Search Results (272)

Background/Objectives: Non-pancreatic hyperlipasemia (NPHL) is associated with high in-hospital mortality, with sepsis being one of the most common etiologies. The prognostic value of hematological parameter-derived inflammatory scores has not been extensively studied in NPHL to date. Methods: The prognostic value of eight inflammatory scores for in-hospital mortality was assessed in a total of 545 NPHL patients from two hospitalized patient cohorts (COVID-19 [n = 144] and non-COVID-19 [n = 401], the latter stratified as bacterial sepsis [n = 111] and absence of systemic infection [n = 290]). We assessed the neutrophil-to-lymphocyte ratio (NLR), derived NLR (dNLR), neutrophil-to-lymphocyte and platelet ratio (N/(LP)), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), aggregate index of systemic inflammation (AISI), systemic inflammation index (SII), and systemic inflammation response index (SIRI), comparing their prognostic value among etiological groups. Results: Patients with bacterial sepsis were older, had more comorbidities, and experienced worse outcomes, including longer hospitalization (median: 15, 7, and 11 days; p < 0.001), higher ICU admission rates (75.7%, 33.8%, and 47.9%, p < 0.001), and increased mortality (45.0%, 13.8%, and 38.2%, p < 0.001), compared to those without systemic infection or with COVID-19-induced NPHL. Overall, NLR, dNLR, and N/(LP) were the most accurate predictors of in-hospital mortality at admission (AUROC: non-infection: 0.747; 0.737; 0.772; COVID-19: 0.810; 0.789; 0.773, respectively). The accuracy of NLR decreased in bacterial sepsis, and only N/(LP) and PLR remained associated with in-hospital mortality (AUROC: 0.653 and 0.616, respectively). Conclusions: The prognostic performance of hematological parameter-derived inflammatory scores in NPHL is etiology-dependent. NLR is the most accurate prognostic tool for mortality in the absence of bacterial sepsis, while N/(LP) is the best score in sepsis-induced NPHL. Full article

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

Overuse of antibiotics is a concern in ‘culture-negative sepsis’ but it is unclear whether this is due to infection with viruses, fungi or other microbes that are not easily cultured, or whether it results from inflammatory processes. In a prospective study, we enrolled 50 preterm neonates with culture-positive sepsis (CP), culture-negative sepsis (CN), and asymptomatic preterm controls (CO). The microbiome of stool, skin, and blood, including bacterial, viral and fungal components and serum cytokine profiles were evaluated. The microbiome alpha or beta diversity did not differ between CN and CO groups. A MaAsLin analysis revealed increased relative abundances of specific bacterial and fungal genera in stool and skin samples in the CN group compared to CO. The virome analysis identified 24 viruses from skin samples, but they were not statistically different among the three groups. The cytokine and chemokine biomarker profiles were elevated in the CP group but were not statistically different between the CN and CO groups. Although the CN group had a longer hospital stay and higher BPD rates than the controls in unadjusted analyses, these differences were not significant after adjusting for gestational age and birth weight. The CN infants demonstrated microbial shifts without systemic immune activation or significantly worse clinical outcomes, supporting the rationale for discontinuing antibiotics in the absence of positive cultures. 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: Bacterial co-infections in patients with viral pneumonia might increase mortality. In this study we aimed to evaluate their effect on the mortality of critically ill patients with viral pneumonia. Methods: A systematic search was conducted in PubMed, Web of Science, Scopus and Cochrane from inception until 30 March 2025. We included studies comparing the effect on mortality of bacterial co-infections in critically ill patients with viral pneumonia. The risk of bias was assessed by the Newcastle–Ottawa Scale. Results: From 3643 studies, 10 were included in our study with a total of 2862 COVID-19 patients and 4573 influenza patients. Seven studies were retrospective and three prospective. In total, 359/2862 of the COVID-19 and 904/4573 of the influenza patients were co-infected. Co-infections increased mortality in five out of the six studies evaluating COVID-19 patients and in two out of the eight studies evaluating influenza patients. Conclusions: The majority of the included studies were retrospective, which may limit the accuracy of these results. The exclusion of non-English literature may have led to the omission of relevant data. Based on our results, the impact of bacterial co-infection may be more pronounced in patients with COVID-19 pneumonia admitted to the ICU than in patients with influenza pneumonia. 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

Background: During the influenza A(H1N1) and COVID-19 pandemics, empirical antibiotic treatment (EAT) was widely administered to critically ill patients despite low rates of confirmed bacterial co-infection (COI). The clinical benefit of this practice remains uncertain and may contradict antimicrobial stewardship principles. Objective: To evaluate whether EAT at ICU admission reduces ventilator-associated pneumonia (VAP) incidence or ICU mortality in critically ill patients with pandemic viral pneumonia, stratified by presence of COI. Methods: This retrospective analysis combined two national multicentre ICU registries in Spain, including 4197 adult patients requiring invasive mechanical ventilation for influenza A(H1N1) or COVID-19 between 2009 and 2021. Primary outcomes were ICU mortality and VAP incidence. Analyses were stratified by microbiologically confirmed bacterial COI. Propensity score matching, Cox regression, General Linear (GLM), and random forest models were applied. Results: Among patients without COI (n = 3543), EAT was not associated with lower ICU mortality (OR = 1.02, 95%CI 0.81–1.28, p = 0.87) or VAP (OR = 1.02, 95%CI 0.79–1.39, p = 0.89). In patients with confirmed COI (n = 654), appropriate EAT was associated with reduced VAP (17.4% vs. 36.3%, p < 0.001) and ICU mortality (38.4% vs. 49.6%, OR = 1.89, 95%CI 1.13–3.14, p = 0.03) compared to inappropriate EAT. Conclusions: EAT was not associated with a lower incidence of VAP or higher survival rates and could be harmful if administered incorrectly. These findings support a more targeted approach to antibiotic use, guided by microbiology, biomarkers and stewardship principles. Full article

Background: The need for innovative therapeutic strategies to enhance patient outcomes has increased due to the rise in bacterial co-infections associated with COVID-19. Methods: In this study, ten hybrid compounds were synthesized by combining two known pharmaceutical scaffolds to enhance antibacterial activity and overcome resistance mechanisms. The synthesized compounds were evaluated for their antibacterial activity against five Gram-negative and seven Gram-positive bacterial strains. In silico pharmacokinetic and drug-likeness properties of selected active compounds (12–16, 19, 21, and 23) were predicted using the SwissADME web tool. Results: Compounds 12–16, 19, 21, and 23 demonstrated significant antibacterial activity, with compound 16 (a ciprofloxacin-containing hybrid) exhibiting the most potent effect, showing a minimum inhibitory concentration (MIC) of 7.8125 µg/mL against all tested bacterial strains. The in silico analysis revealed favorable pharmacokinetic profiles, drug-likeness, lipophilicity, and water solubility of most hybrid compounds. Discussion: The synthesized hybrid compounds exhibited enhanced antibacterial activity and desirable pharmacokinetic properties, particularly compound 16. These findings suggest the potential of these molecules in combating bacterial pathogens, especially those implicated in co-infections in COVID-19 infections. Conclusions: The study presents promising hybrid antibacterial agents with potential application as adjunct therapies for treating COVID-19-associated bacterial co-infections. Further investigation is needed, which may lead to effective treatments for managing secondary bacterial infections in viral disease contexts. Full article

Background/Objectives: Nucleoside precursors and derivatives play pivotal roles in the development of antimicrobial and antiviral therapeutics. The 2022 global outbreak of monkeypox (Mpox) across more than 100 nonendemic countries underscores the urgent need for novel antiviral agents. This study aimed to synthesize and evaluate a series of 5′-O-(palmitoyl) derivatives (compounds 2–6), incorporating various aliphatic and aromatic acyl groups, for their potential antimicrobial activities. Methods: The structures of the synthesized derivatives were confirmed through physicochemical, elemental, and spectroscopic techniques. In vitro antibacterial efficacy was assessed, including minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) determinations for the most active compounds (4 and 5). The antifungal activity was evaluated based on mycelial growth inhibition. Density functional theory (DFT) calculations were employed to investigate the electronic and structural properties, including the global reactivity, frontier molecular orbital (FMO), natural bond orbital (NBO), and molecular electrostatic potential (MEP). Molecular docking studies were conducted against the monkeypox virus and the Marburg virus. The top-performing compounds (3, 5, and 6) were further evaluated via 200 ns molecular dynamics (MD) simulations. ADMET predictions were performed to assess drug-likeness and pharmacokinetic properties. Results: Compounds 4 and 5 demonstrated remarkable antibacterial activity compared with the precursor molecule, while most derivatives inhibited fungal mycelial growth by up to 79%. Structure-activity relationship (SAR) analysis highlighted the enhanced antibacterial/antifungal efficacy with CH₃(CH₂)₁₀CO– and CH₃(CH₂)₁₂CO–acyl chains. In silico docking revealed that compounds 3, 5, and 6 had higher binding affinities than the other derivatives. MD simulations confirmed the stability of the protein-ligand complexes. ADMET analyses revealed favorable drug-like profiles for all the lead compounds. Conclusions: The synthesized compounds 3, 5, and 6 exhibit promising antimicrobial and antiviral activities. Supported by both in vitro assays and comprehensive in silico analyses, these derivatives have emerged as potential candidates for the development of novel therapeutics against bacterial, fungal, and viral infections, including monkeypox and Marburg viruses. 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

Uterine diseases in cattle are frequently linked to bacterial infections, with pathogens commonly isolated from the uterine lumen. Bovine Gammaherpesvirus Type 4 (BoGHV-4) is notably prevalent in certain regions of Argentina and is associated with uterine diseases in postpartum cattle. This study aims to evaluate the impact of platelet-rich plasma (PRP) on the gene expression related to BoGHV-4 infection in the presence of lipopolysaccharide (LPS), exploring the potential of PRP as a therapeutic alternative. The interaction between LPS and Toll-like receptor 4 (TLR4) plays a crucial role in inflammatory responses, triggering cytokine production and immune activation. Our results show that PRP modulates TLR4 and TNF-α gene expression, indicating a potential inhibitory role in inflammatory processes. Furthermore, PRP alter the temporal dynamics of BoGHV-4 replication by modulating the expression of the viral immediate–early gene (IE-2) and delaying proinflammatory cytokine responses such as IL-8. Notably, PRP enhances IFN-γ expression, which could help prevent tissue damage caused by bacterial and viral coinfection. These findings highlight the potential of PRP as an anti-inflammatory agent with therapeutic benefits in treating uterine diseases, offering an alternative to traditional antibiotic treatments. Full article

The CRISPR–Cas system has transformed molecular biology by providing precise tools for genome editing and pathogen detection. Originating from bacterial adaptive immunity, CRISPR technology identifies and cleaves genetic material from pathogens, thereby preventing infections. CRISPR–Cas9, the most widely utilized variant, creates double-stranded breaks in the target DNA, enabling genetic disruptions or edits. This approach has shown significant potential in antiviral therapies, addressing chronic infections, such as HIV, SARS-CoV-2, and hepatitis viruses. In HIV, CRISPR–Cas9 edits the essential viral genes and disrupts latent reservoirs, while CCR5 gene modifications render the T cells resistant to viral entry. Similarly, SARS-CoV-2 is targeted using CRISPR–Cas13d to inhibit the conserved viral genes, significantly reducing viral loads. Hepatitis B and C treatments leverage CRISPR technologies to target conserved genomic regions, limiting replication and expression. Emerging innovations, such as the PAC-MAN approach for influenza and base-editing systems to reduce off-target effects, further highlight the therapeutic versatility of CRISPR. Additionally, advances in Cas12a and Cas13 have driven the development of diagnostic platforms like DETECTR and SHERLOCK, which provide rapid and cost-effective viral detection. Innovative tools like AIOD-CRISPR enable accessible point-of-care diagnostics for early viral detection. Experimental approaches, such as targeting latent HSV-1 reservoirs, highlight the transformative potential of CRISPR in combating persistent infections. 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

Background and objectives: Acute gastroenteritis (AGE) remains a significant cause of morbidity in children, particularly in low- and middle-income countries. Viral pathogens, including rotavirus (RoV), norovirus (NoV), and adenovirus (HAdV), are among the leading causes of AGE. This study aimed to determine the prevalence of viral, bacterial, and parasitic enteric pathogens associated with AGE among hospitalized children in Northern Jordan. Materials and Methods: A total of 195 stool samples were collected from hospitalized children with AGE during the winter seasons of 2022–2024. Multiplex real-time qPCR assays were performed to detect common pathogens. The prevalence of each pathogen was determined, and co-infections were analyzed. Clinical symptoms, demographic characteristics, and associations between specific pathogens and disease severity were evaluated. Results: Viral pathogens were the predominant cause of AGE, with NoV detected in 53 cases (27.2%; of which 19.0% were NoV GI and 8.2% NoV GII), followed by RoV (24.1%), HAdV (20.0%), HAstV (13.3%), and SaV (12.3%). Co-infections were observed in several cases, particularly among viral infections evoked by RoV, HAdV, and NoV GI. Bacterial and parasitic infections were less prevalent, with Salmonella and Campylobacter spp. detected in 23.1% and 13.8%, respectively. Additionally, Cryptosporidium was identified in two cases (0.5%). Conclusions: Viral pathogens, particularly NoV, RoV, and HAdV, are the leading causes of AGE among hospitalized children in Jordan. Co-infections among viral pathogens were common, whereas bacterial and parasitic infections played a limited role in the disease burden. These findings emphasize the importance of continued surveillance and vaccination efforts, particularly for RoV, to reduce AGE-related hospitalizations in children. Full article