Search Results (4,282)

Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) are clinically relevant pathogens in lung transplant (LT) recipients, but their impact on lung function and the benefit of ribavirin remains uncertain. We conducted a prospective multicenter observational cohort study of adult LT recipients with RSV or hMPV infection diagnosed between 2021 and 2024 at five centers, with follow-up for up to 12 months. Ribavirin was prescribed at the treating physician’s discretion. Multivariable analysis assessed the association between ribavirin and percentage change in forced expiratory volume in the first second (FEV₁) at 90 days, using FEV₁ three months before infection as baseline and adjusting for baseline FEV₁, pre-existing chronic lung allograft dysfunction, and time since transplantation. Seventy-six patients were included; 60 (78.9%) had RSV and 16 (21.1%) hMPV. Lower respiratory tract infection occurred in 48.7%, and an acute ≥10% FEV₁ decline at 14 days was observed in 29.3%. Among patients with lower respiratory tract infection, 45.9% received corticosteroids alone and 37.8% corticosteroids plus ribavirin. No statistically significant between-group differences in allograft dysfunction or mortality were observed. RSV and hMPV infections after LT were frequently associated with lower respiratory involvement and lung function decline. In this observational cohort, ribavirin use was not independently associated with 90-day FEV₁ change; however, residual confounding and limited statistical power preclude conclusions regarding treatment efficacy. Full article

Background: Influenza is primarily a respiratory illness, but it is increasingly linked to acute cardiovascular complications, including myocarditis and sudden cardiac death. Evidence on influenza-associated cardiac involvement remains fragmented and largely derived from case-based reports. Methods: This systematic review followed PRISMA guidelines and was registered with PROSPERO (CRD420251249130). PubMed, Web of Science, and Google Scholar were searched for eligible studies. Case reports and case series were included to characterize rare, severe, or atypical cardiac manifestations that are not captured in larger epidemiological studies. Data on demographics, influenza subtype, cardiac manifestations, investigations, management, and outcomes were extracted. Results: Thirty-three studies (32 case reports and one case series) comprising 36 cases were included. Influenza A was reported in 26 cases and influenza B was reported in 9 cases. Myocarditis was the most common manifestation (19 cases, 53%), including fulminant myocarditis in 9 cases (25%). Cardiogenic shock occurred in seven cases (19%), malignant arrhythmias in four(11%), myocardial infarction–like presentations in three (8%), and cardiac arrest or sudden cardiac death in six cases (17%). Cardiac involvement occurred across all age groups, frequently in patients without pre-existing coronary artery disease. Overall mortality was 44% (16/36), with fatalities reported in both influenza A and B infections. These findings predominantly reflect severe and published cases and may not represent the full clinical spectrum of influenza-associated cardiac involvement. Conclusions: This review highlights that influenza infection has been reported in association with a range of acute cardiac manifestations, particularly myocarditis, including severe and fulminant presentations. However, given the reliance on case reports and case series, the findings are subject to significant publication bias and do not permit the estimation of incidence, risk, or causal inference. These observations should therefore be interpreted as hypothesis-generating. Full article

The mitigation measures adopted to reduce the spread of COVID-19 have not only impacted the transmission of respiratory infections but also other infectious diseases. In this study, we explored the effect of the pandemic on the epidemiology of Central Nervous System (CNS) infections by conducting a retrospective analysis of diagnostic data obtained from cerebrospinal fluids (CSFs) collected before, during, and after the pandemic from patients with acute-suspected neuro-infectious syndrome. The samples were analyzed using a meningitis/encephalitis molecular syndromic panel. A total of 4203 CSFs were split into three groups: pre-pandemic (August 2018–February 2020), pandemic (March 2020–March 2022) and post-pandemic (April 2022–March 2024). Each pathogen was statistically assessed individually, comparing one group vs. another. Results showed that viral pathogens were the most frequently detected across all groups; however, Streptococcus pneumoniae was the single most identified pathogen. Comparison of the pre-pandemic and pandemic groups by statistical analysis showed a significant reduction in neuro-infections caused by enterovirus, S. pneumoniae and N. meningitidis, while the other pathogens were not affected. In conclusion, a reduction in CNS infections caused by respiratory and close-contact-transmitted pathogens, including both viral and bacterial agents, was observed during the period when COVID-19 containment measures were in effect. Full article

Bovine alphaherpesvirus 1 (BoHV-1) acute infection induces respiratory tract disorders and conjunctivitis and suppresses immune responses that may cause bacterial pneumonia. BoHV-1 infection establishes lifelong latency in sensory neurons in trigeminal ganglia (TG), the central nervous system, and certain cells in the pharyngeal tonsil. BoHV-1 is a chronic problem in the cattle industry because stress, including the synthetic corticosteroid dexamethasone, triggers reactivation from latency after an intravenous injection. The BoHV-1 immediate early transcription unit 1 (IEtu1) promoter drives expression of infected cell protein 0 (bICP0) and bICP4, two viral transcriptional regulators. Stress activates the glucocorticoid receptor (GR), and Krüppel-like factor 15 (KLF15) cooperatively transactivates the BoHV-1 IEtu1 promoter if both GR response elements (GREs) are intact. Since the bICP0 gene contains a separate early (E) promoter, we tested the hypothesis that GR+KLF family members transactivate the bICP0 E-promoter. GR+KLF4, both pioneer transcription factors, cooperatively stimulate bICP0 E-promoter activity in mouse neuroblastoma cells (Neuro-2A), and stimulate productive infection. Notably, the bICP0 E-promoter lacks GREs, suggesting that a novel mechanism triggers transactivation. CA motifs and C-rich Sp1 binding sites in bICP0 E-promoter sequences are crucial for transactivation and binding to GR and KLF4. Full article

India has one of the highest public health burdens attributable to air pollution globally. Despite national air quality regulations and control policies, improvements in air quality have been limited, restricting opportunities to evaluate the health benefits of cleaner air under real-world conditions. COVID-19 lockdowns substantially reduced air pollution in India’s megacities, creating a natural experiment for assessing pollution-attributable health benefits. Using ambient PM_2.5 concentration data from United States Embassy and Consulate monitors in Chennai, Hyderabad, Kolkata, Mumbai, and New Delhi during the 2020 and 2021 lockdowns, and World Health Organization AirQ+ software, we estimated the short- and long-term health benefits of maintaining lockdown-related improvements in air quality. PM_2.5 reductions ranging from 28–77% during the first lockdown, if sustained long term, would lead to about 42,778 fewer premature deaths in the short term and 132,000 fewer annual avoidable deaths from all causes under the modeled scenario across the five cities. We also estimated annual reductions of 11,100 deaths from chronic obstructive pulmonary disease, 3900 from lung cancer, 5500 from ischaemic heart disease, 3900 from stroke, and 1240 from acute lower respiratory infection. These findings support stronger air quality standards, emission controls, and policy enforcement to reduce air pollution-related mortality in Indian megacities. Full article

Mannheimia haemolytica (Mh) is a major bovine respiratory pathogen that can trigger marked inflammatory and barrier injuries. This study evaluated the protective effect of oral curcumin pretreatment in a proof-of-concept mouse model of early Mh-induced acute pulmonary injury. Mice received curcumin at 50 or 150 mg/kg/day for seven days before an intranasal Mh challenge and were evaluated 12 h after infection. Curcumin pretreatment was associated with lower lung wet-to-dry ratios, bronchoalveolar lavage fluid protein concentrations, histological injury scores, and serum pro-inflammatory cytokine levels. It was also associated with reduced abundance or phosphorylation of NF-κB/NLRP3-related proteins, increased expression of Nrf2-associated antioxidant proteins, reduced apoptosis, and preservation of the tight-junction protein ZO-1. In addition, curcumin pretreatment was associated with changes in fecal microbial composition and intestinal short-chain fatty acid profiles, including partial recovery of propionic acid. Because this study did not include a curcumin-only group, post-infection treatment, bacterial-burden measurements, pathway-perturbation experiments, or microbiota-causality experiments, the findings support prophylactic host-protective associations in an early mouse model rather than antibacterial activity, therapeutic efficacy after established infection, or causal gut–lung mechanisms. Validation in bovine models is required before veterinary application. Full article

Mucosal microbiota contribute broadly to host defense and immune homeostasis, while the lung and gut microbiota form a particularly important bidirectional ecological and immunological network that shapes pulmonary host defense, inflammatory injury, and tissue repair. In pneumonia, loss of colonization resistance and altered microbial metabolite production may weaken innate and adaptive immunity; respiratory infection, antibiotics, and critical-care exposures can, in turn, remodel both microbial communities. In acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), intestinal barrier failure, circulating microbial products, immune cell trafficking and, in selected settings, lymphatic or hematogenous dissemination of gut-derived organisms may aggravate alveolar–capillary injury. Alveolar macrophages integrate these signals through pattern-recognition, metabolic, and epigenetic pathways, linking microbial ecology to pathogen clearance and inflammatory resolution. The evidence, however, remains uneven. Mechanistic causality rests largely on animal studies, most human data are associative, and trials of microbiota-directed interventions are heterogeneous and strain-specific. This Review examines bacterial and viral pneumonia, sepsis-associated ALI and ventilator-associated injury; separates mechanistic, observational, and interventional evidence; and evaluates probiotics, live biotherapeutic products, microbial metabolites, and dietary approaches. Translation will depend on longitudinal sampling, source-resolved microbial tracking, metabolite-informed patient stratification, and adequately powered trials with clinically relevant endpoints. Full article

Early, rapid, and accurate detection is essential for clinical management and epidemiological control of acute respiratory infections caused by pathogens. Traditional testing methods such as microbial culture, serological testing, and PCR are restrictive in terms of operation and logistics and are therefore not easily used in point-of-care settings. The CRISPR/Cas system is an adaptive prokaryotic immune system composed of clustered regularly interspaced short palindromic repeats and their associated proteins, which has been used as a nucleic acid diagnostic platform with programmable sequence-specific target recognition and signal-amplifying collateral cleavage activity. Existing reviews have mostly focused on the classification of Cas enzymes or amplification strategies; in this review, a pathogen-centric approach was taken, covering viral pathogens (SARS-CoV-2, influenza virus, RSV, HAdV and VZV), bacterial pathogens (Mycobacterium tuberculosis, Streptococcus pneumoniae, Mycoplasma pneumoniae and Staphylococcus aureus) and fungal pathogens (Aspergillus fumigatus and Pneumocystis jirovecii). Key technological advances, such as isothermal amplification coupling, single-vessel integrated reaction designs, amplification-free digital detection, and electrochemical biosensor integration, are evaluated for Cas9-, Cas12-, and Cas13-based systems, with their mechanistic bases outlined. The current challenges that hinder clinical translation, such as sample matrix interference, multiple signal cross-talk, crRNA off-target effects, and the lack of large-scale validation studies, are critically assessed. At the same time, future pathways for portable, integrated, and inexpensive diagnostic platforms are suggested. Full article

Coronavirus disease 2019 (COVID-19) is increasingly recognized as a multisystem disorder associated with persistent metabolic complications extending beyond the acute phase of infection. Accumulating evidence suggests that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may disrupt glucose homeostasis through mechanisms involving pancreatic β-cell dysfunction, insulin resistance, chronic inflammation, oxidative stress, mitochondrial dysfunction, and hypoxia-related signalling. This review summarizes current evidence regarding the molecular and cellular mechanisms linking SARS-CoV-2 infection to impaired insulin secretion and post-COVID metabolic disturbances. Particular emphasis is placed on the regulation of insulin secretion, β-cell compensation and failure, oxidative stress, inflammatory signalling, mitochondrial dysfunction, and the development of the post-COVID metabolic phenotype. Emerging evidence indicates that persistent metabolic abnormalities after COVID-19 may range from transient dysglycaemia to new-onset diabetes mellitus and metabolic syndrome. The review also discusses clinical implications, biomarkers, therapeutic perspectives, and unresolved questions regarding the reversibility of post-COVID β-cell dysfunction. A better understanding of the mechanisms underlying post-COVID metabolic dysfunction may improve risk stratification, facilitate early intervention, and support development of targeted therapeutic strategies aimed at preserving β-cell function and long-term metabolic health. Full article

Background and Clinical Significance: Encephalitis is a rare neurological complication associated with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. In rare cases, focal neuroinflammation can manifest as a mass-like parenchymal lesion, creating profound diagnostic and treatment dilemmas by mimicking primary central nervous system neoplasms. Case Presentation: A 34-year-old female presented with cephalalgia, nausea, confusion, facial palsy, and a new onset of focal impaired awareness seizures (FIAS). Brain magnetic resonance imaging (MRI) revealed a prominent hyperintense lesion within the left temporal lobe with associated vasogenic edema and focal leptomeningeal enhancement highly suspicious of a low-grade glial neoplasm. Although nasopharyngeal RT-PCT was negative, the presence of serum anti-SARS-CoV-2 IgM and IgG suggested recent subclinical SARS-CoV-2 infection. To resolve diagnostic ambiguity and avoid empiric oncological overtreatment, a stereotactic brain biopsy was performed. Histopathology revealed acute neuroinflammation characterized by reactive gliosis, microglial hyperplasia, and perivascular lymphatic cuffing, with no evidence of neoplastic presence. Quantitative tissue RT-PCR confirmed the presence of SARS-CoV-2 (Ct33). Follow-up imaging demonstrated complete resolution of the abnormalities following conservative treatment with corticosteroids and antiepileptics, though mild clinical symptoms persisted for 12 months thereafter. Conclusions: Encephalitis presents a rare yet critical manifestation of SARS-CoV-2. Establishing definitive etiology remains challenging. Stereotactic biopsy is a valuable tool to guide appropriate treatment in cases of ambiguous imaging and clinical findings. Radiographic resolution may precede complete clinical recovery. Full article

Background/Objectives: Acute respiratory infections represent a global health burden due to their high incidence, morbidity and mortality. Despite advances in prevention and treatment, strategies providing broad protection against respiratory pathogens remain limited. This study evaluated the antiviral activity of nasal spray forms based on an antigen complex from opportunistic bacteria, with or without a mucoadhesive copolymer, and their influence on cellular and humoral components of the immune response. Methods: Antiviral activity was assessed in experimental models of SARS-CoV-2 infection in Syrian hamsters and influenza A pneumonia in mice under prophylactic and therapeutic–prophylactic regimens. Parameters of cellular and humoral immune response were assessed using delayed-type hypersensitivity, antibody-forming cell assays, and leukocyte phagocytic activity. Results: Both forms showed comparable influence on cellular and humoral components of the immune response. In a mouse model of lethal influenza pneumonia induced by A/California/04/2009 (H1N1)pdm09 virus, intranasal administration at 100 µg/kg increased mean survival time and survival rate, and reduced body weight loss. In SARS-CoV-2-infected hamsters, both forms reduced clinical signs, body weight loss, weight lung index, lung pathology, and decreased viral titers. The copolymer-containing form showed the most pronounced effect under the therapeutic–prophylactic regimen, with greater protection against body weight loss and stronger suppression of viral replication. Conclusions: The findings support further investigation of these nasal spray forms as candidates for prophylaxis and adjunctive therapy of respiratory infections, particularly when pathogen variability may limit the effectiveness of pathogen-directed treatments. Further mechanistic studies are needed to clarify the pathways underlying the observed antiviral effect. Full article

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes an immune-mediated neurological syndrome, which persists long after infection. Mechanisms for SARS-CoV-2-associated neurological complications are multifactorial, with an increased risk of drug abuse such as methamphetamine (meth). SARS-CoV-2 infection and its viral proteins play pivotal roles in coronavirus disease 2019 (COVID-19)-associated neuroinflammation, which can lead to long COVID. We hypothesize that meth augments activation of the microglial NOD-, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) inflammasome by the SARS-CoV-2 nucleocapsid (N) protein, resulting in neuroinflammation. To test this hypothesis, we investigated the effect of N-protein and meth on NLRP3 inflammasome activation in primary rat microglial cultures using enzyme-linked immunosorbent assay (ELISA), Reverse Transcription quantitative Polymerase Chain reaction (RT-qPCR), western blot (WB), and immunofluorescence assay (IFA). Our results showed that meth augmented N-protein-induced microglial activation, as evidenced by increased ionized calcium-binding adapter 1 (Iba-1) expression. The addition of meth to the microglial cultures treated with N-protein increased proinflammatory cytokine production. Meth augmentation of N-protein-induced neuroinflammation was further supported by increased inducible nitric oxide synthase (iNOS)-mediated nitric oxide (NO) production. The effects of meth on N-protein-associated inflammatory responses were significantly attenuated by MCC950, a specific NLRP3 inhibitor. Moreover, meth-associated NLRP3 activation was either blocked by the opioid sigma1-receptor (σ1_-R) inhibitor BD1047 or by σ1R siRNA knockdown. Taken together, these results demonstrated that meth augmented SARS-CoV-2 N-protein-induced neuroinflammation via microglial σ1_-R and the NLRP3 inflammasome, which may underlie the pathogenesis of neurological manifestations in COVID-19, such as long COVID with meth abuse. These results may also underscore the impact of drug abuse on long COVID and provide targets for the development of therapeutic strategies to control the neurological outcomes of long COVID. Full article

Indoor-air research has largely examined infection, microbial ecology, immune effects and antimicrobial resistance separately, leaving the pathway from indoor biological sources to chronic respiratory outcomes insufficiently integrated. This narrative review synthesises evidence on indoor airborne pathogens and non-viable microbial components as health-relevant biological exposures beyond acute infection. Literature published between 2000 and February 2026 was reviewed from PubMed, Scopus and Web of Science, supplemented by guidance from WHO, ECDC, US EPA and ASHRAE. Viable microorganisms and non-viable components, including endotoxin, β-(1→3)-glucans, microbial DNA and extracellular vesicles, engage epithelial pattern-recognition pathways and promote inflammatory signalling. Findings included 6.5% higher TNF-α and 5% higher IL-8 per log-unit increase in fungal-spore exposure among sawmill workers; uncontrolled asthma in 45% of moisture- or mould-exposed versus 33% of non-exposed children; airborne resistance-gene and mobile-element loads of 0.55–479.44 copies/m³ in hospital departments; and a 32.8% reduction in viral diversity, but no significant reduction in high viral exposure, following classroom HEPA filtration. These findings support biological plausibility but reveal a fragmented evidence base dominated by observational studies, heterogeneous sampling and limited longitudinal exposure–response data. Indoor bioaerosols should be considered continuous exposures within the exposome, requiring research and regulation across microbiology, environmental engineering, medicine and public health. Full article

Background: Early discrimination between viral, bacterial, and mixed respiratory tract infections remains challenging in clinical practice. Conventional microbiological methods may be limited by turnaround time and specimen-related factors, whereas routine inflammatory markers lack sufficient specificity for etiological classification. We investigated whether flow cytometry-derived immune markers combined with C-reactive protein (CRP) could improve early infection stratification. Methods: In this prospective single-center study, adult patients with acute respiratory tract infection and healthy controls were enrolled between 29 July 2025 and 31 January 2026. Peripheral blood CD169 positivity on monocytes (CD169%), neutrophil CD64 index (nCD64 index), monocyte HLA-DR positivity (HLA-DR%), and CRP were measured and compared across viral infection (influenza A, influenza B, or COVID-19), bacterial infection, mixed infection, and healthy control groups. Logistic regression models were developed for three diagnostic tasks: viral versus bacterial infection, mixed versus bacterial infection, and mixed versus viral infection. Model performance was evaluated using receiver operating characteristic (ROC) analysis, DeLong testing, calibration, decision curve analysis (DCA), and bootstrap internal validation. Nomograms were constructed from the final models. Results: A total of 216 infected patients were included: 112 with viral infection, 67 with bacterial infection, and 37 with mixed infection; 50 healthy individuals served as controls. CD169% was increased in viral and mixed infection, whereas the nCD64 index was increased in bacterial and mixed infection. HLA-DR% was lower in bacterial infection. For differentiating viral from bacterial infection, the optimized three-marker model combining CD169%, nCD64 index, and CRP achieved an area under the ROC curve (AUC) of 0.8947 (95% CI: 0.8463–0.9432), with a sensitivity of 81.25% and a specificity of 80.70%. In mixed infection, CD169% was the main discriminator versus bacterial infection, while the nCD64 index and CRP were more informative versus viral infection. The combined model yielded an AUC of 0.7618 (95% CI: 0.6485–0.8751) for mixed versus bacterial infection and 0.8406 (95% CI: 0.7594–0.9218) for mixed versus viral infection. Longitudinal analyses showed that CD169% declined during recovery from viral infection, whereas the nCD64 index and CRP decreased after treatment in bacterial infection; all three markers declined in mixed infection. Conclusions: CD169%, the nCD64 index, and CRP reflect complementary dimensions of the host response to acute infection. Their combined assessment showed good performance for differentiating viral from bacterial infection and provided clinically relevant information in mixed infection. This host-response-based nomogram may serve as a practical adjunct for early etiological stratification and mixed-infection risk assessment. Full article

Respiratory diseases impose a substantial global burden; however, early diagnosis, disease-activity monitoring, and the clinical translation of nucleic acid therapeutics are constrained by the lack of robust biomarkers and efficient delivery systems. This narrative review focuses on four classes of RNA—messenger RNA (mRNA), circular RNA (circRNA), small interfering RNA (siRNA), and microRNA (miRNA)—using exosomes as a representative subtype of extracellular vesicles (EVs) to discuss EV biogenesis, transport, uptake, and engineered cargo loading. We summarize the diagnostic and therapeutic applications of EV-associated nucleic acids in chronic or non-severe respiratory diseases, including asthma, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, and cystic fibrosis, as well as in severe acute conditions such as acute respiratory distress syndrome and severe pneumonia. Biofluid-derived EV-associated RNAs can reflect inflammation, immune dysregulation, epithelial injury, infection, and fibrosis, supporting their potential use in disease classification, monitoring, and prognostic assessment. Natural EVs may modulate inflammation and tissue repair through their endogenous cargo, while engineered EVs can deliver therapeutic nucleic acids to exert anti-inflammatory, anti-infective, antifibrotic, and barrier-restorative effects. However, clinical translation is limited by non-standardized isolation and characterization methods, product heterogeneity, variable cargo loading, and insufficient stability and quality-control frameworks. Continued advances in EV isolation, characterization, nucleic acid loading, potency assessment, and manufacturing control are required to realize the diagnostic and therapeutic potential of EV-associated nucleic acids in respiratory diseases. Full article