Search Results (10,642)

Evidence on hospitalised COVID-19 patients during the Omicron BA.5 wave from Eastern European, vaccine-heterogeneous cohorts remains limited. We conducted a retrospective single-centre cohort study of 395 consecutive adults admitted with laboratory-confirmed COVID-19 to a tertiary infectious-diseases unit in western Romania between 1 July and 31 October 2022. Median age was 72 years (IQR 65–81); 33.2% were unvaccinated, 42.8% had documented prior SARS-CoV-2 infection, and 41.3% were obese. Multivariable logistic regression identified independent predictors of in-hospital mortality and post-acute symptom burden. In-hospital mortality was 15.7% (62/395). Vaccination was independently associated with lower mortality (adjusted odds ratio [aOR] 0.55, 95% CI 0.30–0.99; p = 0.048), as was each 1% increase in admission SpO₂ (aOR 0.83, 95% CI 0.76–0.92; p < 0.001), whereas COPD independently increased mortality risk (aOR 2.42, 95% CI 1.15–5.10; p = 0.020). Interleukin-6 was the most discriminating admission biomarker for in-hospital mortality (AUROC 0.70). Bloodstream bacterial co-infection, detected in 22.5% of patients tested on clinical suspicion, was dominated by gut-derived organisms with case-fatality ≥30%. At discharge, 90.1% reported persistent symptoms, most commonly cognitive (24.6%). Prior SARS-CoV-2 infection independently predicted post-acute symptom burden (aOR 2.96, 95% CI 1.75–5.01; p < 0.001), with a specific cardiopulmonary signature. In this BA.5 cohort, vaccination remained protective; IL-6 was the most informative admission biomarker; bloodstream infections suggested gut translocation; and prior infection was an independent determinant of early post-acute symptom burden. Full article

Bacterial membrane vesicles (BMVs), encompassing outer membrane vesicles (OMVs) released from Gram-negative bacteria and extracellular vesicles (EVs) released from Gram-positive bacteria, have emerged as promising vaccine platforms owing to their intrinsic immunostimulatory properties and capacity to deliver a wide range of antigens. Although conventional vaccines effectively prevent infectious diseases, their long-term efficacy is often limited by antigenic variation and reliance on a restricted number of licensed adjuvants. BMVs, as self-adjuvanting systems, enable both antigen delivery and innate immune activation. BMVs are nanoscale lipid bilayer structures enriched with pathogen-associated molecular patterns (PAMPs), facilitating their recognition and uptake by antigen-presenting cells. This leads to the activation of pattern recognition receptors and the induction of pro-inflammatory cytokines, type I interferons, and adaptive immune responses, including antibody production and Th1- and Th17-biased cellular immunity. Recent studies highlight the versatility of BMVs as vaccine platforms across bacterial, fungal, and viral infection models. BMVs induce protective immunity by promoting both systemic and mucosal immune responses, thereby reducing bacterial burden and limiting pathogen colonization across diverse infection models. These properties have supported their application in viral vaccine development, including influenza and SARS-CoV-2, with the potential to enhance mucosal immunity. Despite these advantages, challenges remain in standardization, safety, and antigen-loading efficiency. Engineered BMVs incorporating protein or mRNA antigens may further enhance antigen presentation and CD8⁺ T cell responses. This review summarizes the biological features, immunological mechanisms, and future potential of BMVs in vaccine development. Full article

Vitamin D has been implicated in immune modulation and susceptibility to respiratory infections, including COVID-19. However, data in asymptomatic pediatric populations, particularly those with household exposure, remain limited. This study aimed to investigate the association between serum vitamin D levels and hematological parameters with SARS-CoV-2 PCR positivity in asymptomatic children, and to evaluate their potential role in early risk stratification. This retrospective study included 127 asymptomatic children (aged 2–18 years) with confirmed household exposure to COVID-19. Participants were classified as PCR-positive (n = 74) or PCR-negative (n = 53). Serum 25(OH)D3 levels and hematological parameters were analyzed. Univariate and multivariable logistic regression analyses were performed to identify independent predictors. Receiver operating characteristic (ROC) curve analysis was used to assess discriminative performance, and a combined multimarker model was constructed. Serum vitamin D levels were significantly lower in PCR-positive children compared to PCR-negative children (17 ± 8 vs. 27 ± 11 ng/mL, p = 0.001). White blood cell (p = 0.002), platelet (p = 0.01), and neutrophil counts (p = 0.01) were significantly reduced, while basophil counts were higher in PCR-positive children (p = 0.02). In multivariable analysis, vitamin D (OR: 0.87, 95% CI: 0.82–0.93, p < 0.001), platelet (p = 0.02), neutrophil (p = 0.02), and basophil counts (p = 0.01) remained independent predictors. ROC analysis showed that vitamin D had moderate discriminative performance (AUC: 0.75, 95% CI: 0.67–0.83), while platelet (AUC: 0.64), neutrophil (AUC: 0.61), and basophil (AUC: 0.62) counts showed modest performance. The combined multimarker model demonstrated improved predictive ability (AUC: 0.80, 95% CI: 0.72–0.88), with sensitivity of 71.6% and specificity of 68.2%. Additionally, vitamin D deficiency was significantly more frequent in PCR-positive children (43% vs. 19%, p = 0.003). Conclusions: Lower vitamin D levels and associated hematological alterations are independently associated with SARS-CoV-2 PCR positivity in asymptomatic children. A combined biomarker approach may improve early risk stratification using simple and routinely available parameters. Further prospective studies are needed to validate these findings and clarify the role of vitamin D in preventive strategies. Full article

Background/Objectives: Maintenance hemodialysis patients are particularly vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This study aimed to evaluate clinical outcomes and identify admission laboratory biomarkers associated with in-hospital mortality in hospitalized hemodialysis patients with coronavirus disease 2019 (COVID-19). Methods: We conducted a retrospective observational study including 130 adult hemodialysis patients with confirmed SARS-CoV-2 infection. Clinical characteristics and admission laboratory parameters were analyzed in relation to in-hospital outcomes using comparative, multivariable logistic regression, and receiver operating characteristic (ROC) curve analyses. Results: The overall in-hospital mortality rate was 34.6%. The median age of the cohort was 66 years, with 64.6% male patients. Non-survivors showed significantly higher levels of inflammatory and tissue-injury markers, including C-reactive protein (CRP) (p < 0.001) and lactate dehydrogenase (LDH) (p < 0.001), together with lower serum albumin (p < 0.001), platelet count (p < 0.001), and lymphocyte levels (p = 0.03). In multivariable analysis, cardiovascular disease, respiratory disease, dyspnea, and ambulatory origin were independently associated with mortality. ROC analysis identified platelet count as the best individual predictor (area under the curve [AUC] = 0.767). An exploratory composite risk score demonstrated excellent discriminative performance (AUC = 0.902). Conclusions: Admission inflammatory and hematological biomarkers are strongly associated with adverse outcomes in hospitalized hemodialysis patients with COVID-19. The integration of clinical and laboratory parameters into a composite risk score may improve early risk stratification and support clinical decision-making in this high-risk population. Full article

Background: Risk factors for severe COVID-19 and in-hospital mortality are well described, but it remains unclear whether the same factors predict mortality after hospital discharge. Distinguishing risk profiles across clinical phases may improve patient management and follow-up strategies. Methods: We conducted a retrospective observational cohort study of 595 adults hospitalized with PCR-confirmed SARS-CoV-2 infection in Portugal (September–November 2020). The primary outcome was all-cause mortality during hospitalization and up to 120 days post-discharge. Secondary outcomes included intensive care unit (ICU) admission, maximum disease severity (WHO Clinical Progression Scale), oxygen supplementation, and length of stay. Univariable and multivariable regression analyses were performed using logistic regression for binary outcomes and linear regression for continuous outcomes. Results: Overall mortality was 22.5%, rising from 14.1% in-hospital to 22.5% at 120-day follow-up (p < 0.001), with 37.3% of deaths occurring post-discharge. ICU admission was required in 17.6% of patients and was significantly associated with obesity (OR = 2.12, 95% CI: 1.39–3.23, p < 0.001) and male sex (OR = 1.78, 95% CI: 1.14–2.78, p = 0.010) in univariable analysis. In contrast, post-discharge mortality was associated with longer hospital stay (18.4 vs. 9.9 days, p < 0.001) and a higher prevalence of malignancy (28.0% vs. 13.1%, p = 0.032), but not with ICU admission. In multivariable logistic regression, oxygen supplementation was the strongest predictor of 120-day mortality (OR = 2.50, 95% CI: 1.38–4.51, p = 0.002). Only pulmonary diseases and obesity were independently associated with maximum disease severity. Conclusions: Risk factors for acute COVID-19 severity differ from those for post-discharge mortality. These findings support a phase-specific approach to risk stratification, suggesting that patients with obesity are at increased risk of early respiratory deterioration, while patients with malignancy may benefit from closer post-discharge follow-up regardless of ICU admission status. Full article

Salivary gland infection by SARS-CoV-2 requires viral entry via routes and mechanisms that remain unresolved. This study examined the expression of the angiotensin-converting enzyme 2 (ACE2) receptor in salivary tissues and basal cell-derived human salivary progenitor cells (hS/PCs), an unstudied potential entry point for SARS-CoV-2. Multiple detection modalities, including immunocytochemistry, Western blotting, flow cytometry and RT-PCR, demonstrated a consistent lack of ACE2 protein and transcript in both tissue specimens and primary salivary epithelial cells. Antigen retrieval at pH 9 was determined to be optimal for immunodetection protocols, yet ACE2 remained undetectable. Small intestine tissue served as a positive control, confirming the validity of the methods and reagents we used. Considering there can be other receptors for SARS-CoV-2, flow cytometric analyses demonstrated that recombinant SARS-CoV-2 spike protein failed to bind to salivary epithelial cells, in contrast to HEK293 cells engineered to overexpress ACE2, which showed robust spike binding. Additional studies showed that patient-derived salivary cells, negative for ACE2, are not infected by the SARS-CoV-2 pseudovirus, while ACE2-positive cells are readily infected. These findings strongly support our conclusion that salivary cells do not serve as major targets for SARS-CoV-2 infection via ACE2, spike protein, or an alternate receptor. Thus, salivary cells are unlikely major targets for SARS-CoV-2 infection, either through direct exposure to viral particles in ductal fluids or via access to basal cells across the basement membrane. Full article

Background: Patients with COVID-19 often develop COVID-19-Associated Coagulopathy (CAC)—an imbalance between procoagulant and anticoagulant pathways resulting from the uncontrolled inflammatory response triggered by SARS-CoV-2 infection. This study aims to investigate the impact of a hematological and inflammatory parameter—the platelet-to-lymphocyte ratio (PLR)—on the severity and mortality of COVID-19. Methods: We conducted a comprehensive search of the PubMed database and yielded 75 articles published in the period of 2020–2025, of which 20 studies that evaluated the prognostic value of PLR on hospital admission in COVID-19 patients were included. The review particularly focuses on ROC analyses and reported AUC values. Results: A total of 20 studies were analyzed, including 13 studies assessing disease severity and 14 studies evaluating mortality. Higher PLR values have been observed in patients with a more severe course of COVID-19 compared to those with milder disease, and in non-survivors compared to survivors. However, the literature shows inconsistency regarding the diagnostic utility of PLR based on ROC curve analysis. The reported AUC values ranged from 0.559 to 0.811 for disease severity differentiation and from 0.474 to 0.758 for mortality, which may be related to the heterogeneity of the study populations included in the analysis. Conclusions: PLR may not serve as a direct bridge between inflammation and coagulation in COVID-19-Associated Coagulopathy, but it is indirectly linked to disease severity and mortality, as it reflects changes in both platelet and lymphocyte counts. It is a complementary marker that may assist clinicians in assessing COVID-19 patients but still requires further investigation. Full article

Human cytomegalovirus (HCMV) remains an important medical problem in multiple patient settings despite the availability of antivirals. In part, this is linked to resistance, cost and restrictions on use in several patient settings. More generally, it remains attractive to increase our arsenal of anti-viral approaches to target HCMV. We previously characterized a potent inhibitor of HCMV infection, DIDS, that displays cysteine reactivity, allowing it to bind virions and neutralize HCMV infection of fibroblasts. We now show that DIDS is inhibitory to cell-free and cell-associated infection of multiple cell types, including cells of the haematopoietic lineage—cells important for latency and dissemination. Consistent with this broad activity, DIDS partially inhibited gB (but not SARS-CoV-2 spike) fusion activity. Intriguingly, further characterization of DIDS activity in myeloid cells revealed that, unlike in all other cell types, DIDS blocked a post-entry event in CD14+ monocytes and also dendritic cell derivatives. Despite viral entry, entry was largely silent, with a failure to activate innate immunity and cell survival pathways known to be activated by HCMV. In contrast, HCMV infection was observed to activate host miRNA expression in CD14+ cells, suggesting a DIDS-insensitive viral function was responsible or, alternatively, that host miRNA expression is a potential anti-viral response to viral internalization. Thus, we report the further characterization of a broad-acting inhibitor of HCMV infection, which may also prove a useful tool to study unique events for the infection of monocytic cells by HCMV—a cell type that is crucial for HCMV dissemination and pathogenesis in vivo. Full article

Hemoglobin A1c is a central biomarker for long-term glycemic control and a key predictor of diabetes-related complications. The COVID-19 pandemic disrupted routine healthcare delivery and introduced potential metabolic effects of SARS-CoV-2 infection, yet the long-term impact of COVID-19 on glycemic trajectories in individuals with diabetes remains unclear. In this retrospective study, we leveraged harmonized electronic health record data from the National Clinical Cohort Collaborative to evaluate changes in HbA1c before and after documented SARS-CoV-2 infection in adults with diabetes (n = 93,320). Patients were required to have repeated HbA1c measurements pre- and post-infection and stable exposure to key antihyperglycemic medications. A paired statistical analysis was used to identify individuals with statistically significant post-infection changes in HbA1c. We then developed and evaluated multiple supervised machine learning classifiers using an 80/20 train–test split and cross-validation to assess demographic, clinical, and structural factors associated with significant glycemic change. Most patients (71%) did not experience a statistically significant change in average HbA1c following COVID-19 infection, and among those who did, decreases were more common than increases. A random forest classifier achieved the best overall performance, and feature importance and SHAP analyses highlighted body mass index, insulin use, age, and socioeconomic proxies as key contributors. These findings suggest that while COVID-19 infection does not substantially alter long-term glycemic control for most patients with diabetes, individual-level clinical and structural factors influence post-infection glycemic variability. Full article

Background/Objectives: Post-COVID-19 condition involves heterogeneous, multisystem symptoms with uncertain recovery. We characterized symptom trajectories from hospitalization to approximately 4 weeks and to 6–8 months and compared the 6–8-month symptom burden with season-matched controls, accounting for serology-identified, previously unrecognized infections. Methods: An individually pair-matched case–control study of adults with RT-PCR–confirmed SARS-CoV-2 and population controls from the Bialystok PLUS cohort, matched on age, sex and a two-month visit window, was performed. All participants underwent anti-nucleocapsid serology. Hospitalized cases were reassessed at approximately 4 weeks and 6–8 months. Cross-sectional outcomes used non-parametric tests and multivariable regression; longitudinal change used paired tests and generalized estimating equations. Results: We included 402 adults (201 post-COVID-19; 201 controls). In hospitalized cases, respiratory symptoms declined rapidly by approximately 4 weeks and remained low at 6–8 months; smell/taste recovered more slowly; fatigue improved modestly; anxiety changed minimally. At 6–8 months, total symptom counts were higher in post-COVID-19 than in controls (median 4 vs. 2), with serology-positive controls intermediate (median 3). Excess burden was concentrated in non-respiratory domains (fatigue, neurocognitive, cardiovascular, and dermatologic), whereas respiratory differences were not significant. In the multivariable model, female sex remained an independent predictor of higher multisystem burden, whereas age, body mass index, hospitalization, and acute biomarker severity were not associated. Conclusions: Six to eight months after symptomatic COVID-19, multisystem symptom burden remains substantial relative to season-matched controls, despite substantial resolution of respiratory complaints. Serology-based identification of previously unrecognized infections indicates an intermediate burden and can guide targeted follow-up. Full article

Background: Alopecia areata (AA) is an autoimmune disease characterized by diverse patterns of non-scarring hair loss. Due to its susceptibility to immune dysregulation and psychological stress, there is growing speculation regarding the potential role of SARS-CoV-2 infection and the COVID-19 pandemic in its development, recurrence, or exacerbation. This retrospective study aimed to evaluate patients affected by AA from a single dermatological center, specifically focusing on the impact of the COVID-19 pandemic on hospitalization rates. Methods: Data comprising demographic characteristics, disease subtype, number, and duration of hospitalizations were digitized and statistically analyzed. The five-year period prior to the pandemic (2015–2019) was compared with the subsequent four years (2020–2023) to assess any changes. Results: The study involved 428 individuals (256 children and 172 adults), with a slight predominance of women (68.2%). The median ages in adults and children were 39.13 years and 8.66 years, respectively. Following the pandemic, there was a 13.81% decrease in the mean age among adult males. Hospitalizations surged by 207.62% after the pandemic, increasing from 223 to 686 admissions. Additionally, the diagnosis of alopecia areata totalis increased significantly by 55.6%. The residential distribution of pediatric patients also shifted notably, with 72.16% residing in urban areas and 27.84% in rural areas between 2020 and 2023. Conclusions: The significant increase in hospitalization rates and the diversity of disease subtypes observed in this study may suggest a potential correlation between COVID-19 and the development or altered course of alopecia areata. A deeper understanding of this association could enhance treatment outcomes in dermatology, ultimately improving patient care. Full article

Background and Objectives: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy has raised concerns regarding possible fetal consequences, including potential effects on auditory system development. Although the current literature suggests that overt congenital hearing loss is uncommon among newborns exposed in utero, subtle cochlear functional alterations may not be detectable through conventional threshold-based screening alone. The objective of this study is to investigate whether in utero exposure to maternal COVID-19 is associated with early cochlear functional changes in newborns, as assessed by frequency-specific transient evoked otoacoustic emission (TEOAE) amplitude ratios, and to determine whether such alterations are accompanied by differences in click-evoked auditory brainstem response (ABR) thresholds. Materials and Methods: This prospective cohort study was conducted between October 2021 and September 2022 and included 61 pregnant women: 30 with laboratory-confirmed SARS-CoV-2 infection during pregnancy (study group) and 31 without documented infection (control group). All newborns underwent standardized audiological evaluation shortly after birth, including otoscopy, TEOAE, click-evoked ABR, and tympanometry. Frequency-specific TEOAE amplitude ratios at 500, 1000, 1500, 2000, and 4000 Hz were compared between groups. A logistic regression analysis was performed to identify audiological predictors of newborn exposure to SARS-CoV-2 in utero. Results: No significant differences were observed in ABR thresholds or in TEOAE “pass/refer” outcomes between the control and study groups, indicating the absence of clinically overt HL. However, newborns exposed to SARS-CoV-2 in utero showed significantly reduced TEOAE amplitude ratios at 2000 Hz (p = 0.0077) and 4000 Hz (p = 0.020). Logistic regression identified the 4000 Hz amplitude ratio as an independent negative predictor of in utero exposure (OR = 0.75; p = 0.0352). No significant differences were detected at lower frequencies. Conclusions: Maternal COVID-19 during pregnancy was not associated with immediate neonatal HL but was linked to subtle high-frequency cochlear functional modulation. Longitudinal audiological follow-up is needed to clarify the clinical significance of these findings. Full article

The surface spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a key target for the development of Coronavirus Disease 2019 (COVID-19) vaccines. Nevertheless, the mutations in the S protein, particularly in its receptor-binding domain region, have resulted in a reduced or complete loss of immunogenicity and/or protective efficacy in early vaccines against the Omicron variant and subvariants. Accordingly, continuous efforts are required to develop effective vaccines against multiple Omicron subvariants to reduce current and future threats. In this study, we designed an mRNA vaccine targeting the S protein of a recent Omicron-XEC subvariant (XEC-S-mRNA) and assessed its immunogenicity, including its broad neutralizing activity, and its protective efficacy against multiple Omicron subvariants. Our results demonstrated that the lipid nanoparticle-formulated mRNA vaccine formed an appropriate particle size with strong stability and successful antigen expression. It elicited durable cellular immune responses and broad neutralizing antibodies against multiple early and recent Omicron subvariants, thereby cross-protecting transgenic mice from challenge with a heterologous Omicron strain (KP.3). Moreover, the vaccine-induced neutralizing antibodies alone were sufficient to prevent Omicron-KP.3 infection. Overall, this study shows promise for further development of the candidate vaccine against current and future Omicron infections. Full article

This study evaluated the diagnostic usefulness of surfactant protein D (SP-D), chemokine C-C motif ligand 2/monocyte chemoattractant protein-1 (CCL2/MCP-1), and interleukin 18 (IL-18) in patients with SARS-CoV-2 infection. The authors focused on lung failure assessment, lung parenchyma involvement, and the early assessment of the risk of developing pulmonary fibrosis at the onset of COVID-19. The study group included 87 patients with COVID-19 and 45 healthy subjects. Concentrations of all three markers were measured using the enzyme immunoassay method. The serum SP-D, CCL2/MCP-1, and IL-18 concentrations were significantly higher in the COVID-19 patients before admission to the hospital than those in the controls (p < 0.001 for all comparisons). Differences were only found in the IL-18 levels between the groups categorized according to disease severity (p < 0.001); levels were significantly higher in patients with critical disease severity compared to those with moderate disease severity (p < 0.001). IL-18 also showed a positive correlation with the disease severity (p = 0.025). SP-D and IL-18 levels varied depending on the amount of oxygen administration (p = 0.017 and p < 0.001, respectively). Among the blood gas parameters, SP-D levels were negatively associated with the partial pressure of arterial oxygen (PaO₂) and oxygen saturation (O₂Sat) (p = 0.026 and p = 0.048, respectively), IL-18 with O₂Sat (p = 0.036), and CCL2/MCP-1 with PaO₂ (p = 0.042). SP-D and IL-18 were significantly negatively correlated with oxygen therapy (p = 0.003 and p = 0.014, respectively). Conversely, CCL2/MCP-1 was significantly positively correlated with the pulmonary involvement severity (p = 0.017) and level of hyaluronic acid (HA), a marker of fibrosis (p = 0.042). We also observed a significant correlation between the IL-18 level and the pulmonary involvement severity (p < 0.001), HA (p < 0.001), and other markers of fibrosis. In summary, our study’s results indicate that SP-D, CCL2/MCP-1, and IL-18 may be used to assess lung function in the early stage of COVID-19 infection; additionally, SP-D may serve as an indicator of alveolar injury, while CCL2/MCP-1 and IL-18 may be markers of lung parenchyma involvement and potential predictors of the development of pulmonary fibrosis. Full article

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects host cells through the interaction between the spike protein receptor-binding domain (RBD) and the human angiotensin-converting enzyme 2 (hACE2) receptor, which is expressed on epithelial cells in various tissues, including the respiratory tract. Therefore, mucosal immunity in the respiratory tract plays a key role in protection against viral infection. Previously, we demonstrated that intranasal administration of antigens (Ags) conjugated with the M cell-targeting peptide Co4B enhances both mucosal and systemic immune responses. That conjugation with human β-defensin 2 (HBD2) increases neutralizing antibody (Ab) responses. Methods: A recombinant antigen conjugate incorporating both Co4B and HBD2 was designed to enhance immunogenicity. Its immunogenicity was evaluated in mice following intranasal immunization. Antigen-specific antibody responses were measured in serum and bronchoalveolar lavage fluid. T-cell responses were evaluated in lungs and spleens. Protective efficacy was assessed using SARS-CoV-2-susceptible hACE2 knock-in mice. Results: Ag-specific Ab levels increased in both serum and bronchoalveolar lavage fluid of mice immunized intranasally with the conjugate. Especially, T-cell responses were significantly enhanced in the lungs and spleens of immunized hACE2 knock-in mice. In challenge experiments, intranasal administration of the conjugate reduced viral load. Moreover, Siglec F was identified as a potential receptor for Co4B, a previously uncharacterized M cell-targeting ligand. Conclusions: A recombinant viral Ag containing Co4B and HBD2 induces virus-specific humoral and cellular immune responses. Although further optimization of the vaccine formulation and administration strategy is needed, this conjugate shows potential as a platform for improving mucosal and systemic immunity. Full article