Search Results (7,577)

Cytomegalovirus (CMV) is a common cause of infection in immunocompromised individuals, such as patients with hematological malignancies or AIDS, but can also occur in patients with other acquired immunodeficiencies. In tissue-invasive diseases, CMV diagnosis requires CMV DNA in the plasma and the histological confirmation of CMV in a tissue or organ. Evidence of CMV colitis requires a characteristic endoscopic picture with ulcers with a well-defined, convex appearance and CMV viral inclusions in the form of an “owl’s eye” on mucosal sections stained with hematoxylin and eosin. CMV-specific immunohistochemistry is the gold standard for identifying CMV in tissue biopsies. It is important to consider a CMV infection in the diagnostic process, as it may delay the diagnosis and the treatment. We present the case of a 78-year-old patient with amiodarone interstitial lung disease who was treated with methylprednisolone. Two weeks after the start of his treatment, he was admitted to the hospital for acute gastroenterocolitis and Addisonian crisis. An examination had confirmed a tissue-invasive CMV disease. He was treated with valganciclovir for a total of six weeks. After the completion of treatment, the patient showed no clinical signs of CMV infection, and both laboratory and histological examinations revealed no residual CMV disease. Tissue-invasive CMV disease can occur in patients with acquired immunodeficiency, which may result from various causes, including glucocorticoid treatment. Full article

Lyme disease is the most common vector-borne disease in the United States. Recent environmental and socioecological changes have led to an increased incidence of Lyme and other tick-borne diseases, which enhances the urgency of identifying and mitigating adverse outcomes of Lyme disease exposure. Lyme disease during pregnancy, especially when untreated, may lead to adverse pregnancy and neonatal outcomes; however, long-term child outcomes following utero exposure to Lyme disease have not yet been systematically assessed. This concise review describes the current state of knowledge of Lyme disease as a congenital infection and the potential effects of in utero exposure to Lyme disease infection on the neurodevelopment of infants and children. We highlight the importance of distinguishing between acute Lyme disease and a chronic condition termed Post-Treatment Lyme Disease Syndrome, as the impacts of both conditions on the developing fetus and subsequent child development may differ. The importance of placental pathology for patients with acute or chronic symptoms of Lyme disease in pregnancy is explored. Future research aiming to understand and protect neurodevelopment after antenatal Lyme disease must carefully collect potentially confounding variables such as symptomatology and treatment, use clear and standard case definitions, and follow children into school-age and beyond. Full article

The aim of our research was to evaluate and analyze serum 25(OH) vitamin D and parathyroid hormone (PTH) levels to investigate whether vitamin D deficiency serves as a risk factor for an increased incidence of acute respiratory infections (ARI) in children. Serum PTH levels were used as an indicator of vitamin D sufficiency, as normal PTH levels require an optimal concentration of 25(OH) vitamin D. The study included 129 children, divided into five subgroups: children with acute bronchopneumonia (n = 42), acute laryngotracheitis (n = 7), acute bronchiolitis (n = 32), acute bronchitis (n = 18), and a control group (n = 30). No statistically significant differences in 25(OH)D levels were observed between the overall population of children with ARI and the control group (p = 0.073). However, significant differences in 25(OH)D levels were identified between the control group and children with bronchopneumonia, acute bronchitis, and laryngotracheitis (p < 0.01, p < 0.05). Regarding PTH levels, statistical significance was found between the control group and the acute bronchiolitis group, due to the high percentage of children with hypervitaminosis in this subgroup. These results highlight the crucial role of vitamin D in the onset and progression of acute respiratory tract infections in children, emphasizing its impact on their overall respiratory health. Full article

Acute Oak Decline (AOD), a bacterial disease previously known in Northern and Central Europe, has recently been reported in Salento (a Mediterranean coastal region of Southern Italy), where holm oak trees exhibiting AOD-like symptoms have tested positive for infection with AOD-related bacteria such as Brenneria goodwinii and Gibbsiella quercinecans. Sampling symptomatic trees, strains BLEC23 (B. goodwinii) and GSAC47 (G. quercinecans) were isolated and identified by partial 16S rRNA and gyrB gene sequencing. Pathogenicity tests demonstrate that these bacteria induce wood necrosis when inoculated in excised branches, providing details for the etiology of AOD in Italy. Phylogenetic analysis indicated a substantial genetic similarity between the Italian strains and those found in various European and non-European countries. These findings leave a space open to the possibility that the bacteria involved in AOD are much more widespread in Europe than the findings indicate, but that their presence is frequently hidden. Full article

Background/Objectives: This study aimed to compare the diagnostic accuracy of the Wells and Geneva scores using a 500 ng/mL D-dimer cutoff, as well as the age-adjusted D-dimer (AADD), YEARS, and pulmonary embolism graduated D-dimer (PEGeD) algorithms, in patients with and without COVID-19. Various D-dimer cutoffs were also evaluated. Methods: This retrospective study included emergency department patients who underwent computed tomography pulmonary angiography (CTPA) for suspected pulmonary embolism (PE). The diagnostic performances of clinical prediction algorithms were compared between COVID-19-positive and -negative groups. Results: We analyzed data from 1423 patients; the PE and COVID-19 positivity rates were 7.3% and 69.9%, respectively. In COVID-19-positive patients, the Wells score with a 500 ng/mL D-dimer cutoff demonstrated 97.22% sensitivity (95% CI: 80.53–100.00) and 4.99% specificity (95% CI: 3.58–6.39). Using AADD raised the specificity to 7.81% (95% CI: 6.08–9.54) while maintaining 97.22% sensitivity (95% CI: 93.43–100.00); similar findings were observed with the Geneva score. The YEARS algorithm had 86.11% sensitivity (95% CI: 78.12–94.10) and 32.75% specificity (95% CI: 29.73–35.78), whereas the PEGeD algorithm showed 86.11% sensitivity (95% CI: 78.12–94.10) and 34.06% specificity (95% CI: 31.00–37.12). Both algorithms demonstrated slightly improved specificity and accuracy in COVID-19-positive patients. Conclusions: The YEARS and PEGeD algorithms showed slight improvements in specificity and accuracy among COVID-19-positive patients. The Wells and Geneva scores maintained higher sensitivity but lower specificity across groups. Adjusting the D-dimer cutoffs increased the specificity but increased the risk of missed diagnoses. Overall, COVID-19 had a minimal impact on PE diagnostic algorithm performances. Full article

Monocytes are crucial players in innate immunity. The human cytomegalovirus (CMV) infection has significant impacts on monocyte effector functions and gene expression. CMV, a β-herpesvirus, disrupts key monocyte roles, including phagocytosis, antigen presentation, cytokine production, and migration, impairing their ability to combat pathogens and activate adaptive immune responses. CMV modulates monocyte gene expression, decreasing their capacity for antigen presentation and phagocytosis while increasing pro-inflammatory cytokine production, which can contribute to tissue damage and chronic inflammation. CMV also alters monocyte migration to sites of infection while promoting trans-endothelial migration, thus aiding viral dissemination. Additionally, the virus affects reactive oxygen species (ROS) production, thereby contributing to end-organ disease associated with CMV infection. Overall, these changes enhance viral persistence during acute infection and facilitate immune evasion during latency. We highlight the clinical significance of these disruptions, particularly in immunocompromised patients such as transplant recipients, where the modulation of monocyte function by CMV exacerbates risks for infection, inflammation, and graft rejection. An understanding of these mechanisms will inform therapeutic strategies to mitigate CMV-related complications in vulnerable populations. Full article

Background: Persistent alterations in taste and smell affect a significant proportion of individuals following COVID-19, representing a component of post-acute COVID-19 syndrome, commonly referred to as long COVID. The degradation of sphingomyelin by acid sphingomyelinase is regarded as a biomarker for acquired demyelinating neuropathies. Objectives: This study was aimed to enroll women who contracted COVID-19 during pregnancy and experienced persistent alterations in taste and/or smell for more than 1 year post-infection, in comparison to pregnant women without any disturbances in these senses. Methods: The patients were subjected to a questionnaire investigating smell and taste disorders more than 1 year after the infection. Then, the levels of acid sphingomyelinase in the plasma of the participants were assessed. Results: The results showed that in women who had been pregnant and who had been infected with SARS Cov-2 during the COVID period and who still had taste and smell disorders 1 year later, plasma acid sphingomyelinase levels were double that of pregnant women who had contracted the infection during the COVID period but had not reported taste and smell disorders and that of pregnant women analyzed after the COVID period. Conclusions: The results suggest a hypothesis that the persistence of sensory disturbances in long COVID was probably due to a failure to utilize brain circuitry with demyelination resulting from chemosensory dysfunction of the olfactory epithelium. Full article

West Nile Virus, an arthropod-borne RNA virus, may result in severe neurological disease. West Nile neuroinvasive disease is characterized by meningitis, encephalitis, and possible acute flaccid paralysis. Here, we report a case of neuroinvasive WNV in a 65-year-old woman hospitalized for hyperpyrexia, chills, intense asthenia, and continuous vomiting. Within days, her clinical condition worsened with the onset of severe neurological symptoms, leading to her death within 10 days despite supportive therapies being administered. The diagnosis of West Nile disease was made through nucleic acid amplification testing (NAAT) on blood and cerebrospinal fluid. However, in the final stages of the illness, cerebrospinal fluid collection was not possible due to the patient’s critical condition, and a nasopharyngeal swab was used instead. The nasopharyngeal swab facilitated the collection of a sample, which was subsequently analyzed for the presence of the virus and allowed for sequencing, showing that it was a strain that had been circulating in Sardinia for some time and had demonstrated its pathogenicity by causing the death of a hawk in 2021. This case report highlights the rapid progression and severity of WNV infection, particularly in vulnerable individuals, and suggests the potential utility of nasopharyngeal swabs as a less invasive option for sample collection. It also underscores the potential for the zoonotic transmission of the virus from birds to humans through vectors, emphasizing the importance of monitoring and controlling WNV outbreaks, especially in regions where such circulation is observed. Full article

Post-Coronavirus Disease 2019 (post-COVID-19) syndrome represents a cluster of persistent symptoms following Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection that can severely affect quality of life. The pathogenic mechanisms and epidemiology in different regions are still under evaluation. To assess the outcomes of post-COVID-19 syndrome, we performed a questionnaire-based, cross-sectional study in previously infected individuals. Out of 549 respondents, (male:female ratio: 0.32), 29.5% had persistent symptoms at 3 months, 23.5% had persistent symptoms at 6 months, and 18.3% had persistent symptoms at 12 months after the initial infection. The most common symptoms included fatigue (8.7%), sleep disturbances (7.1%), and cognitive impairment (6.4%). The risk of developing post-COVID-19 syndrome increased for those with more symptoms in the acute phase (OR 4.24, p < 0.001) and those experiencing reinfections (OR 2.405, p < 0.001), while SARS-CoV-2 vaccination halved the risk (OR = 0.489, p = 0.004). Individuals with post-COVID-19 syndrome had a 5.7-fold higher risk of being diagnosed with a new chronic condition, with 44% reporting cardiovascular disease, and a 6.8-fold higher likelihood of needing medical care or leave. Affected individuals reported significant impairments in mobility, pain/discomfort, and anxiety/depression, with 20.7% needing to adjust their work schedules. Overall, patients with post-COVID-19 syndrome require ongoing monitoring and rehabilitation, and further socio-economic impact studies are needed. Full article

The zoonotic transmission of influenza A viruses (IAVs) and coronaviruses (CoVs) may result in severe disease. Cleavage of the surface glycoproteins hemagglutinin (HA) and spike protein (S), respectively, is essential for viral infectivity. The transmembrane serine protease 2 (TMPRSS2) is crucial for cleaving IAV HAs containing monobasic cleavage sites and severe acute respiratory syndrome (SARS)-CoV-2 S in human airway cells. Here, we analysed and compared the TMPRSS2-dependency of SARS-CoV, Middle East respiratory syndrome (MERS)-CoV, the 1918 pandemic H1N1 IAV and IAV H12, H13 and H17 subtypes in human airway cells. We used the peptide-conjugated morpholino oligomer (PPMO) T-ex5 to knockdown the expression of active TMPRSS2 and determine the impact on virus activation and replication in Calu-3 cells. The activation of H1N1/1918 and H13 relied on TMPRSS2, whereas recombinant IAVs carrying H12 or H17 were not affected by TMPRSS2 knockdown. MERS-CoV replication was strongly suppressed in T-ex5 treated cells, while SARS-CoV was less dependent on TMPRSS2. Our data underline the importance of TMPRSS2 for certain (potentially) pandemic respiratory viruses, including H1N1/1918 and MERS-CoV, in human airways, further suggesting a promising drug target. However, our findings also highlight that IAVs and CoVs differ in TMPRSS2 dependency and that other proteases are involved in virus activation. Full article

Introduction: Cystic fibrosis transmembrane conductance regulator (CFTR) modulators have greatly improved outcomes in persons with CF (pwCF); however, there is still significant heterogeneity in clinical responses, particularly with regard to respiratory infection and inflammation. Exogenous administration of ketones has profound systemic anti-inflammatory effects and produces several nutrient-signaling and metabolic effects that may benefit multiple organ systems affected in pwCF. This pilot study was designed to determine the feasibility of administration of a ketone monoester (KME) to increase circulating D-beta hydroxybutyrate concentrations (D-βHB) and to improve subjective measures of CF-specific quality of life and markers of inflammation in serum and sputum in adults with CF. Methods: Fourteen participants receiving modulator therapy were randomized to receive either KME (n = 9) or placebo control (PC, n = 5) for 5–7 days during hospitalization for treatment of acute pulmonary exacerbation or as outpatients under standard care. Results: The KME was well tolerated, with only mild reports of gastrointestinal distress. D-βHB concentrations increased from 0.2 ± 0.1 mM to 1.6 ± 0.6 mM in the KME group compared to 0.2 ± 0.0 to 0.3 ± 0.1 in the PC group (p = 0.011) within 15 min following consumption and remained elevated, relative to baseline, for over 2 h. Pulmonary function was not altered after single- or short-term KME administration, but participants in the KME group self-reported higher subjective respiratory scores compared to PC in both cases (p = 0.031). Plasma inflammatory markers were not statistically different between groups following the short-term (5–7 d) intervention (p > 0.05). However, an exploratory analysis of plasma pre- and post-IL-6 concentrations was significant (p = 0.028) in the KME group but not PC. Sputum IFNγ (p = 0.057), IL-12p70 (p = 0.057), IL-1β (p = 0.100), IL-15 (p = 0.057), IL-1α (p = 0.114), and MPO (p = 0.133) were lower in the KME group compared to PC but did not achieve statistical significance. Conclusions: With the emerging role of exogenous ketones as nutrient signaling molecules and mediators of metabolism, we showed that KME is well tolerated, increases circulating D-βHB concentrations, and produces outcomes that justify the need for large-scale clinical trials to investigate the role of KME on whole-body and tissue lipid accumulation and inflammation in pwCF. Full article

In the detection of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), several methods have been employed, including the detection of viral ribonucleic acid (RNA), nucleocapsid (N) proteins, spike proteins, and antibodies. RNA detection, primarily through polymerase chain reaction tests, targets the viral genetic material, whereas antigen tests detect N and spike proteins to identify active infections. In addition, antibody tests are performed to measure the immune response, indicating previous exposure or vaccination. Here, we used the developed terahertz chemical microscope (TCM) to detect different concentrations of N protein in solution by immobilizing aptamers on a semiconductor substrate (sensing plate) and demonstrated that the terahertz amplitude varies as the concentration of N proteins increases, exhibiting a highly linear relationship with a coefficient of determination (R² = 0.9881), indicating that a quantitative measurement of N proteins is achieved. By optimizing the reaction conditions, we confirmed that the amplitude of the terahertz wave was independent of the solution volume. Consequently, trace amounts (0.5 μL) of the N protein were successfully detected, and the detection process only took 10 min. Therefore, this study is expected to develop a rapid and sensitive method for the detection and observation of the SARS-CoV-2 virus at a microdetection level. It is anticipated that this research will significantly contribute to reducing the spread of novel infectious diseases in the future. Full article

Long COVID or Post-Acute Sequelae of SARS-CoV-2 infection (PASC) is a condition characterized by numerous lingering symptoms that persist for weeks to months following the viral illness. While treatment for PASC is still evolving, several therapeutic approaches beyond traditional antiviral therapies are being investigated, such as immune-modulating agents, anti-inflammatory drugs, and various supportive interventions focusing at alleviating symptoms and enhancing recovery. We aimed to summarize the breadth of available evidence, identify knowledge gaps, and highlight promising non-antiviral therapies for Long COVID/PASC. We followed the framework of a scoping methodology by mapping existing evidence from a range of studies, including randomized clinical trials, observational research, and case series. Treatments evaluated include metformin, low-dose naltrexone (LDN), dexamethasone, statins, omega-3 fatty acids, L-arginine, and emerging therapies like intravenous immunoglobulin (IVIg) and therapeutic apheresis. Early findings suggest that metformin has the strongest clinical evidence, particularly from large phase 3 trials, while LDN and dexamethasone show potential based on observational studies. However, many treatments lack robust, large-scale trials. This review emphasizes the need for further research to confirm the efficacy of these treatments and guide clinical practice for Long COVID management. Full article

Backgroud: This prospective randomized trial evaluated the clinical efficacy of inhaled colistin administered through two distinct nebulizer types, a vibrating mesh nebulizer (VMN) and a jet nebulizer (JN), in the treatment of ventilator-associated pneumonia caused by multidrug-resistant bacteria. In addition, an in vitro model was used to determine the optimal delivery of colistin. Method: Thirty-two patients prescribed intravenous (IV) colistin inhalation were randomized to receive either a VMN (n = 17) or a JN (n = 15), then compared to the control group (IV alone) over a 7-to 10-day period. The primary endpoint was the clinical pulmonary infection score (CPIS), and the secondary endpoints were the Sequential Organ Failure Assessment (SOFA) score, Acute Physiology and Chronic Health Evaluation (APACE) score, and duration of ventilator use. Results: Results from in vitro testing demonstrated that VMN delivered a significantly higher colistin dose than JN (35.68 ± 3.55% vs. 23.56 ± 3.31%; p < 0.001) when positioned at the humidifier inlet. Compared to the IV alone group, the IV with inhalation group yielded significant improvements in CPIS, SOFA score, and APACHE score on day 7; nevertheless, clinical outcomes between the two nebulizers were statistically indistinguishable. Conclusions: In conclusion, although VMN delivers a higher dose in vitro, both nebulizers yielded comparable clinical outcomes. This study was registered at US Clinical Trial Registration (NCT04633317). Full article

Tularemia is an acute infectious disease classified as a natural focal infection, requiring continuous monitoring of both human and animal morbidity, as well as tracking of pathogen circulation in natural reservoirs and vectors. These efforts are essential for a comprehensive prevention and containment strategy. The causative agent, Francisella tularensis, comprises three subspecies—tularensis, holarctica, and mediasiatica—which differ in their geographic distribution and virulence. The ability to directly detect the pathogen and differentiate between subspecies has enhanced diagnostics and allowed a more accurate identification of circulation areas. Real-time PCR protocols for identification of F. tularensis subspecies tularensis and holarctica have been developed, utilizing specific primers and probes that target unique genomic regions. In this study, we present the development of a new real-time PCR assay for the detection of Francisella spp. and differentiation of F. tularensis subsp. mediasiatica. The specificity of the assay was tested on DNA from 86 bacterial species across 31 families unrelated to Francisella spp., as well as on DNA collections of F. tularensis subsp. mediasiatica and F. tularensis subsp. holarctica. The limit of detection (LOD95%) for real-time PCR in detecting Francisella spp. was 0.297 fg (0.145 genomic equivalents, GE) for holarctica DNA and 0.733 fg (0.358 GE) for mediasiatica DNA. The LOD95% for subspecies differential identification of mediasiatica was 8.156 fg (3.979, GE). The high sensitivity and specificity of these developed protocols enable direct detection of pathogens in biological and environmental samples, thereby improving the efficiency of tularemia surveillance in Kazakhstan. Full article