Search Results (263)

Respiratory syncytial virus (RSV) represents one of the main respiratory infections found among immunocompromised patients. Objective: The study analyzes the incidence of RSV infection in different populations of immunocompromised patients as organ transplant recipients (lung, other solid organs, hematopoietic stem cells) and oncologic patients (solid organ malignancy and hematological malignancy) compared to a group of non-immunocompromised patients. We also assessed the prevalence of viral, bacterial, and mycotic coinfection. Moreover, we aimed at evaluating the efficacy of ribavirin treatment in terms of mortality reduction. Methods: We conducted a retrospective analysis on a total of 466 transplant patients undergoing bronchoscopy with bronchoalveolar lavage for suspected viral disease or surveillance between 2016 and 2023, compared to 460 controls. Results: The incidence of RSV was significantly higher in immunocompromised patients, particularly in those with lung and bone marrow transplants. Among RSV+ patients, a higher prevalence of viral (influenza virus), bacterial (S. pneumoniae, M. pneumoniae, Nocardia spp.), and fungal (Aspergillus spp.) coinfections were observed. The efficacy of ribavirin in reducing mortality did not show significant differences compared to supportive therapy alone. Conclusions: The results of our exploratory study suggest that immunocompromised patients are particularly vulnerable to RSV infection and coinfections. Our hypothesis-generating data warrant the need for future studies aimed at exploring preventive and therapeutic strategies for RSV infection in these high-risk patient groups. Full article

Vaccine-induced thrombotic thrombocytopenia (VITT) is a rare thrombotic disorder first identified in 2021 as a catastrophic syndrome associated with anti-SARS-CoV-2 adenoviral vector (AdV)-vaccine administration. It is characterized by the presence of oligo- or monoclonal anti-PF4 antibodies able to induce in vitro platelet activation in the presence of PF4. In addition to this immune-based pathomechanism, random splicing events of the Adv-vector DNA encoding for SARS-CoV-2 spike protein resulting in the secretion of soluble spike variants have been postulated as a possible pathophysiological mechanism. More recently, some novel clinical-pathological anti-PF4-associated entities also characterized by thrombosis, thrombocytopenia, and VITT-like antibodies but independent from heparin or AdV-vaccine administration have been identified. To date, these VITT-like disorders have been reported following the administration of vaccines different from anti-SARS-CoV-2 AdV-vaccines, like human papillomavirus (HPV) and mRNA-based COVID-19 vaccines, following a bacterial or viral respiratory infection, and in patients with a monoclonal gammopathy of undetermined significance. The purpose of this review is to provide an update on the knowledge on VITT pathogenesis, focusing on recent findings on anti-PF4 antibodies, on a possible genetic predisposition to VITT, on VITT-antibody intracellular activated pathways, on lipid metabolism alterations, and on new VITT-like disorders. Full article

Background/Objectives: Recurring infections in children with allergies pose significant clinical challenges, with these conditions often exacerbating each other through complex immunological interactions. This narrative review examines the connection between recurring infections and allergic conditions in pediatric patients, focusing on how immune system dysfunction influences infection susceptibility in respiratory allergies. Methods: A comprehensive literature search across PubMed, Web of Science, and SciELO databases was conducted from January 2014 to May 2024. Studies involving children and adolescents up to 18 years old with diagnosed respiratory allergies were included, while reviews, opinion pieces, case reports, and studies not addressing immune–infection interactions were excluded. Results: Analysis reveals significant immune dysfunction in allergic children, affecting both innate and adaptive immunity components. Children with allergic rhinitis and asthma demonstrate decreased interferon-gamma production, increasing vulnerability to viral infections (particularly rhinovirus) and bacterial infections such as Mycoplasma pneumoniae. Rhinovirus represents the most common pathogen, present in 75% of asthma exacerbations. Atopic children exhibit markedly higher bacterial infection rates, with 27.1% showing Mycoplasma pneumoniae involvement versus 4.9% in non-atopic children. Conclusions: Recurring infections in allergic pediatric patients result from significant immune dysfunction involving altered cytokine production and immune cell function. These complex interactions highlight the need for targeted therapeutic approaches that enhance immune responses and reduce infection risks. Future research should focus on identifying specific biomarkers and immune mechanisms for developing more effective interventions. Full article

Conventional diagnostic methods (CDMs) for lower respiratory infections (LRIs) have limitations in detecting causative pathogens. This study evaluates the utility of shotgun metagenomic sequencing (SMS) as a complementary diagnostic tool using bronchoalveolar lavage (BAL) fluid. Sixteen BAL fluid samples from pneumonia patients with positive CDM results—including bacterial/fungal cultures; PCR for Mycobacterium tuberculosis or cytomegalovirus; and the BioFire^® FilmArray^® Pneumonia Panel (BioFire Diagnostics LLC, Salt Lake City, UT, USA)—underwent 10 Gb SMS on the Illumina NovaSeq 6000 platform (Illumina, San Diego, CA, USA). Reads were aligned to the NCBI RefSeq database; with fungal identification further supported by internal transcribed spacer (ITS) analysis. Antibiotic resistance genes (ARGs) were annotated using the Comprehensive Antibiotic Resistance Database. Microbial reads accounted for 0.00002–0.04971% per sample. SMS detected corresponding bacteria in 63% of cases, increasing to 69% when subdominant taxa were included. Fungal reads were low; however, Candida species were identified in four samples via ITS. No viral reads were detected. ARGs meeting perfect match criteria were found in two cases. This is the first real-world study comparing SMS with CDMs, including semiquantitative PCR, in BAL fluid for LRI. SMS shows promise as a supplementary diagnostic method, with further research needed to optimize its performance and cost-effectiveness. Full article

Background/Objectives: Infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a global pandemic with far-reaching impacts on human activities. Moreover, direct viral damage and uncontrolled inflammation have been proposed as contributing factors to the severity of SARS-CoV-2 disease. Lipopolysaccharide binding protein (LBP) is also well recognized for its capability to trigger and modulate the host’s innate immune system by attaching to bacterial substances. Nevertheless, the pandemic has further emphasized the critical role of an effective host immune response in controlling viral infection and highlighted the detrimental effect of immune dysregulation. This study aimed to assess plasma levels of LBP and inflammatory biomarkers in SARS-CoV-2 patients with different malnutrition status and severity levels. Methods: This cross-sectional study was carried out in King Khalid University Hospital in Riyadh from December 2020 to December 2021. A total of 166 SARS-CoV-2 patients were recruited including 80 critical and 86 non-critical patients. Medical history, anthropometrical parameters, disease outcome information, and relevant biochemical parameters were extracted from medical records. Plasma samples were collected to test for LBP and inflammatory cytokines. Finally, nutritional risk was assessed by the Nutrition Risk Screening-2002 (NRS-2002) tool. Results: This cross-sectional study found no significant differences in LBP levels between critical and non-critical SARS-CoV-2 patients. However, LBP levels significantly correlated with IL-10, TNF-α and IL-6/IL-10 levels (Spearman’s rho = 0.430, 0.276 and −0.397 respectively; p < 0.001). Conclusions: This study confirmed the elevated inflammatory cytokines in hospitalized SARS-CoV-2 patients and their association with disease severity and malnutrition. These findings may support the mechanism of gut inflammation in order to develop new interventions that lower inflammatory biomarkers, disease severity, and aid in SARS-CoV-2 prevention and management. Full article

Influenza A virus (IAV) is a major cause of respiratory illness in humans and animals. Secondary bacterial infections, especially those caused by Staphylococcus aureus (SA), significantly increase influenza-related morbidity and mortality. However, the mechanisms underlying these co-infections remain unclear. In this study, we examined how IAV infection influences SA-induced inflammation in lung epithelial cells. Our study was conducted based on in vitro experiments. First, we infected MLE-12 cells with IAV, confirming viral replication and the resulting cell damage. SA was then introduced 24 h or 36 h post-infection, and the cellular responses were measured. We assessed cell viability, cell-free DNA, Citrullinated histone H3, and the mRNA expression of TLR4 and proinflammatory cytokines. Our results showed that IAV+SA stimulation significantly increased upregulated TLR4 expression and inflammatory damage. To further explore TLR4’s role, we used the inhibitor TAK-242 and a TLR4 siRNA knockdown. Both approaches reduced the inflammatory response triggered by IAV and SA stimulation. These findings suggest that TLR4 is a key mediator in the enhanced inflammation observed during IAV and SA co-infection, offering a potential target for therapeutic intervention. Full article

The COVID-19 pandemic has had a profound impact on healthcare systems worldwide, with severe consequences on the global economy and society. The clinical presentation of SARS-CoV-2 infection varies widely, ranging from asymptomatic cases to severe disease and death. Coinfection with other respiratory pathogens in SARS-CoV-2-positive individuals may exacerbate symptom severity and lead to poorer clinical outcomes. Background/Objectives: This study is the first to investigate the prevalence of viral and bacterial co-infections in SARS-CoV-2-positive individuals in Cyprus. Methods: A total of 1111 SARS-CoV-2-positive nasopharyngeal swab samples collected from non-hospitalized patients were analyzed for the presence of 18 viral and 3 bacterial respiratory pathogens. Results: Of these, 51 samples (4.6%) were found to have at least one additional respiratory pathogen. The most frequently detected viruses were rhinovirus/enterovirus (n = 28; 2.5%) and adenovirus (n = 8; 0.7%), while the bacterial pathogens identified were Legionella pneumophila (n = 1; 0.1%) and Bordetella pertussis (n = 1; 0.1%). The highest proportion of co-infections was observed in the youngest age group (<10 years), where 52.9% of co-infections were identified, followed by the 30–39 age group, which accounted for 15.7% of cases. Among single respiratory virus co-infections, rhinovirus/enterovirus (27.5%) and adenovirus (13.7%) were the most frequently detected in the <10 age group, followed by RSV (3.9%), bocavirus, influenza B, HMPV A + B, and coronavirus NL63 (each at 2%). Conclusions: The current study underscores the importance of simultaneous testing for SARS-CoV-2 and other respiratory pathogens, as this may have significant implications for both individual patient care and healthcare services. Full article

Respiratory viruses are widespread in the community, affecting both the upper and lower respiratory tract. This review provides an updated synthesis of the epidemiology, pathophysiology, clinical impact, and management of severe respiratory viral infections in critically ill patients, with a focus on immunocompetent adults. The clinical presentation is typically nonspecific, making etiological diagnosis challenging. This limitation has been mitigated by the advent of molecular diagnostics—particularly multiplex PCR (mPCR)—which has not only improved pathogen identification at the bedside but also significantly reshaped our understanding of the epidemiology of respiratory viral infections. Routine mPCR testing has revealed that respiratory viruses are implicated in 30–40% of community-acquired pneumonia hospitalizations and are a frequent trigger of acute decompensations in patients with chronic comorbidities. While some viruses follow seasonal patterns, others circulate year-round. Influenza viruses and Pneumoviridae, including respiratory syncytial virus and human metapneumovirus, remain the principal viral pathogens associated with severe outcomes, particularly acute respiratory failure and mortality. Bacterial co-infections are also common and substantially increase both morbidity and mortality. Despite the growing contribution of respiratory viruses to the burden of critical illness, effective antiviral therapies remain limited. Neuraminidase inhibitors remain the cornerstone of treatment for severe influenza, whereas therapeutic options for other respiratory viruses are largely lacking. Optimizing early diagnosis, refining antiviral strategies, and systematically addressing bacterial co-infections are critical to improving outcomes in patients with severe viral pneumonia. Full article

Respiratory infections are the most common infectious diseases among children, representing a cause of death and generating a significant number of hospitalisations. The aim of the study was to analyse the epidemiological and clinical characteristics of viral pathogens causing respiratory tract infections in newborns and young children admitted to Galati pediatric hospital between October 2022 and December 2023. The diagnosis was performed using multiplex RT-PCR panels, which allowed simultaneous identification of respiratory pathogens (viruses and bacteria). From a total of 803 hospitalised patients with respiratory diseases, 607 (75.6%) children had a positive result for at least one respiratory virus and 96 patients (11.9%) were identified with bacterial infections. Mixed coinfections were found in almost half of the patients (44.5%). Most of RSV positive children had an increased length of stay, more than 7 days. It was shown a decline in severe cases of viral respiratory infections with prolonged hospitalisation as patients age up to 5 years. Full article

Inflammatory cardiomyopathy is a condition that is characterised by the presence of inflammatory cells in the myocardium, which can lead to a significant deterioration in cardiac function. The etiology of this condition involves multiple factors, both infectious and non-infectious causes. While it is primarily associated with viral infections, other potential causes include bacterial, protozoal, or fungal infections, as well as a wide variety of toxic substances and drugs, and systemic immune-mediated pathological conditions. In spite of comprehensive investigation, the presence of inflammatory cardiomyopathy accompanied by left ventricular dysfunction, heart failure or arrhythmia is indicative of an unfavourable outcome. The reasons for the occurrence of either favourable outcomes, characterised by the absence of residual myocardial injury, or unfavourable outcomes, marked by the development of dilated cardiomyopathy, in patients afflicted by the condition remain to be elucidated. The relative contributions of pathogenic agents, genomic profiles of the host, and environmental factors in disease progression and resolution remain subjects of ongoing discourse. This includes the determination of which viruses function as active inducers and which merely play a bystander role. It remains unknown which changes in the host immune profile are critical in determining the outcome of myocarditis caused by various viruses, including coxsackievirus B3 (CVB3), adenoviruses, parvoviruses B19 and SARS-CoV-2. The objective of this review is unambiguous: to provide a concise summary and comprehensive assessment of the extant evidence on the pathogenesis, diagnosis and treatment of myocarditis and inflammatory cardiomyopathy. Its focus is exclusively on virus-induced and virus-associated myocarditis. In addition, the extant lacunae of knowledge in this field are identified and the extant experimental models are evaluated, with the aim of proposing future directions for the research domain. This includes differential gene expression that regulates iron and lipid and metabolic remodelling. Furthermore, the current state of knowledge regarding the cardiovascular implications of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is also discussed, along with the open questions that remain to be addressed. Full article

This review article highlights the surveillance of bacterial, viral, and parasitic diseases in donkey populations in China. Key findings highlight significant threats from Equine herpesviruses (EHV-8 and EHV-1), which cause encephalitis, abortion, and respiratory distress. Several parasitic infections including Giardia duodenalis, Cryptosporidium spp., Enterocytozoon bieneusi, and Toxoplasma gondii present important zoonotic concerns across multiple regions of China. Additionally, this review synthesizes current knowledge on donkey microbiota across various body sites and examines their functional significance in health and disease. The complex relationship between the microbiota and host health represents a critical area of research in donkeys. Recent molecular advancements have enhanced our understanding of the diverse microbial ecosystems inhabiting different body sites in donkeys and their profound impact on health outcomes. As single-stomach herbivores, donkeys possess complex microbial communities throughout their digestive tracts that are essential for intestinal homeostasis and nutritional processing. Significant variations in microbiota composition exist across different intestinal segments, with the hindgut displaying greater richness and diversity compared to the foregut. Beyond the digestive system, distinct microbial profiles have been characterized across various body sites including the skin, oral cavity, reproductive tract, and body secretions such as milk. The health implications of donkey microbiota extend to critical areas including nutrition, immune function, and disease susceptibility. Research demonstrates how dietary interventions, environmental stressors, and physiological states significantly alter microbial communities, correlating with changes in inflammatory markers, antioxidant responses, and metabolic functions. Additionally, specific microbial signatures associated with conditions like endometritis and respiratory disease suggest the potential for microbiota-based diagnostics and therapeutics. The identification of antibiotic-resistant strains of Proteus mirabilis and Klebsiella pneumoniae in donkey meat highlights food safety concerns requiring enhanced monitoring systems and standardized safety protocols. These findings provide a foundation for improved donkey healthcare management, including targeted disease surveillance, microbiota-based interventions, and protective measures for those working with donkeys or consuming donkey-derived products. Full article

Background: The MeMed BV^® BV score is a novel, promising host-protein score, differentiating bacterial from viral infections, that combines the expression levels of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), interferon gamma-induced protein-10 (IP-10), and C-reactive protein (CRP). The aim of our study was to determine its diagnostic accuracy in hospitalized febrile children. Methods: A prospective study was performed from December 2023 to April 2024 in two pediatric clinics at “Aghia Sophia” Children’s Hospital, Athens, Greece. Patients > 3 months old, presenting with fever, clinical suspicion of acute infection, and symptoms onset up to 7 days prior were considered eligible. Patients with cancer, Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), Tuberculosis (TB), and immunodeficiency were excluded. Two pediatricians reviewed the clinical, laboratory, microbiological, and radiological data and assigned the final diagnosis. The experts were blinded to the BV scores. Results: One hundred and thirty-five patients were enrolled. The predominant medical condition was respiratory tract infection (59.3% lower, 26.7% upper). Twenty-nine (21.5%) patients were diagnosed with bacterial infections. The BV score demonstrated a sensitivity of 96.2%, specificity of 88.7%, and negative predictive value (NPV) of 98.9% for bacterial infections. Equivocal BV scores were reported in 8.9% of cases and were excluded from calculations. The area under the curve was 0.96 (95% CI: 0.93–0.99). A ROC curve analysis was performed, and the optimal cut-off score was estimated at 60, providing a sensitivity of 93.1%, specificity of 88.7%, and NPV of 97.9%. Conclusions: In our study population, the BV score showed high sensitivity and NPV in bacterial infection diagnosis. Further studies are needed to assess the possibility of replacing the “equivocal” range with a narrower one or a specific cut-off value. Full article

Background: Acute pharyngitis is one of the most prevalent disorders seen in general practitioners’ consultations. Most cases of acute pharyngitis in adults are caused by respiratory viruses and are self-limited. However, clinical manifestations of viral pharyngitis can overlap with bacterial pharyngitis, mainly caused by group A Streptococcus (GAS). A rapid antigen test for GAS can help diagnose streptococcal pharyngitis, but misdiagnosing S. pyogenes infection in a patient with a viral condition can lead to inappropriate antibiotic use. Some patients with a sore throat due to a virus or other causes will test positive for GAS because of carriage. The aim of our study was to analyze rapid strep test results in healthy adults. Methods: A cohort study was conducted in an outpatient clinic in Wroclaw. We used the rapid strep test BIOSYNEX STREP A. Results: A total of 350 healthy volunteers (≥18 years old) were enrolled in this study. The presence of Streptococcus pyogenes, based on a rapid strep test, was detected in 17 adults (4.9%). The strep test positivity rate was higher in younger adults. Conclusions: In healthy individuals in Poland, the prevalence of pharyngeal carriage of GAS is 4.9%. This finding emphasizes that the rapid antigen detection test should only be used in cases of suspected bacterial pharyngitis to avoid inappropriate antibiotic use. Full article

Lower respiratory infections, mostly caused by viral or bacterial pathogens, remain a leading global cause of mortality. The differences between animal models and humans contribute to inefficiencies in drug development, highlighting the need for more relevant and predictive, non-animal models. In this context, AlveolAir™, a fully primary in vitro 3D human alveolar model, was characterized and demonstrated the sustained presence of alveolar type I (ATI) and type II (ATII) cells. This model exhibited a functional barrier over a 30-day period, evidenced by high transepithelial electrical resistance (TEER). These findings were further validated by tight junctions’ confocal microscopy and low permeability to Lucifer yellow, confirming AlveolAir™ as robust platform for drug transport assays. Additionally, successful infections with H1N1 and SARS-CoV-2 viruses were achieved, and antiviral treatments with Baloxavir and Remdesivir, respectively, effectively reduced viral replication. Interestingly, both viruses infected only the epithelial layer without replicating in endothelial cells. These findings indicate AlveolAir™ as a relevant model for assessing the toxicity and permeability of xenobiotics and evaluating the efficacy of novel antiviral therapies. Full article

Background/Objectives: The viral pandemic caused by the SARS-CoV-2 virus has affected millions of people. However, it was noticed that high mortality was often a result of bacterial co-infections. One of the main pathogens responsible for secondary infections in patients with viral respiratory tract infections, including COVID-19, is Staphylococcus aureus. In recent years, the number of infections caused by drug-resistant strains of S. aureus has been growing rapidly, often exceeding the number of infections caused by antibiotic-sensitive strains. In addition, biofilm-related infections are more difficult to treat due to the lower sensitivity of biofilm structure to antibiotics. Bacteriophages are seen as alternative treatment of bacterial infections. Therefore, in our work, we have analyzed the efficacy of three Kayviruses against S. aureus strains isolated from COVID-19 patients. Methods: We analyzed the ability of tested phages to remove S. aureus biofilm both from polystyrene plates as well as from the surface of pulmonary epithelial cells. Results: We have observed that tested Kayviruses had a broad host range. Furthermore, phages were able to effectively reduce biofilm biomass and number of viable cells in pure culture. During our research, none of the tested phages was shown to have a negative effect on cell viability and were able to inhibit the negative effect S. aureus had on cell condition. Conclusions: Our results show tested phages were effective in reducing the biofilm of S. aureus strains isolated from COVID-19 patients, had no adverse effect on lung epithelial cell viability. Therefore, it should be recognized that the properties of three studied Kayviruses give them an advantage in the selection of phages for treatment of staphylococcal infections. Full article