-CoV-2 infection in nonhospitalized individuals of European ancestry, with protective immunity attributed to preexisting cross-reactive CD8+ T-cells directed against HLA-B*15:01-restricted Spike-derived S919-927 peptide (B15/S919+CD8+ T-cells). However, fundamental questions remained on the abundance and clonotypic nature of CD8+ T-cell responses in HLA-B*15:01-positive patients who succumbed to life-threatening COVID-19. Here, we analyzed B15/S919+CD8+ T-cell responses in COVID-19 patients from independent HLA-typed COVID-19 patient cohorts across three continents, Australia, Asia and Europe. We assessed B15/S919+CD8+ T-cells in COVID-19 patients across disease outcomes ranging from asymptomatic to hospitalized critical illness. We found that severe/critical COVID-19 patients mounted B15/S919+CD8+ T-cell responses lacking a highly expanded key public B15/S919+CD8+ T-cell receptor (TCR; TRAV9-2/TRBV7-2) which recurred across multiple individuals in COVID-19 patients with a mild disease. Instead, B15/S919+CD8+ T-cell responses in life-threatening disease had a prevalence of an alternate TCR clonotypic motif (TRAV38-2/DV8/TRBV20-1), potentially contributing, at least in part, to why B15/S919+CD8+ T-cells in severe COVID-19 patients were less protective. Interestingly, the frequency, memory phenotype, and activation profiles of circulating B15/S919+CD8+ T-cells did not differ across disease severity. Moreover, B15/S919+CD8+ T-cells were better maintained into convalescence compared to other SARS-CoV-2-specificities. Our study thus provides evidence on the differential nature of the TCR clonal repertoire in 22.37% of HLA-B*15:01-positive COVID-19 patients who developed severe or critical disease in our cohorts, comparing to HLA-B*15:01-expressing individua
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Journal articleBokobza I, Le Sayec M, Bossley C, et al., 2025,
Spirometry thresholds for clinical trial eligibility: time for urgent re-evaluation
, THORAX, ISSN: 0040-6376 -
Journal articleAgache I, Adcock IM, Baraldi F, et al., 2025,
Personalised therapeutic approaches for asthma
, Journal of Allergy and Clinical Immunology, Vol: 156, Pages: 503-522, ISSN: 0091-6749Differences in host susceptibility and environmental exposures result in significant heterogeneity in asthma clinical expression, natural evolution and response to treatment. These differences are influenced by many factors including genomics, epigenomics, transcriptomics, proteomics and metabolomics, many of which are modified by environmental and allergic exposures. The complex and multiple characteristics that interact in asthma development and progression pose significant challenges for personalized management. This review aims to guide the clinician in its management decisions by reviewing each of the components important in developing this therapeutic paradigm and by providing several integrated goals for precision or personalized medicine for asthma. Biologic characteristics of asthma in relation to the genomics, exposome and hypersensitivity reactions (allergic responsiveness) resulting in the asthma diathesis are discussed. Further insights including the use of targeted biologics and allergen immunotherapy are provided, while discussing the importance of targeting the epithelium, mucus production, airway smooth muscle and the small airways. We examine the value of multivariate cluster analyses as a new paradigm that can inform treatment decisions and the potential of adaptive trial design to evaluate known and novel predictive biomarkers and characterize disease heterogeneity.
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Journal articleNakawesi J, Sow Tao Min T, Johansson C, 2025,
Natural killer cells are dispensable for virus control in Rag2-/- mice during primary RSV infection
, European Journal of Immunology, Vol: 55, ISSN: 0014-2980Respiratory syncytial virus (RSV) is one of the major causes of severe lower respiratory tract infections, especially in children, the elderly and immunocompromised individuals. Complications arising from viral infections in these age groups can present therapeutic challenges as most of these individuals have impaired adaptive immunity. Using the T- and B cell-deficient Rag2-/- mice, the mechanisms that mediate protection in immunocompromised hosts during RSV infection can be investigated. RSV-infected Rag2-/- mice showed no symptoms of disease or chronic inflammation in the lungs and airways despite the presence of infectious virus in their lungs several months after infection. Interestingly, Natural Killer (NK) cells, the main innate cells with anti-viral cytotoxic effector functions, were recruited two days earlier in the lungs of Rag2-/- mice compared to wildtype mice, resulting in early production of IFN-. However, depletion of NK cells did not affect disease severity or viral load. Together, these results suggest that the NK cells are largely dispensable for virus control during primary RSV infection in Rag2-/- mice.
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Journal articleAdams E, Peel T, 2025,
Chronic mountain sickness: a comprehensive review of current management and proposals for novel therapies
, High Altitude Medicine and Biology, Vol: 26, ISSN: 1527-0297Adams, Edmund and Tamlyn Peel. Chronic mountain sickness: A comprehensive review of current management and proposals for novel therapies. High Alt Med Biol. 26:318–327, 2025.—Chronic mountain sickness (CMS) is an acquired condition affecting 5%–10% of high-altitude residents. Lifelong exposure to chronic hypoxia triggers excessive erythrocytosis, resulting in an expanded hematocrit. Patients present with symptoms such as dyspnea, fatigue, and palpitations. Complications such as pulmonary hypertension and heart failure are often fatal. Relocation to sea level remains the only definitive management of CMS but poses an unacceptable personal burden. Long-term oxygen therapy provides symptomatic relief, but dependency issues remain a concern. Phlebotomy reduces hematocrit and offers short-term symptom relief. However, side effects and cultural conflicts continue to pose challenges. Acetazolamide, enalapril, and medroxyprogesterone have lowered hematocrit and alleviated symptoms in human trials. Further research into systemic side effects, application in women, and long-term use is required. Methylxanthines, adrenergic blockers, almitrine, and dopamine antagonists showed promise in murine and/or short-term human trials, highlighting the need for further long-term human trials. Inhibition of hypoxia-inducible factor and Janus Kinase-signal transducer and activator of transcription pathways is currently used to suppress hematocrit in polycythemia vera, demonstrating potential application in CMS. Topiramate may stimulate ventilation via acid-base modulation, thus providing therapeutic value. Similarly, the effect of aspirin and caffeine on ventilation may provide a low-cost, accessible intervention.
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Journal articleEsneau C, Bryant NE, Johnston SL, et al., 2025,
Opportunities for rhinovirus-targeted RNA therapeutics: A narrative review
, Cmi Communications, Vol: 2Background Rhinoviruses (RVs), first identified as common causative agents of the common cold, are now recognised as significant contributors to exacerbations of chronic respiratory diseases (asthma, chronic obstructive pulmonary disease, cystic fibrosis), and severe lower respiratory tract infections in infants, the elderly and the immunocompromised. Despite their significant impact, no RV vaccines or RV-specific antivirals have been approved for use, largely due to the viruses’ extensive antigenic diversity and limited antibody cross-reactivity across the ∼180 RV subtypes. This complexity has long hindered traditional therapeutic approaches. By enabling rapid adaptation to viral diversity and targeting previously non-targetable but highly conserved regions of the viral genome, RNA-based technologies offer promising new approaches to overcome these challenges. Objectives This narrative review provides an update on RV virology and epidemiology, an overview of attempts to develop treatments for RV, and describes recent advances in RNA therapeutics in the prevention and treatment of other viral pathogens that could be adapted for use against RVs. Sources This narrative review was conducted through a comprehensive literature search using PubMed® and Web of Science™ with search terms related to the development of RNA therapeutics for respiratory viruses and picornaviruses. The methodology is further defined in the body of the text. Content and implications Recent developments in RNA therapeutics for similar respiratory viruses and related RNA viruses have shown promise, both in preventing infection through mRNA vaccination and treating infections with various RNA-based antivirals. Developing effective RV-targeting therapeutics is imperative to reduce both the clinical and economic burden of RV infections.
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Journal articleHughes D, Frost F, 2025,
Aspergillus and Pseudomonas lung infections: that's what friends are spore
, ERJ Open Research, Vol: 11, ISSN: 2312-0541 -
Journal articleQuintero Santofimio V, van der Plaat D, Fuertes E, et al., 2025,
Gene-occupational exposure interactions in small airways obstruction in the UK Biobank: a cross-sectional study
, Occupational and Environmental Medicine, Vol: 82, Pages: 444-450, ISSN: 1351-0711Objectives: Small airways obstruction (SAO) has been associated with lifetime exposure to several agents in the workplace. Whether this association is modified by genetic variants is unknown. Methods: Using data from 147,317 adults (33,552 with SAO; 108,762 without SAO) participating in the UK Biobank, we conducted a genome-wide association analysis to identify genetic variants associated with SAO at baseline, defined as the forced expiratory volume in 3 seconds to 6 seconds ratio (FEV3/FEV6) below the lower limit of normal. We assigned occupational exposures using the ALOHA+ job exposure matrix. Using cross-sectional data from 38,911 participants (8,363 with SAO; 30,548 without SAO), who had complete job histories, we assessed whether the identified genetic variants interacted with occupational exposure on SAO using logistic regression models adjusted for confounders. Additionally, we investigated whether gene-occupational exposure signals were associated with gene expression in lung tissue. Results: We identified 36 genetic variants significantly associated with SAO. Eight of these significantly modified the association of SAO with pesticides, vapour, gases, dusts, fumes (VGDF), and metals, with participants homozygous for the reference allele being at increased risk of SAO when exposed to these agents. Only two of these genetic variants (rs9273529 and rs644045) appeared to affect gene expression in lung tissue. We found no significant interactions with solvents.Conclusions: Using a large population-based cohort, we identified genetic variants that interact and modify the association between SAO and several common workplace exposures. Further research is needed to confirm these effect modifications results and clarify potential biological mechanisms.
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Journal articleCarty L, Dobra R, Francis J, et al., 2025,
Qualitative Experiences and Depression/Anxiety Scores in Parents of Children With Cystic Fibrosis Transmembrane Conductance Regulator Related Metabolic Syndrome
, PEDIATRIC PULMONOLOGY, Vol: 60, ISSN: 8755-6863 -
Journal articleCestelli L, Amaral A, Benediktsdottir B, et al., 2025,
The association between systemic inflammation, lung function and respiratory symptoms in the BOLD study in Northern Europe
, Scientific Reports, Vol: 15, ISSN: 2045-2322The role of systemic inflammation in the pathogenesis of respiratory diseases is increasingly recognized, but the relationship between individual inflammatory markers, lung function and respiratory symptoms is not well established. We studied 1,238 adults participating in the first follow-up of the Burden of Obstructive Lung Disease (BOLD) cohort study in Sweden, Norway, Iceland, and Estonia in 2019–2021. Systemic inflammation was assessed using total white blood cell (WBC) count and WBC sub-populations (neutrophils, lymphocytes, monocytes, eosinophils, basophils and neutrophil-to-lymphocyte ratio (NLR)). In regression models adjusted for gender, age, smoking status, body mass index and study site, all WBC sub-populations, except for lymphocytes, were associated with chronic airflow obstruction (CAO) and wheeze. In never smokers, increased neutrophils were associated with reduced lung volumes (FEV1 β coef. with 95%CI -1.95 (-3.33, -0.57) p = 0.006; FVC − 1.94 (-3.18, -0.69) p = 0.002), but not CAO. Only increased basophils were associated with CAO in never smokers (OR with 95%CI 2.70 (1.28, 5.72) p = 0.009). In former smokers, increased neutrophils, monocytes and eosinophils were significantly associated with reduced FEV1, reduced FVC, CAO and wheeze. In current smokers, inflammatory markers were associated with cough (neutrophils OR with 95%CI 1.49 (1.10, 2.01) p = 0.010; monocytes 1.24 (0.99, 1.55) p = 0.058; basophils 2.56 (1.12, 5.86) p = 0.026). Systemic inflammation may be related to both obstructive and restrictive respiratory impairment in the general population, with associations that vary by smoking status.
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Journal articleIto K, 2025,
Can inhaled antifungals provide a viable solution for treatment-refractory pulmonary fungal infections?
, EXPERT REVIEW OF ANTI-INFECTIVE THERAPY, Vol: 23, Pages: 537-540, ISSN: 1478-7210 -
Journal articlePott H, Sykes DL, Charriot J, et al., 2025,
Breathing barriers: bridging lung health, research, and awareness
, The Lancet Respiratory Medicine, Vol: 13, Pages: 665-667, ISSN: 2213-2600 -
Journal articleGuan S, Ogger P, Farias A, et al., 2025,
Sustained lung inflammation post SARS-CoV-2 infection in mice is associated with increased pulmonary T cells
, European Journal of Immunology, Vol: 55, ISSN: 0014-2980Many SARS-CoV-2 patients experience chronic pulmonary symptoms and long-term inflammation despite viral clearance. While these clinical manifestations have been linked to the dysregulation of the adaptive immune response, the underlying immunopathology remains poorly understood due to a lack of suitable animal models. To investigate long-term pulmonary consequences of SARS-CoV-2 infection, we used a genetic cross of 129 mice and C57BL/6 (B6)-K18-hACE2 transgene mice, a model previously shown to survive infection. 129xB6-K18-hACE2 mice or littermate controls were infected with a low dose (5 × 102 PFU) of ancestral SARS-CoV-2. Complete viral clearance and full recovery from weight loss occurred by day 8 post-infection. However, prolonged inflammation in the lung and airways persisted up to day 28 post-infection and was associated with the presence of CD4+ and CD8+ T cells, particularly CD8+ effector T cells. This model may therefore prove valuable for further understanding of drivers of long-term lung inflammation and for testing therapeutic strategies and clinically relevant interventions that can target long-term pulmonary inflammation following SARS-CoV-2 infection.
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Journal articleKhan AA, Vernugopan V, Wallis G, et al., 2025,
Artificial stone silicosis presenting as suspected Tuberculosis: A series of 3 cases at a district general hospital
, Clinical Infection in Practice, Vol: 27Silicosis is an ancient condition re-emerging globally due to outbreaks of accelerated disease related to the use of artificial stone. The initial presentations of three patients with silicosis due to artificial stone exposure at a district general hospital in London, all of whom presented with clinical symptoms and radiological features assumed to be tuberculosis, are reported. The associations between silica exposure and this infection are also described. This series aims to highlight that artificial stone silicosis is now a significant occupational lung disease in the UK of which clinicians working in infectious diseases should be aware of.
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Journal articleKrishnan JA, Cao B, Chotirmall SH, et al., 2025,
Using the 2024 national academies of science, engineering, and medicine definition of long Covid implications for pulmonary and critical care medicine
, American Journal of Respiratory and Critical Care Medicine, Vol: 211, Pages: 1391-1396, ISSN: 1073-449XSARS-CoV-2 emerged in late 2019, leading to the COVID-19 pandemic (1). In the initial months of the pandemic, the number of hospitalizations for respiratory failure caused by acute respiratory distress syndrome increased exponentially, and the global case fatality rate reached 3.4% with large regional variations (2, 3). An unprecedented number of research studies were launched around the globe, aiming to understand and prevent severe acute illness (4–7). Over the past 5 years, the public health impact of acute COVID-19 has evolved considerably, with increases in population-level immunity due to natural infections and the increasing availability of proven effective vaccines, antiviral agents, immunomodulators, monoclonal antibodies, and the ever-changing landscape of SARS-CoV-2 variants with reduced pathogenicity but enhanced immune evasion and infectivity (8–12).
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Journal articleBoivin W, Loeb M, Openshaw P, et al., 2025,
Seasonal influenza vaccination: Overcoming immunosenescence with enhanced vaccines (vol 24, 100662, 2025)
, VACCINE: X, Vol: 25, ISSN: 2590-1362 -
Journal articleMontes de Oca M, Perez-Padilla R, Celli B, et al., 2025,
The global burden of COPD: epidemiology and effect of prevention strategies
, The Lancet Respiratory Medicine, ISSN: 2213-2600 -
Journal articleBah MS, Htet KKK, Bisson GP, et al., 2025,
Assessment of comorbidities, risk factors, and post tuberculosis lung disease in National Tuberculosis Guidelines: A scoping review
, PLOS GLOBAL PUBLIC HEALTH, Vol: 5 -
Journal articleNafees AA, Khan AA, Rabbani U, et al., 2025,
Prevalence and factors associated with respiratory symptoms in an urban population: findings from BOLD study in Karachi, Pakistan
, Discover medicine, Vol: 2, ISSN: 3004-8885ObjectiveOur study investigated the prevalence and risk factors of respiratory symptoms (RS) in an adult population aged ≥ 40 years in urban Karachi, Pakistan.MethodsA population based cross-sectional study was conducted. Multi-stage cluster random sampling technique was used to enroll 1052 participants. Questionnaire based on the Burden of Obstructive Lung Disease (BOLD) study protocol was used to assess chronic cough, chronic phlegm, wheezing and shortness of breath (SOB). Logistic regression analyses were conducted to determine the risk factors associated with RS.ResultsThe overall weighted prevalence of RS in our study was; chronic cough: 12% (95% CI: 9.7–14.8), chronic phlegm: 11.8% (95% CI: 9.4–14.7), wheezing in last 12 months: 11.5% (95% CI: 9.4–14.0), and shortness of breath (SOB): 30.4% (95% CI: 25.6–35.7). Increasing age and ever smoker were significant risk factors for all RS. Females had higher risk of chronic cough. Lower level of education and higher BMI were associated with wheezing and SOB. Exposure to passive smoking was found to be significant risk factor for SOB.ConclusionWe found a higher prevalence of respiratory symptoms among adult population in urban Karachi, specifically about 30.4% reported shortness of breath (SOB). Certain preventable risk factors (smoking and being exposed to passive smoking) were identified. Targeted interventions such as community education and localized air quality monitoring could help mitigate the burden of respiratory symptoms.
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Journal articleJohansson C, 2025,
RORing for oral tolerance
, Science, Vol: 389, Pages: 236-237, ISSN: 0036-8075
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